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.

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.

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.

The prognostic nutritional index (PNI), calculated from serum albumin and lymphocyte count, reflects a patient’s immune-nutritional status and has been proposed as a prognostic marker in hepatocellular carcinoma (HCC). However, its role in advanced HCC patients treated with atezolizumab plus bevacizumab (Ate/Bev) remains unclear. In this study, we aimed to evaluate the prognostic value of PNI in patients receiving first-line Ate/Bev therapy.

We retrospectively analyzed 362 patients with unresectable HCC who received Ate/Bev between November 2020 and June 2023 across two centers. Based on prior literature, a cutoff of 45 was used to classify patients into low-PNI (<45) and high-PNI (≥45) groups. Propensity score matching was performed to balance baseline characteristics.

After propensity score matching, 130 patients (65 per group) were included in the analysis. The high-PNI group showed a significantly lower incidence of grade ≥ 3 treatment-related adverse events (10.8% vs. 24.6%, p = 0.039), a higher objective response rate (38.4% vs. 20.0%, p = 0.037), and significantly longer overall survival (16.7 vs. 7.9 months, p = 0.009). Although progression-free survival was longer in the high-PNI group (4.8 vs. 3.0 months), the difference was not statistically significant (p = 0.597). Multivariate analysis confirmed that PNI was an independent predictor of overall survival (hazard ratio: 0.574, 95% confidence interval: 0.353–0.933, p = 0.025), after adjusting for vascular invasion, alpha-fetoprotein levels, concurrent therapy, and post-treatment interventions.

PNI is an independent prognostic factor for overall survival in advanced HCC patients treated with Ate/Bev in real-world clinical practice. Incorporating PNI into routine assessments may enhance risk stratification and guide therapeutic decision-making.

Human papillomavirus (HPV) is a double-stranded circular DNA virus with a genome of approximately 7–8 kb. This study aimed to establish an overlapping extension polymerase chain reaction method for the amplification of the entire genome of HPV16.

The HPV16 genome was divided into two larger fragments (with lengths of 3.9 kilobases and 5.3 kilobases, respectively), each of which had overlapping regions of more than 500 base pairs. A nested primer (outer primer: Fout/Rout; inner primer: Fin/Rin) was used to amplify each fragment. The key reaction parameters were optimized, including the selection of two highly accurate DNA polymerases; and a series of diluted samples (initial concentration of 2,000 copies/microliter, diluted to 2, 20, 200, and 2,000 copies/microliter) were used for amplification tests to evaluate the sensitivity of this method.

This study demonstrated high sensitivity for HPV16 detection, with effective amplification of samples as low as 2 copies/µL. For low-concentration samples (<200 copies/µL), the Thermo Fisher enzyme showed 50% and 75% effective amplification success rates at 2 copies/µL and 20 copies/µL, respectively, while the Vazyme enzyme achieved 0% success at both concentrations. Both enzymes enabled stable amplification of high-concentration samples (≥200 copies/µL). The amplified products matched the theoretical size, and Illumina sequencing confirmed Q30 ≥ 96% and >98% identity with the HPV16 reference sequence (K02718.1).

This study provides a highly sensitive and specific method for the full-genome sequence analysis of HPV16, which is applicable to HPV16 full-genome sequencing, variation analysis, and other research.

Primary biliary cholangitis (PBC) is a chronic cholestatic disorder in which symptoms exert a direct influence on patients’ quality of life. Beyond pruritus and fatigue, patients with PBC are also prone to developing osteoporosis (OP). This skeletal condition not only heightens the likelihood of fractures but is also associated with elevated mortality. With the overall prevalence of PBC rising, a parallel increase in OP incidence among these patients can be anticipated. Early recognition, preventive strategies, and appropriate therapeutic approaches are essential for preserving patients’ quality of life. Nevertheless, current data on the management of OP in PBC remain limited. Most existing recommendations are extrapolated from studies on postmenopausal OP. However, these findings have not been effectively adapted into practical management protocols for PBC-related OP, largely due to distinct pathophysiological mechanisms between the two conditions. The absence of well-established preventive and therapeutic measures continues to represent a major obstacle in addressing OP among patients with PBC. This review offers a detailed synthesis of the epidemiology, underlying mechanisms, and therapeutic considerations of OP linked to PBC.

Alpinia calcarata (A. calcarata) Roscoe (Family: Zingiberaceae) is a rhizomatous perennial herb used in traditional medicine to treat inflammatory conditions. This study aimed to develop a topical emulgel dosage form by incorporating the essential oil of A. calcarata rhizome and to investigate it’s in vitro anti-inflammatory activity. A thin-layer chromatographic fingerprint of the essential oil of A. calcarata rhizome was developed. Then, an emulsion base containing plant oil was formulated and incorporated within a Carbopol gel base. The physical characteristics of this formulation were evaluated subsequently. The anti-inflammatory mechanism of the emulgel was determined by in vitro blood cell membrane stabilization assay and thrombolytic activity assay. The results were statistically analyzed by one-way analysis of variance. The thin-layer chromatographic fingerprint of the test oil demonstrated several bands with unique retention factor values. The formulated herbal emulgel was white, viscous, and homogeneous in appearance. The spreadability was 118 g·cm/M, and the pH of the emulgel was 6.30 at 25°C. The A. calcarata emulgel significantly (p < 0.05) inhibited heat-induced in vitro hemolysis, with the highest activity at a 50 µg/mL dose (87.68 ± 0.35%) compared to the placebo. Furthermore, this activity was found to be dependent on the essential oil concentration (r2 = 0.99) of the emulgel. Therefore, it was concluded that the essential oil of A. calcarata rhizome is an effective active ingredient to be used in a topical emulgel formulation, whereas the diverse phytochemicals present in the essential oil would be the underlying source of its anti-inflammatory activity.

Empirical and theoretical studies can be distinguished among the areas of investigation of the renin-angiotensin-aldosterone system (RAAS) and its relationship with the development of cardiovascular diseases. Theoretical work is based mainly on the bioinformatic analysis of key elements of RAAS (genes, proteins, metabolites), on calculations and predictions of protein interactions, and on mechanisms of RAAS gene expression regulation. An associative gene network based on big data analysis allows us to reveal relationships among the proteins, regulatory pathways, and biological processes acting in RAAS, as well as to identify new diagnostic markers, therapeutic targets, putative molecular mechanisms of the development of RAAS-associated diseases, drug interactions, and drug toxicity.

The reconstruction and analysis of associative gene networks were performed using ANDSystem. The regulation of RAAS-associated gene expression was analyzed by transcription factor (TF) binding sites (TFBSs) prediction in the proximal promoters of these genes and by studying interactions between TFs themselves using the Ensembl Biomart web service and AnimalTFDB 4.0. The recognition of potential TFBSs in RAAS gene promoters was performed using MoLoTool.

According to the centrality criteria of the RAAS associative gene network, the following proteins were identified as exerting a significant influence on information interplay between network components: IL6, EDN1, TNFA, MK01, LEP, and JUN. Analysis of the ten identified TFs and their TFBSs among the genes in the RAAS network under study revealed clusters of three to 26 genes regulated by them.

Components with the highest values of centrality and vertex degrees were identified in the reconstructed associative gene network of the RAAS, and ten TFs supposed to regulate 26 RAAS genes were determined.