Liver Function Research Articles

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.

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.

Dietary deacetylated chitin nanoparticles confer protection against diazinon toxicity in male African catfish: evaluation of immune-biochemical, antioxidant, and reproductive profiles.

Currently, deacetylated chitin (chitosan) nanoparticles (CNPs) are successfully utilized in aquaculture practices. This trial demonstrates the efficacy of CNPs in combating diazinon (DZN) toxicity in African catfish, Clarias gariepinus, via monitoring hepato-renal function, serum immune trait, hormonal function, and hepato-renal antioxidant activity. Four groups were allocated as follows: a control group, a CNPs group (0.66ml/L CNPs), a DZN exposed group (0.598ppm, 1/10 LC50), and a DZN + CNPs group (0.598ppm DZN + 0.66ml/L CNPs), all for 30days. Exposure to 0.598 PPm DZN resulted in a severe decline in the immune parameters (albumin, globulin, immunoglobulins (IgG, IgM), and total proteins), neurological indicator, acetylcholinesterase (AchE), reproductive hormones (Testosterone(T.) and Luteinizing Hormone(LH)), and the superoxide dismutase(SOD) and totalantioxidant capacity(TAC) readings in both hepatic and renal samples. Moreover, a clear increment in hepatic and renal indicators (AST, ALT, urea, and creatinine),lipid peroxidation(LPO), and some reproductive indices including follicle stimulating hormone(FSH) and serum 17-β estradiol (E2) was clearly increased. Interestingly, the dietary inclusion of CNPs markedly palliated the toxicity by DZN with significant improvement in the immune-reproductive indices, plus normalizing the values of hepato-renal function and augmenting the activity of antioxidant parameters. Thus, the present study demonstrates the efficacy of CNPs in mitigating low-dose DZN toxicity, resulting in significant improvements in physiological, biochemical, and reproductive parameters. This highlights the promising potential of CNPs as a viable strategy for enhancing the health of C. gariepinus, thereby promoting the sustainability of the aquaculture industry and safeguarding human health.

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.

SLC13A2 promotes hepatocyte metabolic remodeling and liver regeneration by enhancing de novo cholesterol biosynthesis.

Metabolic requirements of dividing hepatocytes are prerequisite for liver regeneration after injury. In contrast to transcriptional dynamics during liver repair, its metabolic dependencies remain poorly defined. Here, we screened metabolic genes differentially regulated during liver regeneration, and report that SLC13A2, a transporter for TCA cycle intermediates, is decreased in rapid response to partial hepatectomy in mice and recovered along restoration of liver mass and function. Liver-specific overexpression or depletion of SLC13A2 promoted or attenuated liver regeneration, respectively. SLC13A2 increased cleavage of SREBP2, and expression of cholesterol metabolism genes, including LDLR and HMGCR. Mechanistically, SLC13A2 promotes import of citrate into hepatocytes, serving as building block for ACLY-dependent acetyl-CoA formation and de novo synthesis of cholesterol. In line, the pre-administration of the HMGCR inhibitor lovastatin abolished SLC13A2-mediated liver regeneration. Similarly, ACLY inhibition suppressed SLC13A2-promoted cholesterol synthesis for hepatocellular proliferation and liver regeneration in vivo. In sum, this study demonstrates that citrate transported by SLC13A2 acts as an intermediate metabolite to restore the metabolic homeostasis during liver regeneration, suggesting SLC13A2 as a potential drug target after liver damage.

Comparing laboratory toxicity of selective intra-arterial radionuclide therapy for primary and metastatic liver tumors: resin versus glass microspheres.

To compare the acute (within 30days of treatment) laboratory toxicities of Yttrium-90 (Y-90) resin and glass microspheres. Selective intra-arterial radionuclide therapies (SIRTs) with Y-90 resin and glass microspheres were retrospectively reviewed. Liver-hematological data were collected at baseline and at 1week and 1month follow-up. The percentage change of laboratory data and the albumin-bilirubin (ALBI) score were calculated. A total of 219 SIRTs (n: 110 resin, n: 109 glass) from 177 patients were included. There was no difference in age, liver pathologies, extrahepatic disease, baseline liver function tests, and total blood counts between the two microsphere groups. Administered activity was higher in treatments with Y-90 glass microspheres (p < 0.001). An increase in serum liver enzymes was observed after treatment with both microspheres. The difference between the treatment groups was the higher percentage increase of AST and ALT at the first week following Y-90 glass treatment (p < 0.001). However, this situation was not observed after 1month. No difference in the percentage change of other laboratory parameters was found between two groups. The number of patients with an increase [resin n: 24 (24.7%) vs glass n: 26 (27.1%), p: 0.711) and decrease [resin n: 13 (13.4%) vs glass n: 8 (8.3%), p: 0.258] in the ALBI grade after SIRT was similar among groups. An increase in liver enzymes was observed in the early period after SIRT with both microspheres. No significant difference in liver and hematological data was detected during early follow-up between the two groups, except that the percentage increase of AST and ALT were higher at the first week in the Y-90 glass group, possibly due to higher administered activity.

