The rate of functional cure (HBsAg loss) remains unsatisfactory following pegylated interferon (PEG-IFN) treatment in chronic hepatitis B. To optimize PEG-IFN administration, this study aimed to evaluate virological markers to predict functional cure and/or hepatitis B e antigen (HBeAg) loss.

Relevant studies assessing virologic markers for predicting functional cure and HBeAg loss after PEG-IFN therapy were systematically retrieved from PubMed, Embase, the Cochrane Library, and Web of Science up to November 2023. Predictive effectiveness was evaluated via the summary receiver operating characteristic curve.

We analyzed 38 studies (6,179 patients). HBsAg decline at week 24 had the greatest discriminative ability according to the area under the receiver operating characteristic curve (AUROC) (0.89) and sensitivity (0.88) for predicting functional cure, whereas baseline HBsAg had a comparable AUROC (0.86) and highest specificity (0.79), with both being significantly better than baseline hepatitis B core-related antigen and hepatitis B virus (HBV) RNA (all P < 0.001). For HBeAg loss or seroconversion, HBV RNA, HBV DNA, HBeAg, and HBeAg decline at week 12, as well as HBV DNA and HBeAg decline at week 24, all exhibited comparable predictive values (AUROC = 0.75–0.78). HBV RNA and HBeAg levels at week 24 showed optimal sensitivity (0.87), and HBeAg decline at week 12 had the highest specificity (0.83).

HBsAg decline at week 24 and baseline HBsAg levels are better predictors of functional cure than novel virologic markers, while on-treatment HBV RNA and HBeAg levels and dynamic changes are the most reliable indicators for HBeAg loss.

Metabolic dysfunction–associated steatotic liver disease (MASLD), defined by the American Association for the Study of Liver Diseases as hepatic steatosis with at least one cardiometabolic risk factor, affects approximately 30–40% of adults worldwide. This condition may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. The rising prevalence, alongside obesity and type 2 diabetes, underscores the need for early risk stratification and integrated therapeutic strategies. Circadian homeostasis, orchestrated by the suprachiasmatic nucleus and core clock gene feedback loops, synchronizes hepatic metabolic pathways with environmental light–dark cycles. The objective of this review is to evaluate the role of circadian disruption and metabolic dysfunction in the development of hepatic steatosis, as well as to assess current and potential treatment modalities for both disorders. Circadian disruption through shift work, artificial light at night, sleep restriction, and chrono-nutritional misalignment destabilizes hepatic clocks, promoting insulin resistance, dyslipidemia, inflammation, and steatosis. Experimental models demonstrate that clock gene dysfunction alone can induce steatohepatitis, while progressive MASLD further impairs central circadian regulation, establishing a self-reinforcing chrono-metabolic cycle. Pharmacologic therapies, including glucagon-like peptide-1 receptor agonists and thyroid hormone receptor-β agonists, improve histologic endpoints and fibrosis regression, although heterogeneity among clinical trials precludes direct comparison. Recent evidence characterizing MASLD as a predominantly nocturnal metabolic disorder further highlights persistent nighttime insulin dysregulation despite weight loss, emphasizing the potential role of circadian-targeted interventions such as melatonin. In conclusion, the peripheral circadian clock is intricately linked with MASLD pathogenesis, and metabolic dysfunction, in turn, disrupts circadian pathways. Several pharmacologic therapies offer potential for the treatment of MASLD and circadian dysfunction.

PVT is a harmful event in cirrhosis, and the prevention and treatment of PVT are important in the management of cirrhosis and portal hypertension. The study aimed to observe the efficacy of Danggui Buxue Decoction (DBD) on portal vein thrombosis (PVT) in cirrhosis and to elucidate the related mechanism using a modified animal model.

A model of PVT in cirrhosis was established by partial portal vein ligation and intraperitoneal injection of CCl4 in rats, which showed obvious PVT with intra- and extravenous thrombosis as well as liver cirrhosis. Rats were randomly assigned into four groups and received intragastric administration of DBD (12 g/kg/day) or rivaroxaban (20 mg/kg/day) for 6 weeks.

