Hydroxybutyrate Dehydrogenase Research Articles

A Retrospective Study of Biological Risk Factors Associated with Primary Knee Osteoarthritis and the Development of a Nomogram Model.

A high percentage of the elderly suffer from knee osteoarthritis (KOA), which imposes a certain economic burden on them and on society as a whole. The purpose of this study is to examine the risk of KOA and to develop a KOA nomogram model that can timely intervene in this disease to decrease patient psychological burdens. Data was collected from patients with KOA and without KOA at our hospital from February 2021 to February 2023. Initially, a comparison was conducted between the variables, identifying statistical differences between the two groups. Subsequently, the risk of KOA was evaluated using the Least Absolute Shrinkage and Selection Operator method and multivariate logistic regression to determine the most effective predictive index and develop a prediction model. The examination of the disease risk prediction model in KOA includes the corresponding nomogram, which encompasses various potential predictors. The assessment of disease risk entails the application of various metrics, including the consistency index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, the calibration chart, the GiViTi calibration band, and the model for predicting KOA. Furthermore, the potential clinical significance of the model is explored through decision curve analysis (DCA) and clinical influence curve analysis. The study included a total of 582 patients, consisting of 392 patients with KOA and 190 patients without KOA. The nomogram utilized age, haematocrit, platelet count, apolipoprotein a1, potassium, magnesium, hydroxybutyrate dehydrogenase, creatine kinase, and estimated glomerular filtration rate as predictors. The C index, AUC, calibration plot, Giviti calibration band, DCA and clinical influence KOA indicated the ability of nomogram model to differentiate KOA. Using nomogram based on disease risk, high-risk KOA can be identified directly without imaging.

Prevalence and impact of viral myocarditis in patients with severe fever with thrombocytopenia syndrome.

To explore the association and impact between viral myocarditis and mortality in patients with severe fever with thrombocytopenia syndrome. A dynamic analysis was conducted between fatal group and nonfatal group regarding the daily epidemiology data, clinical symptoms, and electrocardiogram (ECG), echocardiogram, and laboratory findings. Outcomes of patients with and without viral myocarditis were compared. The association between viral myocarditis and mortality was analyzed. Among 183 severe fever with thrombocytopenia syndrome patients, 32 were in the fatal group and 151 in the nonfatal group; there were 26 (81.25%) with viral myocarditis in the fatal group, 66 (43.70%) with viral myocarditis in the nonfatal group (p < 0.001), 79.35% of patients had abnormal ECG results. The abnormal rate of ECG in the fatal group was 100%, and in the nonfatal group was 74.83%. Univariate analysis found that the number of risk factors gradually increased on Day 7 of the disease course and reached the peak on Day 10. Combined with the dynamic analysis of the disease course, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase fraction, lactate dehydrogenase, hydroxybutyrate dehydrogenase, neutrophil count, serum creatinine, Na, Ca, carbon dioxide combining power, amylase, lipase, activated partial thromboplastin time and thrombin time had statistically significant impact on prognosis. The incidence of fever with thrombocytopenia syndrome combined with viral myocarditis is high, especially in the fatal group of patients. Viral myocarditis is closely related to prognosis and is an early risk factor. The time point for changes in myocarditis is Day 7 of the course of the disease.

Evaluation of clinical characteristics and risk factors associated with Chlamydia psittaci infection based on metagenomic next-generation sequencing

