The transcription factor sex-determining region Y-related high-mobility group-box gene 9 (SOX9) plays a critical role in organ development. Although SOX9 has been implicated in regulating lipid metabolism in vitro, its specific role in metabolic dysfunction-associated steatohepatitis (MASH) remains poorly understood. This study aimed to investigate the role of SOX9 in MASH pathogenesis and explored the underlying mechanisms.

MASH models were established using mice fed either a methionine- and choline-deficient (MCD) diet or a high-fat, high-fructose diet. To evaluate the effects of SOX9, hepatocyte-specific SOX9 deletion or overexpression was performed. Lipidomic analyses were conducted to assess how SOX9 influences hepatic lipid metabolism. RNA sequencing was employed to identify pathways modulated by SOX9 during MASH progression. To elucidate the mechanism further, HepG2 cells were treated with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor to test whether SOX9 acts via AMPK activation.

SOX9 expression was significantly elevated in hepatocytes of MASH mice. Hepatocyte-specific SOX9 deletion exacerbated MCD-induced MASH, whereas overexpression of SOX9 mitigated high-fat, high-fructose-induced MASH. Lipidomic and RNA sequencing analyses revealed that SOX9 suppresses the expression of genes associated with lipid metabolism, inflammation, and fibrosis in MCD-fed mice. Furthermore, SOX9 deletion inhibited AMPK pathway activation, while SOX9 overexpression enhanced it. Notably, administration of an AMPK inhibitor negated the protective effects of SOX9 overexpression, leading to increased lipid accumulation in HepG2 cells.

Our findings demonstrate that SOX9 overexpression alleviates hepatic lipid accumulation in MASH by activating the AMPK pathway. These results highlight SOX9 as a promising therapeutic target for treating MASH.

The treatment of Helicobacter pylori (H. pylori) infection remains a challenge due to the increasing prevalence of drug-resistant bacteria. It is hypothesized that using more potent acid suppressants, such as potassium-competitive acid blockers (P-CABs) like Vonoprazan, may improve eradication rates. The aim of this study was to compare the effectiveness of H. pylori eradication regimens containing Vonoprazan with those containing proton pump inhibitors for H. pylori infection.

Two hundred and thirty-two patients were assigned to two groups. Group I (treatment-naïve) included: Arm 1 (intervention arm) with 58 patients who received Clarithromycin 500 mg twice daily, Amoxicillin 1 mg twice daily, and Vonoprazan 20 mg twice daily; and Arm 2 (comparator arm) with 58 patients who received Clarithromycin 500 mg twice daily, Amoxicillin 1 mg twice daily, and Esomeprazole 20 mg twice daily. Group II (treatment-experienced) included: Arm 3 (intervention arm) with 58 patients who received Levofloxacin 500 mg once daily, Vonoprazan 20 mg twice daily, Nitazoxanide 500 mg twice daily, and Doxycycline 100 mg once daily; and Arm 4 (comparator) with 58 patients who received Levofloxacin 500 mg once daily, Esomeprazole 20 mg twice daily, Nitazoxanide 500 mg twice daily, and Doxycycline 100 mg once daily. All patients received their treatment regimens for 14 days. H. pylori eradication was assessed four weeks after treatment.

The successful eradication rate was higher in Arm 1 (58.6%) compared to Arm 2 (50%), and higher in Arm 3 (50%) compared to Arm 4 (43.1%). H. pylori eradication regimens including P-CABs were well-tolerated with a low incidence of adverse events.

The results of P-CAB-based eradication regimens are comparable to those of proton pump inhibitor-based regimens.

Camels are commonly administered butylscopolamine (BSA), an antimuscarinic quaternary ammonium derivative, to reduce spasms in the smooth muscles of their urinary and gastrointestinal tracts. However, its presence in body fluids after racing is prohibited by animal racing authorities. The current study aimed to conduct a pilot pharmacokinetic study of BSA in healthy camels. The goal was to obtain initial pharmacokinetic parameters and use these parameters to predict plasma concentrations from the dose and clearance. This will help advise on a withdrawal time for BSA administration before camel racing. The pharmacokinetics of BSA were evaluated in three healthy camels after a single intravenous dose of 0.2 mg/kg body weight. Sensitive liquid chromatography with tandem mass spectrometry was used for the quantification of BSA and the internal standard, ipratropium, in plasma. BSA concentration versus time data were best described by a two-compartment open model. The pharmacokinetic parameters (median and range) were as follows: terminal elimination half-life was 2.29 (1.48–2.46) h, plasma clearance was 1,018.5 (772.4–1,024.0) mL/h/kg, volume of distribution at steady state was 931.9 (700.0–1,068.7) mL/kg, Cmax was 443.9 (351.1–443.9) ng/mL, and Tmax was 0.5 (0.25–0.75) h. BSA’s irrelevant plasma concentration was estimated to be 20 ng/mL. Consequently, it can be concluded that plasma would not contain BSA at the screening level of 20 ng/mL at the usual dose of 0.2 mg/kg body weight 24 h before camel racing.

