Alpha-fetoprotein and des-gamma-carboxy prothrombin can predict the objective response of patients with hepatocellular carcinoma receiving durvalumab plus tremelimumab therapy.

Durvalumab plus tremelimumab (Durva/Treme) combined immunotherapy is the first-line therapy recommended for unresectable hepatocellular carcinoma (HCC). Since sequential therapy is more effective in improving prognosis, tumor markers have been used as predictive biomarkers for response to systemic therapy. This study aimed to investigate the predictive ability of objective response (OR) by tumor markers for Durva/Treme therapy against HCC. In this multicenter study, 110 patients with HCC who received Durva/Treme therapy were retrospectively enrolled. The OR rate was 15.5%. To aid early decision-making regarding OR, we evaluated the predictors contributing to OR in two steps: before (first step) and 4 weeks after (second step) treatment induction. Changes in tumor markers (alpha-fetoprotein [AFP] and des-gamma-carboxy prothrombin [DCP]) from baseline to 4 weeks after treatment (ΔAFP/ΔDCP) were included as the input factors. In the first step, multivariable analysis identified only the baseline AFP level (odds ratio 3.497, p = 0.029) as a predictor of OR. Patients with AFP ≥ 400 ng/mL had a significantly higher OR rate than those with < 400 ng/mL (28.2 vs. 8.5%, p = 0.011), and there was no significant difference in progression-free survival (PFS) between the two groups. When AFP/DCP response was defined as a ≥10% reduction from baseline, multivariable analysis showed that AFP response (odds ratio 6.023, p = 0.042) and DCP response (odds ratio 11.657, p = 0.006) were both independent predictors of OR in the second step. The PFS of patients with AFP or DCP response was significantly longer than that of patients without AFP or DCP response. The study demonstrated that the use of AFP and DCP can predict the OR of patients with HCC receiving Durva/Treme therapy.

Cu-MOFs@AuPtNPs nanozyme-based immunosorbent assay for colorimetric detection of alpha-fetoprotein.

Accurate detection of tumor biomarkers in blood is crucial for diagnosing and treating tumor disease. In this study, a metal enzyme-linked immunosorbent assay (MeLISA) was fabricated for the ultrasensitive and naked-eye detection of tumor biomarker alpha-fetoprotein (AFP) in clinical serum samples. Herein, novel copper metal-organic frameworks and gold platinum nanoparticle composites (Cu-MOFs@AuPtNPs) were synthesized for the first time by an in situ method, which showed an enormous specific surface area and excellent peroxidase (POx) mimicking properties. Cu-MOFs@AuPtNPs linked with antibodies targeting AFP served as a signal nanoprobe to amplify the detection signal. Additionally, the specificity of MeLISA was significantly enhanced through a conventional antigen-antibody reaction and efficient blocking of non-specific sites with BSA. Under optimal conditions, the sandwich-type MeLISA exhibited a wide range from 0.001 to 1000 ng mL-1 (R2 = 0.997) and a low detection limit of 0.86 pg mL-1 (S/N = 3) with acceptable stability, selectivity, and reproducibility. It is noteworthy that the suggested MeLISA performed exceptionally well in detecting clinical serum samples, which were visible to the naked eye and did not require complex platforms. To sum up, the innovative MeLISA based on Cu-MOFs@AuPtNPs provides an alternative method for early cancer diagnosis, particularly in economically backward areas where simple diagnostic apparatus is extremely desirable.

Clinical outcomes of DEB-TACE in locally advanced hepatocellular carcinoma: A 5-year real world experience.