Targeted delivery of polymeric NO-donor micelles to hepatic stellate cells for restoration of liver function and inhibition of hepatic fibrosis.

Liver fibrosis is a prevalent liver disease associated with significant morbidity, and the activation of hepatic stellate cells (HSCs) serves as the primary causative factor driving the progression of liver fibrosis. However, capillarization of liver sinusoidal endothelial cells (LSECs) induced by hepatic fibrosis can reduce nitric oxide (NO) production and bioavailability, which consequently loses the ability to retain HSCs dormant, leading to amplified HSCs activation. Herein, an elaborate micelle (VN-M@BN) loaded with benazepril (BN) was constructed by self-assembly of polymeric NO donor, aiming for the controlled release of NO in liver fibrosis lesions thereby impeding the progression of liver fibrosis. VN-M@BN with the vitamin A (VA) ligand modification was designed to target HSCs for efficient liver fibrosis inhibition. Controlled NO release significantly downregulated α-smooth muscle actin (α-SMA) and induced apoptosis of activated HSCs, thus enhancing the inhibition effects of BN towards HSCs. Furthermore, the in suit antifibrotic treatment results confirmed that VN-M@BN possessed good circulatory stability and targetability to liver fibrotic tissues, thereby effectively ameliorating the collagen deposition and fibrosis process in damaged liver tissues. The NO-based targeted nanodrug system enabled precise delivery of therapeutic drugs to activated HSCs, thereby synergizing the efficacy in treating liver fibrosis with minimal adverse effects.

Investigating the Effect and Potential Mechanism of Rhamnetin 3-O-α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro

Background/Objectives: Rhamnetin 3-O-α-rhamnoside (ARR) is a major flavonoid of the herb Loranthus tanakae Franch. &amp; Sav., which has been used for treating liver diseases in China. However, the protective effect of ARR on the liver has not been reported. Methods: Zebrafish larvae were used as a visual animal model, and liver injury was induced by thioacetamide (TAA) for an acute liver injury (ALI) model. The hepatoprotective activity of ARR was evaluated by assessing liver morphology, liver function indices, oxidative stress, and the mRNA expression levels of inflammation-related genes in the zebrafish model. Additionally, the ROS level, inflammatory factors, and protein expression related to the IKKβ/NF-κB signaling pathway were measured to investigate a potential mechanism of ARR in HepG2 cells. Results: ARR ameliorated TAA-induced growth retardation, reduced liver injury phenotypes, and decreased oxidative stress in the zebrafish. ARR was also able to lower ROS levels in HepG2 cells, effectively inhibit the overactivation of the IKKβ/NF-κB signaling pathway in pathological conditions, inhibit NF-κB p65 translocation from the cytoplasm to the nucleus, and reduce the release of intracellular inflammatory factors. Conclusions: ARR showed significant protective activity against TAA-induced liver injury in in vivo and in vitro models, and its potential mechanism was closely related to the IKKβ/NF-κB signaling pathway.

Arsenic trioxide preconditioning attenuates hepatic ischemia- reperfusion injury in mice: Role of ERK/AKT and autophagy.

Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by Green fluorescent protein-monomeric Red fluorescent protein-LC3 (GFP-mRFP-LC3)staining and transmission electron microscope. A low dose of ATO (0.75μmol/L in vitro and 1mg/kg in vivo)significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitrostudies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.