A growing body of literature has demonstrated improved quality of life in cancer patients who utilize web-based patient portals; however, no studies have investigated their impact on objective clinical measures. The study aimed to evaluate the impact of patient portal utilization on clinical outcomes in cancer care. Patient portal platforms provide patients with direct access to their providers through messaging, medication requests, and other tools. There is a knowledge gap in the literature regarding whether electronic patient portals enhance outcomes in cancer care.

This study is a retrospective analysis of 791 patients with multiple myeloma within the Scripps Health system. The effect of MyScripps electronic patient portal use on unplanned hospital visits and mortality was assessed. Outcomes were also evaluated in relation to the age-adjusted Charlson comorbidity index and chemotherapy use.

Results showed that older, male, Hispanic, and Spanish-speaking patients had lower portal utilization. Those with inactive portal status had higher rates of unplanned hospital visits and mortality. Inactive portal status was an independent predictor of unplanned hospital visits in two multivariable logistic regression analyses. A logistic regression model investigating the interaction between patient portal use and age-adjusted Charlson comorbidity index revealed that active portal status remained a predictor of unplanned hospital visits.

This study highlights the potential to improve clinical outcomes among patients with multiple myeloma, particularly in vulnerable communities, by increasing access to electronic patient portals.

Few cases of tenofovir resistance have been reported, and the appropriate treatment for such cases remains unclear. We aimed to share a case of a chronic hepatitis B mono-infected patient with potential tenofovir resistance who required combined lamivudine and tenofovir therapy to achieve adequate viral suppression. The patient’s viral load (plasma) was monitored using the cobas® hepatitis B virus Test on the cobas® 6800 system. Hepatitis B antiviral drug resistance (AVDR) mutations were assessed by amplicon-based sequencing. Plasma was extracted using the MagNa Pure 24 system, and polymerase chain reaction targeting the polymerase gene (860bp) was performed. Sequencing was conducted on GridION R10.4.1 flow cells, and the resulting FASTQ files were analyzed using DeepChek®-HBV Software. We describe a female patient in her 60s with chronic hepatitis B who was e-antigen positive. She met treatment criteria in May 2020, when her alanine transaminase levels were 1.5 times above the upper limit of normal. She was initially started on entecavir but had to switch to tenofovir alafenamide in June 2020 due to a rash. Despite three years of tenofovir therapy, her viral load remained unsuppressed. AVDR testing identified two suspected tenofovir resistance mutations (V191I and A317S). Since no mutations associated with lamivudine resistance were detected, the patient was treated with a combination of lamivudine and tenofovir, achieving viral suppression after four months. Although rare, tenofovir resistance should be considered in patients with persistent viremia despite long-term therapy. AVDR sequencing facilitated the detection of potential tenofovir resistance and guided treatment decisions, leading to successful viral suppression in this case.

The World Health Organization System for Reporting Pancreaticobiliary Cytopathology introduces a seven-tier category system to standardize terminology and nomenclature. This system includes the following categories: Insufficient/non-diagnostic, benign/negative for malignancy, atypia, pancreaticobiliary neoplasm low-risk/grade, pancreaticobiliary neoplasm high-risk/grade, suspicious for malignancy, and malignant categories. Adopting a standardized reporting scheme facilitates consistent diagnostic criteria among pathologists, thereby reducing report variability and enhancing communication with the clinical team for optimal patient management. The report also highlights the role of critical ancillary tests in improving diagnostic accuracy for pancreatic lesions and discusses practical approaches to managing solid and cystic pancreatic lesions.

Type 1 bipolar disorder (BP) is a mental illness characterized by extreme shifts in mood, oscillating between manic and depressive episodes. It ranks as the sixth most prevalent psychiatric disorder globally, often emerging in the teenage years. This study aimed to identify associations between BP and 15 insertion/deletion (Indel) polymorphisms in the human genome, examining genes including TPA, UCP2, HLA-G, FADS2, ADRA2B, VEGF, PDCD6IP, SLC6A4, TLR2, APOB, TP53, LRPAP1, DHFR, MDM2, and DBH.

This case-control study involved 226 patients with BP and 235 healthy controls. Allele frequencies for each polymorphism in cases and controls were estimated using pooled samples. Polymerase chain reaction was performed for each Indel polymorphism using pooled samples as templates to estimate allele frequencies.

The data presented herein demonstrate a significant association between a 14bp Ins/Del polymorphism in the HLA-G gene and the risk of BP. The deletion allele of this polymorphism increased the risk of BP (odds ratio = 1.434, 95% confidence interval = 1.106–1.859, p = 0.007). Other 14 Indel polymorphisms were not associated with the risk of BP.