PURPOSE: To evaluate outcomes including safety and efficacy of drug-eluting bead trans-arterial chemo-embolization (DEB-TACE) in the treatment of locally advanced hepatocellular carcinoma (LA-HCC). MATERIALS AND METHODS: In this single-center, retrospective study, we evaluated 471 consecutive patients with LA-HCC who underwent DEB-TACE from 2015 to 2020. Efficacy of DEB-TACE was assessed based on the imaging response using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and the biochemical response using alpha-fetoprotein (AFP) levels at 1-month follow-up. Adverse events, progression free survival (PFS), and overall survival were also examined. RESULTS: HCC distribution was bilobar in 49% with largest lesion mean size of 4.3 cm ± 3.2, and a majority of patients (46.7%) were Barcelona Club Liver Cancer (BCLC) stage B. Complete radiologic response was achieved in 120 (25.5%) patients, comparable to a reported 28% rate for conventional TACE. Biochemically, 41 (8.7%) patients achieved complete response, and 113 (24%) had a partial response. A total of 59 (12.5%) patients were successfully bridged to liver transplantation. Major adverse events were observed in 3%, while 7.2% experienced post-embolization syndrome. Mean PFS was 6.7 months ± 6.6, and overall survival was 64%, 16.3%, 2.1% at 1, 3, and 5 years, respectively. CONCLUSION: Based on our real world experience at a single center, DEB-TACE remains the locoregional therapy of choice for LA-HCC due to its favorable safety and efficacy profile.

Diagnostic value of serum inflammatory markers in predicting early refractoriness of transarterial chemoembolization in patients with Barcelona Clinic Liver Cancer Stage 0, A, and B hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is an established therapeutic strategy for intermediate stage Barcelona Clinic Liver Cancer (BCLC) hepatocellular carcinoma (HCC). However, patients who are early refractory to TACE may not benefit from repeated TACE treatment. Our primary objective was to assess the diagnostic value of inflammatory markers in identifying early TACE refractory for patients with early (BCLC 0 and A) or intermediate (BCLC B) stage HCC. We retrospectively reviewed the HCC patients who underwent TACE as the initial treatment in two hospitals. Patients with early TACE refractoriness had significantly poorer median overall survival (OS) (16 vs 40 months, P<0.001) and progression-free survival (PFS) (7 vs 23 months, P<0.001) compared to TACE non-refractory patients. In the multivariate regression analysis, tumor size (P<0.001), bilobular invasion (P=0.007), high aspartate aminotransferase-to-platelet ratio index (APRI) (P=0.007), and high alpha fetoprotein (AFP) level (P=0.035) were independent risk factors for early TACE refractoriness. The predictive model showcasing these factors exhibited high ability proficiency, with an area under curve (AUC) of 0.833 (95%CI=0.774-0.892) in the training cohort, 0.750 (95%CI: 0.640-0.861) in the internal-validation cohort, and 0.733 (95%CI: 0.594-0.872) in the external-validation cohort. Calibration curve analysis revealed good agreement between the actual and predicted probabilities of early TACE refractoriness. Our preliminary study estimated the potential value of inflammatory markers in predicting early TACE refractoriness and provides a predictive model to assist in identifying patients who may not benefit from repeat TACE treatment.

Long Noncoding RNAs MALAT1 and HOTTIP Act as Serum Biomarkers for Hepatocellular Carcinoma.

BACKGROUND: Circulating tumor markers with satisfactory sensitivity and specificity play crucial roles in cancer diagnosis and therapy. This prospective study aimed to evaluate the potential of circulating lncRNAs as biomarkers for hepatocellular carcinoma (HCC). METHODS: A total of 74 patients with HCC and 94 healthy controls were enrolled. The expression levels of candidate genes in serum were detected by qRT-PCR. Receiver operating characteristic (ROC) curve analysis and logistic regression were employed to investigate the diagnostic capacity of lncRNAs. The analysis of 3-year overall survival (OS) was conducted using the Kaplan-Meier method and log-rank test. RESULTS: Of the 9 candidate genes, 6 lncRNAs could be stably detected in serum. The expression levels of circulating MALAT1 and HOTTIP in HCC patients were significantly higher than those in controls (P < 0.001). ROC analysis showed that MALAT1 and HOTTIP were more effective than alpha-fetoprotein (AFP) (P < 0.010) in the diagnosis of HCC, with AUCs of 0.896 and 0.899, respectively. Additionally, a panel consisting of MALAT1, HOTTIP, and AFP was constructed to obtain an AUC of 0.968 with a sensitivity of 87.8% and specificity of 94.7% in HCC diagnosis. Moreover, the upregulation of MALAT1 was not only related to multiple tumor lesions, HCV infection, AST level, and AFP level, but also suggested shorter OS. A high expression level of HOTTIP was associated with metastasis. CONCLUSION: Serum MALAT1 and HOTTIP play indicative roles as non-invasive biomarkers for HCC.

