Expression profiling of stemness markers in testicular germline stem cells from neonatal and adult Swiss albino mice during their transdifferentiation in vitro.

BACKGROUND: Spermatogonial stem cells (SSCs) were considered to be stem cells with limited potencies due to their existence in adult organisms. However, the production of spermatogonial stem cell colonies with broader differentiation capabilities in primary germ cell cultures from mice of select genetic backgrounds (C57BL6/Tg14, ddY, FVB and 129/Ola) indicated that SSCs from these strains were pluripotent. METHODS: We established primary cultures of SSCs from neonatal and adult Swiss 3T3 Albino mice. Stemness of SSC colonies were evaluated by performing real-time PCR and immunofluorescence analysis for a panel of chosen stemness markers. Differentiation potentials of SSCs were examined by attempting the generation of embryoid bodies and evaluating the expression of ectodermal, mesodermal and endodermal markers using immunofluorescence and real-time PCR analysis. RESULTS: Spermatogonial stem cells from neonatal and mature mice testes colonised in vitro and formed compact spermatogonial stem cell colonies in culture. The presence of stem cell markers ALPL, ITGA6 and CD9 indicated stemness in these colonies. The differentiation potential of these SSC colonies was demonstrated by their transformation into embryoid bodies upon withdrawal of growth factors from the culture medium. SSC colonies and embryoid bodies formed were evaluated using immunofluorescence and real-time PCR analysis. Embryoid body like structures derived from both neonatal and adult mouse testis were quite similar in terms of the expression of germ layer markers. CONCLUSION: These results strongly suggest that SSC-derived EB-like structures could be used for further differentiation into cells of interest in cell-based therapeutics.

Ataxia telangiectasia: a rare case report from Nepal.

Introduction and importance: Ataxia telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder with early childhood onset. It is characterized by ataxia, oculocutaneous telangiectasia, immunodeficiency, and lymphoid-origin cancer predisposition due to ataxia telangiectasia mutated gene mutations. Case presentation: The authors present a 19-year-old girl with spastic movements since 18 months, leading to wheelchair dependence. Ocular telangiectasia, dystonic posture, and slurred speech were evident. Diagnosis involved elevated alpha-fetoprotein levels and typical brain imaging. Clinical discussion: A-T due to ataxia telangiectasia mutated gene mutations located on chromosome 11q22-23. It has varied presentations categorized by age and features. Timely diagnosis relies on characteristic symptoms, lab findings, and imaging. Radiation sensitivity and increased cancer risk underscore cautious radiation use. Conclusion: A-T is a complex disorder with no cure. Genetic counseling for parents is vital. Its poor prognosis due to infection susceptibility and cancer risk necessitates supportive care. Comprehensive management, including genetic counseling and careful surveillance, is imperative.

Specific features of epitope-MIPs and whole-protein MIPs as illustrated for AFP and RBD of SARS-CoV-2.

Molecularly imprinted polymer (MIP) nanofilms for alpha-fetoprotein (AFP) and the receptor binding domain (RBD) of the spike protein of SARS-CoV-2 using either a peptide (epitope-MIP) or the whole protein (protein-MIP) as the template were prepared by electropolymerization of scopoletin. Conducting atomic force microscopy revealed after template removal and electrochemical deposition of gold a larger surface density of imprinted cavities for the epitope-imprinted polymers than when using the whole protein as template. However, comparable affinities towards the respective target protein (AFP and RBD) were obtained for both types of MIPs as expressed by the KD values in the lower nanomolar range. On the other hand, while the cross reactivity of both protein-MIPs towards human serum albumin (HSA) amounts to around 50% in the saturation region, the nonspecific binding to the respective epitope-MIPs is as low as that for the non-imprinted polymer (NIP). This effect might be caused by the different sizes of the imprinted cavities. Thus, in addition to the lower costs the reduced nonspecific binding is an advantage of epitope-imprinted polymers for the recognition of proteins.

Association between aneuploidy screening analytes and adverse outcomes in twin gestations.

