Blood Alanine Aminotransferase Research Articles

A Comparison of Kawasaki Disease during the SARS-CoV-2 Pandemic with Multisystem Inflammatory Syndrome in Children

Objectives: The purpose of this study was to compare and contrast Kawasaki disease (KD) with multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic. Methods: A retrospective analysis of the medical records of patients diagnosed with KD and MIS-C at a single institution from July 2020 to November 2021 was performed. Results: The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. The MIS-C patients were older (p < 0.001) and had prolonged hospitalizations (p = 0.023), elevated neutrophil counts (p < 0.001), C-reactive protein (p < 0.001), procalcitonin (p < 0.001), interleukin-6 (p < 0.014), ferritin (p < 0.001), fibrinogen (p < 0.001), troponin I (p = 0.001), NT-proBNP (p < 0.001), and D-dimer levels (p < 0.001). There were more cases of hypotension (p = 0.024), decreased left ventricular function (p = 0.023), and a greater need for corticosteroids (p < 0.001), enoxaparin (p = 0.045), and therapeutic plasma exchange (p < 0.001). Kawasaki disease patients had a greater incidence of rash (p < 0.001), changes in oral mucosa (p < 0.001), conjunctival injection (p < 0.001), extremity changes (p < 0.001), and cervical lymphadenopathy (p < 0.001). They had a longer duration of fever (p < 0.001), elevated white blood cell count (p < 0.001), platelet count (p < 0.001), and alanine aminotransferase level (p < 0.001). The two groups were similar regarding the hemoglobin levels, erythrocyte sedimentation rates, albumin levels, and the frequency of coronary aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Conclusions: Advanced patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas prolonged fever and classical clinical features of KD favor KD.

Clinical value of multiparameteric quantitative ultrasound for assessing high-risk steatohepatitis

Objective: To investigate the clinical value of multiparameteric quantitative ultrasound combined with a non-invasive prediction model for assessing high-risk steatohepatitis. Methods: One hundred and ninety-four cases with metabolic-associated fatty liver disease (MAFLD) who underwent liver biopsy in Huashan Hospital, Fudan University, from June 2021 to September 2022 were selected. Shear wave elastography (SWE), shear wave dispersion (SWD) imaging, and attenuation imaging (ATI) examinations were conducted in all patients before biopsy. High-risk steatohepatitis was defined as a total activity score of ≥4 in patients with steatohepatitis, hepatocellular ballooning, and liver lobular inflammation based on pathological hepatic steatosis, inflammatory activity, and fibrosis scoring system (SAF), and fibrosis stage≥F2. Binary logistic regression analysis was used to identify the factors influencing high-risk steatohepatitis. A predictive model for diagnosing high-risk steatohepatitis was constructed using R language. The DeLong test was used to compare the area under the curve between groups. Measurement data was compared between groups using the t-test or rank-sum test, and count data were compared between groups using the χ2 test. Results: There were 46 cases (23.7%) with high-risk steatohepatitis. The quantitative ultrasound parameters included elastic modulus (OR=2.958, 95%CI: 1.889-4.883, P<0.001), dispersion coefficient (OR=1.786, 95%CI: 1.424-2.292, P<0.001) and attenuation coefficient (OR=42.642, 95%CI: 3.463-640.451, P=0.004). Serological indexes of fasting blood glucose (OR=1.196, 95%CI: 1.048-1.392, P=0.011), alanine aminotransferase (OR=1.012, 95%CI: 1.006-1.019, P<0.001), aspartate aminotransferase (OR=1.027, 95%CI: 1.014-1.042, P<0.001), γ-glutamyl transferase (OR=1.008, 95%CI: 1.001-1.017, P=0.041) and HDL cholesterol (OR=0.087, 95%CI: 0.016-0.404, P=0.003) were the factors influencing its progression. The AUCs of elastic modulus, dispersion coefficient, attenuation coefficient, multiparametric ultrasound model, serological index model, and ultrasound combined with serology model for the diagnosis of high-risk steatohepatitis were 0.764, 0.758, 0.634, 0.786, 0.773 and 0.825, respectively. The results of the DeLong test showed that the ultrasound combined with the serological model was significantly better than the serological index model and the elastic modulus, dispersion coefficient, and attenuation coefficient alone (P=0.024, 0.027, 0.038 and <0.001). Conclusion: The combination of multiparametric quantitative ultrasound is helpful for the non-invasive diagnosis of high-risk steatohepatitis and possesses great clinical significance.

An evaluation of serum blood parameters and amyloid-A levels in women with hyperemesis gravidarum; A prospective observational study.