Efficacy and safety of tripterygium glycosides combined with ACEI/ARB on diabetic nephropathy: a meta-analysis

AimsThis study aims to evaluate the efficacy and safety of tripterygium glycosides combined with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) in treating Diabetic nephropathy and provide high-level evidence to support its standardized application.MethodsLiteratures were retrieved from PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, Wanfang and VIP databases, the search time frame was defined as from the time of establishment to April 2023. This study only included randomized controlled trials of tripterygium glycosides combined with ACEI/ARB in the treatment of diabetic nephropathy, and the final included studies were identified according to the inclusion and exclusion criteria, and meta-analysis of data was performed using RevMan 5.3 software.ResultsA total of 44 RCTs with 3537 DN patients were included in the study. Compared with the control group, tripterygium glycosides combined with ACEI/ARB significantly reducing 24 h-UTP (24 h urine total protein) [SMD = −1.46, 95% CI (−1.70, −1.23), P &amp;lt; 0.00001], increasing effective rate [RR = 1.23, 95% CI (1.17,1.29), P &amp;lt; 0.00001], elevating serum albumin [SMD = 0.85, 95% CI (0.69, 1.02), P &amp;lt; 0.00001], improving serum creatinine [SMD = −0.35, 95% CI (−0.59, −0.11), P = 0.004], with no difference in BUN (blood urea nitrogen) [SMD = −0.17, 95% CI (−0.48,0.13), P = 0.27], the adverse reactions rate was higher than those of the control group [RR = 1.96, 95%CI (1.43, 2.68), P &amp;lt; 0.0001].ConclusionThis study showed that the combination of tripterygium glycosides and ACEI/ARB was more effective than ACEI/ARB alone. However, the side effects of the combined treatment group were higher than those of the control group, especially liver function damage, which also suggested that its safety in the treatment of diabetic nephropathy was worth considering. Therefore, although tripterygium glycosides provided a choice for the clinical treatment of diabetic nephropathy, its side effects limited its clinical application. In future studies, we need to further optimize tripterygium glycosides and reduce its side effects to ensure the safety of clinical application.

Shift work, thyroid function and liver function among subway workers.

Shift work is associated with an increased risk of liver injury. However, whether and how shift work alters liver function remains unclear. This study aimed to investigate the associations between shift work and the liver function parameters, and further explore the mediating roles of thyroid function indicators. We conducted a cross-sectional study involving a convenience sample of 724 subway workers. Multivariate linear regression models were adopted to approximate the effect values for the associations of shift work with liver function parameters and thyroid function indicators. Mediation analyses were used to explore the roles of thyroid function indicators in the association between shift work and liver function parameters. Shift work was associated with increased levels of alkaline phosphatase (ALP), total triiodothyronine (TT3) and free thyroxine (FT4) (β = 6.309, 95% confidence interval [CI] 2.739-9.879, β = 0.328, 95% CI 0.242-0.415 and β = 2.913, 95% CI 1.502-2.884, respectively). In stratification analysis, the positive association between shift work and TT3, FT3 and FT4 was more pronounced among people >30 years old. The increase in shift worker FT3 and aspartate transaminase levels was stronger among alcohol users. Mediation analysis showed that TT3 and FT4 mediated 39% and 29% of the associations between shift work and the increased level of ALP, respectively (all P < 0.05). The results suggest that shift work is associated with increased ALP levels of subway workers, which is partly mediated by the increase of TT3 and FT4 levels.

Mechanistic Insights into Kaempferol's Therapeutic Effects on Postmenopausal Osteoporosis: A Proteomic and Experimental Validation in Ovariectomized Rats.

Postmenopausal Osteoporosis (PMOP) is characterized by decreased bone mass and deterioration of bone microarchitecture, leading to increased fracture risk. Current treatments often have adverse effects, necessitating safer alternatives. Kaempferol, a flavonoid identified as a key active component of the traditional Chinese medicine Yishen Gushu formula, has shown promise in improving bone health, but its mechanisms in PMOP treatment remain unclear. The aim of this study was to investigate the therapeutic effects and underlying mechanisms of kaempferol in the treatment of PMOP. A bilateral ovariectomized (OVX) rat model was established to simulate PMOP. Sixty female Sprague-Dawley rats were divided into six groups: Sham operation, OVX control, OVX with alendronate (ALN), and OVX with kaempferol at doses of 10, 20, and 40 mg/kg. Treatments were administered orally once daily for 12 weeks. Assessments included Bone Mineral Density (BMD), trabecular microarchitecture via histopathology, organ morphology, organ indices, and serum levels of bone metabolism markers (TRACP-5b, BALP, ALP, Ca, P, and Fe) as well as liver and kidney function indicators (ALT, AST, CREA, and urea). Tandem Mass Tag (TMT) quantitative proteomics and bioinformatics analyses were conducted on femur samples to identify differentially expressed proteins (DEPs). Key DEPs were validated using parallel reaction monitoring (PRM), immunohistochemistry, and molecular docking. Kaempferol significantly improved BMD and enhanced trabecular microarchitecture in OVX rats in a dose-dependent manner, comparable to ALN, without causing hepatic, renal, or estrogen- like side effects. Serum bone metabolism markers were normalized with kaempferol treatment. Proteomic analysis identified 902 DEPs associated with kaempferol treatment, involved in processes such as bone remodeling, skeletal system development, and osteoclast function. Key signaling pathways affected included NF-κB, PI3K-AKT, and HIF-1. Notably, kaempferol downregulated five key DEPs-Rac2, Ddb1, Cdc42, Rpl19, and Hist2h4-in the femur, which are crucial for osteoclast resorptive activity, migration, adhesion, and cell cycle progression. Kaempferol exerts therapeutic effects on PMOP by inhibiting key proteins involved in osteoclast function, thereby reducing bone resorption and promoting bone health. These findings suggested that kaempferol is a potential safer alternative for PMOP treatment. Further research is recommended to explore its clinical applications and elucidate detailed mechanisms.