OBJECTIVES: To evaluate associations between serum analytes used for genetic screening and obstetric complications among twin pregnancies. METHODS: This cohort included twins delivered at a tertiary care hospital from 2009 to 2017. Abnormal levels of pregnancy associated plasma protein (PAPP-A), first and second trimester human chorionic gonadotropin (hCG), alpha fetoprotein (AFP), estriol, and inhibin, reported as multiples of the median (MoM), were defined as <5 %ile or >95 %ile for our cohort. Associations between abnormal analytes and preterm delivery, small for gestational age, and pregnancy-associated hypertension were calculated using Fisher's exact test. RESULTS: A total of 357 dichorionic/diamniotic and 123 monochorionic/diamniotic twins were included. Among dichorionic/diamniotic twins, elevated AFP (>3.70 MoM) was associated with increased preterm delivery <34 weeks (44.4 vs. 16.5 %, p=0.007), while elevated inhibin (>4.95 MoM) was associated with increased preterm delivery<37 weeks (94.1 vs. 58.8 %, p=0.004). For monochorionic/diamniotic twins, elevated inhibin (>6.34 MoM) was associated increased preterm delivery <34 weeks (66.7 vs. 24.8 %, p=0.04) and hypertension (66.7 vs. 21.4 %, p=0.03). CONCLUSIONS: Selected abnormal analyte levels were associated with increased rates of adverse outcomes in twin pregnancies, which differed by chorionicity. Our findings assist providers in interpreting abnormal analyte levels in twin pregnancies and may help to identify those at increased risk for adverse outcomes.

CT Findings of Hepatic Metastasis from Hepatoid Adenocarcinoma of the Rectum Mimicking Hepatocellular Carcinoma: A Case Report.

Hepatoid adenocarcinoma (HAC) is a rare form of adenocarcinoma that is diagnosed based on immuno-histochemical findings reminiscent of hepatocellular carcinoma (HCC). The clinical characteristics of HAC include increased levels of serum alpha-fetoprotein and a poor prognosis due to early liver metastasis. In particular, diagnosing liver metastasis of HAC can be challenging owing to radiological findings similar to those of HCC. Although HAC can occur in various organs, the stomach is the most common site. We present the case of a 64-year-old femalewho presented with multiple tumors in the liver. During subsequent examination, rectal cancer was identified and diagnosed as HAC through a biopsy. Herein, we report this case along with a literature review.

Exceptional Long-Term Survival of a Patient With Hepatoid Adenocarcinoma of the Colon and the Treatment Strategy: A Case Report.

Hepatoid adenocarcinoma (HAC) of the colon is a rare type of tumor with hepatocellular differentiation. HAC often produces alpha-fetoprotein (AFP) and metastasizes to lymph nodes and the liver. HAC is usually aggressive with a poor prognosis and has a propensity for intravascular growth and frequent distant metastasis. Because the biology of HAC is not fully understood, there are very limited therapeutic options known to reduce recurrence and improve survival. In addition, because HAC is so rare, it is difficult to acquire data from large randomized clinical trials to guide practice; therefore, case reports can provide valuable information for the treatment of HAC. In this report, we present a case of a 30-year-old male patient with HAC with high AFP levels and liver metastases. The patient underwent hepatic arterial infusion chemotherapy (HAIC) with doxorubicin/oxaliplatin to treat the liver metastasis, and three weeks later, he received radical sigmoid and rectal resection, left liver resection, and ileostomy. Then, the patient received eight cycles of chemotherapy with epirubicin plus folinic acid, fluorouracil, and oxaliplatin (FOLFOX) every three weeks, followed by maintained therapy with capecitabine for 2.5 years without relapse. This case report indicates that, although HAC is usually an aggressive disease with frequent distant metastasis, patients with HAC may still have a good prognosis if treated with appropriate strategy.

A compact microfluidic laser-induced fluorescence immunoassay system using avalanche photodiode for rapid detection of alpha-fetoprotein.

