Gallbladder carcinoma (GBC) is a malignant tumor of the biliary system that is aggressive, difficult to detect early, and has a low surgical resection rate and poor prognosis. Appropriate in vitro growth models are expected to focus on the study of the biological behavior and assess treatment effects. Nonetheless, cancer initiation, progression, and invasion include spatiotemporal changes and changes in the cell microenvironment intracellular communication, and intracellular molecules, making the development of in vitro growth models very challenging. Recent advances in biomaterial methods and tissue engineering, particularly advances in bioprinting procedures, have paved the way for advances in the creative phase of in vitro cancer research. To date, an increasing number of cultured models of gallbladder disease have emerged, such as two-dimensional (2D) GBC growth cell cultures, three-dimensional (3D) GBC growth cell cultures, xenograft models, and 3D bioprinting methods. These models can serve as stronger platforms, focusing on tumor growth initiation, the association with the microenvironment, angiogenesis, motility, aggression, and infiltration. Bioprinted growth models can also be used for high-throughput drug screening and validation, as well as translational opportunities for individual cancer therapy. This study focused on the exploration, progress, and significance of the development of GBC cultural models. We present our views on the shortcomings of existing models, investigate new innovations, and plan future improvements and application possibilities for cancer models.

In this study, we aimed to evaluate the diagnostic values of alpha-fetoprotein (AFP), soluble AXL (sAXL), des-γ-carboxy prothrombin (DCP), the aspartate aminotransferase-to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in hepatocellular carcinoma (HCC) and the possible underlying mechanisms of the correlations between them.

We collected serum samples from 190, 128, and 75 patients with HCC, cirrhosis, and chronic viral hepatitis, and from 82 healthy subjects. Serum levels of AFP, sAXL, and DCP were determined, and APRI and GPR values were calculated. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of single and combined biomarkers.

We detected significant differences between the HCC group and other groups regarding serum AFP, sAXL, DCP, and APRI levels. GPR significantly differed between the HCC group and other groups, except for the liver cirrhosis group. AFP, sAXL, DCP, APRI, and GPR had positive correlations with each other, and AFP showed a higher area under the curve (AUC) and Youden index values, while APRI and DCP showed the highest sensitivity and specificity. Also, when AFP was combined with sAXL, DCP, APRI, and GRP, the highest AUC (0.911) and a higher net reclassification improvement value were obtained compared with those obtained for the individual biomarkers.

AFP, sAXL, DCP, APRI, and GPR are independent risk factors for HCC, and the diagnostic performance of AFP combined with sAXL, DCP, APRI, and GPR for HCC diagnosis was superior to that of the individual biomarkers.

Liver damage in cholestasis is multifactorial, yet bile acid-mediated hepatotoxicity is pivotal. Honey consumption has many physiological effects; it influences detoxification process (phase I, II and III), has antioxidant, anti-inflammatory, immune-stimulant, anti-ulcer, wound/burn healing effects and others. The bile acid ursodeoxycholic acid (UDCA) is currently used off-label to treat neonatal cholestasis. This study aimed to assess the effectiveness of spore-free natural honey to treat neonatal nonobstructive cholestasis.

Thirty infants with cholestasis received spore-free natural honey. Their progression was compared to a control group with cholestasis (28 infants) and a historical group (31 infants) on UDCA.

The mean ± standard deviation (SD) follow-up duration was 29.68 ± 18.68 months. At presentation, the total bilirubin concentrations were 9.5 ± 5.9 mg/dL, 10.9 ± 7 mg/dL and 14 ± 9 mg/dL in the honey, control and UDCA groups, respectively (p = 0.064), and their direct bilirubin concentrations were 6 ± 4 mg/dL, 6.7 ± 4 mg/dL and 8.4 ± 6.9 mg/dL, respectively (p = 0.169). The final total bilirubin concentrations were 1.2 ± 1.7 mg/dL, 4.6 ± 8.2 mg/dL and 7.3 ± 8.9 mg/dL, (p = 0.006), and their final direct bilirubin concentrations were 0.8 ± 1 mg/dL, 2.77 ± 5.2 mg/dL and 5.1 ± 7.2 mg/dL (p = 0.008), with cure achievement in 25, 16 and 16 (p = 0.023), improvement in 3, 5 and 3 (p = 0.565), failure in 2, 3 and 10 (p = 0.016), and death in 0, 4 and 2, respectively (p = 0.095). None suffered from botulism or flaccid paralysis.