IntroductionPsittacosis is a zoonosis caused by Chlamydia psittaci, the clinical manifestations of Psittacosis range from mild illness to fulminant severe pneumonia with multiple organ failure. This study aimed to evaluate the clinical characteristics of Chlamydia psittaci infection diagnosed based on metagenomic next-generation sequencing(mNGS), as well as the risk factors affecting the progress of Chlamydia psittaci infection, in order to improve the effect of therapeutics.MethodsWe retrospectively analyzed the clinical data of patients infected with chlamydia psittaci in the First Affiliated Hospital of Nanchang University from January 2021 to December 2021. The patient’s past medical history, clinical manifestations, laboratory examinations, chest CT results, treatment status, and prognosis data were collected. we also investigated both the pathogenic profile characteristics and the lower respiratory tract microbiota of patients with Chlamydia psittaci pneumonia using mNGS.ResultsAll cases of Chlamydia psittaci in our research have been confirmed by mNGS. Among 46 cases of Chlamydia psittaci pneumonia, Poultry exposure was reported in 35 cases. In severe cases of Chlamydia psittaci pneumonia, Neutrophils, Procalcitonin (PCT), Lactate Dehydrogenase (LDH), Hydroxybutyrate Dehydrogenase (HBDH), Creatine Kinase Isoenzymes-B (CK-MB) and D-Dimer levels were remarkably higher than that of non-severe cases, except for lymphocytes (all P < 0.05). Chest CT scans showed Bilateral (77.8%), multiple lobar lungs (85.2%), pleural effusions (44.4%) involvement in those suffering from severe Chlamydia psittaci pneumonia, whereas its incidence was 0%, 21.1% and 10.5% in non-severe patients, respectively (P < 0.05). Multivariate analysis revealed that higher lymphocyte concentrations (OR 0.836, 95% CI 0.714–0.962, P = 0.041) were the only protective factor for survival. mNGS results indicated that 41.3% of patients (19/46) had suspected coinfections with a coinfection rate of 84.2% (16/19) in the severe group, much higher than that in the non severe group (p < 0.05). No significantly different profiles of lower respiratory tract microbiota diversity were found between non severe group and severe group.ConclusionA history of poultry exposure in patients can serve as an important basis for diagnosing Chlamydia psittaci pneumonia, and patients with severe Chlamydia psittaci pneumonia are more likely to develop elevated inflammatory biomarkers as well as elevated cardiac markers. Higher lymphocyte concentrations are protective factors associated with severe C. psittaci pneumonia. The higher proportion of patients with coinfections in our study supports the use of mNGS for comprehensive early detection of respiratory infections in patients with C. psittaci pneumonia.

Effect of Yangxin Huoxue Jiedu recipe on inflammatory factors and oxidative stress on viral myocarditis in children.

This observation purposed to investigate the effect of the Yangxin Huoxue Jiedu formula on children with viral myocarditis and its effect on inflammatory factors and oxidative response. A total of 121 children with viral myocarditis were randomly divided into two groups, namely the control group (N = 60) and the traditional Chinese medicine group (N = 61). The control group was mainly treated with routine therapy, while the traditional Chinese medicine group was treated with Yangxin Huoxue Jiedu recipes based on the control group. The creatine kinase, creatine kinase myocardial isoenzyme, aspartate aminotransferase, lactic dehydrogenase, hydroxybutyrate dehydrogenase, cardiac troponin I, brain natriuretic peptide, interleukin-6, interleukin-8, and tumour necrosis factor-alpha, superoxide dismutase and malondialdehyde in viral myocarditis patients were tested to estimate the myocardial function, inflammation, and oxidative situation. After Yangxin Huoxue Jiedu treatment, 15 cases were recovered, 20 were excellent, and 21 were effective, which had a significant difference from the control group. The concentration of creatine kinase, creatine kinase myocardial isoenzyme, aspartate aminotransferase, lactic dehydrogenase, hydroxybutyrate dehydrogenase, cardiac troponin I and brain natriuretic peptide was decreased in the traditional Chinese medicine group. The levels of interleukin-6, interleukin-8, and tumour necrosis factor-alpha in the traditional Chinese medicine group were significantly lower than those in the control group. Superoxide dismutase was higher and malondialdehyde was lower than those in the control group. The use of Yangxin Huoxue Jiedu in the treatment of viral myocarditis has a definite clinical effect, which could improve myocardial function, reduce body inflammation, and promote oxidative recovery.

Why Do Empirical Valence Bond Simulations Yield Accurate Arrhenius Plots?

Computer simulations of the temperature dependence of enzyme reactions using the empirical valence bond (EVB) method have proven to give very accurate results in terms of the thermodynamic activation parameters. Here, we analyze the reasons for why such simulations are able to correctly capture activation enthalpies and entropies and how sensitive these quantities are to parametrization of the reactive potential energy function. We examine first the solution reference reaction for the enzyme ketosteroid isomerase, which corresponds to the acetate catalyzed deprotonation of the steroid in water. The experimentally determined activation parameters for this reaction turn out to be remarkably well reproduced by the calculations. By modifying the EVB potential so that the activation and reaction free energies become significantly shifted, we show that the activation entropy is basically invariant to such changes and that ΔS⧧ is instead determined by the specific mixture of the underlying force fields in the transition state region. The coefficients of this mixture do not change appreciably when the EVB potential is modified within reasonable limits, and hence, the estimate of ΔS⧧ becomes very robust. This is further verified by examining a more complex concerted hydride and proton transfer reaction in the enzyme hydroxybutyrate dehydrogenase.

