Clinicopathological features of hepatic fibrinogen storage disease in children / 中华病理学杂志

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.

Postoperative clinicopathological features of the patients with micropapillary lung adenocarcinoma / 医学研究生学报

Objective　Studies are rarely reported on the factors influencing prognosis of surgically resected lung adenocarcinoma with a micropapillary pattern (LAC-MPP). This study aimed to explore the clinicopathological characteristics and risk factors of surgically resected LAC-MPP. Methods　We retrospectively analyzed 384 cases of LAC treated in Henan Cancer Hospital between June 2015 and December 2017, which were classified into an MPP group (n = 82) and a non-MPP control group (n = 302) according to the results of postoperative pathology. We determined the expression of the fusion protein anaplastic lymphoma kinase (ALK), analyzed its association with the clinicopathological features of LAC-MPP, and explored the risk factors of postoperative MPP. Results　Compared with the non-MPP group, the LAC-MPP patients showed a significantly higher expression of ALK (0.03% vs 12.20%, P < 0.05), rate of bronchial invasion (30.80% vs 48.78%, P < 0.05) and vascular tumor thrombus (0.99% vs 25.61%, P < 0.05), but a lower mutation rate of the epidermal growth factor receptor (EGFR) (64.24% vs 51.22%, P < 0.05). Multivariate logistic regression analysis revealed that the expression of ALK, vascular tumor thrombus, and age were significantly associated with the risk of postoperative MPP. Conclusion　There is a high incidence rate of ALK expression in LAC-MPP patients after operation, which may provide some new ideas for the clinical treatment of the disease. Special attention should be paid to the expression of the ALK fusion protein and vascular tumor thrombus, and age in patients with LAC-MPP after operation.

Silymarin protects against acrylamide-induced neurotoxicity via Nrf2 signalling in PC12 cells.

Silymarin (SM) is a well-known antioxidant, anti-inflammatory and anti-cancer compound extracted from the milk thistle. Here, we investigated the protective effect of SM against acrylamide (AA)-induced neurotoxicity, mainly caused by oxidative stress, via activation of the nuclear transcription factor E2-related factor 2 (Nrf2) signalling pathway in PC12 cells. The MTT reduction assay was used to measure cell viability in various drug-treated groups and demonstrated that SM could increase cell viability in AA-treated PC12 cells. We then measured the reactive oxygen species (ROS) levels by the peroxide-sensitive fluorescent probe DCFH-DA and intracellular glutathione (GSH) and malondialdehyde (MDA) levels by absorption spectrophotometry. Our data revealed that SM could reduce ROS and MDA levels and increase GSH levels in AA-induced PC12 cells. To identify a potential mechanism for SM-induced protection, we measured the mRNA and protein expression levels of Nrf2 and its downstream target antioxidants glutathione peroxidase (Gpx), glutamate cysteine ligase catalytic subunit (GCLC) and glutamate cysteine ligase modifier subunit (GCLM) by quantitative real-time PCR and Western blot, respectively. The results suggested that SM could activate Nrf2 signalling and increase the expression of Nrf2, Gpx, GCLC and GCLM in AA-treated PC12 cells. In conclusion, SM can effectively alleviate AA-induced neurotoxicity in PC12 cells.

Key role of peptidoglycan on acrylamide binding by lactic acid bacteria.

The primary purpose of this study was to analyze the ability of four peptidoglycan (PGN) from different lactic acid bacteria to bind acrylamide (AA) and to identify the binding mechanism. In this study, to clarify the possible binding interactions among AA and components of PGN, chemical components, surface structure, amino acids component, and functional groups of peptidoglycans were studied. It was found that PGN from Lactobacillus plantarum 1.0065 had the highest ability to bind AA with 87%. Furthermore, a significant positive relation was found between the carbohydrate content of PGN and percentage of bind AA, and the content of four specific amino acids of PGN and AA binding ability were also positive correlated. Thereinto, alanine of PGN had a significant impact on AA binding among four amino acids. Additionally, the C-O (carboxyl, polysaccharides, and arene), C=O amide, and N-H amines groups of PGN were involved in AA binding.