Spore-free honey is effective in clearing cholestasis in neonates and infants. UDCA use in cholestasis in pediatric age should be abandoned as it is less effective and is associated with a worse outcome.

In order to study the regulating effect of electroacupuncture at specific acupoints on the depression level of drug addicts, we randomly selected 42 drug addicts from Sichuan drug rehabilitation center of women and divided them into treatment group (13), comfort group (10) and control group (19) from April to August 2019. Venous blood was taken before and after treatment, and the serum samples such as Noradrenalin (NA) and brain-derived neurotrophic factor (BDNF) were systematically detected. At the same time, Beck Depression Scale was used to detect the level of depression before and after treatment. Results showed that the level of depression in the real acupuncture group decreased significantly after treatment (p < 0.05). The contents of NA and BDNF in the serum of the real acupuncture group increased after treatment, but did not reach a significant level. In a word, the combination therapy of electroacupuncture can improve the levels of BDNF and NA in drug addicts and adjust their depression level, which is worthy of clinical promotion.

Helicobacter pylori (H. pylori) infection is widely prevalent worldwide. H. pylori infection has been reported to be a risk factor for the development of insulin resistance, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Because treatment for NAFLD, other than weight loss is limited, the treatment for H. pylori infection is well established. It is important to determine whether screening and treatment for H. pylori infection should be considered in patients with no gastrointestinal symptoms. The aim of this mini-review is to evaluate the association between H. pylori infection and NAFLD including epidemiology, pathogenesis, and the evidence for H. pylori infection as a modifiable risk factor for preventing or treating NAFLD.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies. It has high mortality and poor clinical outcomes, but the molecular mechanisms in the pathogenesis of HCC are not understood. The tumor immune microenvironment (TIME) is a highly intricate system with distinct populations of innate and adaptive immune cells, as well as other stromal cells. They interact and evolve with tumor cells to influence tumor growth, migration, invasion, immune evasion, and response to therapy. Emerging evidence has shown noncoding RNAs (ncRNAs) are prominent regulators of TIME in HCC. In this review, we elaborate on the functions and molecular mechanisms of ncRNAs in remodeling TIME of HCC and discuss their diagnostic and therapeutic potential for HCC treatment.

To determine whether liver stiffness measurement (LSM) indicates liver inflammation in chronic hepatitis B (CHB) with different upper limits of normal (ULNs) for alanine aminotransferase (ALT).

We grouped 439 CHB patients using different ULNs for ALT: cohort I, ≤40 U/L (439 subjects); cohort II, ≤35/25 U/L (males/females; 330 subjects); and cohort III, ≤30/19 U/L (males/females; 231 subjects). Furthermore, 84 and 96 CHB patients with normal ALT (≤40 U/L) formed the external and prospective validation groups, respectively. We evaluated the correlation between LSM and biopsy-confirmed liver inflammation, and determined diagnostic accuracy using area under the curve (AUC). A noninvasive LSM-based model was developed using multivariate logistic regression.

Fibrosis-adjusted LSM values significantly increased with increasing inflammation. The AUCs of LSM in cohorts I, II, and III were 0.799, 0.796, and 0.814, respectively, for significant inflammation (A≥2) and 0.779, 0.767, and 0.770, respectively, for severe inflammation (A=3). Cutoff LSM values in all cohorts for A≥2 and A=3 were 6.3 and 7.5 kPa, respectively. Internal, external, and prospective validations showed high diagnostic accuracy of LSM for A≥2 and A=3, and no significant differences in AUCs among the four groups. LSM and globulin independently predicted A≥2. The AUC of an LSM-globulin model for A≥2 exceeded those of globulin, ALT, and AST, but was similar to that of LSM.

LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.

