The conventional electrochemical detection strategy for alpha-fetoprotein (AFP) is limited by the antigen-antibody (Ag-Ab) reactions and suffers from low sensitivity and poor reproducibility due to the inconsistency of Ab-modified electrodes. Herein, we designed and explored a sandwich-type electrochemical sensor for highly sensitive detection of AFP based on aptamer (Apt)-AFP-Ab interaction mode with silver@gold (Ag@Au) core-shell nanoparticles (NPs) as a signal amplifier. AuNPs were electrodeposited onto MXene (Ti3C2TX)-modified glassy carbon electrode (GCE) to get AuNPs/MXene/GCE and further used as the signal amplification substrate. The tetrahedral DNA-linked AFP aptamers were immobilized onto AuNPs/MXene/GCE surface via Au-S bonds and used as the sensing and recognition platform for AFP capturing. Ag@AuNPs with core-shell structures were synthesized, characterized, and bound with Ab as detection elements by catalyzing H2O2 reduction. In the presence of AFP, a stable Apt-AFP-Ab sandwich structure was formed owing to the high affinities of aptamer and Ab toward the target AFP. The catalytic current produced by H2O2 reduction increased linearly with the logarithm of AFP concentration from 5 × 10-4 ng/mL to 1 × 105 ng/mL, accompanied by a low detection limit (1.6 × 10-4 ng/mL). Moreover, the novel sandwich-type electrochemical sensor shows high sensitivity, outstanding selectivity, and promising performance in the analysis of actual samples, displaying a broad application prospect in bioanalysis.

UNASSIGNED: Acute liver failure (ALF) is a severe complication of spontaneous ruptured hepatocellular carcinoma (SRHCC) that requires accurate prediction for effective treatment strategies. We aimed to develop a predictive nomogram to estimate the risk of ALF in patients with SRHCC undergoing treatment.
UNASSIGNED: We performed a retrospective analysis of historical data from 284 patients diagnosed with SRHCC at the First Hospital of Jilin University over the past decade. Variables were selected through univariate and multivariate logistic regression analyses, and a predictive nomogram was constructed. We evaluated its predictive accuracy against the Child-Pugh Score, R.MELD, and ALBI by assessing discrimination, calibration, and net clinical benefit.
UNASSIGNED: Among the 284 patients, 65 developed ALF. The risk factors identified for model development included largest tumor size (LTS), platelet counts, prolonged prothrombin time, and elevated serum α-fetoprotein levels. The nomogram exhibited high accuracy in predicting ALF risk with a C-index of 0.91 (0.87-0.95). The Delong test showed a significant difference between the nomogram and the other three models (p<0.05). The calibration curve for the nomogram fit well, and the decision curve analysis revealed superior net benefit. The optimal cut-off point for the nomogram was determined to be 40, yielding sensitivity, specificity, positive predictive value, and negative predictive value of 83.10%, 87.20%, 65.90% and 94.60%, respectively.
UNASSIGNED: The nomogram we developed provides an optimized tool for predicting ALF in SRHCC patients. Its application can help determine individual patient\'s risk of ALF, enabling more rational and personalized treatment strategies.

This study aimed to investigate whether α-fetoprotein (AFP) could affect the malignant behavior of AFP-producing gastric cancer (AFP-GC) and to explore the relationship between AFP and mesenchymal-epithelial transition factor (c-Met) in AFP-GC. In this study, 23 patients with AFP-GC (AFP[+]) and 18 patients with common gastric cancer (AFP[-]) were evaluated for the c-Met expression using immunohistochemical analysis. The AFP-GC cell line, GCIY, was used. The AFP endoribonuclease-prepared small interfering RNA (siRNA) and eukaryotic AFP overexpression vector were used to increase/knockdown the expression of AFP. Afterward, the c-Met expression was evaluated by polymerase chain reaction and western blot. The proliferation, migration, and invasion of GCIY cells were estimated before and after the AFP overexpression/knockdown. The c-Met expression in both groups was the same (p > 0.05), and AFP[+] group had a higher positive incidence of the c-Met expression than the AFP[-] group (p < 0.01). Furthermore, the c-Met expression frequency was decreased by AFP knockdown and increased by AFP overexpression (p < 0.01). The cell counting kit-8 cell proliferation assay, cell invasion, and migration assays confirmed that the AFP could affect the malignant biological behavior of AFP-GC. These findings suggest that AFP contributes to the malignant biological properties of AFP-GC and the high expression of c-Met in AFP-GC.

