Objective To investigate the clinical features and key diagnostic points of aceruloplasminemia （ACP）， as well as the features of a novel pathogenic mutation. Methods A systematic analysis was performed for the clinical data of one patient with a confirmed diagnosis of ACP， and a literature review was performed based on related articles in China and globally. Results Based on the clinical features of this patient and the analysis of the family， it was clarified that the homozygous c.1944C>G （p.Ser648Arg） mutation in the Ceruloplasmin （CP） gene could cause ACP and was reported for the first time worldwide. Conclusion ACP is an extremely rare autosomal recessive disease due to abnormal iron metabolism caused by a significant reduction in ceruloplasmin， with the main clinical manifestations of retinopathy， diabetes， ataxia， and cognitive impairment， and genetic testing of the CPgene has a relatively high diagnostic value.
Ceruloplasmin

Ovarian cancer in pregnancy is a rare occurrence. Of all ovarian malignancies, <1% comprise immature teratomas. We present the case of a 24-year-old primigravid with an incidental finding of an ovarian new growth during a routine first-trimester ultrasound. The mass was suspicious for malignancy due to an ultrasound finding of a cystically enlarged 8.2 cm × 5.8 cm × 6.2 cm mass, with solid components and with minimal color flow on Doppler. There was an interval increase in the said mass during the second trimester, with an elevated alpha-fetoprotein (AFP) level. The patient underwent surgery at 24 weeks gestation. Histopathology revealed Immature Teratoma, FIGO Grade 3, stage IC1. She delivered to a live, term baby boy through cesarean delivery. Postpartum, she completed four cycles of chemotherapy using bleomycin, etoposide and cisplatin (BEP), and was advised surveillance with serum AFP every 3 months. Due to the limited number of cases of ovarian cancer in pregnancy reported, management is individualized. Dilemma in terms of the timing of surgery, neonatal and maternal outcomes, timing and mode of delivery, and control of tumor metastasis through chemotherapy were met, hence, a multidisciplinary team and patient decision is crucial to achieve successful and desirable outcomes for the mother and the fetus. This is the first case of immature teratoma in pregnancy reported in our institution and in a local setting.

OBJECTIVES

Sacrococcygeal teratomas (SCT) are the most common extragonadal tumors of early childhood. Their clinical characteristics and outcomes of patients with sacrococcygeal tumors who underwent excision in the Philippines has never been described, while numerous retrospective studies have been conducted in other countries.

This was a retrospective, descriptive study over a four-year period (December 2014 to November 2018). The study described the patients’ demographic data, manner of delivery, clinical presentation, prenatal diagnosis of tumor, Altman classification, and alpha fetoprotein levels. These information were obtained from the medical records of the patients. Additional data from the operative technique include the surgical approach, size of the mass, and gross involvement of adjacent structures and the final histopathologic results. Outcomes include the 30-day mortality and morbidity, and tumor recurrence.

A total of 29 patients were included in the study with 22 females (75.86%) and seven males (24.14%). Twentyfive out of the 29 (86.21%) had a sacral or gluteal mass at birth while other presenting factors include a palpable abdominal mass (1), constipation (1), difficulty in urination (1), and an elevated AFP in one postoperative patient. Even if 27 out of the 29 patients underwent a maternal ultrasound, only three patients (10.34%) had a correct ultrasound interpretation of sacrococcygeal teratoma. Age at presentation was problematic, with 12 presenting at greater than one year of age while 10 were brought for consultation at greater than one month old. Only seven presented at the neonatal period. CT scan was the most common imaging tool utilized (37.93%), followed by ultrasound (27.59%). AFP was elevated in ten patients (34.48%). Six of the patients with elevated AFP had mature teratoma, two had yolk sac tumor, one had fibroepithelial polyp, and one was post chemotherapy but had mature teratoma based on the final histopathology report. Fifteen out of the 29 patients had Altman type I tumors (51.72%), seven (24.14%) had type II tumors, six (20.69%) had type III tumors, and only one patient had type IV tumor. Sacral approach in the excision of the sacrococcygeal tumor was performed in 25 patients (86.21%). There was no reported perioperative mortality for patients who underwent surgery for SCT during the study period. Twelve out of the 29 had postop morbidities, three with surgical site infection and three with rectal or vaginal perforation. Five patients had tumor recurrence occurring from two months to three years postoperatively.