This study aimed to investigate whether serum amyloid A (AA) level can be used as a biomarker in women with hyperemesis gravidarum (HEG). This prospective observational study was conducted at the Antalya Training and Research Hospital Gynecology and Obstetrics Clinic, Türkiye, between July and December 2023. Forty women diagnosed with HEG and 40 healthy women were included. No statistically significant differences were observed between the groups in terms of sociodemographic data such as age, body mass index, family history, educational status, economic level, place of residence, occupation, smoking and alcohol use, or drug habits. However, obstetric characteristics such as number of miscarriages, number of dilatation curettages, and gestational age and laboratory values including complete blood count, hematocrit, leukocyte, neutrophil, lymphocyte, platelet, free T4, albumin, alanine aminotransferase, aspartate aminotransferase, urea, creatinine, hs-C-reactive protein, and sodium (P > .05) all differed significantly. In addition, significant differences were observed between the HEG and healthy groups in terms of numbers of gravidities (2 [1-3] vs 1 [0-1], respectively, P < .001), numbers of parities (1 [0-1] vs 1 [0-1], P < .001), numbers of living children (1 [0-2] vs 1 [0-1], P < .001), presenting complaints (nausea 0 [0%], nausea + vomiting 0 [0%], none 40 [100.0%] vs nausea 27 [67.5%], nausea + vomiting 13 [32.5%], none 0 [0%], P < .001), serum thyroid-stimulating hormone (1.16 ± 0.56 vs 1.81 ± 0.624, P = .004), potassium (4.1 ± 0.7 vs 3.8 ± 0.2, P = .001), and AA values (7.29 ± 2.61 vs 10.74 ± 3.04, P < .001). At receiver operating characteristic analysis, the area under the curve (AUC: 0.881) was statistically significant for serum AA (P: <.001), with a cutoff value of ≥ 8.79 ([95% confidence interval] 0.743-0.919, sensitivity 87.4%, specificity 80.2%). The positive predictive value of serum AA was 81.1% and the negative predictive value was 80.4%. The study results showed that serum AA can be used as a diagnostic biomarker in HEG. Prospective studies involving more participants are now required to confirm our results.

Percutaneous transhepatic papillary ballooning and extraction for common bile duct stones: a single-center experience.

At present, some common bile duct stones (CBDSs) cannot be removed by conventional endoscopic treatment. Percutaneous transhepatic papillary ballooning and extraction (PTPBE) is a promising treatment for CBDSs. This study aimed to evaluate the feasibility and efficacy of PTPBE for removing CBDSs. From April 2013 to April 2021, 29 patients with CBDSs underwent PTPBE at The First Affiliated Hospital of Zhengzhou University; their clinical data were retrospectively analyzed. The technical success, clinical success, procedure time, radiation dose, 1-year CBDSs recurrence rate, and incidence of early/late complications were recorded, and white blood cell (WBC) counts and alanine aminotransferase (ALT), C-reactive protein (CRP), total bilirubin (TBIL), and carbohydrate antigen-199 (CA-199) levels were compared before the interventional procedure and 1 month later. The CBDSs were successfully removed in 29 patients (the CBDSs in 20 patients were resolved once, and in 9 patients, they were resolved twice). The mean procedure time and radiation dose were 56.38±13.56 minutes and 732.07±262.23 miligray (mGy), respectively. The technical and clinical success rates were both 100%. The incidence of early complications (including pancreatitis and bile duct bleeding) and late complications (reflux cholangitis) was 10.34% and 3.45%, respectively. The WBC (both P<0.01), ALT (both P<0.01), CRP (both P<0.01), CA-199 (both P<0.01), and TBIL (both P<0.01) significantly decreased before PTPBE and 1 month later. PTPBE is a safe and effective alternative solution for elderly patients who cannot undergo or refuse traditional surgical and endoscopic treatments.

Signalment and laboratory findings in cats with diabetes mellitus in Germany: a retrospective review of laboratory submissions of 129,505 cats.

The aims of this study were to compare signalment and laboratory parameters between diabetic (D) and non-diabetic (ND) cats and poorly-controlled diabetic (PD) and well-controlled diabetic (WD) cats in Germany. Laboratory data from Antech Lab Germany between 2015 and 2018 were retrospectively analysed. Age, sex, red blood cell count (RBC), creatinine (CREA), alkaline phosphatase (AP), alanine aminotransferase (ALT), bilirubin (BILI), cholesterol (CHOL), triglycerides (TRI), glucose (GLU) and total thyroxine (TT4) were compared between D (fructosamine ⩾340 µmol/l) and ND cats, and PD (fructosamine >500 µmol/l) and WD (fructosamine 340-500 µmol/l) cats. The proportion of cats with anaemia (RBC ⩽4.21 ×1012/l), CREA >250 µmol/l, ALT >455 U/l, AP >315 U/l, BILI ⩾35 µmol/l and TT4 > reference interval (RI) was compared between PD and WD cats. Data are presented as median and interquartile range (IQR) and analysed using non-parametric tests. Significance was P<0.05, and effect size was assessed by Cramér V or r. In total, 129,505 cats were included (D: n = 9334 [prevalence 7.2%], WD: n = 5670/9334 [60.7%]). The median age of D and ND cats was 12 years (IQR D 9-14; ND 9-15); there was no difference in sex. A significant difference was found between groups (D vs ND; PD vs WD) for all parameters studied. Considering the effect sizes and medians outside the RI, the only relevant difference was higher CHOL, TRI, AP and GLU in PD compared with WD (CHOL: PD 7.46 [5.85-9.32] vs WD 5.44 [4.32-6.97] mmol/l, P<0.001, r = 0.39; TRI: PD 1.44 [0.84-3.66] vs WD 0.78 [0.5-1.35] mmol/l, P <0.001, r = 0.35; AP: PD 66 [47-92] vs WD 35 [23-59] U/l, P <0.001, r = 0.39; GLU: PD 23.7 [20.15-27.3] vs WD 6.89 [5-11.31] mmol/l, P <0.001, r = 0.69). Laboratory changes in diabetic cats were mild and mainly associated with lipid derangements.