Alpha-fetoprotein (AFP), commonly employed for early diagnosis of liver cancer, serves as a biomarker for cancer screening and diagnosis. Combining the high sensitivity and specificity of fluorescence immunoassay (FIA), developing a low-cost and efficient immunoassay system for AFP detection holds significant importance in disease diagnosis. In this work, we developed a miniaturized oblique laser-induced fluorescence (LIF) immunoassay system, coupled with a microfluidic PMMA/paper hybrid chip, for rapid detection of AFP. The system employed an avalanche photodiode (APD) as the detector, and implemented multi-level filtering in the excitation light channel using the dichroic mirror and optical trap. At first, we employed the Savitzky-Golay filter and baseline off-set elimination methods to denoise and normalize the original data. Then the cutoff frequency of the low-pass filter and the reverse voltage of the APD were optimized to enhance the detection sensitivity of the system. Furthermore, the effect of laser power on the fluorescence excitation efficiency was investigated, and the sampling time during the scanning process was optimized. Finally, a four-parameter logistic (4PL) model was utilized to establish the concentration-response equation for AFP. The system was capable of detecting concentrations of AFP standard solution within the range of 1-500 ng/mL, with a detection limit of 0.8 ng/mL. The entire immunoassay process could be completed within 15 min. It has an excellent potential for applications in low-cost portable diagnostic instruments for the rapid detection of biomarkers.

Assessing recent recurrence after hepatectomy for hepatitis B-related hepatocellular carcinoma by a predictive model based on sarcopenia.

BACKGROUND: Sarcopenia may be associated with hepatocellular carcinoma (HCC) following hepatectomy. But traditional single clinical variables are still insufficient to predict recurrence. We still lack effective prediction models for recent recurrence (time to recurrence < 2 years) after hepatectomy for HCC. AIM: To establish an interventable prediction model to estimate recurrence-free survival (RFS) after hepatectomy for HCC based on sarcopenia. METHODS: We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time, and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography. 94 of these patients were enrolled for external validation. Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort. A nomogram model was developed to predict the RFS of HCC patients, and its predictive performance was validated. The predictive efficacy of this model was evaluated using the receiver operating characteristic curve. RESULTS: Multivariate analysis showed that sarcopenia [Hazard ratio(HR) = 1.767, 95%CI: 1.166-2.678, P < 0.05], alpha-fetoprotein ≥ 40 ng/mL (HR = 1.984, 95%CI: 1.307-3.011, P < 0.05), the maximum diameter of tumor > 5 cm (HR = 2.222, 95%CI: 1.285-3.842, P < 0.05), and hepatitis B virus DNA level ≥ 2000 IU/mL (HR = 2.1, 95%CI: 1.407-3.135, P < 0.05) were independent risk factors associated with postoperative recurrence of HCC. Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease (SAMD) was established combined with other the above risk factors. The area under the curve of the SAMD model was 0.782 (95%CI: 0.705-0.858) in the training cohort (sensitivity 81%, specificity 63%) and 0.773 (95%CI: 0.707-0.838) in the validation cohort. Besides, a SAMD score ≥ 110 was better to distinguish the high-risk group of postoperative recurrence of HCC. CONCLUSION: Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC. A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC, which is superior to other models and contributes to prognosis prediction.

PIVKA-II combined with alpha-fetoprotein for the diagnostic value of hepatic tumors in children: a multicenter, prospective observational study.

BACKGROUND: To investigate whether protein induced by vitamin K antagonist-II (PIVKA-II) combined with alpha-fetoprotein (AFP) can improve the diagnostic and differential diagnostic accuracy of childhood hepatic tumors. METHODS: A multi-center prospective observational study was performed at nine regional institutions around China. Children with hepatic mass (Group T) were divided into hepatoblastoma group (Group THB) and hemangioendothelioma group (Group THE), children with extrahepatic abdominal mass (Group C). Peripheral blood was collected from each patient prior to surgery or chemotherapy. The area under the curve (AUROC) was used to evaluate the diagnostic efficiency of PIVKA-II and the combined tumor markers with AFP. RESULTS: The mean levels of PIVKA-II and AFP were both significantly higher in Group T than Group C (p = 0.001, p < 0.001), in Group THB than Group THE (p = 0.018, p = 0.013) and in advanced HB than non-advanced HB (p = 0.001, p = 0.021). For the diagnosis of childhood hepatic tumors, AUROC of PIVKA-II (cut-off value 32.6 mAU/mL) and AFP (cut-off value 120 ng/mL) was 0.867 and 0.857. The differential diagnostic value of PIVKA-II and AFP in hepatoblastoma from hemangioendothelioma was further assessed, AUROC of PIVKA-II (cut-off value 47.1mAU/mL) and AFP (cut-off value 560 ng/mL) was 0.876 and 0.743. The combined markers showed higher AUROC (0.891, 0.895 respectively) than PIVKA-II or AFP alone. CONCLUSIONS: The serum level of PIVKA-II was significantly higher in children with hepatic tumors, especially those with malignant tumors. The combination of PIVKA-II with AFP further increased the diagnostic performance. TRIAL REGISTRATION: Clinical Trials, NCT03645655. Registered 20 August 2018, https://www. CLINICALTRIALS: gov/ct2/show/NCT03645655 .

