Cervical cancer, driven mainly by persistent high-risk human papillomavirus infection, remains a major public health problem in Bangladesh, with 9,640 new cases and 5,826 deaths in 2022. Early detection of pre-cancerous cervical lesions (PCL) is essential, yet limited evidence exists on factors associated with PCL among Bangladeshi women. This study aimed to identify factors associated with PCL among women attending cervical cancer screening centers at selected tertiary hospitals.

An age-matched (±5 years) case-control study was conducted in two tertiary hospitals. Cases were women who tested colposcopy-positive for PCL, and controls were visual inspection with acetic acid-negative women attending the same screening centers. A total of 38 cases and 76 controls were included. Data were collected through face-to-face interviews using a structured questionnaire. Multivariable logistic regression identified factors associated with PCL, with significance set at p < 0.05.

A history of sexually transmitted infections (adjusted odds ratio (AOR) = 36.73; 95% confidence interval (CI): 3.25–414.83), pelvic infections (AOR = 6.48; 95% CI: 1.24–33.85), not living with a husband (AOR = 4.48; 95% CI: 1.06–18.90), and overweight/obesity (AOR = 3.58; 95% CI: 1.14–11.22) were significantly associated with higher odds of PCL. Menstrual irregularity, genital ulcer history, and number of lifetime sexual partners showed no significant association.

Sexually transmitted infections, pelvic infections, overweight/obesity, and not living with husband were identified as factors associated with PCL. Strengthened infection prevention, lifestyle counseling, and targeted health education may support ongoing cervical cancer prevention efforts in Bangladesh.

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.

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.

Comparative data on sequential transarterial chemoembolization (TACE) after stereotactic body radiation therapy (SBRT) in recurrent hepatocellular carcinoma (HCC) remain limited. This study aimed to evaluate the efficacy of this combination.

We retrospectively reviewed 152 patients with recurrent HCC who met predefined eligibility criteria; 109 received SBRT alone and 43 received SBRT plus TACE. To minimize selection bias, a 2:1 propensity score matching was performed, resulting in 68 patients in the SBRT-alone group and 36 in the SBRT plus TACE group for the final comparative analysis. Overall survival, progression-free survival, and local control were assessed using the Kaplan-Meier method.

The SBRT plus TACE group was associated with numerically higher survival rates, although this difference did not reach statistical significance. The cumulative one-, three-, and five-year overall survival rates were 91.2%, 76.3%, and 61.8% for SBRT alone, compared to 100.0%, 86.1%, and 77.5% for the combination therapy ( p = 0.069). The corresponding progression-free survival rates were 73.1%, 51.1%, and 32.3% versus 88.9%, 58.1%, and 52.3% ( p = 0.091). No acute grade ≥3 toxicities were observed in either group.

In this exploratory analysis of recurrent HCC, the combination of SBRT and TACE demonstrated a favorable trend toward improved survival compared with SBRT alone, without an increase in severe toxicity. While these findings did not reach statistical significance, they establish the safety profile of the combined approach and provide preliminary evidence supporting its potential therapeutic role. This hypothesis-generating study justifies and informs the design of larger, prospective trials to definitively evaluate the efficacy of this regimen.

Reporting quality in clinical research is critical for evidence-based medicine and reproducibility of clinical studies. Previous work has mostly focused on the reporting quality of clinical trials and observational longitudinal studies. However, few studies have examined the reporting quality of trend analyses. Moreover, the reporting of recommended statistical metrics in trend analyses remains largely unclear. Therefore, we assessed the reporting quality of trend analyses based on reporting of recommended statistical metrics. We systematically searched the PubMed for the trend-analysis articles published in 10 leading medicine and oncology journals over an 11-year period (2008–2018). Studies published after 2019 were excluded due to a sudden, significant increase in publication numbers during and immediately after the COVID-19 pandemic. Only original articles, research letters, and meta-analyses/systematic reviews were included. We scored the reporting quality of these articles based on whether they reported p-values, effect sizes, beta/coefficient/slope/annual-percentage-change (APC). 297 articles met the inclusion criteria. Among these, 193 (66.0%) reported p-values and 216 (72.7%) reported effect sizes. Only 13 (5.8%) analyses reported neither p-values/effect sizes nor beta/coefficient/slope/APC. In multivariable regression models, authors affiliated with epidemiology departments were less likely to report effect sizes, whereas those from statistics departments were more likely to do so. Interestingly, U.S.-based senior authors (versus non-U.S.) more likely reported p-values. No factors were independently associated with reporting APC. Overall, the reporting quality of trend analyses in leading medicine and oncology journals appears moderate and warrants improvement. We thus call for increased awareness and further research on reporting quality in trend analyses in oncology research and beyond.