Tannic Acid Suppresses Ferroptosis Induced by Iron Salophene Complex in Kidney Cells and Prevents Iron Overload-Induced Liver and Kidney Dysfunction in Rats.

Iron toxicity intricately links with ferroptosis, a unique form of cell death, and is significantly influenced by lipid peroxidation. Despite its critical role in various diseases and drug development, the association between iron toxicity and ferroptosis remains relatively unexplored. Accidental iron ingestion has emerged as a growing concern, resulting in a spectrum of symptoms ranging from gastrointestinal discomfort to severe outcomes, including mortality. This research introduces tannic acid (TA), which contains numerous phenol groups, as a powerful antiferroptotic agent. In male Wistar rats, even a modest dose of TA (7.5mg/kg) significantly curtailed thiobarbituric acid reactive substances (TBARS), a well-established indicator of lipid peroxidation, and mitigated iron accumulation induced by ferrous sulfate (FeSO4) in the liver and kidney. The evidence supporting TA's protective function against iron-triggered liver and kidney dysfunction was substantiated by assessing specifically the levels of blood urea nitrogen (BUN) and alanine aminotransferase (ALT). In cell models using ferroptosis inducers such as iron-salophene (FeSP) and RAS-selective lethal 3 (RSL3), tannic acid (TA) exhibited superior protective capabilities compared to the traditional iron chelator, deferoxamine (DFO). Nrf2 and HO-1, regulators of antioxidant defense genes, are implicated in controlling ferroptosis. The expression of Nrf2 and HO-1 increased with TA treatment in the presence of FeSP, indicating their role in reducing lipid ROS levels. Additionally, TA significantly reduced the heightened levels of COX2, a marker associated with ferroptosis. In summary, the remarkable antiferroptosis activity of TA is likely due to its combined iron-chelating and antioxidant properties. With its safety profile for oral consumption, TA may offer benefits in cases of accidental iron ingestion and conditions like hemochromatosis.

Prediction of Adverse Maternal Outcomes in Preeclampsia Using the FullPIERS (Preeclampsia Integrated Estimate of Risk) Model in a Tertiary Care Hospital of Eastern India.

Preeclampsia, characterized by hypertensive disorders and systemic inflammatory response, remains a leading cause of maternal morbidity and mortality globally. Effective risk assessment tools are crucial for predicting adverse maternal outcomes. This study evaluates the performance of the fullPIERS (Preeclampsia Integrated Estimate of Risk) model in predicting adverse maternal outcomes within 24 hours of admission for preeclampsia. A cross-sectional study was conducted over one year, involving 100 preeclamptic patients admitted to Nil Ratan Sircar Medical College & Hospital (NRSMCH). Predictor variables were collected within 24 hours of admission and analyzed using the fullPIERS model. The fullPIERS model effectively stratified maternal risk. Adverse outcomes were significantly associated with systolic blood pressure (BP) ≥ 140 mmHg, diastolic BP ≥ 90 mmHg, oxygen saturation ≤ 95%, frontal headache, visual disturbances, chest pain/dyspnea, and abnormal random blood sugar, albumin, alanine aminotransferase, platelet count, and creatinine levels. A fullPIERS score ≥ 30 was strongly predictive of adverse maternal outcomes. The fullPIERS model is a valuable tool for predicting adverse maternal outcomes in preeclampsia, aiding in timely and effective clinical decision-making.