Three-Dimensional Structure of Novel Liver Cancer Biomarker Liver Cancer-Specific Serine Protease Inhibitor Kazal (LC-SPIK) and Its Performance in Clinical Diagnosis of Hepatocellular Carcinoma (HCC).

LC-SPIK is a liver cancer-specific isoform of Serine Protease Inhibitor Kazal and has been proposed as a new biomarker for the detection of HCC given its unique 3D structure, which differs from normal pancreatic SPIK. An ELISA technology based on its unique structure was developed to use LC-SPIK as an effective biomarker for the clinical diagnosis of HCC. AFP, the most widely used biomarker for HCC surveillance currently, suffers from poor clinical performance, especially in the detection of early-stage HCC. In one case-control study, which included 164 HCC patients and 324 controls, LC-SPIK had an AUC of 0.87 compared to only 0.70 for AFP in distinguishing HCC from liver disease controls (cirrhosis, HBV/HCV). LC-SPIK also performed significantly better than AFP for the 81 patients with early-stage HCC (BCLC stage 0 and A), with an AUC of 0.85 compared to only 0.61 for AFP. Cirrhosis is the major risk factor for HCC; about 80% of patients with newly diagnosed HCC have preexisting cirrhosis. LC-SPIK's clinical performance was also studied in HCC patients with viral and non-viral cirrhosis, including cirrhosis caused by metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease (ALD). In a total of 163 viral cirrhosis patients with 93 HCC patients (50 early-stage), LC-SPIK had an AUC of 0.85, while AFP had an AUC of 0.70. For patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while AFP had an AUC of only 0.60. For 120 patients with nonviral cirrhosis, including 62 HCC (23 early-stage) patients, LC-SPIK had an AUC of 0.84, while AFP had an AUC of only 0.72. For the 23 patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while the AUC for AFP decreased to 0.65. All these results suggest that LC-SPIK exhibits significantly better performance in the detection of HCC than AFP in all etiologies of liver diseases. In addition, LC-SPIK accurately detected the presence of HCC in 71-91% of HCC patients with false-negative AFP test results in viral-associated HCC and non-viral-associated HCC.

Prognostic performance of MRI LI-RADS version 2018 features and clinical-pathological factors in alpha-fetoprotein-negative hepatocellular carcinoma.

PURPOSE: To evaluate the role of the magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS) version 2018 features and clinical-pathological factors for predicting the prognosis of alpha-fetoprotein (AFP)-negative (≤ 20 ng/ml) hepatocellular carcinoma (HCC) patients, and to compare with other traditional staging systems. METHODS: We retrospectively enrolled 169 patients with AFP-negative HCC who received preoperative MRI and hepatectomy between January 2015 and August 2020 (derivation dataset:validation dataset = 118:51). A prognostic model was constructed using the risk factors identified via Cox regression analysis. Predictive performance and discrimination capability were evaluated and compared with those of two traditional staging systems. RESULTS: Six risk factors, namely the LI-RADS category, blood products in mass, microvascular invasion, tumor size, cirrhosis, and albumin-bilirubin grade, were associated with recurrence-free survival. The prognostic model constructed using these factors achieved C-index of 0.705 and 0.674 in the derivation and validation datasets, respectively. Furthermore, the model performed better in predicting patient prognosis than traditional staging systems. The model effectively stratified patients with AFP-negative HCC into high- and low-risk groups with significantly different outcomes (p < 0.05). CONCLUSION: A prognostic model integrating the LI-RADS category, blood products in mass, microvascular invasion, tumor size, cirrhosis, and albumin-bilirubin grade may serve as a valuable tool for refining risk stratification in patients with AFP-negative HCC.