Primary yolk sac tumor of the endometrium combined with situs inversus totalis: a case report and literature review.

BACKGROUND: Yolk sac tumor (YST) is a highly malignant germ cell tumor, a majority of which originate from the gonads and are extremely rare from endometrium. CASE PRESENTATION: Here we present a case of a 42-year-old woman suffered from primary pure yolk sac tumor of the endometrium complicated with situs inversus totalis. The patient presented at our hospital with irregular vaginal bleeding. Imageological examination showed a space-occupying lesion in the cervix and the serum Alpha-fetoprotein (AFP) level was significantly high (more than 1210ng/ml). Then she underwent total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection. The subsequent postoperative pathological diagnosis was yolk sac tumor arising from the endometrium. Next, the patient was treated with 6 cycles of chemotherapy with Pingyangmycin, etoposide and cisplatin regimen and was alive without evidence of recurrence or distant metastases for 13 months. CONCLUSIONS: This rare disease needs to be differentiated from endometrial epithelial neoplasia and the significant increase in AFP is helpful for diagnosis. Combined with previous literature reports, comprehensive staging laparotomy or maximum cytoreductive surgery complemented by standard chemotherapy can usually achieve a good efficacy.

An Ovarian Sertoli-Leydig Cell Tumor with Elevated Alpha-Fetoprotein in an Adolescent: A Rare Case Report and Literature Review.

An ovarian Sertoli-Leydig cell tumor is a rare type of sex cord-stromal tumor of the ovary. Typically, it presents as abdominal pain or androgenic manifestations in women in the second to third decade of life. While cases of ovarian Sertoli-Leydig cell tumor associated with increased levels of alpha-fetoprotein are rare, they are reported to be the most common alpha-fetoprotein-producing ovarian non-germ cell tumor. We report the case of a 16-year-old patient, who presented with complaints of amenorrhea that had lasted for one year. Transabdominal ultrasound revealed the presence of a tumor in the right ovary, measuring 9.3 × 5.8 cm in size. The laboratory investigation showed an increased level of alpha-fetoprotein. The patient underwent laparoscopic right salpingo-oophorectomy. Histopathological examination confirmed the presence of a moderately differentiated (G2) Sertoli-Leydig cell tumor in the right ovary. For reproductive-age patients with disease confined to the ovary, fertility-sparing surgery is recommended. According to the current recommendations, the administration of adjuvant chemotherapy is indicated in cases of the presence of heterologous elements, poorly differentiated tumors, or FIGO stages IB-IV. As there were no high-risk factors and no residual disease in this case, there were no indications for further treatment with adjuvant chemotherapy. A recent follow-up visit showed that the patient is in complete remission. This report presents a detailed description of the findings, differential diagnosis, clinical course, chosen treatment, and prognosis. Also, a comprehensive literature review of ovarian Sertoli-Leydig cell tumors, focusing on their clinical presentation, laboratory findings, macroscopic and histopathological features, genetics, clinical management, prognostic factors and follow-up, is provided.

