Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 32% of the US adult population. The present study aimed to utilize the All of Us electronic health record-linked large cohort to assess seven metabolic risk factors (MRFs) simultaneously, the impact by ethnicity and age, and clinical presentations of MASLD.

This study included a MASLD group (n = 15,060) and a frequency-matched control group (n = 75,300). Multivariable analyses were performed to compare the frequencies of MRFs and clinical outcomes between the two groups. Type 1 diabetes was not included in the multivariable analysis. Subgroup analyses were conducted according to race and ethnicity, as well as age.

The overall frequency of MASLD was 6.0%. Compared with the control group, individuals with MASLD had significantly higher independent frequencies of obesity (66.1% vs. 41.3%), type 2 diabetes (39.5% vs. 16.9%), hypertension (64.3% vs. 38.6%), hyperlipidemia (59.8% vs. 37.3%), obstructive sleep apnea (28.9% vs. 13.4%), and hypothyroidism (21.2% vs. 13.4%). Obesity was identified as the strongest independent MRF among Asians, Whites, and Hispanics, particularly in individuals younger than 50 years, whereas hypertension was the strongest independent MRF in Blacks. MASLD was also associated with significantly higher frequencies of cardiac events, including coronary artery disease (17.1% vs. 9.4%) and myocardial infarction (7.1% vs. 4.2%); hepatic events, including cirrhosis (7.5% vs. 1.1%) and hepatocellular carcinoma (0.5% vs. 0.1%); and elevated liver enzymes, including alanine aminotransferase (27.7% vs. 10.1%), aspartate aminotransferase (18.0% vs. 6.4%), and alkaline phosphatase (19.8% vs. 13.1%), compared with the control group.

Our study demonstrated that obesity, hypertension, hyperlipidemia, type 2 diabetes, obstructive sleep apnea, and hypothyroidism were independent MRFs for MASLD overall, but the ranking of these MRFs by odds ratios could vary by ethnicity and age. MASLD presents with significantly higher rates of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase elevation, as well as cardiac and hepatic events.

Mediastinal germ cell tumors (GCTs) are rare malignant neoplasms that occasionally develop somatic-type malignancies (SMs), such as sarcomas, carcinomas, and hematologic malignancies.

We report a unique case of a 16-year-old male patient with a mediastinal GCT that simultaneously developed two different SMs: well-differentiated angiosarcoma and acute megakaryoblastic leukemia (AML). The patient initially presented with left shoulder pain and intermittent shortness of breath. The imaging study demonstrated a 12.5 × 9.0 × 8.5 cm heterogeneous mass in the left anterior mediastinum. The mediastinal mass was resected and showed a cystic mature teratoma with somatic transformation into well-differentiated angiosarcoma and AML. A subsequent bone marrow biopsy confirmed the diagnosis of AML, and next-generation sequencing demonstrated the presence of PTEN and TP53 gene mutations in the AML. Despite aggressive chemotherapy and allogeneic stem cell transplantation, the patient died 10 months after diagnosis.

Our report demonstrates the unique capability of mediastinal GCTs to simultaneously develop two different SMs. The presence of two different SMs in mediastinal GCTs is associated with extremely aggressive behavior and a poor prognosis.

Cannabinoid hyperemesis syndrome is an underrecognized cause of recurrent vomiting, weight loss, and abdominal pain in adolescents, often overlooked due to its nonspecific presentation and overlap with other gastrointestinal conditions. This case report highlights a 13-year-old female who presented with significant weight loss and postprandial bilious vomiting initially attributed to superior mesenteric artery syndrome. Persistent symptoms, despite surgical removal of an incidental ovarian dermoid cyst, prompted reevaluation after nondiagnostic imaging and lack of improvement. Further history obtained on hospital day 12 revealed daily cannabis use since age 10, with reported cessation approximately six weeks prior to admission and probable resumed use approximately two weeks prior to presentation, confirmed by a positive urine toxicology screen for tetrahydrocannabinol consistent with chronic heavy use. Following supportive care and counseling on cannabis cessation, her acute symptoms resolved and she was discharged. She subsequently experienced a symptomatic relapse with resumed cannabis use requiring readmission two months later, but achieved sustained clinical remission at approximately six months following definitive cessation. This case illustrates how incomplete social histories and incidental findings can delay the identification of cannabinoid hyperemesis syndrome and lead to unnecessary procedures, and emphasizes that long-term symptom resolution requires ongoing cannabis abstinence. Early use of validated structured substance use screening tools (CRAFFT, BSTAD, S2BI), with urine toxicology applied as a confirmatory adjunct when the history is unreliable or symptoms remain unexplained, can facilitate timely recognition of cannabinoid hyperemesis syndrome in adolescents with persistent vomiting and abdominal pain, reduce hospital length of stay, and improve outcomes.

