Alanine Aminotransferase Research Articles

Metabolic, hormonal profiles and comorbidities in pituitary Cushing’s syndrome, adrenal Cushing’s syndrome and mild autonomous cortisol secretion: a comparative study

ABSTRACT Purpose Our study aimed to discern disparities in metabolic, hormonal profiles, and comorbidities among patients with pituitary Cushing (PC), adrenal Cushing (AC), and Mild autonomous cortisol secretion (MACS). Methods We conducted a retrospective analysis involving 76 patients diagnosed with PC (n = 26), AC (n = 21), and MACS (n = 29) at our clinic. We compared the groups’ demographic data, clinical characteristics, biochemical profiles, hormonal analyses, and surgical interventions. Results No significant differences were noted in age, height, body mass index, or gender distribution among the groups, although a higher proportion of females was observed across all three groups. However, PC patients exhibited markedly elevated 24-hour urinary cortisol levels compared to AC and MACS patients. Furthermore, alanine aminotransferase, triglycerides, very low-density lipoprotein, insulin, and basal cortisol levels were significantly elevated in PC and AC cases compared to MACS cases. Interestingly, no significant differences were observed in terms of comorbidities among the groups. Conclusion Our findings suggest that urinary cortisol levels were significantly higher in the PC group than in the AC and MACS groups, potentially indicating that high-amplitude adrenocorticotropic hormone stimulation may lead to increased cortisol secretion in PC patients. The increased utilization of imaging methods has facilitated the earlier detection of adrenal incidentalomas, enabling the diagnosis of adrenal Cushing’s cases with milder cortisol elevations. Additionally, the severity of disease symptoms worsens with increasing cortisol levels.Notably, moderate increases in cortisol are associated with heightened comorbidities, underscoring the importance of vigilant management in Cushing’s syndrome patients. Despite a lower degree of hypercortisolism in MACS, there were no differences in comorbidities, suggesting that even mild cortisol secretion abnormalities are sufficient to establish the presence of comorbidities. Even moderate increases in cortisol levels can impact bone metabolism.

Standardisation and toxicity assessment of Dioscorea hispida (Dennst) tubers: Acute and subchronic dosage studies

People worldwide have used Dioscorea hispida Dennst to treat various skin diseases. However, Dioscorea hispida tubers are known to be poisonous because they contain cyanide and dioscorine. This research aimed to standardise Dioscorea hispida dried powder and examine tuber extract toxicity effects (acute and subchronic). This research was carried out with sample standardisation according to the Indonesian Herbal Pharmacopoeia II. The Regulations of the Republic of Indonesia Food and Drug Supervisory Agency carried out acute and subchronic toxicity studies. Wistar rats were administered different doses of the extract, and observations were made for toxic symptoms, body weight changes, mortality, relative organ weights, and histopathological changes in liver and kidney tissues. Serum creatinine, ALT, and AST levels were also measured. Dioscorea hispida tubers from North Sumatra and Lampung met the quality standards, whereas those from West Java did not due to high mold/yeast counts. Acute toxicity studies indicated that doses of 300 mg/kg BW and 1000 mg/kg BW caused toxic symptoms and death, classifying the extract as toxic with an LD50 range of 50-500 mg/kg BW. No toxic symptoms were observed at 50 mg/kg BW. Subchronic studies revealed that elevated doses led to significant liver and kidney damage, evidenced by increased creatinine, ALT, AST levels, and histopathological changes. Dioscorea hispida tubers from North Sumatra and Lampung meet quality standards, but those from West Java do not. The tubers have medicinal potential but exhibit high toxicity at elevated doses, necessitating cautious use and further research to ensure safe application and reduce contaminants.

Clinical and laboratory characteristics of Sjögren's syndrome-associated autoimmune liver disease: a real-world, 10-year retrospective study.