Unveiling Endogenous Serum Peptides as Potential Biomarkers for Hepatocellular Carcinoma in Patients with Liver Cirrhosis.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, mainly associated with liver cirrhosis. Current diagnostic methods for HCC have limited sensitivity and specificity, highlighting the need for improved early detection and intervention. In this study, we used a comprehensive approach involving endogenous peptidome along with bioinformatics analysis to identify and evaluate potential biomarkers for HCC. Serum samples from 40 subjects, comprising 20 HCC cases and 20 patients with liver cirrhosis (CIRR), were analyzed. Among 2568 endogenous peptides, 67 showed significant differential expression between the HCC vs CIRR. Further analysis revealed three endogenous peptides (VMHEALHNHYTQKSLSLSPG, NRFTQKSLSLSPG, and SARQSTLDKEL) that showed far better performance compared to AFP in terms of area under the receiver operating characteristic curve (AUC), showcasing their potential as biomarkers for HCC. Additionally, endogenous peptide IAVEWESNGQPENNYKT that belongs to the precursor protein Immunoglobulin heavy constant gamma 4 was detected in 100% of the HCC group and completely absent in the CIRR group, suggesting a promising diagnostic biomarker. Gene ontology and pathway analysis revealed the potential involvement of these dysregulated peptides in HCC. These findings provide valuable insights into the molecular basis of HCC and may contribute to the development of improved diagnostic methods and therapeutic targets for HCC.

Labeled sandwich-type electrochemical immunosensor based on Ti3C2Tx/AuNP and Ti3C2Tx/HKUST-1/TB composites for early liver cancer detection.

A novel sandwich-type electrochemical immunosensor for the detection of the liver cancer marker alpha-fetoprotein (AFP) in human serum is proposed. The two-dimensional MXene material Ti3C2Tx was first prepared using etching and ultrasonic stripping, and then Ti3C2Tx was used to reduce chloroauric acid to form Ti3C2Tx/AuNP composites which were modified on the surface of the glassy carbon electrodes to form probe-type sensors. The Ti3C2Tx/AuNPs provide a large number of binding sites for the AFP capture antibody (Ab1) and increase the electrochemical reaction active site. The Ti3C2Tx/copper metal-organic frameworks HKUST-1 composite was also prepared by solvothermal method and combined with toluidine blue (TB) and AFP detection antibody (Ab2) to form a labeled sandwich-type electrochemical immunosensor. The sensor achieved trace detection of AFP from 0.1 to 100 ng/mL with a detection limit of 0.073 pg/mL and possesses good selectivity, stability, and reproducibility. The sensor performs well in clinical samples and has good potential for clinical applications.

Biomarker profiling and integrating heterogeneous models for enhanced multi-grade breast cancer prognostication.

BACKGROUND: Breast cancer remains a leading cause of female mortality worldwide, exacerbated by limited awareness, inadequate screening resources, and treatment options. Accurate and early diagnosis is crucial for improving survival rates and effective treatment. OBJECTIVES: This study aims to develop an innovative artificial intelligence (AI) based model for predicting breast cancer and its various histopathological grades by integrating multiple biomarkers and subject age, thereby enhancing diagnostic accuracy and prognostication. METHODS: A novel ensemble-based machine learning (ML) framework has been introduced that integrates three distinct biomarkers-beta-human chorionic gonadotropin (ß-hCG), Programmed Cell Death Ligand 1 (PD-L1), and alpha-fetoprotein (AFP)-alongside subject age. Hyperparameter optimization was performed using the Particle Swarm Optimization (PSO) algorithm, and minority oversampling techniques were employed to mitigate overfitting. The model's performance was validated through rigorous five-fold cross-validation. RESULTS: The proposed model demonstrated superior performance, achieving a 97.93% accuracy and a 98.06% F1-score on meticulously labeled test data across diverse age groups. Comparative analysis showed that the model outperforms state-of-the-art approaches, highlighting its robustness and generalizability. CONCLUSION: By providing a comprehensive analysis of multiple biomarkers and effectively predicting tumor grades, this study offers a significant advancement in breast cancer screening, particularly in regions with limited medical resources. The proposed framework has the potential to reduce breast cancer mortality rates and improve early intervention and personalized treatment strategies.

[Testis-sparing microsurgery for benign testis tumor: A report of 16 cases].