Prostate cancer is a heterogeneous disease with a wide spectrum of pathological, clinical, and molecular features. The diagnosis and classification of prostate cancer have been constantly modified with the incorporation of new data. The 5th edition of the World Health Organization (WHO) Classification of Urinary and Genital Tumors was recently published six years after the 4th edition. In this new edition, the classification of prostate cancer has been refined in the diagnostic criteria, grading, nomenclature, and genomics. This review summarizes significant updates to the new WHO classification of prostate cancer, including high-grade prostatic intraepithelial neoplasia, acinar adenocarcinoma, intraductal carcinoma, ductal carcinoma, and neuroendocrine tumors. Controversial issues in the Gleason grading are discussed, such as intraductal carcinoma and tertiary grade. We also highlight distinct genetic and epigenetic alterations in prostate cancer that may contribute to its diverse clinicopathologic features. Overall, the 5th edition of the WHO classification provides a comprehensive assessment of prostate cancer with morphologic, immunohistochemical, genomic, and clinical data, which may represent an optimal paradigm for diagnosing and treating prostate cancer.

As for resection for colorectal liver metastasis (CRLM), securing an adequate surgical margin is important for achieving a better prognosis. However, it is often difficult to achieve adequate margins for the resection of CRLM. So the current survival impact of sub-centi/millimeter surgical margins in hepatectomy for CRLM should be evaluated. In the current era of multidisciplinary treatment options, this review focused on the prognostic impact of a sub-centi/millimeter surgical margin width in hepatectomy for CRLM. We systematically reviewed retrospective studies that clearly described the surgical margin width for hepatectomy for CRLM. We selected studies conducted since 2000 that involved patients diagnosed as having CRLM. We focused on studies that investigated not only surgical margins, but also microscopic surgical curability such as R0 (microscopically complete resection) or R1 (microscopically incomplete resection), which clearly describe their definitions. Based on our literature review, 1, 2, or 5 mm was considered the minimum surgical margin width for hepatectomy for CRLM. Although a surgical margin width of 1 mm is acceptable for hepatectomy for CRLM, submillimeter margins, which are defined as R1 in many reports, are only acceptable for limited patients such as those who have undergone preoperative chemotherapy. Zero-mm margins are also acceptable in limited patients such as those who show a good response to preoperative chemotherapy. New chemotherapy agents have been reported to reduce the prognostic impact of a narrow surgical margin width. The incidence of margin recurrence, which is a major concern regarding R1 resection of CRLM, is about 20–30% according to the majority of earlier reports. As evaluations of the actual prognostic impact of the surgical margin remain difficult, further study is warranted.

Cervical cancer has caused numerous deaths in women worldwide over the past few decades. It is a serious clinical problem that needs to be solved, though its morbidity and mortality have declined in recent years. The current treatments against cervical cancer are hysterectomy, radiotherapy, and chemotherapy, with certain limitations. Meanwhile, progress has been made in the screening and prevention of cervical cancer, focusing on human papillomavirus (HPV) infection, which is considered a necessary but insufficient cause. This review summarizes our current knowledge of screening and prevention of cervical cancer and its relation to HPV.

Aminoacyl-tRNA synthetases (ARSs) participate in tumor initiation and progression but their involvement in hepatocellular carcinoma (HCC) is not clear. This study aimed to investigate the prognostic value and underlying mechanisms of ARS in HCC.

Data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium, Gene Expression Omnibus and Human Protein Atlas databases. The prognostic model was constructed with the use of Cox regression and least absolute shrinkage and selection operator regression. Kaplan-Meier survival analysis, enrichment analysis, single sample gene set enrichment analysis and tumor mutation burden calculation were performed with R to evaluate the model and explore the underlying mechanism. Wilcoxon tests were used for comparisons between groups.

Aspartyl-tRNA synthetase 2 (DARS2), tyrosyl-tRNA synthetase 1 (YARS1) and cysteinyl-tRNA synthetase 2 (CARS2) were identified as prognostic biomarkers and enrolled in model construction. The area under receiver operating characteristic curve of the model was 0.775. The model was used to assign patients from TCGA into low- and high-risk groups. Those in the high-risk group had a worse prognosis (p<0.001). The clinical significance of the model was tested in different clinical subgroups. Genetic mutation analysis had a higher TP53 mutation frequency in high-risk group. Enrichment analysis and study of immune-related cells and molecules found that the high-risk group was characterized by immune-cell infiltration and immunosuppression states.

A novel ARS family-based model of HCC prognosis was constructed. TP53 mutation frequency and immune-suppressive status accounted for a worse prognosis in patients included in the high-risk group.

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a useful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vaccine response has been observed in liver transplant recipients, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data comparing the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavirus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospective studies are required to investigate the duration of immunity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.

This study evaluates the association of haplotypes of vitamin D receptor (VDR) genes (BsmI-ApaI-TaqI) with blood lead (B-Pb) levels.