Prediction of survival and analysis of prognostic factors for patients with AFP negative hepatocellular carcinoma: a population-based study.

PURPOSE: Hepatocellular carcinoma (HCC) has a poor prognosis, and alpha-fetoprotein (AFP) is widely used to evaluate HCC. However, the proportion of AFP-negative individuals cannot be disregarded. This study aimed to establish a nomogram of risk factors affecting the prognosis of patients with AFP-negative HCC and to evaluate its diagnostic efficiency. PATIENTS AND METHODS: Data from patients with AFP-negative initial diagnosis of HCC (ANHC) between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results database for model establishment and validation. We randomly divided overall cohort into the training or validation cohort (7:3). Univariate and multivariate Cox regression analysis were used to identify the risk factors. We constructed nomograms with overall survival (OS) and cancer-specific survival (CSS) as clinical endpoint events and constructed survival analysis by using Kaplan-Meier curve. Also, we conducted internal validation with Receiver Operating Characteristic (ROC) analysis and Decision curve analysis (DCA) to validate the clinical value of the model. RESULTS: This study included 1811 patients (1409 men; 64.7% were Caucasian; the average age was 64 years; 60.7% were married). In the multivariate analysis, the independent risk factors affecting prognosis were age, ethnicity, year of diagnosis, tumor size, tumor grade, surgery, chemotherapy, and radiotherapy. The nomogram-based model related C-indexes were 0.762 (95% confidence interval (CI): 0.752-0.772) and 0.752 (95% CI: 0.740-0.769) for predicting OS, and 0.785 (95% CI: 0.774-0.795) and 0.779 (95% CI: 0.762-0.795) for predicting CSS. The nomogram model showed that the predicted death was consistent with the actual value. The ROC analysis and DCA showed that the nomogram had good clinical value compared with TNM staging. CONCLUSION: The age(HR:1.012, 95% CI: 1.006-1.018, P-value < 0.001), ethnicity(African-American: HR:0.946, 95% CI: 0.783-1.212, P-value: 0.66; Others: HR:0.737, 95% CI: 0.613-0.887, P-value: 0.001), tumor diameter(HR:1.006, 95% CI: 1.004-1.008, P-value < 0.001), year of diagnosis (HR:0.852, 95% CI: 0.729-0.997, P-value: 0.046), tumor grade(Grade 2: HR:1.124, 95% CI: 0.953-1.326, P-value: 0.164; Grade 3: HR:1.984, 95% CI: 1.574-2.501, P-value < 0.001; Grade 4: HR:2.119, 95% CI: 1.115-4.027, P-value: 0.022), surgery(Liver Resection: HR:0.193, 95% CI: 0.160-0.234, P-value < 0.001; Liver Transplant: HR:0.102, 95% CI: 0.072-0.145, P-value < 0.001), chemotherapy(HR:0.561, 95% CI: 0.471-0.668, P-value < 0.001), and radiotherapy(HR:0.641, 95% CI: 0.463-0.887, P-value:0.007) were independent prognostic factors for patients with ANHC. We developed a nomogram model for predicting the OS and CSS of patients with ANHC, with a good predictive performance.

Portable photoelectrochemical immunoassay with micro-electro-mechanical-system for alpha-fetoprotein in hepatocellular carcinoma.

Early detection of cancer has a profound impact on patient survival and treatment outcomes considering high treatment success rates and reduced treatment complexity. Here, we developed a portable photoelectrochemical (PEC) immune platform for sensitive testing of alpha-fetoprotein (AFP) based on Pt nanocluster (Pt NCs) loaded defective-state g-C3N4 photon-electron transducers. The broad forbidden band structure of g-C3N4 was optimized by the nitrogen doping strategy and additional homogeneous porous structure was introduced to further enhance the photon utilization. In addition, the in-situ growth of Pt NCs provided efficient electron transfer catalytic sites for sacrificial agents, which were used to further improve the sensitivity of the sensor. Efficient photoelectric conversion under a hand-held flashlight was determined by the geometry of the transducer and the energy band design, and the portable design of the PEC sensor was realized. The developed sensing platform exhibited a wide linear response range (0.1-50 ng mL-1) and low limit of detection (0.043 ng mL-1) for AFP under optimum conditions. This work provides a new idea for designing portable PEC biosensing platforms to meet the current mainstream POC testing needs.