Early detection of sacrococcygeal teratomas even in the prenatal period is the norm in certain areas of the world, but in our country, prenatal detection is still a challenge. Even if the majority of the patients presented with a gluteal mass at birth, less than a third were brought to our tertiary government hospital in neonatal life. The sacral approach for SCT excision was employed for the great majority of our patients, but due to the advanced age at diagnosis and locally advanced disease, morbidities occurred in about a third of the patients. Therefore, early detection prenatally and early referral to a pediatric surgical center should be achievable goals for physicians dealing with these patients.

OBJECTIVE: To retrospectively analyze the results of second-trimester serological prenatal screening and explore the factors which may influence the false-positive rate (FPR). METHODS: From January 2013 to December 2022, false-positive samples with follow-up outcomes from 632,825 second-trimester serological prenatal screening samples tested at Sichuan Provincial Maternity and Child Health Care Hospital were selected as the study group, while true-negative samples were 1 : 1 matched as the control group by propensity-score matching (PSM). Univariate and binary logistic regression models were used to analyze the influencing factors. This study was approved by the Medical Ethic Committee of Sichuan Provincial Maternity and Child Health Care Hospital (Ethic No. 20240607-270). RESULTS: The study and control groups were each matched with 305,998 cases. Univariate analysis showed that sampling season, the difference between ultrasound and gestational weeks calculated by last menstrual period (LMP), monthly median multiple of the median (mMoM) of alpha-fetoprotein (AFP), and monthly mMoM of free β -human chorionic gonadotropin (free β -hCG) were significantly different between the two groups (P < 0.05). Binary logistic regression analysis showed that Winter (OR = 0.938; 95%CI: 0.893 ~ 0.985), monthly AFP mMoM ≥ 1.11 (OR = 0.846; 95%CI: 0.761 ~ 0.941), monthly free β -hCG mMoM ≥ 0.89 (OR = 0.827; 95%CI: 0.737 ~ 0.929) are protective factors for FPR increase, whilst Spring (OR = 1.124; 95%CI: 1.072 ~ 1.179), Summer (OR = 1.121; 95%CI: 1.062 ~ 1.183), the difference between ultrasound and gestational weeks calculated by LMP of 8 ~ 14 days (OR = 1.319; 95%CI: 1.241 ~ 1.402), < 14 days (OR = 1.689; 95%CI: 1.542 ~ 1.850), monthly AFP mMoM of 0.90 ~ 0.94 (OR = 1.088; 95%CI: 1.046 ~ 1.131), and monthly free β -hCG mMoM of 1.05 ~ 1.10 (OR = 1.046; 95%CI: 1.000 ~ 1.094), ≥ 1.11 (OR = 1.062; 95%CI: 1.002 ~ 1.126) are risk factors for FPR increase. CONCLUSION Sampling season, difference between ultrasound and gestational weeks by LMP, monthly AFP mMoM, and monthly free β -hCG mMoM are risk factors for FPR during serological prenatal screening. Screening laboratories should look for the cause of abnormal FPR through such factors and adjust them accordingly.
Humans ; Female ; Pregnancy ; Propensity Score ; Pregnancy Trimester, Second/blood* ; Retrospective Studies ; China ; False Positive Reactions ; Adult ; Prenatal Diagnosis/methods* ; alpha-Fetoproteins/analysis* ; Logistic Models ; Chorionic Gonadotropin, beta Subunit, Human/blood*

Fetuin-B (FETUB) is a glycoprotein mainly synthesized and secreted by the liver. It is involved in many physiological and pathological processes including glucose metabolism, inflammatory response, nonalcoholic fatty liver disease, myocardial infarction, tumor and so on. In recent years, FETUB has also been confirmed to play roles in the female reproductive system. FETUB may affect follicular development and play an important role in in vivo and in vitro fertilization. In addition, serum FETUB level is elevated significantly during pregnancy and labor. FETUB expression is changed in a variety of reproductive diseases (polycystic ovary syndrome, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy). In this review, we summarize FETUB related studies in female reproduction, and focus on the roles of FETUB in female reproductive physiology and pathology, in order to provide information for the pathogenesis of reproductive disorders.
Humans ; Female ; Pregnancy ; Polycystic Ovary Syndrome/physiopathology* ; Fetuin-B/physiology* ; Pregnancy Complications/metabolism* ; Animals ; Diabetes, Gestational/physiopathology* ; Cholestasis, Intrahepatic/metabolism* ; Reproduction/physiology* ; Ovarian Follicle/physiology*