DBD attenuated collagen deposition and reduced thrombus formation in model livers, increased portal vein blood flow, expanded the portal vein diameter, and reduced prothrombin time and international normalized ratio in the model rats. In addition, DBD reduced hepatic von Willebrand factor and plasminogen activator inhibitor-1 expression and increased hepatic fibrin degradation product content in the liver tissues of model rats.

We modified a model of cirrhotic PVT in rats and found that DBD had a good effect on PVT and liver fibrosis, with the mechanisms related to the enhancement of portal vein blood flow and the protection against endothelial cell injury.

Amaranth is conventionally consumed as a significant source of nutrients and bioactive compounds and is a potential alternate crop. The present study aimed to validate the folklore and ethnomedicinal claims regarding the utilization of foliar tissues of the pseudocereal Amaranthus hypochondriacus L. for their pharmacological propensities, primarily focusing on bioactive polyphenolic compounds and associated anti-degenerative properties, in view of the scarce evidence available on the same.

Reverse-phase high-performance liquid chromatography coupled with a photodiode array assay of nineteen significant bioactive polyphenolic compounds, along with their in vitro antioxidant-based pharmacological properties (superoxide and hydroxyl radical scavenging properties, metal-chelating and reducing properties, radical scavenging properties, anti-lipid peroxidation and protein coagulation properties, and α-glucosidase and α-amylase inhibitory activities), were assessed and compared for foliar extracts of ten promising experimental accessions of Amaranthus hypochondriacus, grown in two different seasons (summer and winter).

The results exhibited germplasm-specific variations in the pharmacological potential of foliar tissues of the experimental amaranths, which can be substantiated by data showing a close correlation between the abundance of bioactive polyphenolic compounds (naringin, myricetin, naringenin, apigenin, rutin, catechin, quercetin) and in vitro antioxidant (2,2-diphenyl-1-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay, hydroxyl radical scavenging, reducing, and metal-chelating) properties, as well as anti-diabetic (inhibition of α-glucosidase and α-amylase activities) and anti-inflammatory (anti-lipid peroxidation) attributes. Accessions IC107144 and IC47434 stood out as the most promising medicinal crops based on overall in vitro anti-degenerative properties and the bioavailability of polyphenolic compounds.

Overall, the results validated the traditional ethnomedicinal claim regarding the utilization of foliar tissues of the underutilized pseudocereal Amaranthus hypochondriacus L., and identified lead germplasms (IC107144 and IC47434) as low-cost natural sources of bioactive compounds, potentially promoting their pharmacological utilization.

Infectious diarrhea is a gastrointestinal illness that results in around 1.7 billion cases and 525,000 deaths annually, particularly among children under five, according to the World Health Organization. While some Cameroonian medicinal plants show promise for treating diarrhea, many plants are used without established scientific evidence of their efficacy. These plants include Tithonia diversifolia (T. diversifolia) and Solanum torvum (S. torvum), which are traditionally used to treat diarrheal symptoms. This study sought to investigate the anti-Shigella activity of leaf extracts from T. diversifolia and S. torvum.

Extracts from T. diversifolia and S. torvum were obtained by successive maceration in solvents of increasing polarity, including hexane, dichloromethane, ethyl acetate, methanol, and water. The as-prepared extracts (10) were evaluated for antibacterial activity against selected Shigella species using an in vitro experiment. The mode of action of the bioactive extracts was determined in Shigella through growth kinetic analysis.

Hexane extract from S. torvum (St-HEX-F) and dichloromethane extract from T. diversifolia (Td-DCM-F) inhibited the growth of Shigella flexneri NR-518 and Shigella boydii NR-521 with minimum inhibitory concentration (MIC) values of 500 and 1,000 µg/mL, respectively. Shigella flexneri and Shigella boydii were the most sensitive strains, whereas Shigella sonnei was the most resistant strain. Bacterial growth kinetics revealed that St-HEX-F and Td-DCM-F are bacteriostatic at MIC and bactericidal at 2×MIC and 4×MIC.