Insulin resistance is a common extrahepatic manifestation of hepatitis C virus (HCV) infection (HCVi), but its mechanism is poorly understood. While systemic insulin resistance is documented, portal insulin dynamics, a key regulator of hepatic metabolism, remain unexplored. This study aimed to investigate the relationship between insulin, the gut-liver axis, and immunometabolic changes in patients with HCV.

HCV patients were evaluated before (HCVi; n = 29) and after sustained virologic response (SVR) achieved with sofosbuvir/velpatasvir treatment (SVR, n = 23) (NCT02400216). Liver biopsies, portal blood, and peripheral blood were collected at both phases. Statistical analyses were conducted using Wilcoxon rank-sum tests, Mann-Whitney tests, and Pearson’s correlation coefficients to assess differences and associations across insulin, glucose, cytokines, metabolites, immune cells, and hepatic liver transcriptomics to elucidate impaired insulin homeostasis in HCVi.

HCV patients had significantly reduced portal insulin compared to SVR (p = 0.02), while peripheral insulin, portal glucose, and peripheral glucose remained unchanged. Portal insulin correlated positively with proinflammatory cytokines and vascular injury markers and negatively with CD8/CD62L/CD45RA/CD3 cells (naive cytotoxic T-cells) and non-standard nucleotides. Hepatic transcriptomic analysis revealed portal insulin correlated positively with immune and negatively with amino acid pathways, reflecting insulin’s role in the perturbations of immunometabolism during HCVi.

Lower portal insulin during HCVi is associated with changes consistent with altered pancreatic insulin secretion and decreased hepatic insulin extraction. The observed correlations support a potential relationship between the immune response and insulin dynamics, indicating an interplay between the immune system, metabolism, and insulin in HCVi, with clinical implications for the management of dysglycemia.

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.

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.

Liver fibrosis is a pivotal and reversible stage in the progression of chronic liver disease. However, the mechanisms underlying fibrosis reversal remain unclear, and effective diagnostic biomarkers are lacking in clinical practice. In this study, we aimed to elucidate the role and molecular mechanisms of glutathione S-transferase Mu 3 (GSTM3) in liver fibrosis reversal, and preliminarily determine whether GSTM3 can serve as a novel biomarker for liver fibrosis reversal.

Carbon tetrachloride-induced mouse models of liver fibrosis and spontaneous reversal were established. Proteomic analysis was used to identify proteins shared between liver tissue and serum that were continuously downregulated during fibrosis reversal. The expression of GSTM3 was evaluated in the livers of mice undergoing fibrosis reversal and in clinical samples from patients with liver fibrosis. Hepatic stellate cells (HSCs) were transfected with Gstm3-silencing RNA or an overexpression plasmid to assess the effects on fibrosis markers. RNA sequencing analyses were performed, and the underlying molecular mechanisms were investigated.

Proteomic analysis revealed significantly decreased GSTM3 levels in both hepatic tissue and serum in mice undergoing fibrosis reversal, and its expression was negatively correlated with the extent of reversal. GSTM3 levels were markedly increased in the hepatic tissue and serum of patients with liver fibrosis. GSTM3 expression was upregulated in transforming growth factor-β-stimulated HSCs. GSTM3 knockdown inhibited the expression of fibrosis markers, such as collagen type I α1 and tissue inhibitor of metalloproteinase 1, whereas its overexpression promoted their expression. Mechanistic studies indicated that GSTM3 knockdown activated peroxisome proliferator-activated receptor γ (PPARγ) signaling and downregulated its downstream targets, cluster of differentiation 36 and fatty acid-binding protein 4, thereby suppressing HSC activation.

GSTM3 knockdown promotes liver fibrosis reversal via PPARγ signaling-mediated inhibition of HSC activation. Therefore, GSTM3 is a promising therapeutic target and diagnostic biomarker for liver fibrosis.