Objective:b> To study using isotope-labeled relative and absolute quantitative proteomics methodologies to screen for salivary biological markers as a simple, non-invasive tool for identifying hepatitis B-related HCC at an early stage. Methods:b> Saliva samples were collected to extract salivary proteins. Isotope-labeled relative and absolute quantitative proteomics were used to analyze the differentially expressed proteins between the hepatocellular carcinoma (HCC) and non-HCC groups. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were used to verify differential proteins and identify markers in liver cancer tissues and saliva. Statistical analysis was used to analyze the diagnostic efficiency of salivary biomarkers. Results:b> 152 differentially expressed salivary proteins were screened out between the HCC and non-HCC groups. Western blot, immunohistochemistry, and enzyme-linked immunosorbent assays validated that the expressions of α-1-acid glycoprotein 1 (ORM1) and alpha-fetoprotein (AFP) were significantly increased in HCC (P < 0.05). There was a significant correlation between salivary AFP and serum AFP (P < 0.05). HCC was diagnosed when salivary α-1-acid glycoprotein 1 combined with AFP. The area under the receiver operating characteristic curve was 0.8726 (95% confidence interval: 0.8104 ~ 0.9347), the sensitivity was 78.3%, and the specificity was 88%. Conclusion:b> Salivary AFP and α-1-acid glycoprotein 1 can serve as potential biomarkers for hepatitis B-related hepatocellular carcinoma.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/pathology* ; alpha-Fetoproteins/metabolism* ; Biomarkers ; Hepatitis B ; ROC Curve ; Glycoproteins ; Biomarkers, Tumor

Objective:b> To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods:b> Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results:b> A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion:b> Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; alpha-Fetoproteins/metabolism* ; Endoplasmic Reticulum/metabolism* ; Golgi Apparatus/metabolism* ; Vesicular Transport Proteins ; Liver Cirrhosis/complications* ; Hepatitis B/complications* ; ROC Curve ; Hepatitis B virus/metabolism* ; Biomarkers, Tumor

Objective:b> To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods:b> A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results:b> The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion:b> CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.
Humans ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/pathology* ; Prognosis ; Carnosine ; alpha-Fetoproteins/metabolism* ; Biomarkers, Tumor/genetics* ; Liver Cirrhosis/diagnosis* ; ROC Curve