Baseline and change in serum lipid and uric acid level over time and incident of nonalcoholic fatty liver disease (NAFLD) in Chinese adults

Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values < 0.05). The multivariable model showed that baseline BMI, diastolic blood pressure (DBP), TG, TC, HDL-C, LDL-C, UA, fT4, fT3, ALT and changes in TG, HDL-C, and UA were associated with the 1-year risk of developing NAFLD. The risk of NAFLD increased by 56% [OR 1.56, 95% Confidence Interval (CI) 1.32–1.87] and 40% (OR 1.40, 95% CI 1.19–1.64) for each standard deviation (SD) increase in altered TG values (1.01 mmol/L) and altered UA values (55 µmol/L) respectively. Conversely, for each SD (0.27 mmol/L) increase in HDL-C change, the 1-year risk of incident NAFLD was reduced by 50% (OR 0.50, 95% CI 0.40–0.62). The present study suggested that increases in TG and UA, and decreases in HDL-C, significantly increase the risk of developing NAFLD. Therefore, more attention should be paid to these factors in the management and prevention of NAFLD.

Ameliorative Potential of Ginger for Mitigating Liver Damage Caused by Fluopyram in Male Albino Rats

Fluopyram is a widely used new generation broad spectrum fungicide and a variety of biochemical and histopathological alterations in the livers of albino rats. These include inflammatory cells, dilated sinusoids, haemorrhage, dilation of central veins, congestion and presence of erythrocytes. Significant increase in blood alanine aminotransferase (ALT), aspartate amino transferase (AST), acid phosphatise (ACP) and decrease in alkaline phosphatise (AKP) enzyme levels were seen in high dose of fluopyram treated rats as compared to control. The oxidative stress and antioxidant enzymes showed a significant reduction in superoxide dismutase (SOD), catalase (CAT) and increase in malondialdehyde (MDA) level. Rats treated with fluopyram and ginger showed improved histopathological changes in liver. Ginger extract also showed decreased serum levels of malondialdehyde and raised serum levels of antioxidant enzymes. According to the current study, strong antioxidant activity of ginger mediates its protective effect against fluopyram induced liver damage.

Risk of low levels of blood group antibodies mediating hemolysis in ABO-incompatible neonates with negative three hemolysis tests.

To explore the risk of low-level blood group antibody-mediated hemolysis in ABO-incompatible newborns with negative three hemolysis tests, aiming to assist in the identification and management of neonatal jaundice. A retrospective case-control study was performed in 892 children with jaundice. The patients were divided into three groups: group I, ABO compatible, negative three hemolysis tests; group II, ABO incompatible, negative three hemolysis tests; and group III, ABO incompatible, positive three hemolysis tests. We analyzed the differences in clinical data, blood routine and biochemical laboratory results. (1) Patients in group II had higher levels of mean corpuscular volume (MCV), standard deviation of red blood cell volume distribution width (RDW-SD), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and bile acid (BA) than those in group I (P < 0.05). However, there were no statistically significant differences in the MCV, ALT, ALP and BA levels between groups II and III (P > 0.05). (2) Mean corpuscular hemoglobin concentration (MCHC) >359.5 g/L, cell volume distribution width (RDW-CV) >15.95%, and reticulocyte count (RET) >4.235% were identified as independent predictors of positive hemolysis test results (P < 0.001). The combination of MCHC, RDW-CV, and RET% yielded an AUC of 0.841. Low-level blood group antibody-mediated hemolysis may occur in ABO-incompatible neonates even when three hemolysis tests are negative. Changes in liver function parameters must be monitored. The combination of MCHC, RDW-CV, and RET% can be used to improve the detection rate of HDN.

Assessment of Liver Involvement in Patients With Type 2 Diabetes Mellitus in Basrah City, Iraq, Using FibroScan and Correlation With Risk Factors.

Background Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases caused by the accumulation of fat in the liver, which can progress to fibrosis, cirrhosis, and primary liver cancer. Insulin resistance is a causative factor in the development of NAFLD. FibroScan, or transient elastography, is a noninvasive imaging technique for evaluating liver disease. Aim To use FibroScan for evaluating liver involvement in type 2 diabetes mellitus (T2DM) patients with some associated risk factors. Materials and methods A cross-sectional prospective study was conducted from February to August 2023 in the outpatient clinic of Basrah Gastroenterology and Hepatology Hospital. Data collection included demographic data, past medical history, and biochemical tests including fasting blood sugar (FBS), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid profile (consisting of low-density lipoprotein (LDL), high-density lipoprotein (HDL), serum triglycerides, and total cholesterol), then, patients underwent FibroScan examination. Results The study included 50 patients with T2DM, of whom 23 (46%) were male and 27 (54%) were female. The mean age of the studied population was 47.72 ± 8.31 years, with a range of 28-64 years. The mean BMI was 28.44 ± 4.24, with most patients being either overweight or obese. The fibrosis score was 4.74 ± 1.02 kPa (stage 0), while the mean steatosis score was 282.88 ± 44.99 (grade III). Diastolic blood pressure (BP), serum ALT, and serum HDL level were the variables that showed statistically significant differences when compared according to the stages of steatosis measured by FibroScan, with p-values of 0.016, 0.048, and 0.028, respectively. Conclusion Some risk factors associated with diabetes, such as dyslipidemia, liver enzymes, and BP, are highly associated with the development of steatosis rather than fibrosis.