To investigate the clinical and laboratory features of Sjögren's syndrome-associated autoimmune liver disease (SS-ALD) patients and identify potential risk and prognostic factors. SS patients with or without ALD, who visited Tongji Hospital between the years 2011 and 2021 and met the 2012 American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome, were retrospectively enrolled. The clinical and laboratory data of the enrolled patients, including autoimmune antibodies, were collected and analyzed with principal component analysis, correlation analysis, LASSO regression, and Cox regression. A total of 117 SS-ALD patients were confirmed out of 568 SS patients. Compared to SS-non-ALD patients (n = 451), SS-ALD patients exhibited more severe involvement of the hepatic and hematologic systems, albeit with less pronounced typical SS symptoms. Disease activity was higher in SS-ALD patients, as indicated by elevated ESR, CRP, and IL-6 levels, particularly in the SS-overlap subgroup. Furthermore, SS-AIH patients without AIH-specific autoantibody testing or with negative testing results had higher AST and ALT levels than those who were autoantibody-positive. Our predictive model, incorporating IgG, IgM, AST, GGT, ALT, and C4, effectively identified ALD complications in SS patients, achieving an AUC of 0.924. Additionally, a grimmer prognosis was associated with higher baseline AST and ALT levels. SS-ALD patients often manifest with an insidious onset and atypical SS symptoms, yet frequently exhibit severe systemic involvement, intense inflammatory and immune responses, and a poor prognosis. To improve the clinical outcomes in SS-ALD patients, regular monitoring, early identification, and active treatment should be applied. Key Points • The study provided a detailed profile of clinical and laboratory features of SS-ALD and SS-non-ALD patients, contributing to a predictive model of ALD complications in SS patients • SS-ALD patients manifested with an insidious onset but exhibited severe systemic involvement, robust inflammatory and immune responses, and poor prognosis • SS-AIH patients without available testing for AIH-specific autoantibodies or with negative results demonstrated worse liver function, thus routine screening for autoimmune liver antibodies is recommended in SS patients • More severe baseline liver function status was associated with poorer therapeutic responses to routine medications, so early detection and timely intervention are essential for SS patients.

Cross-trait multivariate GWAS confirms health implications of pubertal timing

Pubertal timing is highly variable and is associated with long-term health outcomes. Phenotypes associated with pubertal timing include age at menarche, age at voice break, age at first facial hair and growth spurt, and pubertal timing seems to have a shared genetic architecture between the sexes. However, puberty phenotypes have primarily been assessed separately, failing to account for shared genetics, which limits the reliability of the purported health implications. Here, we model the common genetic architecture for puberty timing using a multivariate GWAS, with an effective population of 514,750 European participants. We find 266 independent variants in 197 loci, including 18 novel variants. Transcriptomic, proteome imputation and fine-mapping analyses reveal genes causal for pubertal timing, including KDM4C, LEPR, CCNC, ACP1, and PCSK1. Linkage disequilibrium score regression and Mendelian randomisation analysis establish causal associations between earlier puberty and both accelerated ageing and the risk of developing cardiovascular disease and osteoporosis. We find that alanine aminotransferase, glycated haemoglobin, high-density lipoprotein cholesterol and Parabacteroides levels are mediators of these relationships, and establish that controlling oily fish and retinol intake may be beneficial for promoting healthy pubertal development.

The effects of intermittent fasting on antioxidant and inflammatory markers and liver enzymes in postmenopausal, overweight and obese women with rheumatoid arthritis: a randomized controlled trial

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting postmenopausal women. This study investigated the effects of intermittent fasting (IF) on antioxidant and inflammatory markers and liver enzymes in postmenopausal, overweight and obese women with RA. This 8-week randomized controlled trial included 44 postmenopausal women with RA divided into an intervention group following a 16:8 IF diet and a control group maintaining their usual diet and received recommendations for healthy eating. Inflammatory indices, oxidative stress markers, and liver enzymes were measured at baseline and post intervention. The IF group showed significant decreases in serum malondialdehyde (MDA) levels (P = 0.02) and neutrophil-to-lymphocyte ratio (P = 0.018) and increased catalase levels (P = 0.004) compared to the control group. Liver enzymes aspartate transaminase (AST) and alanine transaminase (ALT) also decreased significantly in the IF group (P = 0.02 and P = 0.03, respectively). No significant differences were observed in the other measured parameters between groups. In conclusion, the 16:8 IF diet demonstrated beneficial effects on some oxidative stress markers, inflammatory indices, and liver enzymes in postmenopausal, overweight, and obese women with RA. These findings suggest that IF may be an effective non-pharmacological intervention for managing RA in this population, potentially addressing both primary disease symptoms and associated metabolic complications. Further research is needed to elucidate the long-term effects and mechanisms of IF in the management of RA.