Clinical manifestations and prognostic factors analysis of patients hospitalised with acute exacerbation of idiopathic pulmonary fibrosis and other interstitial lung diseases

BackgroundAcute exacerbation (AE) is a life-threatening condition taking place not only in idiopathic pulmonary fibrosis (IPF) but also in interstitial lung diseases (ILD) other than IPF (non-IPF ILD). This study...

Effects of long-term dehydration on stress markers, blood parameters, and tissue morphology in the dromedary camel (Camelus dromedarius).

Dromedary camels robustly withstand dehydration, and the rough desert environment but the adaptation mechanisms are not well understood. One of these mechanisms is that the dromedary camel increases its body temperature to reduce the process of evaporative cooling during the hot weather. Stress in general, has deleterious effects in the body. In this study, we sought to determine the effects of dehydration and rehydration on stress parameters in the dromedary camels and how it pacifies these effects. Nineteen male camels were randomly divided into control, dehydrated and rehydrated groups, and fed alfalfa hay ad-libitum. The dehydrated and rehydrated groups were water-restricted for 20 days after which the rehydrated camels were provided with water for 72 h. The control and dehydrated camels were slaughtered at day 20 from the start of experiment whereas the rehydrated group was killed 72 h later. Many biochemical, hematological histopathological parameters and gene analysis were performed in relevant tissues collected including blood, plasma, and tissues. It was observed that severely dehydrated camels lost body weight, passed very hard feces, few drops of concentrated urine, and were slightly stressed as reflected behaviorally by loss of appetite. Physiologically, the stress of dehydration elicited modulation of plasma stress hormones for water preservation and energy supply. Our results showed significant increase in cortisol, norepinephrine and dopamine, and significant decrease in epinephrine and serotonin. The significant increase in malondialdehyde was accompanied with significant increase in antioxidants (glutathione, retinol, thiamin, tocopherol) to provide tissue protection from oxidative stress. The physiological blood changes observed during dehydration serve different purposes and were quickly restored to normality by rehydration. The dehydrated/rehydrated camels showed reduced hump size and serous atrophy of perirenal and epicardial fat. The latter changes were accompanied by significantly increased expression of genes encoding proteins for energy production (ANGPTL4, ACSBG1) from fat and significantly decreased expression of genes (THRSP; FADS 1&2) encoding proteins enhancing energy expenditure. This process is vital for camel survival in the desert. Dehydration induced no major effects in the vital organs. Only minor degenerative changes were observed in hepatic and renal cells, physiological cardiomyocyte hypertrophy in heart and follicular hyperplasia in splenic but lipidosis was not depicted in liver hepatocytes. Ketone bodies were not smelled in urine, sweat and breathing of dehydrated animals supporting the previous finding that the ß hydroxybutyrate dehydrogenase, a key enzyme in ketone body formation, is low in the camel liver and rumen. Rehydration restored most of blood and tissues to normal or near normal. In conclusion, camels are adapted to combat dehydration stress and anorexia by increasing anti-stressors and modulating genes involved in fat metabolism.

The Prognostic Value of Common Cardiovascular Biomarkers in the Survival of Patients with DLBCL