Coinfection of viruses in children with community-acquired pneumonia

BackgroundVirus, particularly respiratory tract virus infection is likely to co-occur in children with community-acquired pneumonia (CAP). Study focusing on the association between common viruses coinfection and children with CAP is rare. We aimed to study the association between seven common viruses coinfection and clinical/laboratory indexes in children with CAP.MethodsSix hundred and eighty-four CAP cases from our hospital were enrolled retrospectively. Seven common viruses, including influenza A (FluA), influenza B (FluB), human parainfluenza virus (HPIV), Esptein-Barr virus (EBV), coxsackie virus (CoxsV), cytomegalovirus (CMV), and herpes simplex virus (HSV) were investigated for their associations with CAP. We analyzed the differences of hospitalization days, white blood cell (WBC), c-reactive protein (CRP), platelet (PLT), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), urine red blood cell (uRBC), blood urea nitrogen (BUN), serum creatinine (Scr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CKMB) among different viruses coinfection groups by using one-way ANOVA analysis. The differences of clinical/laboratory indexes between ordinary and severe pneumonia groups, as well as non-virus vs multi co-infection viruses groups, and single vs multi co-infection viruses groups by using independent samples T test. Receiver operating characteristic (ROC) curve analyses were applied to test the the predictive value of the clinical/laboratory parameters for the risk of viruses coinfections among CAP. Binary logistic analysis was performed to test the association between various indexes and viruses co-infection.ResultsEighty-four multiple viruses coinfections yielded different prognosis compared with that in 220 single virus coinfection. CMV coinfection was associated with longest hospitalization days, highest ALT, AST and CKMB level. HSV coinfection was associated with highest WBC count, CRP, ESR, and BUN. EBV coinfection was associated with highest PLT and PCT level. FluB coinfection was associated with highest Scr level. CoxsV coinfection was associated with highest uRBC, LDH and CK level. ROC curve analyses showed that CK had the largest area under the curve (AUC: 0.672, p < 10–4) for the risk of viruses coinfections risk in CAP. Significant association between PLT, uRBC, BUN, CK, and CKMB and virus coinfection risk in CAP was observed.ConclusionsMultiple viruses coinfections indicated different prognosis. Different viruses coinfection yielded varying degrees of effects on the cardiac, liver, kidney and inflamatory injury in CAP. The alterations of clinical/laboratory parameters, particularly CK may be associated with the risk of viruses coinfections in CAP.

Inflammation patterns in early post-operative cholangitis predict long-term outcomes in biliary atresia: a potential role of non-suppurative cholangitis.

Frequent post-operative cholangitis in biliary atresia (BA) affects the long-term native liver survival. This study assessed the characteristics of early cholangitis and their influence on the prognosis. Forty-three patients with BA who underwent surgery between 2000 and 2020 were analyzed for routine inflammatory markers. Early cholangitis characteristics were compared between native liver survivor (NLS) and living donor liver transplant (LDLT) patients. Among the 43 patients, 30 (69.8%) experienced 130 episodes of cholangitis. In the area under the receiver operating characteristics curve (AUROC) analysis, the cutoff value of the total cholangitis episodes was 3, with an area under the AUROC curve of 0.695 (95% confidence interval 0.522-0.868). Before 3years old, 113 episodes (86.9%) of cholangitis were observed. The white blood cell, C-reactive protein, and alanine aminotransferase values at cholangitis onset did not markedly differ between the LDLT and NLS groups. Conversely, the neutrophil-to-lymphocyte ratio in the NLS group was significantly lower than in the LDLT group (0.85 vs. 1.63, p < 0.001). Cholangitis in the NLS group was lymphocyte-dominant and atypical in its pathogenesis. Lymphocyte-dominant cholangitis is non-suppurative, and future research should clarify its pathogenesis to improve the treatment and prognosis of BA.