OBJECTIVE: To investigate the safety and clinical effect of testis-sparing microsurgery (TSMS) in the treatment of benign testis tumor (BTT). METHODS: We retrospectively analyzed the clinical data on 16 cases of BTT treated in the Department of Andrology of the Affiliated Hospital of Qingdao University from October 2020 to February 2023. The median age of the patients was 23 years. All the tumors were unilateral, 7 in the left and 9 in the right side, with a median diameter of 1.85 cm (1.0－3.5 cm). The patients all underwent color Doppler flow imaging (CDFI), MRI, semen analysis and examination of serum T, alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH), followed by TSMS. The boundaries between the tumors and normal testis tissue were accurately identified under the microscope, and the tumors and the adjacent normal testis tissue 2 mm from their margins were excised completely. Bipolar coagulation forceps were used for wound hemostasis to maximally preserve the normal testis tissue. The resected specimens were subjected to fast frozen pathology intraoperatively, and the patients were followed up for 14－40 months by regular scrotal CDFI, MRI and examinations of serum T and semen parameters. RESULTS: The levels of serum T, AFP, HCG and LDH and semen parameters were all within the normal range preoperatively. TSMS were successfully completed in all the cases, and all were pathologically confirmed as BTT according to the latest edition of WHO Classification of Tumors: Urinary and Male Genital Tumors. CDFI showed normal blood supply within the testis tissue at 1 month after surgery. No signs of intra-testicular tumor residue, recurrence or metastasis, nor significant changes in the levels of serum T, AFP, HCG or LDH or semen parameters were observed during the follow-up as compared with the baseline. Natural conception was achieved in 2 cases at 16 and 18 months respectively after surgery. CONCLUSION: BTT can be differentially diagnosed by CDFI and MRI before surgery and confirmed by histopathology. TSMS can achieve complete excision of the tumor, maximal sparing of the normal testis tissue and thereby effective preservation of male fertility.

Performance evaluation and characterization of pre-analytical effects by sample types and storage conditions on tumor marker measurement by the point-of-care test platform IchromaTM II.

Tumor markers should be measured regularly and accurately to prevent, diagnose, and monitor cancers efficiently. We aimed to characterize the pre-analytical factors effecting on the analytical performance of point-of-care test (POCT) platform IchromaTM II (Boditech Med Inc., Gangwon-do, Korea) for alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and prostate specific antigen (PSA) and evaluate their consequences in clinical practice. Based on comprehensive evaluation for the analytical performance of IchromaTM II including precision, linearity, and method comparison performed according to CLSI guidelines, pre-analytical factors of sample types and conditions were extensively analyzed. A total of five sample types [serum, plasma (PL) and whole blood (WB) from EDTA tube, PL and WB from sodium heparin tube] from 40 patients were used for comparing among specimen types. Additionally, stability was assessed up to 21 h at room temperature, refrigerated for 8 days, and frozen for 16 weeks by using 4 levels of pooled patient samples which were measured in triplicate. Precision, linearity and correlation with central laboratory analyzers observed in all three tumor markers were within acceptable criteria. However, variable degrees of percent deviations were observed according to sample type and storage conditions. Only EDTA PL samples presented clinically acceptable percentage biases for all three tumor markers when stored at room temperature or refrigerated condition. Positive bias of CEA and PSA in storage duration until 16 weeks were observed when stored in frozen condition. While IchromaTM II showed an adequate analytical performance as a POCT platform with simple operating procedures for the measurement of tumor markers, clinical laboratories should be aware of stability issues when different types of blood specimens are practically utilized.

Impact of pre-sarcopenia on outcomes of transarterial chemoembolization in unresectable hepatocellular carcinoma.