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.

Safety and recommendation of voriconazole for invasive pulmonary aspergillosis in severe liver disease patients: a retrospective cohort study

BackgroundInvasive pulmonary aspergillosis (IPA) is a common opportunistic infection in patients with severe liver disease (SLD), which increases the mortality of patients. The aim of this study was to evaluate the efficacy and safety of voriconazole for IPA in patients with SLD and explore an optimal antifungal regimen.MethodsThis was a retrospective cohort study of SLD patients diagnosed with proven or probable IPA at Beijing Youan Hospital, Capital Medical University between January 1, 2012 to January 31, 2023. Univariate and multivariate logistic regression analysis were performed to identify the impact of voriconazole on outcomes of SLD patients with IPA.ResultsA total of 142 patients were enrolled and categorized into voriconazole group (n = 92), echinocandins group (n = 26) and a combination of voriconazole and echinocandins group (n = 24). The 28-day all-cause mortality was lower in voriconazole group compared to the other groups (p = 0.033). Voriconazole monotherapy was associated with lower short-term mortality (OR 0.223, 95%CI 0.070–0.650, p = 0.008) and did not seem to exacerbate hepatic function deterioration in SLD patients with IPA (OR 0.259, 95%CI 0.094–0.674, p = 0.007) when compared to echinocandins monotherapy. Among the three subgroups of voriconazole monotherapy, no-loading dose regime demonstrated a superior response to IPA therapy compared to the standard-dose regimen (OR 0.264, 95%CI 0.068–0.845, p = 0.035).ConclusionVoriconazole monotherapy demonstrated good tolerability with lower mortality in SLD patients with IPA. A no-loading dose voriconazole regimen is proposed for IPA treatment in SLD patients, yet pharmacokinetic studies combined with prospective studies are needed for further validation.

Rh-relaxin-2 attenuates oxidative stress and neuronal apoptosis via ERK-nNOS-NO pathway after germinal matrix hemorrhage in rats

Oxidative stress and neuronal apoptosis could be an important factor leading to post-hemorrhagic consequences after germinal matrix hemorrhage (GMH). Previously study have indicated that relaxin 2 receptor activation initiates anti-oxidative stress and anti-apoptosis in ischemia-reperfusion injury. However, whether relaxin 2 activation can attenuate oxidative stress and neuronal apoptosis after GMH remains unknown. To investigate the beneficial effect of relaxin 2 on oxidative stress injury and neuronal apoptosis by GMH, a total of 150 rat pups were subjected to GMH by an intraparenchymal injection of bacterial collagenase. Recombinant human relaxin-2 (rh-relaxin-2) was administered intraperitoneally injections at 1 h and 13 h after GMH. Lenti-virus with sgRXFP1 and sgCtrl was administered intracerebroventricular (i.c.v.) on the left side of the brain to inhibit the RXFP1 at 2d prior to GMH induction, and LY321499, ERK inhibitor, was administered by i.c.v. injection at 1 h on the left side of the brain prior to GMH induction, respectively. Co-immunoprecipitation, immunofluorescence, TUNEL, Fluoro-Jade C, DHE staining, western blot, Nitrix Oxide (NO) quantification and side effect experiments were performed to evaluate post-GMH. We found endogenous relaxin-2 interacts with RXFP1 and both protein colocalized in neurons on the first day after GMH. Additionally, RXFP1 activation with rh-relaxin-2 significantly inhibited oxidative stress and neuronal apoptosis in GMH + rh-relaxin-2 group compared with GMH + vehicle group. Moreover, rh-relaxin-2 treatment significantly inhibited the phosphorylation of ERK and nNOS, as well as upregulated expression of Bcl2 and NO and downregulated expression of Bax and Romo 1. The beneficial effects of rh-relaxin-2 were reversed by i.c.v. injection of lenti-virus with sgRXFP1 and LY321499, respectively. Furthermore, the side effect experiment showed rh-relaxin-2 did not affect neurological behavior and the function of liver and kidney. In conclusion, our finding showed that rh-relaxin-2 attenuated oxidative stress and neuronal apoptosis after GMH through RXFP1-ERK-nNOS-NO signaling pathway.