Predictive value of plasma exosome count for the prognosis in septic patients

To investigate the predictive value of plasma exosome count for the prognosis of patients with sepsis. A prospective observational study was conducted. The patients with sepsis admitted to intensive care unit (ICU) of Zhejiang Hospital from November 2020 to December 2021 were enrolled as the study subjects. On the 1st day of admission to the ICU, the patient's gender, age, underlying disease, infection site, mean arterial pressure (MAP) and severity scores were recorded, and venous blood was taken for detecting the blood routine, blood biochemistry, and procalcitonin (PCT), and arterial blood was taken for blood gas analysis, simultaneously, the patient's noradrenaline (NA) dosage was recorded. On the 1st, 3rd, 5th, and 7th day of ICU admission, plasma exosomes were extracted, and the number of exosomes was detected by nanoparticle tracking analyzer. The endpoint of observation was the death of the patient 28 days after admission to the ICU. The differences in baseline data and plasma exosome counts of patients with different 28-day prognosis were analyzed and compared. The Spearman correlation method was used to analyze the correlation between plasma exosome counts and other clinical indicators. Binary multivariate Logistic regression analysis was used to screen the 28-day death risk factors of septic patients. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of each index on the 28-day death of septic patients. The Kaplan-Meier method was used to analyze the 28-day survival curve. A total of 26 patients with sepsis were enrolled, of whom 21 survived and 5 died on the 28th day. Compared with the survival group, the patients in the death group had lower MAP, higher sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, white blood cell count (WBC), cardiac troponin I (cTnI), and worse oxygenation. The plasma exosome count on the 1st day of ICU admission in the death group was significantly higher than that in the survival group (×1015/L: 16.96±9.11 vs. 5.20±2.42, P < 0.05). Subsequently, the plasma exosome counts in both groups continued to decrease, and there was no statistically significant difference between the two groups. Spearman correlation analysis showed that the plasma exosome count on the 1st day of ICU admission in septic patients was significantly positively correlated with SOFA score, APACHE II score, blood lactic acid (Lac), alanine aminotransferase (ALT) and NA dosage (r values were 0.572, 0.585, 0.463, 0.411, 0.696, all P < 0.05), and it significantly negatively correlated with MAP and oxygenation index (PaO2/FiO2; r values were -0.392 and -0.496, both P < 0.05). Multivariate Logistic regression analysis showed that plasma exosome count on the 1st day of ICU admission was an independent risk factor for 28-day death in septic patients [odds ratio (OR) = 1.385, 95% confidence interval (95%CI) was 1.075-1.785, P = 0.012]. ROC curve analysis showed that the area under the ROC curve (AUC) of plasma exosome count on the 1st day of ICU admission for predicting 28-day death in septic patients was 0.800 (95%CI was 0.449-1.000); when the optimal cut-off value was 14.50×1015/L, the sensitivity was 80.0% and the specificity was 100%. According to the optimal cut-off value of 1-day plasma exosome count, the patients were divided into two groups for Kaplan-Meier survival curve analysis, and the results showed that the cumulative survival rate of patients with plasma exosome count < 14.50×1015/L was significantly higher than that of patients with plasma exosome count ≥ 14.50×1015/L (Log-Rank test: χ 2 = 19.100, P < 0.001). The plasma exosome count of septic patients is significantly increased on the 1st day of admission to the ICU, which is related to the severity, and can predict the risk of death at 28 days.

Physiological Effects of Alloxan on Serum Glucose Levels and Liver Function Test in Male Rabbit

Diabetes is a metabolic disorder characterized by elevated blood glucose levels that can lead to various complications. Exploring the physiological alterations in rabbits can provide valuable insights for the development of therapeutic interventions. This research delves into the impact of diabetes on the physiological and biochemical parameters of male rabbits. Objectives: To compare the physiological parameters like body temperature, heart rate, respiration rate, and oxygen saturation) and body weight and biochemical parameters, including blood glucose levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, lactate dehydrogenase (LDH), and total protein levels in diabetic and non-diabetic rabbits. Methods: An experiment on 30 male rabbits divided into diabetic and control groups measured physiological parameters like body temperature, heart rate, respiration rate, and oxygen saturation. Body weight and blood glucose levels were tracked, and blood samples were taken for ALT, AST, creatinine, LDH, cholesterol, triglycerides and total protein levels. Statistical analysis was conducted to compare the physiological and biochemical parameters between the diabetic and control groups. Results: The results showed that induced diabetes in male rabbits affects their physiological and biochemical parameters significantly. Diabetic rabbits had lower body temperature, heart rate, respiration rate, and oxygen saturation compared to the control group. They also had higher body weight and blood glucose levels. Biochemical analysis showed increased ALT, AST, and creatinine levels, and decreased LDH and total protein levels in diabetic rabbits. Conclusions: These results demonstrate the extensive impact of diabetes on rabbit physiology and biochemistry, offering insights for future diabetes research.

A random forest model to predict the efficacy of KL-A167 in previously treated recurrent or metastatic nasopharyngeal carcinoma based on the data from the KL167-II-05-CTP study.