Sarcopenia's impact on hepatocellular carcinoma (HCC) outcomes is well-documented, but the effects of pre-sarcopenia remain unclear. This study investigates the impact of pre-sarcopenia on tumor response and survival in patients with unresectable HCC undergoing transarterial chemoembolization (TACE). We retrospectively evaluated muscle volume using the SliceOmatic software in patients with unresectable HCC treated with TACE. Pre-sarcopenia was defined by Japan Society of Hepatology standards (men: 42 cm2/m2; women: 38 cm2/m2). Pre-sarcopenia and non-pre-sarcopenia groups were compared, and Cox proportional hazards model was used to identify survival-influencing variables. Subgroup analysis was conducted stratified by the tumor burden, using serum alpha-fetoprotein (AFP) levels at a diagnostic cutoff value of 200 ng/mL. Of the 100 patients, 39 had pre-sarcopenia. The presence of pre-sarcopenia was not associated with tumor complete response achievement. The median overall survival (OS) was significantly lower in the pre-sarcopenia group (18 months) than in the non-pre-sarcopenia group (30 months; log-rank P = 0.039). Subgroup analysis among 77 patients with AFP < 200 ng/mL revealed that OS was particularly poor in the pre-sarcopenia group (16 vs. 34 months; log-rank P < 0.001). Multivariate analysis identified increased AFP (adjusted hazard ratio [HR] per 10-unit increase 1.142; P < 0.001), higher Model for End-Stage Liver Disease score (adjusted HR per 1-unit increase 1.176; P < 0.001), and pre-sarcopenia (adjusted HR 2.965; P < 0.001) as predictors of shorter OS. Pre-sarcopenia is a significant predictor of increased mortality in patients with unresectable HCC undergoing TACE, especially in those with AFP < 200 ng/mL, suggesting its potential as a target for early intervention.

Ultrasensitive Electrochemical Biosensor Based on Efficient PDA-APDMAO Antifouling Interface and Dual-Signal Ratio Strategy for Trace Detection of Alpha-Fetoprotein in Human Serum.

In electrochemical analysis, developing biosensors that can resist the nonspecific adsorption of interfering biomolecules in human serum remains a huge challenge, which depends on the design of efficient antifouling materials. Herein, 3-aminopropyldimethylamine oxide (APDMAO) biomimetic zwitterions were prepared as antifouling interfaces. Among them, the unique positive and negative charges (N+-O-) of APDMAO promoted its hydrogen bonding with water molecules, forming a firm hydration barrier that endowed it with strong and stable antifouling performance. Meanwhile, its inherent amino groups could copolymerize with the biomimetic adhesive dopamine to form a thin layer of quinone intermediates, providing conditions for the subsequent binding of aptamers and signal probes. Importantly, the biomimetic APDMAO with functional groups and one-step oxidation characteristics solved the challenges of zwitterionic synthesis and modification, as well as improved biocompatibility of the sensing interface, thereby expanding the application potential of zwitterions as antifouling materials in sensing analysis. Thiol-containing alpha-fetoprotein (AFP) aptamers modified with methylene blue (MB) were coupled under controllable potential, greatly reducing the incubation time, which promoted the productization application of biosensors. In addition, the ratio sensing strategy using MB as internal standard factors and concanavalin-silver nanoparticles (ConA-Ag NPs) as signal probes was introduced to reduce background and instrument interferences, thus improving detection accuracy. On this basis, the proposed antifouling electrochemical biosensor achieved sensitive and accurate AFP detection over a wide dynamic range (10 fg/mL-10 ng/mL), with a low detection limit of 3.41 fg/mL (3σ/m). This work provides positive insights into the development of zwitterionic antifouling materials and clinical detection of liver cancer markers in human serum.

Leveraging SEER data through machine learning to predict distant lymph node metastasis and prognosticate outcomes in hepatocellular carcinoma patients.