Background Diffused large B-cell lymphoma (DLBCL) is a subgroup of highly heterogenous and aggressive hematological malignancy. IPI scoring tools have been used to predict survival in DLBCL patients retrospectively. Moreover, it is indicated that cardiovascular biomarkers can predict long-term survival in myelodysplastic syndrome. To structure a more accurate prognostic model directing survival, we constructed retrospective research in our clinical institution with common cardiovascular biomarkers, for instance, IL-6, Troponin I, BNP, hydroxybutyrate dehydrogenase and creatine phosphokinase. Besides, other risk factors of cardiovascular diseases such as lipids are also taken into consideration. Method We retrospectively researched a total of 284 patients who were first diagnosed with DLBCL from January 2011 to November 2022, among whom 205 patients were sequenced by next-generation sequencing (NGS) before receiving therapy. Characteristics of democracy and clinical data were collected and analyzed. The primary objective is to investigate the prognostic value of common cardiovascular biomarkers in the long-term survival of DLBCL patients. Results A total of 284 patients were enrolled with a median follow-up time of 21.8 months. The inclusive criteria are: patients who are newly diagnosed with DLBCL and clinical data of cardiovascular mark can be retrospect, moreover, to eliminate the influence of cardiac failure we excluded those whose ejection fraction was lower than 30%. There are 78 patients with high levels of BNP (HIGH-BNP group) and 119 patients with high levels of IL-6 (HIGH-IL6 group). In the HIGH-BNP group, overall survival is poorer than the control group (p&amp;lt;0.001, HR=3.07, 95%CI 1.97-4.78). Besides, in the HIGH-IL6 group, the tendency shows similitude, with a lower survival ratio (p=0.025, HR=2.65, 95%CI 1.30-5.40). Among 205 patients who received NGS sequencing, 2270 genes mutation have been detected. the most frequently detected genes are PIM1 (324, 14.3%), KMT2D (73, 3.2%), BCL6 (80, 3.5%), TP53 (63, 2.8%) and MYD88 (57, 2.5%). Conclusion Cardiovascular biomarkers can properly predict DLBCL patient survival.

Explainable machine-learning algorithms to differentiate bipolar disorder from major depressive disorder using self-reported symptoms, vital signs, and blood-based markers

Background and objectiveCaused by shared genetic risk factors and similar neuropsychological symptoms, bipolar disorder (BD) and major depressive disorder (MDD) are at high risk of misdiagnosis, which is associated with ineffective treatment and worsening of outcomes. We aimed to develop a machine learning (ML)-based diagnostic system, based on electronic medical records (EMR) data, to mimic the clinical reasoning of human physicians to differentiate MDD and BD (especially BD depressive episodes) patients about to be admitted to a hospital and, hence, reduce the misdiagnosis of BD as MDD on admission. In addition, we examined to what extent our ML model could be made interpretable by quantifying and visualizing the features that drive the predictions. MethodsBy identifying 16,311 patients admitted to a hospital located in western China between 2009 and 2018 with a recorded main diagnosis of MDD or BD, we established three sub-cohorts with different combinations of features for both the MDD-BD cohort and the MDD-BD depressive episodes cohort, respectively. Four different ML algorithms (logistic regression, extreme gradient boosting (XGBoost), random forest, and support vector machine) and four train-test splits were used to train and validate diagnostic models, and explainable methods (SHAP and Break Down) were utilized to analyze the contribution of each of the features at both population-level and individual-level, including feature importance, feature interaction, and feature effect on prediction decision for a specific subject. ResultsThe XGBoost algorithm provided the best test performance (AUC: 0.838 (0.810–0.867), PPV: 0.810 and NPV: 0.834) for separating patients with BD from those with MDD. Core predictors included symptoms (mood-up, exciting, bad sleep, loss of interest, talking, mood-down, provoke), along with age, job, myocardial enzyme markers (creatine kinase, hydroxybutyrate dehydrogenase), diabetes-associated marker (glucose), bone function marker (alkaline phosphatase), non-enzymatic antioxidant (uric acid), markers of immune/inflammation (white blood cell count, lymphocyte count, basophil percentage, monocyte count), cardiovascular function marker (low density lipoprotein), renal marker (total protein), liver biochemistry marker (indirect bilirubin), and vital signs like pulse. For separating patients with BD depressive episodes from those with MDD, the test AUC was 0.777 (0.732–0.822), with PPV 0.576 and NPV 0.899. Additional validation in models built with self-reported symptoms removed from the feature set, showed test AUC of 0.701 (0.666–0.736) for differentiating BD and MDD, and AUC of 0.564 (0.515–0.614) for detecting patients in BD depressive episodes from MDD patients. Validation in the datasets without removing the patients with comorbidity showed an AUC of 0.826 (0.806–0.846). ConclusionThe diagnostic system accurately identified patients with BD in various clinical scenarios, and differences in patterns of peripheral markers between BD and MDD could enrich our understanding of potential underlying pathophysiological mechanisms of them.

Downregulated Circulating Long Non-coding RNA GAS6-AS1 Screens and Predicts Acute Myocardial Infarction.