e18012 Background: KL-A167 is a fully humanized monoclonal antibody targeting programmed cell death-ligand 1. KL167-Ⅱ-05-CTP study had evaluated the efficacy and safety of KL-A167 in Chinese patients with previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). The results of KL167-Ⅱ-05-CTP study showed that not all patients with R/M NPC could benefit from KL-A167 therapy, and an effective model to predict the efficacy of KL-A167 is necessary. Methods: The baseline data of clinical characteristics, laboratory examination and imaging of patients with R/M NPC in KL167-Ⅱ-05-CTP study were collected, who received KL-A167 therapy. The progression-free survival (PFS) was selected as the predicted variable. Patients were randomly divided into training cohort (70%) and test cohort (30%). In the training cohort, uni-Cox regression was used to estimate the value in predicting PFS, and least absolute shrinkage and selection operator (LASSO)-Cox regression was performed to screen clinical, laboratory and imaging indexes to build random forest model. The accuracy of this random forest model was validated in the test cohort. Results: In this study, 137 patients with R/M NPC were enrolled, and the median PFS of them was 2.689 (95% confidence interval [ CI]: 1.475-4.098) months. A total of 14 indexes with P &lt; 0.05 were selected to perform LASSO-Cox regression, and 10 indexes (blood lactate dehydrogenase, blood creatinine, left ventricular ejection fraction, body temperature, weight, blood lymphocyte count, blood chloride ion concentration, Eastern Cooperative Oncology Group performance status, blood triglyceride and blood alanine aminotransferase) were used to build prediction model. The C-index of risk score from this model was 0.820 and 0.790 in the training and test cohort, respectively. Patients were divided into the high and low risk groups according to the median risk score, and the median PFS of the high risk group was shorter than that of the low risk group (training cohort: 1.377 vs. 4.197 months, P &lt; 0.001, hazard ratio [ HR] = 1.142, 95% CI: 1.111-1.175; test cohort: 3.475 vs. 10.984 months, P &lt; 0.001, HR = 1.100, 95% CI: 1.060-1.142). Conclusions: In this study, a random forest model based on 10 clinical, laboratory and imaging indexes was constructed and showed a potential value in predicting the PFS of KL-A167 therapy in Chinese patients with previously treated R/M NPC, which could help to guide clinical trials and practices.

The safety and feasibility of laparoscopic anatomical left hemihepatectomy along the middle hepatic vein from the head side approach

BackgroundLaparoscopic left hemihepatectomy (LLH) is commonly used for benign and malignant left liver lesions. We compared the benefits and drawbacks of LLH from the head side approach (LLHH) with those of conventional laparoscopic left hemihepatectomy (CLLH). This study was conducted to investigate the safety and feasibility of LLHH by comparing it with CLLH.MethodsIn this study, 94 patients with tumor or hepatolithiasis who underwent LLHH (n = 39) and CLLH (n = 55) between January 2016 and January 2023 were included. The preoperative features, intraoperative details, and postoperative outcomes were compared between the two groups.ResultsFor hepatolithiasis, patients who underwent LLHH exhibited shorter operative time (p = 0.035) and less blood loss (p = 0.023) than those who underwent CLLH. However, for tumors, patients undergoing LLHH only showed shorter operative time (p = 0.046) than those undergoing CLLH. Moreover, no statistically significant differences in hospital stay, transfusion, hospital expenses, postoperative white blood cell (WBC) count, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were observed between the two groups (p &amp;gt; 0.05) for tumor or hepatolithiasis. For hepatocellular carcinoma (HCC), no differences in both overall survival (p = 0.532) and disease-free survival (p = 0.274) were observed between the two groups.ConclusionLLHH is a safe and feasible surgical procedure for tumors or hepatolithiasis of the left liver.

Effects of acute carbon monoxide poisoning on liver damage and comparisons of related oxygen therapies in a rat model

Acute carbon monoxide (CO) poisoning may cause liver damage and liver dysfunction. Therefore, in this study, we aimed to compare the efficiency of normobaric oxygen (NBO) and high-flow nasal cannula oxygen (HFNCO) treatments on liver injury. For that purpose, 28 male Wistar albino rats were divided into four groups (Control, CO, CO + NBO, and CO + HFNCO). The control group was allowed to breath room air for 30 min. Acute CO poisoning in CO, CO + NBO, CO + HFNCO was induced by CO exposure for 30 min. Thereafter, NBO group received 100% NBO with reservoir mask for 30 min. HFNCO group received high-flow oxygen through nasal cannula for 30 min. At the end of the experiment, all animals were sacrificed by cardiac puncture under anesthesia. Serum liver function tests were measured. Liver tissue total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels, tissue histomorphology and immunoexpression levels of Bax, Caspase 3, TNF-α, IL-1β, and NF-κB were also examined. Our observations indicated that acute CO poisoning caused significant increases in blood COHb, serum aminotransferase (AST), alanine aminotransferase (ALT0, alkaline phosphatase (ALP), total protein, albumin, and globulin levels but a decrease in albumin to globulin ratio (all, p < 0.05). Furthermore, acute CO poisoning significantly increased the OSI value, and the immunoexpresssion of Bax, Caspase 3, TNF-α, IL-1β, and NF-κB in liver tissue (all, p < 0.05). These pathological changes in serum and liver tissue were alleviated through both of the treatment methods. In conclusion, both the NBO and HFNCO treatments were beneficial to alleviate the acute CO poisoning associated with liver injury and dysfunction.