The HLA-G 14bp Indel polymorphism exhibits a significant correlation with the risk of BP in this study. This finding contributes to understanding the etiology of BP.

Pyrrolizidine alkaloids (PAs), widely distributed in plants, are known to induce liver failure. Hepatic platelet accumulation has been reported during the progression of PA-induced liver injury (PA-ILI). This study aimed to investigate the mechanisms underlying platelet accumulation in PA-ILI.

Cases of PA-ILI, non-PA-ILI, and control subjects were collected from patients hospitalized at Zhongshan Hospital, Fudan University (Shanghai, China) between 2012 and 2019. A mouse model of PA-ILI was established using monocrotaline administration. Liver RNA sequencing was performed, and gene interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins online database. Low-molecular-weight heparin and recombinant a disintegrin and metalloproteinase with a thrombospondin type I motif member 13 (ADAMTS13) were applied. The necrotic liver area, hepatic platelet accumulation, and von Willebrand factor (VWF) deposition were examined using hematoxylin and eosin staining and immunofluorescence assay.

Hepatic platelet accumulation, necrotic area expansion, and increased VWF expression were observed in both PA-ILI patients and mice. The Search Tool for the Retrieval of Interacting Genes/Proteins database indicated that ADAMTS13 regulates VWF expression and was differentially expressed in the livers of PA-ILI mice. Plasma and hepatic ADAMTS13 levels were significantly downregulated in both PA-ILI patients and mice. Systemic administration of recombinant ADAMTS13 decreased hepatic platelet accumulation, downregulated VWF expression, and mitigated mouse hepatic necrosis.

Hepatic platelet accumulation in PA-ILI was confirmed in both patients and mice. Deficiency of ADAMTS13 plays a critical role in platelet accumulation in PA-ILI, suggesting that ADAMTS13 could be a potential therapeutic target for this condition.

Severe COVID-19 pneumonia often requires high concentrations of oxygen, which can potentially lead to oxidative stress and lung injury. This study aimed to investigate the impact of different oxygen therapy modalities on oxidative stress by comparing malondialdehyde (MDA) levels, an oxidative stress marker, and glutathione (GSH), an antioxidant marker, in patients with severe COVID-19 pneumonia.

This study included 50 patients with COVID-19 pneumonia who received oxygen therapy using a reservoir mask at ≥15 L/m, high-flow oxygen therapy at 60 L/m, or oxygen therapy with noninvasive mechanical ventilation at fraction of inspired O2 (FiO2) levels of ≥60%. GSH and MDA levels were measured 48 h after starting oxygen therapy at FiO2 ≥ 60% and 48 h after switching to nasal cannula oxygen therapy at 2–4 L/m.

Overall, 60% (n = 30) of the patients were men, and 40% (n = 20) were women. In patients with accompanying hypertension, MDA levels, which were higher during oxygen therapy at FiO2 ≥ 60%, decreased significantly after switching to nasal cannula oxygen therapy at 2–4 L/m (p = 0.046). A significant difference in MDA was not found after switching to lower oxygen flow (p = 0.064) in patients with underlying diabetes mellitus. GSH levels in patients with underlying diabetes mellitus were higher during oxygen therapy at FiO2 ≥ 60% and decreased significantly after switching to nasal cannula oxygen therapy at 2–4 L/m (p = 0.021).

This study compared MDA and GSH levels among patients receiving oxygen therapy at high and low concentrations for severe COVID-19 pneumonia. The results revealed that patients who died of COVID-19 pneumonia had significantly higher mean MDA levels than those who survived. In patients with underlying HT, MDA levels, which were higher during oxygen therapy at FiO2 ≥ 60%, decreased during nasal oxygen therapy at 2–4 L/m; this difference was significant. The increase in serum MDA levels during high-flow oxygen therapy and the decrease during low-flow therapy in patients with COVID-19 pneumonia accompanied by hypertension suggest that oxidative stress due to hyperoxia should be taken into consideration.

Gelsemium elegans Benth (G. elegans) is a traditional medicinal plant; however, it is highly toxic, and toxicity varies significantly between species. The cause of this difference has not been clarified. Humantenirine is an important toxic alkaloid in G. elegans, and its metabolism has been poorly studied. This study aimed to compare the different metabolites formed by human liver microsomes, pig liver microsomes, and goat liver microsomes.

High-performance liquid chromatography/quadrupole time-of-flight mass spectrometry was used to study the metabolism of humantenirine in human liver microsomes, pig liver microsomes, and goat liver microsomes.

A total of eight metabolites (M1-M8) were identified, and three major metabolic pathways were found: demethylation (M1), dehydrogenation (M2, M3, M7), and oxidation (M4, M5, M6, M8).

Based on these results, it is hypothesized that demethylation is the major detoxification pathway for humantenirine, providing important information to better understand the metabolism and toxicity differences between species of G. elegans.