Acute myocardial infarction seriously threatens human health and life quality, which needs novel biomarkers to improve its early detection and development prediction. This study aimed to assess the potential of long non-coding RNA GAS6-AS1 in discriminating acute myocardial infarction patients and predicting patients' outcomes. The circulating expression of GAS6-AS1 in 83 acute myocardial infarction patients and 62 healthy individuals was evaluated using polymerase chain reaction. The value of GAS6-AS1 in the distinguishing acute myocardial infarction patients was evaluated with receiver operating characteristic analysis, and its prognosis predictive potential was assessed by Kaplan-Meier and Cox analysis. Additionally, the correlation of GAS6-AS1 with patients' critical features was evaluated by Spearman's correlation analysis. Significant downregulation of GAS6-AS1 was observed in the plasma of acute myocardial infarction patients relative to healthy individuals. Reduced GAS6-AS1 could discriminate acute myocardial infarction patients from healthy controls and indicate patients' unoptimistic prognosis. Moreover, GAS6-AS1 was found to be negatively cor-related with the levels of creatine kinase, creatine kinasemyocardial bland, lactic dehy-drogenase, hydroxybutyrate dehydrogenase, troponin T, and positively correlated with the ejection fraction of acute myocardial infarction patients. Changes in circulating GAS6-AS1 in acute myocardial infarction served as a potential diagnostic and prognostic biomarker of acute myocardial infarction.

A nomogram for predicting the severity of COVID-19 infections among patients in Chengdu, China

Introduction: Although most COVID-19 infections are currently mild, poor prognoses and fatalities continue to occur, which remain a threat to the safety of people in China. The goal of this study was to create an efficient model that combines the clinical characteristics with computed tomography (CT) scores at the time of admission to predict the severity of COVID-19. Methodology: A total of 346 COVID-19 patients in the current study, of whom 46 had severe infections and 300 had non-severe infections according to the clinal outcomes. Clinical, laboratory, CT findings, and CT scores at admission were collected. To identify the independent risk factors, univariable and multivariable logistic regression analyses were performed. A nomogram model was built with the extracted risk factors. The calibration curve and decision curve (DCA) operated to validate model performance. Results: The receiver operating characteristic curve indicated that the severity CT score had an area under the curve of 0.933 (95% CI, 0.901-0.965) and a cut-off value of 6.5 (sensitivity, 95.70%; specificity, 78%). The CT score, age, lactic dehydrogenase and hydroxybutyrate dehydrogenase levels, and hypertension were exacted for the nomogram. The nomogram had good calibration (P = 0.539) and excellent clinical value based on the DCA. Conclusions: The nomogram presented herein could be a valuable model to predict severe COVID-19 among patients in Chengdu, China.

Prognostic significance of modified lung immune prognostic index in osteosarcoma patients.

Purpose: Osteosarcoma is the most common primary malignancy of bone with a dismal prognosis for patients with pulmonary metastases. Evaluation of osteosarcoma prognosis would facilitate the prognosis consultation as well as the development of personalized treatment decisions. However, there is limited effective prognostic predictor at present. Lung Immune Prognostic Index (LIPI) is a novel prognostic factor in pulmonary cancers, whereas, the prognostic significance of LIPI in osteosarcoma has not yet been well clarified. In this study, we firstly explore the prognostic role of LIPI and further modify this predictive model in osteosarcoma. Patients and methods: A retrospectively study was conducted at Musculoskeletal Tumor Center of West China Hospital between January 2016 and January 2021. Hematological factors and clinical features of osteosarcoma patients were collected and analyzed. The area under curve (AUC) and optimal cuff-off of each single hematological factor was calculated. Results: In this study, lactate dehydrogenase (LDH), derived neurtrophil to lymphocyte ratio (dNLR), and Hydroxybutyrate dehydrogenase (HBDH) have higher AUC values. LIPI was composed of LDH and dNLR and was further modified by combing the HBDH, forming the osteosarcoma immune prognostic index (OIPI). OIPI divided 223 osteosarcoma patients divided into four groups, none, light, moderate, and severe (p < 0.0001). OIPI has a higher AUC value than LIPI and other hematological indexes in t-ROC curve. According to the univariate and multivariate analysis, pathological fracture, metastasis, NLR, platelet–lymphocyte ratio (PLR), and OIPI were associated with the prognosis; and metastasis and OIPI were independent prognostic factors of osteosarcoma patients. An OIPI-based nomogram was also established and could predict the 3-year and 5-year overall survival. In addition, OIPI was also revealed correlated with metastasis and pathological fracture in osteosarcoma. Conclusion: This study first explore the prognostic significance of LIPI in osteosarcoma patients. In addition, we developed a modified LIPI, the OIPI, for osteosarcoma patients. Both the LIPI and OIPI could predict the overall survival of osteosarcoma patients well, while OIPI may be more suitable for osteosarcoma patients. In particular, OIPI may have the ability to identify some high-risk patients from clinically low-risk patients.