Investigating the impact of Multiwalled Carbon Nanotubes exposure on enzymatic activities and histopathological variations in Swiss albino mice

Present study was conducted to evaluate the detrimental impacts of exposure of Multi-walled Carbon Nanotubes (MWCNT-NP) on enzymatic activities and tissue structures in Swiss albino mice. The experimental groups of mice received MWCNT-NP for specific time period (seven or fourteen days). Two distinct doses of the MWCNT-NP solution were given orally: 0.45 µg and 0.90 µg, and the distilled water was given to the control group. Serum samples were extracted at 7 and 14 days after the experiment by centrifuging whole blood for 15 min at 3,000 rpm. An enzyme-linked immunosorbent test (ELISA) was used to measure many enzyme assays, such as Angiotensin Converting Enzymes (ACE), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase enzyme. Hematoxylin and Eosin (H&E) staining of tissue samples was done along with a histopathological examination. During a 14-day exposure, ACE, NADPH Oxidase, ALT, and AST enzyme levels were significantly higher in the exposed groups (0.45 µg and 0.90 µg) than in the control group (p < 0.05). Male mice exposed to MWCNT-NP showed substantial histological damage in the relevant organs as well as elevated enzyme activity levels. Present study showed a comprehensive and practical assessment of the toxicity associated with MWCNT-NP of different geometries and functionalization.

Post-hoc analysis of the tofogliflozin post-marketing surveillance study (J-STEP/LT): Tofogliflozin improves liver function in type 2 diabetes patients regardless of BMI.

Patients with type 2 diabetes are at high risk of developing steatotic liver disease (SLD). Weight loss has proven effective in treating metabolic dysfunction-associated steatotic liver disease (MASLD) in obese patients with type 2 diabetes, with sodium-glucose cotransporter 2 (SGLT2) inhibitors showing promising results. However, lean MASLD is more prevalent in Japan, necessitating alternative approaches to body weight reduction. We used the J-STEP/LT dataset including up to 3-year treatment data to analyze the effects of the SGLT2 inhibitor tofogliflozin on liver function and treatment safety and conducted a subgroup analysis based on body mass index (BMI; kg/m2, <20, 20-<23, 23-<25, 25-<30, and ≥30). This study included 4,208 participants. Tofogliflozin significantly reduced alanine aminotransferase (ALT) levels in participants with baseline ALT levels >30 U/L across all BMI groups, with median changes of -12, -16, -13, -15, and -15 U/L, respectively (P = 0.9291 for trends). However, median changes in body weight with tofogliflozin were -2.00, -2.75, -2.00, -3.00, and -3.80 kg, respectively (P < 0.0001 for trends), with no significant weight loss observed in the BMI <20 group. ALT levels were also significantly decreased in participants who did not lose weight. Safety assessments according to BMI and age categories revealed no clear differences in the frequency of adverse events. Tofogliflozin reduced ALT levels without substantial body weight reduction among lean participants. These findings suggest that SGLT2 inhibitors may be a viable treatment option for non-obese patients with type 2 diabetes and SLD.