Objective:b> To investigate the clinical value of serum glypican-3 (GPC3) detection in predicting recurrence of primary hepatocellular carcinoma (HCC). Methods:b> Through univariate and multivariate logistic regression analysis, the patients pathologically diagnosed with HCC in our hospital from March 2019 to January 2021 were enrolled as the experimental group (n=113), and patients with follow-up time longer than 6 months were included in the prognosis group(n=64). At the same time,20 healthy individuals and 20 individuals with benign liver disease from the physical examination center were enrolled by simple random sampling as control group (n=40). The serum GPC3 and alpha-fetoprotein (AFP) levels were respectively detected by ELISA and chemiluminescence. Then, the study explored the influential factors of the recurrence in HCC patients and constructed the HCC-GPC3 recurrence predicting model by logistic regression. Results:b> In the research, the sensitivity of GPC3 for the diagnosis of HCC was 61.95% (70/113) and AFP was 52.21% (59/113), meanwhile, the specificity of GPC3 could reach 87.50% (35/40) and AFP was 90.00% (36/40),respectively; The serum GPC3 levels of HCC patients with progressive stage, tumor size≥3 cm, vascular cancer thrombosis and portal venous thromboembolism were significantly higher than that of HCC patients with early stage, tumor size<3 cm, vascular cancer thrombosis and portal venous thromboembolism (Z=2.677, 2.848, 2.995, 2.252, P<0.05), independent of different ages, presence or absence of ascites, peritoneal metastasis, cirrhosis, intrahepatic metastasis (Z=-1.535, 1.011, 0.963, 0.394, 1.510, P>0.05), respectively. Univariate analysis showed that there were no statistically significant differences between the recurrence group and the non-recurrence group in terms of different age, tumor size, presence or absence of vascular cancer thrombosis, ascites, peritoneal metastasis, cirrhosis and AFP levels (χ²=2.012, 0.119, 2.363, 1.041, 0.318, 0.360, Z=0.748, P>0.05); The ratio of those with the progressive stage, portal venous thromboembolism and intrahepatic metastasis and GPC3 levels were all higher in the recurrence group than in the non-recurrence group (χ²=4.338, 11.90, 4.338, Z=2.805, P<0.05).Including the above risk factors in the logistic regression model, the logistic regression analysis showed that the stage, the presence of portal venous thromboembolism,intrahepatic metastasis and GPC3 levels were correlated with the prognosis recurrence of HCC patients (Wald χ² =b>4.421, 5.681, 4.995, 4.319, P<0.05), and the HCC-GPC3 recurrence model was obtained as: OcScore=-2.858+1.563×[stage]+1.664×[intrahepatic metastasis]+2.942×[ portal venous thromboembolism]+0.776×[GPC3]. According to the receiver operating characteristic curve(ROC), the area under the curve(AUC)of the HCC-GPC3 prognostic model was 0.862, which was better than that of GPC3 alone (AUC=0.704). The cut-off value of model SCORE was 0.699 (the cut-off value of GPC3 was 0.257 mg/L), furthermore, the total sensitivity and specificity of model were 83.3% and 82.4%, which were better than those of GPC3(60.0% and 79.4%).Kaplan-Meier showed that the median PFS was significantly shorter in HCC patients with high GPC3 levels (≥0.257 mg/L) and high values of the model SCORE (≥0.700) (χ²=12.73, 28.16, P<0.05). Conclusion:b> Besides diagnosing of HCC, GPC3 can may be an independent risk indicator for the recurrence of HCC and can more efficiently predicting the recurrence of HCC patients when combined with the stage, the presence or absence of intrahepatic metastasis and portal venous thromboembolism.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/diagnosis* ; alpha-Fetoproteins/analysis* ; Biomarkers, Tumor ; Glypicans ; Ascites ; Venous Thromboembolism ; Peritoneal Neoplasms ; Liver Cirrhosis

INTRODUCTION: The diagnosis of Wilson disease (WD) is plagued by biochemical and clinical uncertainties. Thus, calculated parameters have been proposed. This study aimed to: (a) compare the diagnostic values of non-caeruloplasmin copper (NCC), NCC percentage (NCC%), copper-caeruloplasmin ratio (CCR) and adjusted copper in WD; and (b) derive and evaluate a discriminant function in diagnosing WD. METHODS: A total of 213 subjects across all ages who were investigated for WD were recruited. WD was confirmed in 55 patients, and the rest were WD free. Based on serum copper and caeruloplasmin values, NCC, NCC%, CCR and adjusted copper were calculated for each subject. A function was derived using discriminant analysis, and the cut-off value was determined through receiver operating characteristic analysis. Classification accuracy was found by cross-tabulation. RESULTS: Caeruloplasmin, total copper, NCC, NCC%, CCR, adjusted copper and discriminant function were significantly lower in WD compared to non-WD. Discriminant function showed the best diagnostic specificity (99.4%), sensitivity (98.2%) and classification accuracy (99.1%). Caeruloplasmin levels <0.14 g/L showed higher accuracy than the recommended 0.20 g/L cut-off value (97.7% vs. 87.8%). Similarly, molar NCC below the European cut-off of 1.6 umol/L showed higher accuracy than the American cut-off of 3.9 umol/L (80.3% vs. 59.6%) (P < 0.001). NCC%, mass NCC, CCR and adjusted copper showed poorer performances. CONCLUSION Discriminant function differentiates WD from non-WD with excellent specificity, sensitivity and accuracy. Performance of serum caeruloplasmin <0.14 g/L was better than that of <0.20 g/L. NCC, NCC%, CCR and adjusted copper are not helpful in diagnosing WD.
Humans ; Hepatolenticular Degeneration/diagnosis* ; Copper/analysis* ; Ceruloplasmin/metabolism* ; Repressor Proteins