A Real-World Experience on a Chinese Population of Patients With Unresectable Hepatocellular Carcinoma Treated With Nivolumab.

Background: For unresectable hepatocellular carcinoma (HCC), nivolumab (anti-programmed death receptor-1 (PD-1)) is used as non-curative interventions. The aim of the study was to focus on the real-world experience of nivolumab applied to patients with HCC. Methods: Unresectable HCC patients receiving nivolumab treatments at Taichung Veterans General Hospital, from June 2018 to May 2020, were recruited. Exclusion criteria were Child-Pugh stage C, poor performance status, a lack of compliance or intolerable to drug treatments. The tumor radiological responses and survival outcomes of enrolled patients were collected and analyzed. Results: Among a total of 57 patients, most of them were classified as Child-Pugh stage A (70.2%) and Barcelona Clinic Liver Cancer (BCLC) stage C (66.7%). Nivolumab was given to 14 (24.6%) as the primary-line, and 43 patients (75.4%) as the secondary-line systemic treatments. The mean therapeutic duration was 6.5 months. Objective response rate (ORR) was 24.6%, and disease control rate (DCR) was 42.1%. The overall median progression-free survival (PFS) was 5.8 months (95% confidence interval (CI): 1.1 - 10.6), and overall survival (OS) was 11.5 months (95% CI: 4.3 - 17.8). Immune-related adverse event (IRAE) was 8.8%. Presence of alpha-fetoprotein (AFP) response (a decline in AFP ≥ 10% from baseline) during therapy predicted the tumor radiological response (to objective response: hazard ratio (HR): 4.89, 95% CI: 1.14 - 21.00; to disease control: HR: 4.71, 95% CI: 1.32 - 16.81). Those with tumor radiological responses showed longer PFS and OS. Conclusions: Decline in AFP during therapy has a predicting role on HCC radiological responses to nivolumab. Achieving radiological responses had better survival outcomes.

Construction and Validation of a Novel Nomogram Predicting Recurrence in Alpha-Fetoprotein-Negative Hepatocellular Carcinoma Post-Surgery Using an Innovative Liver Function-Nutrition-Inflammation-Immune (LFNII) Score: A Bicentric Investigation.

Purpose: We developed a nomogram based on the liver function, nutrition, inflammation, and immunity (LFNII) score to predict recurrence-free survival (RFS) post-resection in patients with hepatocellular carcinoma (HCC) exhibiting alpha-fetoprotein (AFP) negativity (AFP ≤20 ng/mL). Patients and Methods: Clinical data of 661 patients diagnosed with alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) who underwent surgical resection at two medical centers between 2012 and 2021 were collected. A total of 462 and 199 patients served as the training and validation sets, respectively. Pre-operative blood markers were collected and analyzed for LFNII. The LFNII score was formulated using the least absolute shrinkage and selection operator Cox regression model. A nomogram model was developed using the training set to incorporate other relevant clinicopathological indicators and predict postoperative recurrence. Model discrimination was assessed using the receiver operating characteristic curve, calibration was evaluated using a calibration curve, and clinical applicability was assessed using clinical decision curve analysis. A comparison with liver cancer staging was performed using the nomogram model. Finally, a cohort study was conducted to validate our findings. Results: We derived the LFNII scores from nine indicators. Elevated LFNII scores correlated with unfavorable clinicopathological features. The LFNII score area under the curve revealed superior predictive efficacy at 1-, 2-, and 5-year RFS intervals, with values of 0.675, 0.658, and 0.633, respectively. Multivariate Cox analysis revealed that a high LFNII score independently increased RFS risk in patients with AFP-NHCC. The C-index of the LFNII-nomogram model was 0.686 (95% confidence interval [CI], 0.651-0.721). The nomogram model's clinical application value surpassed that of standard HCC staging systems. Conclusion: The LFNII score-derived nomogram effectively predicted the RFS of patients with AFP-NHCC after curative resection.

Predictive value of coagulation function, alpha-fetoprotein and placental growth factor in patients with perilous placenta previa.