Concurrence of osteonecrosis and steroid myopathy secondary to oral steroid therapy in a patient with ABCB1 gene polymorphisms: A case report

Glucocorticoids (GCs) are widely used in various autoimmune diseases. Side effects may occur in patients with long-term or high-dose GC usage. Among them, steroid myopathy and osteonecrosis are two severe forms. We report a patient with pemphigus vulgaris on GC-treatment who developed muscle weakness when a cumulative dose of methylprednisolone reached about 20g (14-80mg/d for 2.5 years). Laboratory tests showed slightly elevated lactate dehydrogenase and hydroxybutyrate dehydrogenase. MRI revealed osteonecrosis in the femoral head, distal femur, and proximal tibia of both legs. The biopsy of the right quadriceps revealed atrophy of type II myofiber without leukocyte infiltration, which was suggestive of steroid myopathy. Genotyping of the patient showed 5G/5G genotype of the PAI-1 gene and CC genotype of the ABCB1 gene (C3435T), suggesting she was sensitive to GCs. The patient’s lesions were considered to be GC-induced adverse events, which were improved with tapering GC. Therefore, it is important to recognize steroid-induced musculoskeletal side effects and genotyping favors personalized medication.

Effects of Fatty-Type and Lean-Type on Growth Performance and Lipid Droplet Metabolism in Pekin Ducks.

The reasons for differences in lipid depositions between fatty-type (F-T) and lean-type (L-T) ducks remain unknown. The present study aimed to compare the growth performance, lipid deposition, and gene expression related to lipid droplet formation in F-T and L-T Pekin ducks. One-day-old, 140 each L-T and F-T male ducks were selected and distributed separately into 20 replicate cages. All ducks were fed commercial diets up to 35 d of age. F-T ducks had a higher average daily gain from 21 to 28 d of age. On 35-day-old, F-T ducks had higher serum levels of high- and low-density lipoprotein cholesterol, cholesterol, albumin, and hydroxybutyrate dehydrogenase activity than L-T ducks. F-T ducks had higher abdominal fat and subcutaneous fat percentages than those in L-T ducks. Liver histological examination showed that L-T ducks contained more lipid droplets in the liver, which gradually decreased with increasing age. The average adipocyte area and diameter of abdominal fat and subcutaneous fat in the F-T and L-T ducks increased with age and were higher in F-T ducks than those in L-T ducks. Furthermore, the gene expression of perilipin 1, perilipin 2, angiopoietin-like protein 4, adipose triglyceride lipase, alpha/beta-hydrolase domain-containing protein 5 (ABHD5), and serine/threonine kinase 17a in the liver, abdominal fat, and subcutaneous fat of F-T ducks was higher than that in L-T ducks, and it increased with age. Compared to L-T ducks, F-T ducks had higher expression of ABHD5 in the abdominal fat and subcutaneous fat and lower expression in the liver. Thus, F-T ducks displayed lower hepatic lipid deposition and a higher percentage of abdominal fat and subcutaneous fat, suggesting that F-T ducks had higher lipid storage capacity due to increased gene expression related to lipid droplets.

An overview of prognostic value of neurologic and cardiac biomarkers in patients with COVID-19 sequelae.

Many studies conducted after the pandemic period revealed that, while COVID-19 primarily injured thelungs, it also affects other organs in the form of cardiovascular complications, metabolic derangements, renal damage, and so on. Although we know that inflammatory cascades, complement activation, and pro-inflammatory cytokines are all involved in vasculitic processes that cause organ damage, we do not know the exact mechanism ofcomplications such as acute respiratory distress syndrome (ARDS), cardiovascular ischemia, deep vein thrombosis, pulmonary thromboembolism, and brain injuries (embolism) that are frequently observed in COVID 19. The currently available biomarkers do not predict theseverity of the aforementioned complications. As aresult, more specific biomarkers such as serum calcium binding protein (S100B), glial fibrillary acid protein (GFAP), myelin basic protein (MBP), neuron-specific enolase (NSE), hs-TNI, (highly sensitive cardiac troponin)- HBDH, (Hydroxybutyrate Dehydrogenase), CK-MB (creatine kinase myocardial band), ST2 (suppression of tumorigenicity 2) are in need for early detection & improved clinical outcome.

