A preliminary discussion on carnosine dipeptidase 1 as a potential novel biomarker for the diagnostic and prognostic evaluation of hepatocellular carcinoma / 中华肝脏病杂志

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: 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: 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: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.

Analysis of clinical characteristics and risk factors of hepatic fibrosis in children with chronic hepatitis B combined with metabolic-related fatty liver disease / 中华肝脏病杂志

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI (P < 0.001), triglyceride (TG, P < 0.001), total cholesterol (P = 0.016) and the incidence of metabolic syndrome (P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups (P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI (OR = 1.258, 95% CI: 1.145 ~ 1.381, P = 0.001) and TG (OR = 12.334, 95% CI: 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD (OR = 4.104, 95% CI: 1.703 ~ 9.889, P = 0.002), liver inflammation (OR = 3.557, 95% CI: 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase (OR = 1.019, 95% CI: 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.

Significance of histological assessment in drug-induced liver injury / 中华肝脏病杂志

Liver histological assessment is of great clinical significance for the diagnosis, classification, and prognosis prediction of drug-induced liver injury (DILI). Liver histological evaluation can effectively supplement RUCAM. The clinical phenotypes of DILI are complex and diverse, including acute, chronic and severe hepatic injury. DILI has multiple insult-targets, including hepatocytes, cholangiocytes, and vascular endothelial cells and others. The pathological damage patterns are similar to many types of non-DILI liver diseases, therefore making differential diagnosis difficult. New anti-tumor drugs such as immune checkpoints inhibitors and targeted therapy are widely used in clinical antineoplastic practice, thus the growing incidence of related liver injury occurs. Liver histological examination can effectively assess the pathological phenotypes and severity of DILI, so as to guide treatment. In uncommon conditions such as special types of DILI (such as hepatic vascular disease), DILI with other competitive etiology overlapping, chronic DILI, and DILI induced liver failure, liver histological assessment can provide strong support for identifying the cause, rational treatment, and prognosis. Currently, the histological evaluation system for drug-induced liver injury seems to be a lack of consensus, and the diagnosis of DILI is short of highly specific and sensitive serological markers. All in all, liver histological assessment plays a crucial role in the diagnosis and differential diagnosis of DILI.

Impacts of passive smoking on learning and memory ability of mouse offsprings and intervention by antioxidants / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To determine the impact of passive smoking and the protective effect of antioxidants such as vitamin E and quercetin on learning and memory ability of mouse offsprings.</p><p><b>METHODS</b>A passive smoking model of pregnant mice was established. Learning and memory ability was evaluated by the water maze test and long term potentiation (LTP). Nitric oxide (NO), content, nitric oxide synthase (NOS), acetylcholinesteras (Ache) activity in brain, vitamin E concentration, and reactive oxygen species (ROS) in serum were determined. The latency period (the time during which the mice swim from the starting position to the ending position) and errors (the number of mice entering the blind end) in control and antioxidant intervention groups were compared with those in the smoke exposure group after 6 days.</p><p><b>RESULTS</b>The latency period as well as errors in the air, control diet, tobacco smoke (TS), and vitamin E diet groups were decreased significantly as compared with the TS and control diet groups (P<0.05). LTP was restrained in the TS and control diet groups. LTP in all the antioxidant diet groups was significantly increased compared with the TS and control diet groups. In addition, NOS and acetylcholinesteras (Ache) activitiy was significantly higher in the TS and control diet groups than in the air and control diet group. NO content was not significantly different among the different groups, and significantly lower in the TS and vitamin E diet groups than in the TS group, control diet group, quercetin diet group, and mixture diet group (P<0.05). Vitamin E concentration and ROS activity in serum were correlated with the outcome of water maze and LTP.</p><p><b>CONCLUSION</b>Passive smoking reduces LTP formation by disturbing the hippocampus function of mice, by decreasing NOS and Ache activity and increasing NO content. Antioxidants (especially vitamin E) partially improve the learning and memory ability of offsprings whose mothers are exposed to tobacco smoke during pregnancy.</p>

Significance of detection of serum sialic acid and Epstein-Barr virus VCA-IgA in diagnosis and monitoring radiotherapy effectiveness in nasopharyngeal carcinoma patients / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To understand the significance of detection of serum sialic acid (SA) and Epstein-Barr virus VCA-IgA (EBV-CA-IgA) in diagnosis and monitoring radiotherapy effectiveness of nasopharyngeal carcinoma (NPC) patients.</p><p><b>METHODS</b>Serum SA and EBV-CA-IgA were detected in 65 cases with NPC before radiotherapy and one months after radiotherapy and 21 cases one year after radiotherapy for NPC with local recurrence and/or distant metastasis. Healthy persons and patients with benign lesions of head and neck were also enrolled as control group.</p><p><b>RESULTS</b>SA and EBV-CA-IgA of NPC patients before radiotherapy were significantly higher than those in control group (P<0.01). The sensitivity of combination of SA and EBV-CA-IgA (96.9%) was higher than those determined alone (P<0.05). The SA level of NPC patients after radiotherapy and without recurrence after radiotherapy was reduced significantly compared to the NPC patients before radiotherapy (P<0.01). The SA level of NPC patients with recurrence was significantly higher than that in NPC patients without recurrence (P<0.01), whereas the positive rate of EBV-CA-IgA changed little.</p><p><b>CONCLUSION</b>Dynamic detection of serum SA may be a valuable technique for diagnosis and monitoring radiotherapy effectiveness in NPC patients. The combined determination of the two indexes can raise the positive rate of patients with NPC.</p>

Expression of thymidine phosphorylase in cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the thymidine phosphorylase (TP) expression in different types of cancer and its correlation with tumor microvessel density (MVD).</p><p><b>METHODS</b>The expression of TP and MVD was detected by immunohistochemistry method. In a series of 251 cancer patients there were 48 patients with gastric cancer, 53 with colorectal cancer, 47 with breast cancer, 56 with cervical cancer, 47 with lung cancer. Normal gastric (n = 25), colorectal (n = 25), cervical (n = 17) and lung (n = 25) tissues around the cancer were also examined.</p><p><b>RESULTS</b>The TP expression rate was 64.6% in gastric cancer, 67.9% in colorectal cancer, 80.9% in breast cancer, 82.1% in cervical cancer, and 63.8% in lung cancer, which was significantly higher than that in normal tissues (P = 0.0000). TP expression was positively correlated with MVD in gastric, colorectal, breast, and cervical cancers. The correlation was not statistically significant in lung cancer.</p><p><b>CONCLUSION</b>This study indicates that TP overexpression in cancer may be associated with tumor angiogenesis.</p>