OBJECTIVES: This study aims to develop and validate machine learning-based diagnostic and prognostic models to predict the risk of distant lymph node metastases (DLNM) in patients with hepatocellular carcinoma (HCC) and to evaluate the prognosis for this cohort. DESIGN: Utilizing a retrospective design, this investigation leverages data extracted from the Surveillance, Epidemiology, and End Results (SEER) database, specifically the January 2024 subset, to conduct the analysis. PARTICIPANTS: The study cohort consists of 15,775 patients diagnosed with HCC as identified within the SEER database, spanning 2016 to 2020. METHOD: In the construction of the diagnostic model, recursive feature elimination (RFE) is employed for variable selection, incorporating five critical predictors: age, tumor size, radiation therapy, T-stage, and serum alpha-fetoprotein (AFP) levels. These variables are the foundation for a stacking ensemble model, which is further elucidated through Shapley Additive Explanations (SHAP). Conversely, the prognostic model is crafted utilizing stepwise backward regression to select pertinent variables, including chemotherapy, radiation therapy, tumor size, and age. This model culminates in the development of a prognostic nomogram, underpinned by the Cox proportional hazards model. MAIN OUTCOME MEASURES: The outcome of the diagnostic model is the occurrence of DLNM in patients. The outcome of the prognosis model is determined by survival time and survival status. RESULTS: The integrated model developed based on stacking demonstrates good predictive performance and high interpretative variability and differentiation. The area under the curve (AUC) in the training set is 0.767, while the AUC in the validation set is 0.768. The nomogram, constructed using the Cox model, also demonstrates consistent and strong predictive capabilities. At the same time, we recognized elements that have a substantial impact on DLNM and the prognosis and extensively discussed their significance in the model and clinical practice. CONCLUSION: Our study identified key predictive factors for DLNM and elucidated significant prognostic indicators for HCC patients with DLNM. These findings provide clinicians with valuable tools to accurately identify high-risk individuals for DLNM and conduct more precise risk stratification for this patient subgroup, potentially improving management strategies and patient outcomes.

Hepatocellular carcinoma as a complication of chronic Budd-Chiari syndrome (BCS) in a child.

Hepatocellular carcinoma (HCC) is an extremely rare long-term complication of Budd-Chiari syndrome (BCS) which may occur due to long-term venous congestion causing fibrosis, cirrhosis and subsequent hepatocellular dysplasia or anaplasia. This complication is even rarer in paediatric BCS and warrants early diagnosis for a favourable prognosis. Benign regenerative nodules seen with BCS are difficult to differentiate from malignant nodular lesion of HCC, thereby making serial imaging less sensitive for early diagnosis of HCC in BCS. Surveillance guidelines like adults do not exist in monitoring chronic paediatric BCS due to rarity of this complication. Six monthly serum alpha-fetoprotein monitoring in addition to radiological surveillance improves the sensitivity of early detection of HCC transformation in BCS and should be the way ahead in paediatric BCS as well. We describe a paediatric patient who presented with advanced HCC after 25-month follow-up for BCS.

Ionic liquid-reinforced Hydroxyapatite@nano-TiO2 as a green platform for Immuno-electrochemical sensing applications.

In contemporary society, developing dependable point-of-care (POC) biosensors for the timely detection of cancer markers is crucial. Among various sensor types, screen-printed electrode (SPE)-based sensors, particularly electrochemical ones, stand out as promising candidates for POC applications. Despite ongoing efforts to create numerous SPE-based sensors, there is a continuous pursuit to enhance their sensitivity and analytical capabilities. This study presents an advanced electrochemical sensor designed to sensitively detect the hepatocellular carcinoma (HCC) marker Alpha-fetoprotein (AFP) in saliva. The sensor employs a gold SPE modified with hydroxyapatite, TiO2 nanoparticles, 1-butyl-3-methylimidazolium bis(trifluoromethyl sulfonyl)imide ionic liquid (IL), and AFP monoclonal antibodies. After thorough characterization and optimization using cyclic voltammetry (CV) and differential pulse voltammetry (DPV), the biosensor exhibited a broad detection range (0.01-400 ng/mL), a low limit of detection (LOD) at 0.058 ng/mL, and demonstrated high selectivity, repeatability, reproducibility, and stability. Furthermore, when tested with spiked human saliva samples, the biosensor displayed excellent recovery and robustness, showcasing its potential for noninvasive and POC diagnosis of HCC. In an environmentally conscious evaluation, the biosensor's greenness was assessed using the AGREE metric, yielding a high score of 0.85. This score indicates the biosensor's alignment with the principles of green analytical chemistry, underlining its eco-friendly attributes. This innovative electrochemical sensor contributes to the ongoing efforts for efficient and reliable POC diagnostic tools and aligns with a broader commitment to developing environmentally friendly solutions.