Potential antihyperlipidemic effects of myrcenol and curzerene in high-fat fed rats

The study evaluated the anti-hyperlipidemic effects of myrcenol and curzerene on a high fat diet induced hyperlipidemia rat model. Thirty male albino rats were fed on a high-fat diet for four months. The HFD-induced hyperperlipidemia rats were treated with rosuvastatin (10 mg/kg), curzerene (130 mg/kg) and myrcenol (100 mg/kg) for four weeks. Blood samples were collected for further analysis. Aorta and heart were harvested for histopathological evaluation. Hepatic lipase and HMG-CoA reductase were determined by ELISA. FST and Y-maze tests were performed to assess the stress level in hyperlipidemia rats. The phytochemical compounds (Curzerene and Myrcenol) and the standard drug (Rosuvastatin) resulted in decreased body weight as well as reduced levels of LDL, TG, TC, AST and ALT as compared to the diseased group. Additionally, the treated groups displayed improved HDL levels and less depressed behavior. The ELISA results revealed that the Curzerene and myrcenol had significantly increased the protein concentration of hepatic lipase than the diseased group whereas both compounds significantly lowered the HMG-CoA reductase concentrations compared to the diseased group. The findings suggested that myrcenol and curzerene had the potential to be therapeutic agents for managing hyperlipidemia and reducing the risk of heart-related conditions associated with high lipid levels.

The Improvement Effects of Weizmannia coagulans BC99 on Liver Function and Gut Microbiota of Long-Term Alcohol Drinkers: A Randomized Double-Blind Clinical Trial

Background/Objectives: With the improvement of living standards, alcoholic liver disease caused by long-term drinking has been a common multiple disease. Probiotic interventions may help mitigate liver damage caused by alcohol intake, but the mechanisms need more investigation. Methods: This study involved 70 long-term alcohol drinkers (18–65 years old, alcohol consumption ≥20 g/day, lasting for more than one year) who were randomly assigned to either the BC99 group or the placebo group. Two groups were given BC99 (3 g/day, 1 × 1010 CFU) or placebo (3 g/day) for 60 days, respectively. Before and after the intervention, blood routine indicators, liver function, renal function, inflammatory factors and intestinal flora were evaluated. Results: The results showed that intervention with Weizmannia coagulans BC99 reduced the levels of alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, serum total bilirubin, blood urea nitrogen, uric acid and ‘blood urea nitrogen/creatinine’. Weizmannia coagulans BC99 also reduced the levels of pro-inflammatory factors TNF-α and IL-6 and increased the levels of anti-inflammatory factor IL-10. The results of intestinal flora analysis showed that Weizmannia coagulans BC99 regulated the imbalance of intestinal flora, increased the beneficial bacteria abundance (Prevotella, Faecalibacterium and Roseburia) and reduced the conditionally pathogenic bacteria abundance (Escherichia-Shigella and Klebsiella). Both LEfSe analysis and random forest analysis indicated that the increase in the abundance of Muribaculaceae induced by BC99 was a key factor in alleviating alcohol-induced liver damage. Conclusions: These findings demonstrate that Weizmannia coagulans BC99 has the potential to alleviate alcoholic liver injury and provide an effective strategy for liver protection in long-term drinkers.

Protective Effects of Schizochytrium Microalgal Fatty Acids on Alcoholic Liver Disease: A Network Pharmacology and In Vivo Study.

This study aimed to elucidate the hepatoprotective mechanisms of microalgal fatty acids (MFA) from Schizochytrium against alcoholic liver disease (ALD) through network pharmacology and invivo analysis. Network pharmacology and molecular docking methodologies were employed to predict the potential mechanisms of MFA against ALD. To substantiate these predictions, an acute alcoholic liver injury mouse model was utilized to assess the impact of MFA on serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total protein (TP), and albumin (ALB). Additionally, liver histopathology and the expression levels of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) protein were evaluated. Seven active ingredients and 53 potential targets (including 7 core targets) for ALD treatment were identified in MFA. Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that these seven core targets are implicated in various biological pathways, notably those associated with cancer, viral infections, and the PI3K/AKT signaling pathway. Furthermore, molecular docking studies demonstrated that docosahexaenoic acid and docosapentaenoic acid in MFA exhibited strong binding affinity for these seven crucial targets. Animal experiments demonstrated that administration of MFA significantly decreased the levels of AST, ALT, and ALP, while increasing the levels of ALB and TP in mice with acute alcoholic liver injury. Moreover, MFA ameliorated liver tissue pathology and markedly down-regulated the expression of PI3K and AKT proteins in the liver. These results suggest that MFA may possess therapeutic potential for ALD by targeting multiple pathways, with its mechanisms likely involving the inhibition of the PI3K/AKT signaling pathway.