The VDR polymorphism results for 100 occupationally lead-exposed (LEx) workers in the battery industry and 100 non-lead-exposed controls (controls) from the Delhi-NCR region were analyzed for haplotypes. PCR-RFLP was used to identify three VDR polymorphisms (TaqI, BsmI and ApaI), and the VDR haplotype and linkage disequilibrium (D′) were analyzed in these subjects.

B-Pb, together with the total vitamin D, calcium and phosphorus levels, were reported in the previous study conducted by the investigators. Eight possible haplotypes were observed among the three single nucleotide polymorphisms (BsmI-ApaI-TaqI). Furthermore, significant differences in haplotype frequency were observed between LEx workers and controls for the “baT” haplotype (X2 = 4.9, p = 0.02). Importantly, higher B-Pb levels were observed for the “baT” haplotype of the BsmI-ApaI-TaqI polymorphism, and BsmI and ApaI had the highest D′ and r2 values. However, significant variations in vitamin D, calcium and phosphorus levels were not observed between these haplotypes.

The “baT” haplotype of VDR polymorphisms might be a potential risk factor for lead toxicity, especially in exposed individuals. Hence, this haplotype may be considered during the screening of occupationally exposed individuals, in order to identify those who are susceptible to developing lead toxicity.

Post-acute sequelae of SARS-CoV-2 (PASC) or long COVID is a major public health problem. The underlying mechanism(s) of this disease remains unclear, and there is a lack of effective therapies. We report a case of a 47-year-old patient who experienced breakthrough acute COVID-19 with PASC after two doses of COVID-19 vaccination, and its symptom resolution following a course of the novel combination of antiviral nirmatrelvir-ritonavir. One of several leading hypotheses on the pathogenesis of PASC is a persistent viral reservoir. This case report raises important questions on the potential role of antiviral therapies in long COVID, and the need for further research and clinical trials in this field of study.

As liquid biopsy attracts more attention for the clinical detection and diagnosis of cancer, the need to establish reliable biomarkers has emerged. Plasma has received extensive study. However, for genitourinary (GU) cancers, urine can be the ideal body fluid. Urine can be collected in large quantities for frequent biomarker analysis and disease monitoring with relative ease. New biomarker studies are of great importance due to the limitations of the present diagnostic tests used for cancer detection and monitoring. Recently, many promising studies have investigated the role of cell-free DNA, DNA methylation, extracellular RNAs, and exosome cargos as biomarkers for GU cancer detection. This review explores the recent literature on the discovery of novel urinary biomarkers and their utility in detecting GU cancers. In small-scale studies, several novel biomarkers have shown preliminary evidence of superior clinical sensitivity and specificity compared to conventional GU cancer screening methods. With the use of these new urinary biomarkers, routine non-invasive screening and tumor monitoring may be possible.

The COVID-19 pandemic has caused symptoms of anxiety, distress, and depression in the general population. In order to develop interventions that target psychological problems, it is necessary to determine individual factors that have an impact on the development of psychological problems. The present study examined the effects of emotion dysregulation, attachment style and perceived social support on psychological problems in the context of COVID-19 using a sample of people living in Türkiye.

The sample consisted of 517 participants. In addition to the Demographic and COVID-19-related Information Form, a number of questionnaires were used, including the Depression, Anxiety and Stress Scale (DASS-21), Experiences in Close Relationships Revised (ECR-R), Impact of Event Scale Revised (IES-R), Difficulties in Emotion Regulation Scale-Brief Form (DERS-16), and Multidimensional Scale of Perceived Social Support (MSPSS).

The findings revealed that perceived social support, emotion dysregulation and attachment anxiety did not have serial mediation effects in the relationship between the impact of COVID-19, and depression or stress. However, there were serial mediating effects of perceived social support, emotion dysregulation, and attachment anxiety in the relationship between the impact of COVID-19 and anxiety. That is, the effects of the impact of COVID-19 (X) on anxiety (Y) through emotion dysregulation (M2) and attachment anxiety (M3) (bootstrap = 0.007, 95% CI = −0.001, 0.015), and through perceived social support, emotion dysregulation, and attachment anxiety (bootstrap = 0.005, 95% CI = 0.001, 0.013) were significant.

These findings suggest the role of individual appraisals in the initial stages of the COVID-19 outbreak.