UNASSIGNED: Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage Hepatocellular carcinoma (HCC) patients. However, predicting the survival of HCC patients receiving TACE remains challenging.
UNASSIGNED: In this retrospective study, we analyzed a total of 1805 HCC patients who received TACE. The patients were randomly divided into a training set (n = 1264) and a validation set (n = 541). We examined various prognostic factors within the training set and developed a simple ALFP (ALBI grade, AFP, and Prothrombin time) score, which was subsequently validated using the independent validation set.
UNASSIGNED: Our multivariate analysis revealed that baseline ALBI grade 2 or 3, AFP ≥ 100 ng/mL, and PT > 13.1 s were independent unfavorable prognostic factors for HCC patients receiving TACE (p < 0.05). Based on these findings, we constructed the ALFP score, which assigns 1 point each for ALBI grade 2 or 3, AFP ≥ 100 ng/mL, and PT > 13.1 s. The score has a range of 0 to 3, and higher scores are associated with poorer outcomes. The median overall survival (OS) varied significantly among different ALFP score groups, both in the training set and the validation set (p < 0.001). We further examined the ALFP score in subgroups based on tumor diameter and the number of intrahepatic lesions. In each subgroup, higher ALFP scores were consistently associated with lower OS (p < 0.05).
UNASSIGNED: Our study confirms the prognostic value of the ALFP score in predicting the survival of HCC patients undergoing TACE. The score incorporates easily obtainable baseline parameters and provides a simple and practical tool for risk stratification and treatment decision-making in HCC patients.

In this study, a sensitive photoelectrochemical immunosensor with dye-enhanced anodic photocurrent response was proposed for sensitive detection of α-fetoprotein (AFP). Specifically, europium-doped TiO2 (Eu-TiO2) was used as the photoelectrochemical functional material and coated onto indium tin oxide (ITO) electrode. Doxorubicin (DOX) as an excellent fluorescent dye was encapsulated in the hydrophobically modified alginate (HMA). Then the dye-loaded HMA was modified onto the surface of Eu-TiO2 to further sensitize the photocurrent response. The results showed that the photoelectrical signal was enhanced and stabilized due to the effect of sensitization of DOX on Eu-TiO2 material. The constructed PEC sensor revealed a good linear response to AFP antigen ranging from 0.5 to 100 ng/mL with a detection limit of 0.41 pg/mL. The clinical patient\'s serum test results obtained from the proposed PEC immunosensor were consistent with those obtained from the commercial electrochemilunescence assay. The proposed PEC sensing method could be a promising analytical tool for the detection of AFP in clinical analysis.

A vaginal yolk sac tumor (YST) is a rare malignant germ cell tumor for infants and children, and it has been >50 years since the first case was reported. The treatment strategy has changed markedly in the past 50 years, from radical surgical treatment to conservative surgery combined with chemotherapy, and then to combined chemotherapy alone. The present study reports the case of a primary vaginal YST in a 13-month-old girl that was successfully treated by tumor resection combined with chemotherapy. The clinical symptoms, imaging features and treatment characteristics are described in detail, as well as the postoperative treatment. There was no local recurrence or metastasis for the 2 years of follow-up to date. A literature review was also conducted to investigate the clinicopathological features, treatment and prognosis of this tumor. Overall, surgery combined with bleomycin, etoposide and carboplatin combination chemotherapy can be an effective option for vaginal YST.

Hepatocellular carcinoma (HCC) is one of the top five contributors to the cancer burden in China, with a poor prognosis and heavy disability-adjusted life year burden. The criteria used for HCC prognosis are complicated and therefore restricted in routine clinical practice. Multiple factors influence HCC malignancy and progression. In this study, we retrospectively evaluated 173 patients with HCC who underwent curative resection for 9 years to evaluate the correlation of a combination of γ-glutamyl transferase (γ-GT), protein induced by vitamin K absence or antagonist-II (PIVKA-II), and α-fetoprotein (AFP) with the long-term survival of patients with HCC. Multivariate analysis revealed that the γ-GT level was an independent prognostic factor for recurrence. The prediction rate of early recurrence with γ-GT, PIVKA-II, and AFP levels individually was 63.5%, 79.4%, and 39.7%, respectively, whereas the prediction rate of early recurrence was 95.2% with the combination of γ-GT, PIVKA-II, and AFP levels as a composite indicator. Our long-term retrospective study revealed that γ-GT, PIVKA-II, and AFP can aid in predicting long-term prognosis of HCC recurrence. The combination of γ-GT, PIVKA-II, and AFP can further aid in identifying patients with early recurrence. Together, γ-GT, PIVKA-II, and AFP may a be used to develop a new prediction method to improve the prognosis of patients with HCC, and our results indicate the requirement of more active HCC treatment strategies.