26-Week Repeated-Dose Toxicity Study of a Novel Antiarrhythmic Drug Sulcardine Sulfate in Sprague-Dawley Rats.

Sulcardine sulfate (Sul) is a novel antiarrhythmic agent blocking multiple channels and exhibits unique pharmacological properties such as lower APD-dependent prolongation and reduced arrhythmia risk. Sul is currently in Phase III clinical trials, yet studies on its long-term toxicological profile and potential target organs remain unexplored. This study investigated the related toxicity of Sul in Sprague Dawley (SD) rats through repeated oral administration for 26 weeks, followed by a 4-week recovery period. Consistent with the clinical intended mode of administration, Sul was administered via oral gavage at daily doses of 0, 175, 350, and 700/525 mg/kg in rats. On account of clinically observed body weight loss of male and female rats in the high-dose group compared with the control group, with one female rat in the high-dose group dying after 8 weeks of administration, the high dose was adjusted to 525 mg/kg. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in male rats significantly increased in the medium- and high-dose groups, whereas female rats in these groups showed a significant rise in alkaline phosphatase (ALP) levels, accompanied by varying degrees of weight gain in the liver and lungs. Additionally, brownish-red pigment deposition was observed in hepatocytes and Kupffer cells across all dosing groups, along with foam cell deposition in the alveolar cavities. Concomitant toxicokinetics showed that the drug accumulated to some extent in the animals. Consequently, the liver and lungs were identified as potential target organs, and the no observed adverse effect level (NOAEL) was determined to be 175 mg/kg.

Utilizing Invasive Pterygoplichthys pardalis as a Sustainable Fish Meal Substitute and Euphorbia hirta Extract Supplement: Effects on Growth Performance, Organosomatic Indices, Hematological Profiles, and Serum Biochemistry in Chinese Bullfrogs (Hoplobatrachus chinensis)

This research examined the efficacy of substituting commercial fish meal (CFM) with Pterygoplichthys pardalis meal (PPM) in Hoplobatrachus chinensis diets, with and without Euphorbia hirta extract (EHE) supplementation. The study utilized six dietary treatments: a control diet (0% PPM, no EHE) and five experimental diets with varying PPM levels (0%+, 25%+, 50%+, 75%+, and 100%+), each fortified with 300 mg/kg EHE. The experiment spanned 90 days. The analysis revealed that PPM exhibited superior amino acid profiles compared to CFM, both in quality and quantity, while CFM demonstrated higher fatty acid content. The growth metrics showed a significant decline only in the group receiving 100% PPM replacement with EHE supplementation. Most organosomatic indices remained consistent across the treatments, with the exception of intraperitoneal fat, which decreased in all EHE-supplemented groups. Blood parameters, including white blood cells, red blood cells, and hematocrit, along with serum proteins (total protein, globulin, and albumin), displayed an upward trend in all EHE-supplemented groups. The 50%+ and 75%+ PPM replacement groups exhibited significantly elevated serum glucose levels (p &lt; 0.05). Liver enzymes (alanine transaminase and aspartate transaminase) showed no significant variations among the treatments. The results indicate that PPM can serve as an effective replacement for up to 75% of CFM in H. chinensis feed, without compromising their growth performance. Moreover, supplementing with EHE helps to enhance essential biochemical indices in the body, without adversely affecting liver function. This investigation offers valuable perspectives on the development of sustainable aquaculture feed and the potential application of invasive fish species in aquatic animal nutrition.