New-onset COVID-19–related diabetes: an early indicator of multi-organ injury and mortally of SARS-CoV-2 infection

ObjectiveThe pandemic of 2019 coronavirus (SARS-CoV-2) disease (COVID-19) has imposed a severe public health burden worldwide. Most patients with COVID-19 were mild. Severe patients progressed rapidly to critical condition including acute respiratory distress syndrome (ARDS), multi-organ failure and even death. This study aims to find early multi-organ injury indicators and blood glucose for predicting mortality of COVID-19.MethodsFasting blood glucose (FBG) ≥7.0 mmol/L for two times during hospitalization and without a history of diabetes were defined as new-onset COVID-19-related diabetes (CRD). Indicators of injuries for multiple organs, including the lung, heart, kidney and liver, and glucose homeostasis were specifically analyzed for predicting death.ResultsA total of 120 patients with a severity equal to or greater than Moderate were hospitalized. After excluding patients with history of diabetes, chronic heart, kidney, and liver disease, 69 patients were included in the final analysis. Of the 69 patients, 23 were Moderate, 20 were Severe, and 26 were Critical (including 16 deceased patients). Univariable analysis indicated that CRD, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK) and creatinine (Cr) were associated with death. Multivariable analysis indicated that CRD was an independent predictor for death (HR = 3.75, 95% CI 1.26–11.15). Abnormal glucose homeostasis or CRD occurred earlier than other indicators for predicting poor outcomes. Indicators of multiple organ injury were in parallel with the expression patterns of ACE2 (the SARS-CoV-2 receptor) in different organs including pancreatic islet.ConclusionsNew-onset COVID-19-related diabetes is an early indicator of multi-organ injury and predictor for poor outcomes and death in COVID-19 patients. As it is easy to perform for clinical practices and self-monitoring, glucose testing will be helpful for predicting poor outcomes to facilitate appropriate intensive care.

Kinetic Characterization of a Crystallized Putative Hydroxybutyrate Dehydrogenase from the Opportunistic Pathogen Burkholderia cenocepacia

Burkholderia cenocepaciais an opportunistic pathogen posing risk among individuals with cystic fibrosis or who are immune compromised. The crystal structure of a putative hydroxybutyrate dehydrogenase (HBDH), based on sequence analysis, from Burkholderia cenocepaciahas been solved by the Seattle Structural Genomics Center for Infectious Disease and deposited in the Protein Database (PDB ID 4TRR). We sought to determine if the protein is an HBDH and to determine the kinetic parameters of the enzyme. HBDHs catalyze the reversible conversion of acetoacetate to hydroxybutyrate utilizing the cofactor NAD(H). The SSGCID kindly provided us the construct encoding a His‐tagged BcHBDH. The protein was overexpressed in E. coli, purified to approximate homogeneity using nickel affinity chromatography, and activity assayed spectrophotometrically. The putative BcHBDH is confirmed to have HBDH activity and the kinetic parameters for the enzyme were determined in both the direction of acetoacetate and hydroxybutyrate formation. BcHBDH has a catalytic efficiency of 2.85x104 mM‐1 sec‐1 and 1.21x105mM‐1 sec‐1 in the direction of hydroxybutyrate formation for acetoacetate and NADH, respectively. In the direction of acetoacetate formation, the enzyme has a catalytic efficiency of 4.1x103 mM‐1 sec‐1 and 2.86x104 mM‐1 sec‐1 for hydroxybutyrate and NAD+, respectively. By comparing both the structure and kinetic parameters to known kinetically characterized and crystallized HBDHs, we conclude the protein from Burkholderia cenocepacia is an HBDH.