Confinement Effect Enhanced Bipolar Electrochemistry: Structural Color Coding Coupled with Wireless Electrochemiluminescence Imaging Technology.

In this work, SiO2/CNTs photonic crystal beads were constructed by doping CNTs into SiO2 photonic crystals, which have an angle-independent responsive structural color and can be used as bipolar electrodes due to their good electrical conductivity. In addition, the bipolar electrode-electrochemiluminescence (BPE-ECL) experiments and finite element simulation prove that the low driving voltage can trigger the bipolar electrode electrochemical reactions by confinement effect. Inspired by this, it is the first to combine the SiO2/CNTs structural color coding scheme with low-drive voltage induced wireless BPE-ECL imaging based on the confinement effect of microchannels to achieve simultaneous immune detection of ovarian cancer biomarkers (CA125, CEA, AFP). The detection limits of successfully constructed high-throughput BPE-ECL biosensor for AFP, CEA, and CA125 are 0.72 ng/mL, 0.95 ng/mL, and 1.03 U/mL, respectively, and have good stability and specificity, which expands the application of electrochemiluminescence and lays a foundation for the development of electrochemiluminescence coding technology.

Potential contribution of alpha-fetoprotein level to biomarker of pregnancy outcome in Asian elephants.

Alpha-fetoprotein (AFP) is a structural serum glycoprotein that plays vital roles in reproduction and mammalian development. Analysis of serum prolactin (PRL) is considered one of the useful methods for diagnosing pregnancy in Asian elephants. However, the expression profiles of AFP in pregnant and nonpregnant Asian elephants remain unclear, nor is the relationship with PRL. In this study, serum seven gonadal hormones and AFP in three pregnant and seven nonpregnant Asian elephants were analysed by via radioimmunoassay (RIA) and enzyme-linked immunosorbent (ELISA) assay. We found that the mean (±SD) concentration of prolactin (PRL) in pregnant (136.782 ± 30.987 ng/mL) elephants was significantly higher than that in nonpregnant elephants (52.803 ± 21.070 ng/mL; p ≤ 0.0005). The mean (±SD) concentration of AFP in pregnant elephants (11.598 ± 0.824 ng/mL) was significantly higher than that in nonpregnant elephants (7.200 ± 2.283 ng/mL; p ≤ 0.05). Furthermore, the AFP concentration was positively correlated with the PRL concentration in the 10 Asian elephants studied. In conclusion, our findings suggest that serum AFP concentration is a potential biomarker of pregnancy outcomes in Asian elephants.

A novel chemiluminescence sensor for alpha-fetoprotein detection based on an aptamer-luminol modified magnetic graphene oxide and copper-based MOF composite.

Herein, an aptamer-luminol modified magnetic graphene oxide and copper-based MOF composite was prepared and used to build a novel target-triggered "turn on" chemiluminescence (CL) sensor for alpha-fetoprotein (AFP) detection. Magnetic graphene oxide (MGO) was functionalized with the complementary sequence of the AFP aptamer (cDNA), and then MGO-cDNA was linked to aptamer modified luminol (Apt-luminol) through the complementary base pairing effect. The functionalized magnetic graphene oxide (MGO-cDNA/Apt-luminol) was prepared as a specific magnetic separation and signal switch material. ZnONPs-Au@CuMOFs shows excellent catalytic performance and was used as a catalyst for the luminol-H2O2 reaction. AFP will specifically recognize and bind to Apt on MGO-cDNA/Apt-luminol when AFP is present, which causes luminol release and triggers the CL reaction. The released luminol encounters ZnONPs-Au@CuMOFs and produces strong CL intensity. Therefore, a novel target-triggered "turn on" CL method with high selectivity and sensitivity for detecting AFP has been established. The linear range and detection limit were 1.0 × 10-4-50 ng mL-1 and 4.2 × 10-5 ng mL-1, respectively. The sensor also exhibited good selectivity, reproducibility and stability, and was finally used for AFP detection in serum samples.