Direct reprogramming of fibroblasts into functional hepatocytes via CRISPRa activation of endogenous Gata4 and Foxa3.

The ability to generate functional hepatocytes without relying on donor liver organs holds significant therapeutic promise in the fields of regenerative medicine and potential liver disease treatments. Clustered regularly interspaced short palindromic repeats (CRISPR) activator (CRISPRa) is a powerful tool that can conveniently and efficiently activate the expression of multiple endogenous genes simultaneously, providing a new strategy for cell fate determination. The main purpose of this study is to explore the feasibility of applying CRISPRa for hepatocyte reprogramming and its application in the treatment of mouse liver fibrosis. The differentiation of mouse embryonic fibroblasts (MEFs) into functional induced hepatocyte-like cells (iHeps) was achieved by utilizing the CRISPRa synergistic activation mediator (SAM) system, which drove the combined expression of three endogenous transcription factors- Gata4, Foxa3 , and Hnf1a -or alternatively, the expression of two transcription factors, Gata4 and Foxa3 . In vivo , we injected adeno-associated virus serotype 6 (AAV6) carrying the CRISPRa SAM system into liver fibrotic Col1a1-CreER ; Cas9fl/fl mice, effectively activating the expression of endogenous Gata4 and Foxa3 in fibroblasts. The endogenous transcriptional activation of genes was confirmed using real-time quantitative polymerase chain reaction (RT-qPCR) and RNA-seq, and the morphology and characteristics of the induced hepatocytes were observed through microscopy. The level of hepatocyte reprogramming in vivo is detected by immunofluorescence staining, while the improvement of liver fibrosis is evaluated through Sirius red staining, alpha-smooth muscle actin (α-SMA) immunofluorescence staining, and blood alanine aminotransferase (ALT) examination. Activation of only two factors, Gata4 and Foxa3 , via CRISPRa was sufficient to successfully induce the transformation of MEFs into iHeps. These iHeps could be expanded in vitro and displayed functional characteristics similar to those of mature hepatocytes, such as drug metabolism and glycogen storage. Additionally, AAV6-based delivery of the CRISPRa SAM system effectively induced the hepatic reprogramming from fibroblasts in mice with live fibrosis. After 8 weeks of induction, the reprogrammed hepatocytes comprised 0.87% of the total hepatocyte population in the mice, significantly reducing liver fibrosis. CRISPRa-induced hepatocyte reprogramming may be a promising strategy for generating functional hepatocytes and treating liver fibrosis caused by hepatic diseases.

Effects of a blend of acidifiers added continuously to the drinking water of nursery piglets

Context Adding organic and inorganic acids to the drinking water is a potential alternative to improve production results in nursery piglets, and a strategy for reducing the use of antimicrobials. Aims To assess the effects of adding a blend of organic and inorganic acids to drinking water on the oxireduction potential (ORP) of water, and growth performance, biochemical, antioxidant and blood gas profiles, intestinal morphometry, biometry of organs, and intestinal microbiome of nursery piglets. Methods Experiment involved 1080 female piglets assessed over 30 days (Landrace × Large White, weaned at 26 days of age, weighing 6.8 ± 0.29 kg), randomly assigned to the following three treatments: (1) piglets received drinking water of natural pH of 7.39 (pH7.39), (2) piglets received drinking water of pH of 5.31 (pH5.31), and (3) piglets received drinking water of pH of 3.40 (pH3.40), with eight replicates and 45 piglets/stall. Piglets had ad libitum access to diet and water throughout the experiment, and received different diets in each phase. Key results Receiving drinking water of pH3.40 promoted a higher ORP, and a lower total water consumption was observed in Starter II piglets with pH5.31. There was no treatment effect on the performance, but mortality was lower in starter piglets in the pH3.40 treatment. Animals in the pH3.40 treatment had lower blood alanine aminotransferase and aspartate aminotransferase activities, differing from the result obtained for total cholesterol concentrations. Animals in the pH3.40 treatment showed a lower concentration of total protein than did piglets in the pH7.39 treatment. Piglets in the pH3.40 treatment had higher weights of empty stomach, spleen, and liver with gallbladder than did those in the pH7.39 treatment. Animals in the pH3.40 treatment showed a lower relative abundance of the Escherichia–Shigella genus and bacteria of Enterobacteriaceae family than did those in the pH5.31 treatment. Conclusions Acidification of drinking water to pH3.40 for nursery piglets can be used to partially increase the ORP of the water, and promote a greater weight of organs with metabolic and immune functions, while decreasing mortality. In addition, acidification of drinking water does not compromise performance or intestinal histology, but improves the profile of the intestinal microbiome in piglets. Implications This research has provided new information on the effects of acidifiers in the drinking water for nursery piglets and has shown their potential use for bolstering general health.