Glutamine relieves the hypermetabolic response and reduces organ damage in severe burn patients: A multicenter, randomized controlled clinical trial

BackgroundSevere burns can cause a hypermetabolic response and organ damage. Glutamine is a conditionally essential amino acid with various pharmacological effects. In this study, whether glutamine could alleviate the hypermetabolic response and maintain organ function after burn injury was analyzed. MethodsA multicenter, randomized, single-blind, parallel controlled trial was conducted to evaluate the efficacy of glutamine in decreasing hypermetabolism after burn injury. Physiological and biochemical indexes, such as vital signs, metabolic hormones, metabolic rate, and organ damage, were recorded on the 7th and 14th days after treatment. ResultsIn total, 55 adult burn patients with a total burn surface area (TBSA) of 30–70% were included in this study and randomly divided into the burn control (B, 28 patients) and burn+glutamine (B+G, 27 patients) groups. Except for the glutamine administration, the groups did not differ in the other treatments and nutrition supplements. The levels of diamine oxidase (DAO), lactulose/mannitol (L/M), β2-microglobulin, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBD) and cardiac troponin l (cTnl) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). The levels of resting energy expenditure (REE), serum catecholamines, glucagon, lactate and Homeostasis model assessment (HOMA) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). No significant difference was found in the length of hospitalization or the mortality rate between the two groups (p > 0.05). ConclusionsGlutamine moderately alleviates the hypermetabolic response and reduces organ damage after severe burns. Therefore, the early application of glutamine, which is effective and safe, should be used as an active intervention as early as possible.

Serum hydroxybutyrate dehydrogenase and COVID-19 severity and mortality: a systematic review and meta-analysis with meta-regression.

Alterations in cardiac and renal biomarkers have been reported in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis to investigate serum concentrations of hydroxybutyrate dehydrogenase (HBDH), a combined marker of myocardial and renal injury, in hospitalized COVID-19 patients with different disease severity and survival status. We searched PubMed, Web of Science and Scopus, between December 2019 and April 2021, for studies reporting HBDH in COVID-19. Risk of bias was assessed using the Newcastle–Ottawa scale, publication bias was assessed with the Begg’s and Egger’s tests, and certainty of evidence was assessed using GRADE. In 22 studies in 15,019 COVID-19 patients, serum HBDH concentrations on admission were significantly higher in patients with high disease severity or non-survivor status when compared to patients with low severity or survivor status (standardized mean difference, SMD = 0.90, 95% CI 0.74 to 1.07, p < 0.001; moderate certainty of evidence). Extreme between-study heterogeneity was observed (I2 = 93.5%, p < 0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and the direction of the effect size were not substantially modified. A significant publication bias was observed. In meta-regression, the SMD of HBDH concentrations was significantly associated with markers of inflammation, sepsis, liver damage, non-specific tissue damage, myocardial injury, and renal function. Higher HBDH concentrations were significantly associated with higher COVID-19 severity and mortality. This biomarker of cardiac and renal injury might be useful for risk stratification in COVID-19. (PROSPERO registration number: CRD42021258123).

Comparison of Clinical Characteristics for Distinguishing COVID-19 From Influenza During the Early Stages in Guangdong, China.

Background: To explore the differences in clinical manifestations and infection marker determination for early diagnosis of coronavirus disease-2019 (COVID-19) and influenza (A and B).Methods: A hospital-based retrospective cohort study was designed. Patients with COVID-19 and inpatients with influenza at a sentinel surveillance hospital were recruited. Demographic data, medical history, laboratory findings, and radiographic characteristics were summarized and compared between the two groups. The chi-square test or Fisher's exact test was used for categorical variables, and Kruskal–Wallis H-test was used for continuous variables in each group. Receiver operating characteristic curve (ROC) was used to differentiate the intergroup characteristics. The Cox proportional hazards model was used to analyze the predisposing factors.Results: About 23 patients with COVID-19 and 74 patients with influenza were included in this study. Patients with influenza exhibited more symptoms of cough and sputum production than COVID-19 (p < 0.05). CT showed that consolidation and pleural effusion were more common in influenza than COVID-19 (p < 0.05). Subgroup analysis showed that patients with influenza had high values of infection and coagulation function markers, but low values of blood routine and biochemical test markers than patients with COVID-19 (mild or moderate groups) (p < 0.05). In patients with COVID-19, the ROC analysis showed positive predictions of albumin and hematocrit, but negative predictions of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), and erythrocyte sedimentation rate. Multivariate analysis revealed that influenza might associate with risk of elevated CRP, PCT, and LDH, whereas COVID-19 might associated with high HBDH.Conclusion: Patients with influenza had more obvious clinical symptoms but less common consolidation lesions and pleural effusion than those with COVID-19. These findings suggested that influenza likely presents with stronger inflammatory reactions than COVID-19, which provides some insights into the pathogenesis of these two contagious respiratory illnesses.