Relationship between butyrylcholinesterase activity and hepatic transaminases: a cross-sectional study in agricultural workers from Peru

IntroductionChronic exposure to pesticides causes various adverse health effects, mainly at a neurological level. However, there is little evidence focused on liver tissue injury and transaminase activity as indicators of effect.MethodsA cross-sectional study was designed based on medical-occupational records of workers from an agro-export company in Peru to associate the levels of butyrylcholinesterase (BChE) transaminases (ALT and AST). Occupational medical records were reviewed to obtain demographic and occupational information and laboratory values of BChE activity and transaminases.ResultsWe evaluated 459 records, and 69.9% were men. The mean age was 34.9 ± 11.5 years. BChE, ALT, and AST levels were 6238.8 ± 709.1 U/l, 34.4 ± 12.5 U/l, and 22.4 ± 8.5 U/l, respectively. The proportion of inhibited BCHE and elevated transaminase levels was 15.3% and 21.6%, respectively. We found a significant association between BChE inhibition and elevation of transaminases (AST: PR = 0.798, 95%CI: 0.716–0.889; ALT: PR = 0.419, 95%CI: 0.239–0.736).ConclusionThe potential usefulness of transaminases is shown as a biomarker of exposure and monitoring in occupational health programs for the agro-industry.

Outcomes of Cyclosporine Treatment in Pediatric Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS): A Retrospective Cohort Analysis.

Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) is a rare but severe hypersensitivity reaction. This retrospective cohort study compared the efficacy of systemic corticosteroids, the current first-line therapy, with cyclosporine, an emerging alternative therapy, in pediatric DReSS patients. We analyzed 14 cases of pediatric patients (<18 years) admitted to The Hospital for Sick Children between January 2016 and September 2023. Five patients received cyclosporine, while nine were treated with systemic corticosteroids. Cyclosporine treatment was associated with shorter hospital stays (median 6 days vs. 9 days) and faster normalization of alanine aminotransferase levels (25.0 days vs. 40.0 days) compared to corticosteroids. While cyclosporine was well-tolerated, corticosteroid therapy was linked to adverse events, including corticosteroid-induced diabetes (n=2), disease flares during tapering (n=3), and the need for treatment intensification (n=2). These findings suggest that cyclosporine may be a promising alternative for managing pediatric DReSS.

Safety and efficacy of PD-1 inhibitor (sintilimab) combined with transarterial chemoembolization as the initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria

BackgroundNumerous studies have demonstrated limited survival benefits of transarterial chemoembolization (TACE) alone in the treatment of intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria. The advent of immunotherapy, particularly immune checkpoint...

Replacement of fishmeal with Quinoa Husk (Chenopodium quinoa) for mitigating multiple stresses in Pangasianodon Hypophthalmus

The fishmeal is boon for aquaculture production in this recent pollution and climate change era. However, the demand of fishmeal is enhancing in many folds which needs to find alternative to fishmeal in cheap price. The present investigation addresses these issues with quinoa husk (QH). An experiment was performed to evaluate replacement of fishmeal by QH in different proportionate at 0, 15, 20, 25, 30 and 35%. The study was designed with 12 treatments as control, stressors group (concurrent exposed to ammonia, arsenic and high temperature stress, NH3+As+T), group fed with QH at 15, 20, 25, 30 and 35% without and with stressors (NH3+As+T) in Pangasianodon hypophthalmus for 105 days. The optimization of QH dose for growth performance such as food conversion ratio, growth rate, protein efficiency ratio and specific growth rate with respect to protein percentage and obtained 26%. The oxidative enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and glutathione peroxidase (GPx) in gill, kidney and liver tissues were significantly lowered by replacement of fishmeal by QH at 25% in fish reared under arsenic and ammonia toxicity and high temperature stress (NH3+As+T). The neurotransmitter enzyme (AChE) in brain tissue was noticeably enhanced by QH at 25%. The aspartate amino transferase (AST) and alanine amino transferase (ALT) as well as malate dehydrogenase (MDH) and lactate dehydrogenase (LDH) in gill and liver were significantly reduced by QH at 25% in fish reread under multiple stresses (NH3+As+T). The nitro blue tetrazolium (NBT), blood glucose, albumin, globulin, total protein, A:G ratio, myeloperoxidase (MPO) and total immunoglobulin (Ig) were noticeably improved by supplementation of QH at 25–30% in fish reared under NH3+As+T. The amylase, protease and lipase were significant improved with replacement of fishmeal by QH at 25%. The histo-pathological alterations were marked in liver and gill tissues, whereas these tissues were protected by QH at 25% in fish reared under control and stress condition (NH3+As+T). The present study revealed that replacement of fishmeal at 25% by QH could be a better replacement for improvement in anti-oxidative status, acetylcholine esterase and growth performance in fish reread under NH3+As+T stress.