ATP-binding cassette (ABC) transporters are transmembrane proteins involved in the translocation of bilirubin, bile acids, phospholipids, and cholesterol into bile canaliculi. Mutations in particular genes encoding these transporters—including BSEP (ABCB11 gene), MDR3 (ABCB4 gene), sterolin-1 and sterolin-2 (ABCG5/8 genes), and MRP2 (ABCC2 gene)—result in a wide spectrum of liver diseases, ranging from benign conditions such as Dubin-Johnson syndrome to more severe presentations like progressive familial intrahepatic cholestasis. The severity of disease is influenced by many factors, including zygosity, mutation type, and environmental modifiers such as hormones, consanguinity, and founder effects. Homozygous and compound heterozygous mutations typically result in severe and early-onset diseases, while heterozygous single-allelic mutants generally result in milder diseases. Next-generation genetic testing has proven to have high diagnostic value and is important for prognostication. With knowledge of the underlying specific mutations, there is also potential for future targeted therapy for many severe diseases. The aim of this review is to update and discuss the hepatic diseases associated with ABC transporter mutations, the genetic and environmental effects that influence the severity of disease, typical presentations of these cholestatic hepatic diseases, diagnostic considerations, and treatment options.

Vulvovaginal candidiasis, an infection caused by an abnormal proliferation of Candida species in the vagina and vulva, is particularly relevant, affecting up to 75% of women of reproductive age. Because of antifungal drug resistance, a significant number of plants are used to treat vaginal candidoses in Cameroon. Thus, the scientific validation of the use of these plants in treating candidiasis is valuable. This study sought to identify medicinal plants used to treat vaginal infections in the Dschang district and evaluate the antifungal activity of the most promising plants on five Candida species.

The ethnobotanical survey was conducted in Dschang (Menoua Division, West Cameroon) through individual interviews using a semi-structured questionnaire. Extracts from seventeen plants were obtained by maceration using water or a water–ethanol solution (3:7; v/v). Antifungal activity was evaluated using the microdilution method.

Forty-eight plants belonging to 33 families were identified as treating vaginal infections. Decoction and formulation of ovules were the prevalent modes of plant preparation, with leaves and bark being the predominant plant organs used. Out of thirty-four extracts tested, two (CSEHAlc and MIEHAlc) showed antifungal activity, with minimum inhibitory concentrations ranging from 0.315 to 2.5 mg/mL. The determination of the minimum fungicidal concentrations revealed the fungicidal orientation of these bioactive extracts.

This study identifies medicinal plants used to treat vaginal infections in Dschang and their modes of preparation. The in vitro antifungal screening of selected plants indicated Mangifera indica and Canarium schweinfurthii as the anti-Candida plants that can be further exploited for antifungal drug discovery.

Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection leads to severe systemic inflammation, increasing non-AIDS morbidity and mortality risk. CD39 ectoenzyme on T-cells, which catalyzes the conversion of pro-inflammatory purines to immunosuppressive adenosine, plays an important role in inflammation control. The role of CD39+ T-cells in systemic inflammation during HIV/HCV coinfection under antiretroviral therapy (ART) remains unexplored. This study aimed to identify specific patterns of CD39 expression on T-cells in ART-treated HIV/HCV coinfected patients and assess their relationship with systemic inflammation.

We conducted a case-control study that enrolled 41 HIV/HCV coinfected patients on stable ART (cases) and 23 healthy controls. CD39 expression on blood CD4+ and CD8+ T-cells, including CD45RA+ and CD45RA– subsets, was quantified using flow cytometry. Cytokines were assessed using multiplex and enzyme-linked immunosorbent assays.

A significant proportion of CD4+ T-cells expressed CD39 in both groups (cases – 24.0%; controls – 16.1%). That was not true for CD8+ T-cells (cases – 3.2%; controls – 2.8%). CD39 expression was higher on CD45RA+ than CD45RA– CD4+ T-cells (cases – 39.4% vs. 19.0%; controls – 24.6% vs. 9.2%). HIV/HCV coinfected patients exhibited a significantly increased proportion of CD39+ CD4+ T-cells compared to uninfected controls (P < 0.01). A negative correlation was observed between the percentage of CD39+ CD4+ CD45RA– T-cells and levels of pro-inflammatory chemokines monocyte chemoattractant protein 1 (R = –0.392; P < 0.01) and eotaxin (R = –0.325; P < 0.05).

The data suggest a compensatory expansion of cells with regulatory properties that is ultimately insufficient to control systemic immune activation.

Synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy (MSA), are a group of neurodegenerative diseases characterized by the oligomerization of α-synuclein protein in neurons or glial cells. Various splicing isoforms of α-synuclein have been described, each with different aggregation properties. The α-synuclein gene (SNCA) has been identified as a highly significant genetic risk locus associated with various synucleinopathies across populations. This study aimed to assess the association of SNCA genetic variants with MSA and the levels of SNCA transcripts in peripheral blood mononuclear cells (PBMCs) from MSA and PD patients.