OBJECTIVE: To analyze the predictive value of coagulation function, alpha-fetoprotein (AFP) and placental growth factor (PIGF) for postpartum hemorrhage in patients with perilous placenta previa (PPP). METHODS: The clinical data of 104 PPP patients were retrospectively analyzed. The patients were divided into a hemorrhage group (n=68) and a non-hemorrhage group (n=36). A total of 55 healthy pregnant women were recruited as controls. The coagulation function, AFP and PIGF were compared between the three groups. Multivariate logistic regression was performed to determine independent risk factors for hemorrhage. RESULTS: PT, TT, APTT, FIB and AFP were significantly higher while PIGF was lower in the PPP group than the control group (all P<0.05). Placental adhesion (OR 3.924, 95% CI 1.389-11.083, P=0.01), anterior placenta (OR 4.583, 95% CI 1.589-13.22, P=0.005), AFP (OR 0.208, 95% CI 0.068-0.635, P=0.006) and PIGF (OR 3.963, 95% CI 1.385-11.34, P=0.01) were independent risk factors for hemorrhage. CONCLUSION: Coagulation function, AFP and PIGF could predict postpartum hemorrhage in PPP patients.

Ratiometric electrochemical immunoassay based on 2D Co/Fe MOF decorated with toluidine blue and Fc-labeled Schiff base for accurate assay of alpha-fetoprotein in clinical serum.

The high level of alpha-fetoprotein (AFP) expression is closely related to hepatocellular carcinoma (HCC). Herein, a dual signal ratiometric electrochemical immunosensor based on chitosan-ferrocenecarboxaldehyde-spindle gold (Chit-Fc-SAu) and Co/Fe metal-organic framework-toluidine blue/polydopamine (Co/Fe MOF-TB/PDA) was proposed for quantitative analysis of AFP. Specifically, Chit-Fc-SAu worked as a substrate to trap more primary antibodies (Ab1) generating the first electrochemical signal from Fc. Thanks to the large specific surface area, the synergistic and electronic effects of Co/Fe MOF nanosheets, and the rich functional groups of PDA, Co/Fe MOF-TB/PDA could load more secondary antibodies (Ab2) and signal molecules (TB) providing another amplified electrochemical signal. In the presence of AFP, Ab1-AFP-Ab2 formed a sandwich structure, and as the AFP concentration increased, the peak current ratio of TB to Fc (ITB/IFc) also increased. The dual signal ratiometric strategy can avoid environmental signal interference and achieve signal self-calibration, thereby improving the accuracy and reproducibility of detection. After a series of exploration, this self-calibrated ratiometric immunosensor exhibited a wide linear range (0.001-200 ng mL-1), a low detection limit (0.34 pg mL-1), and good repeatability. When applied to the assay of clinical serum samples, the detection results of ratiometric sensor were consistent with that of commercial electrochemiluminescence (ECL) immunoassay, significantly superior to that of non-ratiometric sensor. The self-calibrated strategy based on ratiometric sensor helps to improve the accuracy of AFP in clinical diagnosis.

Surgical Intervention After Lenvatinib Treatment in Patients With Advanced Hepatocellular Carcinoma.

BACKGROUND/AIM: The survival and prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who underwent surgical intervention after lenvatinib treatment is not well-understood. PATIENTS AND METHODS: Seventy-six patients with advanced HCC who had lenvatinib treatment were retrospectively analyzed. RESULTS: Of 70 patients who were treated with lenvatinib, 14 patients underwent surgical intervention after lenvatinib treatment for 4-28 weeks. Progression-free survival (PFS) was significantly longer in patients who underwent surgical intervention than in patients with non-surgical treatment (median, 8.6 vs. 5.1 months, p=0.019). Non-significantly longer overall survival (OS) was also observed in patients with surgical intervention compared to patients with non-surgical treatment (median, unreached vs. 21.0 months, p=0.206). In patients who underwent surgical intervention, two patients had a partial response, and 12 had stable disease according to RECIST ver. 1.1 criteria. The serum alpha-fetoprotein (AFP) level was significantly lower after lenvatinib treatment than before lenvatinib treatment (median, 19.2 vs. 196.5 ng/ml, p=0.0081). Eleven patients underwent curative surgery with a 14% major postoperative complication (Clavien-Dindo ≥IIIa) rate. Patients who exhibited decreases in AFP levels or maintained AFP levels within the normal range during lenvatinib treatment had significantly longer PFS (median, 8.6 vs. 3.0 months, p=0.0009) and OS (median, unreached vs. 12.4 months, p=0.012) compared to those with persistently elevated AFP levels beyond the normal range. CONCLUSION: Surgical intervention after lenvatinib treatment for advanced HCC was associated with longer PFS. Patients exhibiting decreased AFP levels or maintaining AFP levels within the normal limit may be suitable candidates for surgical intervention after lenvatinib treatment for advanced HCC.