Extracts from T. diversifolia and S. torvum possess anti-Shigella activity and could be used as a potential source of active ingredients for developing new treatments against diarrhea caused by multidrug-resistant Shigella.

Antimitochondrial antibody (AMA)-negative primary biliary cholangitis (PBC) is a rare presentation of PBC that comprises 5%–10% of all PBC patients. The pathogenesis of AMA-negative PBC appears to be similar to that of AMA-positive PBC. AMA-negative PBC presents similarly to AMA-positive PBC, with symptoms of cholestasis, fatigue, and pruritus most commonly reported. Defective bicarbonate production, resulting in acidification of bile and bile acids, has been proposed as the primary mechanism of damage to bile ducts and hepatocytes and is reflected in elevations of alkaline phosphatase and aminotransferases. Chronic damage can lead to the development of cirrhosis. The diagnosis is made by the finding of AMA negativity by ELISA or assays of similar sensitivity and a positive PBC-specific antinuclear antibody (ANA; anti-glycoprotein 210 and anti-speckled 100 kDa protein) test. In cases in which anti-glycoprotein 210 and anti-speckled 100 kDa protein assays are also negative, a liver biopsy is required to make the diagnosis after exclusion of other causes of cholestasis by magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography. Treatment for AMA-negative PBC is the same as for AMA-positive cases, with ursodeoxycholic acid as the first-line treatment. Current treatment is most effective in early stages, where it slows but does not eliminate progression. Risk stratification by validated tools such as the GLOBE and UK-PBC scores remains useful in AMA-negative PBC.

5-methylcytosine RNA modification is a key regulator of neuroblastoma oncogenesis and differentiation. NSUN6, a 5-methylcytosine-specific messenger RNA methyltransferase, modulates messenger RNA methyltransferase activity and translation termination. Yet, its potential link to neuroblastoma risk has not been previously reported. The present study aimed to reveal the relationship between NSUN6 gene polymorphisms and the risk of neuroblastoma in children from Jiangsu province.

In this case-control study, we investigated three NSUN6 gene polymorphisms (rs3740102 A>C, rs12780826 T>A, and rs61842187 G>C) in 402 neuroblastoma cases and 473 controls, all of whom were children from Nanjing City, Jiangsu Province, China. DNA from these subjects was assessed using the TaqMan method. Multivariate logistic regression analysis was employed to examine the association between NSUN6 gene polymorphisms and neuroblastoma risk. Additionally, the Genotype-Tissue Expression database was utilized to elucidate the impact of these polymorphisms on NSUN6 and nearby gene expression. Kaplan-Meier analysis and the non-parametric test were conducted on the R2 platform to assess the relationship between gene expression, prognosis, and neuroblastoma risk.

Carriage of two to three protective genotypes (rs3740102 AA/AC, rs12780826 TT/TA, rs61842187 CC) was significantly associated with a lower risk of neuroblastoma (adjusted odds ratio = 0.41, 95% confidence interval = 0.23–0.73, P = 0.002), with consistent results across all subgroups. Expression quantitative trait locus analysis showed these single-nucleotide polymorphisms may upregulate the expression of NSUN6 and CACNB2. Furthermore, higher NSUN6 and CACNB2 expression was correlated with a potentially lower risk of neuroblastoma, improved overall survival (NSUN6: P = 2.54e-03; CACNB2: P = 6.35e-06) and event-free survival (NSUN6: P = 7.90e-04; CACNB2: P = 4.64e-06), as well as a lower likelihood of MYCN amplification.

NSUN6 rs3740102 AA/AC, rs12780826 TT/TA, and rs61842187 CC genotypes may be associated with a better prognosis of neuroblastoma. This association may be related to the potential upregulation of NSUN6 gene expression and a lower likelihood of MYCN amplification.

Infections are frequent and lethal complications of acute-on-chronic liver failure (ACLF). Reliable biomarkers to distinguish fungal from bacterial infections remain limited. Given the central role of immune dysfunction in ACLF, we aimed to evaluate the diagnostic value of serum cytokines in differentiating invasive pulmonary aspergillosis (IPA) from bacterial pneumonia (BP) in HBV-associated ACLF.