In this retrospective case–control study, 96 MSA patients, 1086 PD patients, and 485 healthy volunteers were included. PCR followed by restriction endonuclease analysis was used to detect four SNCA single-nucleotide polymorphisms (rs356219, rs3756063, rs11931074, and rs356168) in these individuals. In addition, RT-qPCR was performed to detect the levels of α-synuclein transcripts (SNCA mRNA isoforms -140, -126, and -112) in PBMCs of 24 MSA patients (including parkinsonian (MSA-P) and cerebellar (MSA-C) variants), 31 PD patients, and 32 healthy volunteers.

The frequency of the ‘T’ allele (of rs11931074) was significantly higher in MSA patients than in the healthy controls. The level of SNCA-140 mRNA was significantly decreased in MSA and PD patients compared with the controls, while the level of SNCA-112 mRNA was significantly increased in MSA-P patients than in PD patients and the controls. SNCA-112 mRNA/SNCA-140 mRNA and SNCA-112 mRNA/SNCA-126 mRNA ratios were significantly increased in MSA patients than in the controls.

The SNCA rs11931074 polymorphism is associated with MSA. There is a pronounced alteration in the expression of SNCA transcripts in PBMCs of MSA and PD patients.

Autoimmune hepatitis (AIH) frequently coexists with extrahepatic autoimmune diseases (EADs), but their prevalence, characteristics, progression, and treatment effect in the Han Chinese population remain unclear. This study aimed to evaluate the prevalence and spectrum of EADs and to assess their clinical features, disease course, and treatment outcomes in Han Chinese patients with AIH.

Medical records of 371 Han Chinese patients with AIH (diagnosed from March 2016 to October 2023) were retrospectively analyzed.

Among the 371 AIH patients, 304 (81.94%) were female, with a median age of 52.5 years (interquartile range, 46.0–61.0). A total of 23.98% (89/371) had at least one EAD, including 27.06% (82/303) in type 1 AIH, 11.11% (7/63) in antibody-negative AIH, and none in type 2. A single EAD was the most common (20.21%, 75/371). The most frequent EADs were Sjogren’s syndrome (8.63%) and autoimmune thyroid disease (8.36%). Compared with patients without EADs, those with EADs had lower alanine aminotransferase, red blood cell, and hemoglobin levels, but higher aspartate aminotransferase/alanine aminotransferase ratio and antinuclear antibody (ANA) positivity (all P < 0.05). ANA positivity was independently associated with EADs (odds ratio = 2.209, 95% confidence interval = 1.242–3.927, P = 0.007). After three months of treatment, the complete biochemical response rate was lower in the EADs group than in the non-EADs group (40.0% vs. 55.3%, P = 0.024), whereas no significant differences were observed at 6, 12, 24, or 36 months (all P > 0.05).

In the Han Chinese population, 23.98% of AIH patients had EADs, with Sjogren’s syndrome and autoimmune thyroid disease being the most common. ANA positivity was a significant risk factor for EADs. EAD patients had a poorer initial treatment response at three months, but comparable long-term biochemical response from six months.

As the leading cause of chronic liver disease globally, metabolic dysfunction-associated steatotic liver disease (MASLD) lacks effective therapies. This study aimed to investigate the therapeutic potential and molecular mechanisms of oxytocin (OXT) in MASLD.

Integrated bioinformatics analysis of MASLD datasets was carried out to identify OXT-related metabolic disturbances. Serum OXT levels were quantified using an enzyme-linked immunosorbent assay in 113 MASLD patients and 63 healthy controls. Mechanistic assays were conducted using oleic acid (OA)-induced, lipid-loaded HepG2 cells and high-fat diet-fed C57BL/6 mice, and OXT was administered intraperitoneally in vivo and supplemented in vitro.

Bioinformatics analysis revealed significant changes in OXT expression levels, particularly in fatty acid metabolism. Elevated OXT expression levels in MASLD patients were identified as an independent prognostic factor. In vitro, OXT significantly reduced OA-induced lipid accumulation in HepG2 cells, while in vivo, it decreased body weight, liver injury, and serum cholesterol levels in high-fat diet-fed mice. Mechanistically, OXT enhanced the expression level of phosphorylated AMP-activated protein kinase (AMPK) and suppressed the levels of sterol regulatory element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS). Blockade of AMPK with the chemical inhibitor Compound C reversed the ability of OXT to suppress the SREBP1c/FAS axis and reduce lipid accumulation in hepatocytes. Additionally, OXT inhibited the nuclear translocation of SREBP1c in OA-treated cells.

The findings demonstrate that OXT may serve as a potential therapeutic agent for MASLD by regulating the AMPK/SREBP1c/FAS pathway in lipid metabolism.