Development of a Reliable GADSAH Model for Differentiating AFP-negative Hepatic Benign and Malignant Occupying Lesions.

Purpose: Developing a high-value, convenient, and validated differential diagnosis model to differentiate alpha-fetoprotein (AFP) negative hepatic occupying lesions and assist clinicians in early identification and intervention. Patients and Methods: A total of 340 patients with AFP-negative hepatic occupying lesions who were admitted to the Guangxi Medical University Cancer Hospital between August 2021 and April 2023 were included in the final retrospective analysis. The data were randomly divided into training and validation sets in a 7:3 ratio after performing multiple interpolations. In the training set, laboratory variables and models were screened using least absolute shrinkage and selection operator regression analysis, comparison of five machine learning algorithms, and univariate, as well as multivariate logistic regression analysis. A diagnostic prediction nomogram model was developed. We evaluated and validated the model using the receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Results: We identified six significant predictive factors from the results of multivariate logistic analysis in the training set and incorporated them into the nomogram model for diagnosing AFP-negative hepatic malignant occupying lesions (HMOL). The diagnostic nomogram, including gender, age, des-gamma-carboxy prothrombin (DCP), serum ferritin (SF), AFP, and hepatitis B surface antigen (HBsAg), achieved an area under the curve of 0.905 discriminated patients with HMOL from those with benign occupying lesions. Additionally, calibration curves demonstrated the close alignment between the nomogram predictions and the ideal curve, along with the consistency between predictions and actual results. Moreover, the DCA curves illustrated indicated benefit for all patients. These finding were confirmed by the validation set. Conclusion: The GADSAH model specifically targets the discrimination of malignant and benign liver lesions in AFP-negative patients. It offers a noninvasive, cost-effective, and efficient approach for diagnosing such cases.

Serum alpha-fetoprotein response as a preoperative prognostic indicator in unresectable hepatocellular carcinoma with salvage hepatectomy following conversion therapy: a multicenter retrospective study.

Background: This study evaluates the efficacy of alpha-fetoprotein (AFP) response as a surrogate marker for determining recurrence-free survival (RFS) in patients with unresectable hepatocellular carcinoma (uHCC) who undergo salvage hepatectomy following conversion therapy with tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody-based regimen. Methods: This multicenter retrospective study included 74 patients with uHCC and positive AFP (>20 ng/mL) at diagnosis, who underwent salvage hepatectomy after treatment with TKIs and anti-PD-1 antibody-based regimens. The association between AFP response-defined as a ≥ 80% decrease in final AFP levels before salvage hepatectomy from diagnosis-and RFS post-hepatectomy was investigated. Results: AFP responders demonstrated significantly better postoperative RFS compared to non-responders (P<0.001). The median RFS was not reached for AFP responders, with 1-year and 2-year RFS rates of 81.3% and 70.8%, respectively. In contrast, AFP non-responders had a median RFS of 7.43 months, with 1-year and 2-year RFS rates at 37.1% and 37.1%, respectively. Multivariate Cox regression analysis identified AFP response as an independent predictor of RFS. Integrating AFP response with radiologic tumor response facilitated further stratification of patients into distinct risk categories: those with radiologic remission experienced the most favorable RFS, followed by patients with partial response/stable disease and AFP response, and the least favorable RFS among patients with partial response/stable disease but without AFP response. Sensitivity analyses further confirmed the association between AFP response and improved RFS across various cutoff values and in patients with AFP ≥ 200 ng/mL at diagnosis (all P<0.05). Conclusion: The "20-80" rule based on AFP response could be helpful for clinicians to preoperatively stratify the risk of patients undergoing salvage hepatectomy, enabling identification and management of those unlikely to benefit from this procedure.