This retrospective case-control study enrolled ACLF patients admitted to the Tongji Hospital, between 2018 and 2022. Patients were categorized into IPA, BP, and non-infection groups. The BP and non-infection groups were propensity score-matched to the IPA cases. Serum cytokines levels (IL-1β, sIL-2R, IL-6, IL-8, IL-10, TNF-α) and clinical data were collected, with the diagnostic performance of these cytokines as biomarkers assessed via ROC curves.

A total of 32 IPA, 96 BP, and 96 non-infection patients were enrolled, with balanced baseline characteristics. Compared with the non-infection group, the IPA group had higher sIL-2R (1,606.00 vs. 1,211.50 U/mL, P = 0.019) and IL-6 (69.03 vs. 15.98 pg/mL, P < 0.001) levels, but lower IL-8 levels (62.20 vs. 132.00 pg/mL, P = 0.025). The BP group showed elevated sIL-2R (1,792.00 U/mL), IL-6 (49.42 pg/mL), IL-10 (13.40 pg/mL) levels compared to the non-infection group (all P < 0.001). Also, IL-8 was lower in the IPA group than in the BP group (62.20 vs. 176.00 pg/mL, P < 0.001) and its assessment could best distinguish IPA from BP (AUC = 0.743, cut-off = 76.60 pg/mL; sensitivity = 66.7%, specificity = 82.1%).

Serum IL-8 exhibited superior diagnostic value for IPA in patients with HBV-ACLF and could effectively discriminate Aspergillus infections from bacterial infections.

Despite the emergence of new approaches in acute myeloid leukemia (AML) treatment in recent years, the overall prognosis remains poor. Particularly for elderly patients and relapsed/refractory cases, the five-year survival rate consistently remains below 30%. While traditional chemotherapy regimens can rapidly suppress tumor burden and alleviate clinical symptoms, they suffer from limitations such as insufficient targeting, prominent toxic side effects, and a tendency to induce drug resistance. Immunotherapy offers a novel therapeutic pathway for AML due to its advantages of precise targeting, long-lasting antitumor effects, and a controllable safety profile. However, single-agent immunotherapy demonstrates limited clinical response rates in AML and struggles to achieve complete tumor cell clearance. In this context, combination regimens of chemotherapy and immunotherapy are increasingly becoming the focus of research. This review aims to summarize the rationale and advances in the combination of immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy, antibody-drug conjugates, bispecific antibodies, and cancer vaccines with chemotherapy for the treatment of AML. We have detailed the preclinical research and clinical trial progress of each combined regimen, analyzed the core challenges—including off-target toxicity, high tumor heterogeneity, and limited efficacy in specific AML subtypes—and further propose targeted solutions and future development directions, such as exploring novel specific antigens, developing multi-targeted drugs, and formulating precision individualized treatment plans. The clinical application of such combined strategies is attracting increasing attention. In conclusion, chemo-immunotherapy combinations represent a highly promising therapeutic paradigm for AML, harnessing the synergy of chemotherapy-mediated immune microenvironment remodeling and the specific antitumor activity of immunotherapies to overcome single-agent limitations and deliver meaningful survival benefits.

Breast cancer (BCA) is one of the most common cancers worldwide, with a high rate of mortality and morbidity in women. This review focuses on the applications of nanotechnology, nanomaterials, and nanoparticles (NPs) in BCA, encompassing diagnosis and therapy. Nanotechnologies, nanocarriers, and nano-encapsulations versus their corresponding counterparts for BCA diagnosis and therapy have been discussed. Various drug formulations into different nanocarriers (lipid NPs, nanoemulsions, polymeric NPs, and metal-based NPs) enhanced their bioavailability and therapeutic efficacy, overcoming the limitations of conventional formulations. Additionally, clinical specialists have achieved improved outcomes in the detection and monitoring of BCA at various stages using nanotechnology, ultimately leading to an improved quality of life for patients.