Clinical study on the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes.

At present, the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent, to explore the efficacy of laparoscopic jejunoileal side to side anastomosis in the treatment of type 2 diabetes, the report is as follows. To investigate the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes mellitus (T2DM). We retrospectively analyzed the clinical data of 78 patients with T2DM who were treated via jejunoileal lateral anastomosis. Metabolic indicators were collected preoperatively, as well as at 3 and 6 months postoperative. The metabolic indicators analyzed included body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), 2-hour blood glucose (PBG), glycated hemoglobin (HbA1c), fasting C-peptide, 2-hour C-peptide (PCP), fasting insulin (Fins), 2-hour insulin (Pins), insulin resistance index (HOMA-IR), β Cellular function index (HOMA-β), alanine aminotransferase, aspartate aminotransferase, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein, and uric acid (UA) levels. SBP, DBP, PBG, HbA1c, LDL-C, and TG were all significantly lower 3 months postoperative vs preoperative values; body weight, BMI, SBP, DBP, FBG, PBG, HbA1c, TC, TG, UA, and HOMA-IR values were all significantly lower 6 months postoperative vs at 3 months; and PCP, Fins, Pins, and HOMA-β were all significantly higher 6 months postoperative vs at 3 months (all P < 0.05). Side-to-side anastomosis of the jejunum and ileum can effectively treat T2DM and improve the metabolic index levels associated with it.

Evaluating two rechallenge strategies of immune checkpoint inhibitors: Durvalumab plus tremelimumab in advanced hepatocellular carcinoma

AbstractAimThis study aimed to evaluate the safety and efficacy of durvalumab plus tremelimumab in patients with advanced hepatocellular carcinoma who have previously received atezolizumab plus bevacizumab (Atez/Bev). Additionally, it seeks to assess the feasibility of administering immunotherapy after the occurrence of immune‐mediated adverse events (imAEs) in real‐world clinical practice.MethodsThis retrospective study analyzed data from patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab at four Japanese institutions. Clinical outcomes, adverse events, tumor dynamics, and serum cytokine and chemokine levels were evaluated, with a focus on efficacy following prior Atez/Bev treatment.ResultsDurvalumab plus tremelimumab was administered to 68 patients. The objective response rate was 10.3%, and the disease control rate was 58.8%. Median progression‐free survival was 3.1 months (95% confidence interval 2.0–4.9). imAEs occurred in 50.0% of patients, with colitis being the most common (22.1%). Durvalumab was safely readministered to 14 patients after imAE resolution, although five experienced recurrence. Among 33 patients (48.5%) previously treated with Atez/Bev, improved responses were noted, including two partial responses. Tumor growth dynamics decreased in 60.0% of patients receiving sequential therapy. Common adverse events included elevated liver enzymes (aspartate aminotransferase 50.0%, alanine aminotransferase 48.5%), pruritus (45.6%), and rash (44.1%).ConclusionsDurvalumab plus tremelimumab therapy is feasible with proper imAE management and patient selection. Sequential treatment following Atez/Bev offers clinical benefit in advanced hepatocellular carcinoma, although some may experience rapid progression. Further biomarker research is needed to optimize immunotherapy strategies.