α-Fetoprotein (AFP) is a kind of fetal protein that is related to tumor, the increasing concentration of which gives birth to a large variety of diseases, such as liver cancer. Therefore, the detection method with super sensitivity, high selectivity, and less time consumption under trace concentrations in early stage of diseases is becoming a necessity. In recent years, nanomaterials have been regarded as significant resources for the exploration of efficient biosensors with high sensitivity, selectivity, speed, as well as simple process, due to their excellent optical, electrical, and chemical properties. In this paper, we reviewed the research progress of AFP biosensors with enhanced sensitivity and selectivity by nanoparticles. Representative examples have also been displayed in this paper to expound the nanotechnologies utilized in the early detection of AFP. Furthermore, challenges of the clinical application of AFP biosensors based on nanotechnology have been elaborated, as well as the development opportunity in this field in the future. This review provides a comprehensive overview on the various nano-biosensor for AFP detection based on functional nanotechnology.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) varies considerably among patients with the same disease stage and characteristics, and only about two thirds show high levels of α-fetoprotein (AFP), a common prognostic indicator for HCC. Here, we assessed whether the combination of presurgical serum levels of AFP and carbohydrate antigen 19-9 (CA19-9) can predict the prognosis of HCC patients after hepatectomy.
METHODS: The clinicopathological characteristics and post-hepatectomy outcomes of 711 HCC patients were retrospectively reviewed. The patients were classified into three groups based on whether their preoperative serum levels of both AFP and CA19-9 were higher than the respective cut-offs of 400 ng/ml and 37 U/ml [double positive (DP)], the level of only one marker was higher than the cut-off [single positive (SP)], or neither level was higher than the cut-off [negative (N)]. The overall survival (OS) and recurrence-free survival (RFS) rates were estimated using Kaplan-Meier curves. Univariate and multivariate survival analyses were performed to identify the clinicopathological factors significantly associated with HCC prognosis.
RESULTS: The 1-year, 3-year, and 5-year RFS and OS rates in the N group were significantly higher than those in the SP group, while the DP group showed the lowest rates. Multivariate Cox regression analysis showed that large tumor size (> 5 cm), multiple tumors (≥ 2), incomplete tumor capsule, positive microvascular invasion, Barcelona Clinic Liver Cancer C stage, and CA19-9 level > 37 U/mL were independent risk factors for RFS and OS in HCC patients. Moreover, aspartate aminotransferase levels > 40 U/L proved to be an independent prognostic factor for OS.
CONCLUSIONS: The combination of serum AFP and CA19-9 levels may be a useful prognostic marker for HCC patients after hepatectomy.

Ramucirumab is indicated for patients with advanced hepatocellular carcinoma (HCC) and α-fetoprotein (AFP) ≥400 ng/mL following sorafenib. Here, we prospectively studied ramucirumab following non-sorafenib systemic therapies.
This open-label, non-comparative cohort of REACH-2 enrolled patients with advanced HCC, Child-Pugh class-A liver disease, and AFP ≥400 ng/mL who had received 1-2 lines of therapy, excluding sorafenib or chemotherapy. Ramucirumab was administered 8 mg/kg intravenously Q2W. The primary endpoint was safety. Secondary endpoints were overall survival, progression-free survival, objective response rate (RECIST v1.1), time to progression, pharmacokinetics, and patient-reported outcomes. Final analysis occurred after all enrolled patients completed ≥3 treatment cycles or discontinued treatment.
Between April 27, 2018, and March 29, 2021, 47 patients were treated at 21 investigative sites in Asia, Europe, and USA. The most frequently reported grade ≥3 adverse events, regardless of causality, were hypertension (11%), proteinuria (6%), hyponatremia (6%), and AST increased (6%). Two patients died from adverse events (myocardial infarction and upper gastrointestinal hemorrhage), deemed related to treatment. Median progression-free survival, time to progression, and overall survival were 1.7 months, 2.8 months, and 8.7 months, respectively. The objective response rate was 10.6% with a median duration response of 8.3 months. Median time to deterioration in FHSI-8 total score was 4.4 months.
Ramucirumab demonstrated consistent and meaningful clinical activity with no new safety signals following non-sorafenib therapies in patients with advanced HCC and AFP ≥400 ng/mL. This represents one of the first sequencing studies for patients with advanced HCC not treated with sorafenib.