N-acetylcysteine use in a cocaine-induced liver failure: a case report

BackgroundCocaine intoxication and abuse is a worldwide problem that can be the cause of numerous acute medical complications, including severe acute hepatitis. Although these cases are scarce, they are extremely serious and may lead to liver transplantation or death. Management of toxic hepatitis, once the causative agent has been discontinued, is essentially symptomatic, based on clinical and biological monitoring and prevention of complications related to acute hepatitis.Case detailsWe present a case of a 28-year-old woman admitted to the emergency department for acute hepatitis due to cocaine intoxication. In addition to a sharp rise in her liver enzymes, the patient also presented metabolic acidosis, renal failure, and rhabdomyolysis. Treatment consisted of administering N-acetylcysteine (NAC), dialysis, and additional supportive measures. An improvement in the liver function with a decrease in transaminases occurred after the NAC administration. The toxicokinetics of major cocaine metabolites and clinical chemistry concentrations were monitored.ConclusionIn addition to the usual management measures for acute hepatitis, the administration of N-acetylcysteine should be investigated further, although it is currently used only in cases of acetaminophen acute toxic hepatitis.

Su’al-Qinya: Unani Perspective on Iron Deficiency Anemia, its Pathogenesis, and Therapeutic Interventions

Anemia, a pervasive global health concern, affects millions worldwide. This study aims to provide an in-depth examination of anemia from the perspective of Unani medicine, exploring its etiology, pathogenesis, and treatment modalities. A comprehensive review of classical Unani texts and contemporary research reveals that anemia is attributed to alterations in blood composition, impaired liver function, and nutrient deficiencies. Unani practitioners employ a holistic approach, incorporating regimenal therapy, herbal remedies, and lifestyle modifications to address the underlying causes of anemia. This study highlights the significance of integrating Unani principles into modern healthcare practices, providing a complementary approach to addressing anemia and promoting overall well-being. This study aims to explore the Unani perspective on anemia, examining its etiology, pathogenesis, and treatment modalities, and highlighting the potential benefits of integrating Unani principles into modern healthcare practices. This study demonstrates the relevance of Unani medicine in understanding and addressing anemia, emphasizing the importance of a holistic approach to healthcare. By integrating Unani principles into modern healthcare practices, healthcare providers can offer a more comprehensive and patient-centred approach to managing anemia and promoting overall well-being. Keywords: Su’al-Qinya, Faqru-dam, Qillatu-dam, Anemia, Unani medicine, Iron deficiency anemia.

Procedural sedative effect of remimazolam in ICU patients on invasive mechanical ventilation: a randomised, prospective study

BackgroundInvasive procedures and environmental factors in the intensive care unit (ICU) may cause anxiety and discomfort in patients, who often require sedation therapy. The aim of this study was to assess the safety of remimazolam tosilate for procedural sedation in ICU patients receiving mechanical ventilation following endotracheal intubation. Eighty patients from a single centre were randomly assigned to either the propofol group or the remimazolam group. Blood tests were conducted to evaluate changes in lactate, blood lipids, liver and kidney function, and inflammatory markers, and patients’ vital signs were observed over several periods. This study compared the incidence of delirium, the impact on liver and kidney function, circulatory effects, and changes in blood lipids between the two groups. These findings have optimised the selection of medications, providing ICU patients with more options for sedation therapy.MethodsIn this single-centre randomised controlled trial, intubated patients were randomly assigned to the remimazolam group or the propofol group. Under the same analgesic regimen, the two groups received remimazolam and propofol for procedural sedation.ResultsOur primary outcome was the mean arterial pressure (MAP), which significantly differed on Days 4 and 7 (P = 0.021, control group vs. experimental group = 85.23 ± 11.24 vs. 94.36 ± 13.18, P = 0.023, 83.55 ± 8.94 vs. 92.66 ± 7.02). With respect to liver and kidney function, the ∆AST value in the remimazolam group was significantly lower than that in the control group on Day 7 (P = 0.023). There were significant differences in triglyceride (TG) levels on Days 4 and 7 (P = 0.020) and in the ∆LDL on Day 7 (P = 0.027). Furthermore, the rates of dyslipidaemia and delirium in the remimazolam group were lower than those in the propofol group (85.0%, n = 40 vs. 90.0%, n = 40; 27.5%, n = 40 vs. 55%, n = 40).ConclusionRemimazolam is a novel benzodiazepine that has demonstrated promising applications in general anaesthesia and procedural sedation; however, its use in ICU sedation is still in the early stages of research. Current evidence suggests that remimazolam is a safe sedative that is particularly well suited for patients with haemodynamic instability. Large sample-size randomised clinical trials are warranted.