Effects of Different Molasses Levels and Slow-Release Urea Combinations on Growth Performance, Serum Biochemistry, Rumen Fermentation, and Microflora of Holstein Fattening Bulls

The aim of this study was to investigate the effects of different combinations of molasses levels and slow-release urea on Holstein fattening bulls. Sixty Holstein fattening bulls of a similar age, weight, and health status were randomly divided into four groups of fifteen Holstein fattening bulls each. All of the treatments were as follows: (1) basic diet group (CON); (2) 2% molasses slow-release urea group (LMU); (3) 4% molasses slow-release urea group (MMU); and (4) 6% molasses slow-release urea group (HMU). The results of the study showed that the MMU had an outstanding performance, with a 13.3% increase in average daily weight gain compared with the control group, a significant decrease in feed conversion ratio (p &lt; 0.05), and a significant increase in apparent digestibility of crude protein (p &lt; 0.05). In terms of serum biochemical indices, blood ammonia and alanine aminotransferase (ALT) concentrations were significantly higher in the MMU than in the CON (p &lt; 0.05). The rumen pH of all treatment groups was lower than that of the CON (p &lt; 0.05), whereas the concentrations of microbial crude protein (MCP), as well as acetic acid, propionic acid, and total volatile fatty acids (TVFA) were significantly higher in both the MMU and HMU (p &lt; 0.05). The dominant phyla in each group were Bacteroidetes, Firmicutes, and Patescibacteria, and the relative abundance of Bacteroidetes in the MMU increased by 5.47% compared with that in the CON. In the MMU, Prevotellaceae, Lachnospiraceae, and Ruminococcaceae increased by 9.03%, 0.67%, and 3.43%, respectively, compared with the CON. The economic benefit analysis showed that the daily feeding cost of fattened cattle in the MMU was reduced by RMB 1.62 yuan, and the daily farming benefit of each cow was increased by RMB 7.19 yuan. In conclusion, the MMU was effective in improving the growth performance of fattening cows, optimizing rumen fermentation, reducing cost, and increasing profit, which is a nutritional strategy with great application value.

Toxicity assessment of a phytomedicine based on an almond extract from the fruit of Balanites aegyptiaca (L.) DELILE (Zygophyllaceae) intended for helminthiases care in Burkina Faso

Balanites aegyptiaca (L.) Delile (Zygophyllaceae) is a medicinal plant used in traditional medicine in Burkina Faso to treat helminthiasis. Using an ethnopharmacological approach, the "Institut de Recherche en Sciences de la Santé (IRSS)" has developed a phytomedicine based on an almond extract from the fruit of this plant for the treatment of helminthiasis. This study aimed to assess the acute and subacute oral toxicity and in vivo mutagenicity of phytomedicine. The acute toxicity study was carried out following OECD guideline 423 by administering a single dose of 2000 mg/kg body weight (bw) of phytomedicine orally to female mice. For subacute toxicity, OECD guideline 407 was used. Four batches of 10 rats (5 males and 5 females) were used, including a control batch and three treated batches receiving a daily oral administration of the phytomedicine at doses of 250, 500, or 1000 mg/kg bw for 28 days. The mutagenicity test was performed according to OECD guideline 474; five batches of 10 mice (5 males and 5 females) were given oral doses of 500, 1000 or 2000 mg/kg bw of phytomedicine, colchicine as a positive control at 5mg/kg bw and distilled water as a negative control. In the acute toxicity test, the LD50 was estimated at 5000 mg/kg bw. The subacute toxicity study showed no mortality or signs of toxicity in rats. Biochemical analysis revealed no significant differences between control rats and those treated with the phytomedicine for glucose, creatinine, total cholesterol, triglycerides, AST, chlorine, calcium, and potassium. On the other hand, serum levels of ALT, total protein, PO43-, and Na+ were significantly reduced in some treated rats. The mutagenicity test showed no change in micronucleus frequency between treated and control mice. This study showed that phytomedicine based on an extract of B. aegyptiaca fines would present less danger to users. Keywords: Balanites aegyptiaca, acute toxicity, subacute toxicity, micronucleated erythrocytes, phytomedicine.