The Evaluation of Biochemical Parameters in Positive COVID-19 RealTime PCR Patients: A Retrospective Study

Coronavirus, a member of the beta coronavirus family, encompasses a range of illnesses from common colds to severe disorders. SARS-CoV-2, transmitted mainly through respiratory droplets that are generated by a patient who is sneezing, coughing and talking, caused the global pandemic COVID-19 in 2020. The virus primarily targets the respiratory system especially in the lung cell, leading to diverse symptoms and severe consequences. This study was carried out in the COVID-19 Isolation Centre in Mukalla City, Yemen, to evaluate biochemical tests in COVID-19 patients. In the retrospective single-centre study on 116 COVID-19 patients, some of biochemical Analysed Parameters were glucose, Liver function tests, renal function tests, lipid profile, and proinflammatory markers; convenience sampling based on existing records for socio-demographics, medical history, and biochemistry were analysed by using a spectrophotometry and Chemiluminescent immunoassay analyser. used SPSS version 25 to analyse data. Most COVID-19 patients in Mukalla City (91.4 % of those over 46 years old) have common symptoms such as fever, cough, and respiratory problems. The study found links between chronic health disorders (hypertension 96.6 %, diabetes mellitus 94.8 %) and greater vulnerability to COVID-19. Blood glucose levels substantially impact COVID-19 occurrences (p 0.0001). Some liver function tests are associated with COVID-19 (total protein, albumin, LDH, and GGT) (p = 0.044, 0.010, 0.0001, and 0.0001, respectively). Urea and creatinine levels imply renal function and their significant association (p=0.001 for both), whereas uric acid had no significant association with COVID-19 (p = 0.134). However, lipid profile tests lack statistical significance; they do identify trends. Proinflammatory markers CRP and ferritin strongly correlate with positive COVID-19 patients (p=0.0001 for both). In conclusion, COVID-19 significantly affects glucose metabolism, liver function, renal dynamics, and inflammatory markers, necessitating vigilant monitoring for clinical care and informing future research.

The Effects of Chromium and Tin Present in the Environment and Seawater on Biochemical Parameters in Male Rabbits

The biochemical effects of exposure to potassium dichromate (K₂Cr₂O₇) and tin chloride (SnCl₂) on important liver and kidney function parameters and oxidative stress markers in experimental groups compared to controls are evaluated in this study. Male animals were split into three groups: a control group, a group that received K₂Cr₂O₇, and a group that received SnCl₂. Biochemical parameters, such as total protein, albumin, bilirubin, urea, creatinine, glucose, liver enzymes (AST and ALT), and plasma TBARS, were measured. The results showed that the K₂Cr₂O₇ and SnCl₂ groups had significantly lower levels of total protein and albumin than controls, indicating impaired protein synthesis. With SnCl₂ having a more noticeable effect, bilirubin levels were higher in the experimental groups, indicating hepatic impairment. Urea and creatinine levels rose as a result of both toxicants, indicating renal impairment, especially in the K₂Cr₂O₇ group. Both therapy groups had noticeably higher glucose levels, which is an indicator of metabolic problems. In line with hepatocellular damage, the experimental groups' hepatic enzyme activity (AST and ALT) was noticeably elevated. Furthermore, lipid peroxidation marker TBARS levels were markedly increased, indicating increased oxidative stress, with K₂Cr₂O₇ showing a greater effect. In summary, exposure to K₂Cr₂O₇ and SnCl₂ resulted in notable biochemical changes, with K₂Cr₂O₇ exhibiting more marked oxidative and nephrotoxic effects and SnCl₂ having a greater influence on hepatic function and protein synthesis. These results highlight the necessity of more investigation into these chemicals' toxicological processes.