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1.
Int J Dev Neurosci ; 83(3): 257-266, 2023 May.
Article in English | MEDLINE | ID: mdl-36808642

ABSTRACT

PURPOSE: To explore the application value of voxel-based morphometric (VBM) in prenatal diagnosis of microcephaly. METHODS: A retrospective study of magnetic resonance imaging of fetuses with microcephaly was performed using a single-shot fast spin echo sequence; semiautomatic segmentation of grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF); calculation of their volumes; and VBM analysis of their GM. Two independent samples t-test was used to statistically analyse the fetal GM volume in the microcephaly and normal control groups. Total intracranial volume (TIV), GM volume, WM volume, and CSF volume were linearly regressed against gestational age and compared between the two groups. RESULTS: In the fetus with microcephaly, GM volume of frontal lobe, temporal lobe, cuneus, anterior central gyrus, and posterior central gyrus decreased significantly (P < 0.001, corrected by family-wise error at mass level). The GM volume of microcephaly was significantly lower than that of the control group (except for 28 weeks of gestation) (P < 0.05). TIV, GM volume, WM volume, and CSF volume were all positively correlated with gestational age, and the curves in the microcephaly group were all lower than those in the control group. CONCLUSION: Compared with the normal control group, the GM volume of microcephaly fetuses decreased, and there were significant differences in many brain regions through VBM analysis.


Subject(s)
Microcephaly , Nervous System Malformations , Humans , Pregnancy , Female , Microcephaly/diagnostic imaging , Retrospective Studies , Brain/diagnostic imaging , Brain/pathology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Magnetic Resonance Imaging/methods , Fetus/diagnostic imaging
2.
Oncogene ; 41(12): 1809-1820, 2022 03.
Article in English | MEDLINE | ID: mdl-35140332

ABSTRACT

Molecular reprogramming of stromal microarchitecture by tumour-derived extracellular vesicles (EVs) is proposed to favour pre-metastatic niche formation. We elucidated the role of extravesicular tissue inhibitor of matrix metalloproteinase-1 (TIMP1EV) in pro-invasive extracellular matrix (ECM) remodelling of the liver microenvironment to aid tumour progression in colorectal cancer (CRC). Immunohistochemistry analysis revealed a high expression of stromal TIMP1 in the invasion front that was associated with poor progression-free survival in patients with colorectal liver metastases. Molecular analysis identified TIMP1EV enrichment in CRC-EVs as a major factor in the induction of TIMP1 upregulation in recipient fibroblasts. Mechanistically, we proved that EV-mediated TIMP1 upregulation in recipient fibroblasts induced ECM remodelling. This effect was recapitulated by human serum-derived EVs providing strong evidence that CRC release active EVs into the blood circulation of patients for the horizontal transfer of malignant traits to recipient cells. Moreover, EV-associated TIMP1 binds to HSP90AA, a heat-shock protein, and the inhibition of HSP90AA on human-derived serum EVs attenuates TIMP1EV-mediated ECM remodelling, rendering EV-associated TIMP1 a potential therapeutic target. Eventually, in accordance with REMARK guidelines, we demonstrated in three independent cohorts that EV-bound TIMP1 is a robust circulating biomarker for a non-invasive, preoperative risk stratification in patients with colorectal liver metastases.


Subject(s)
Colorectal Neoplasms , Extracellular Vesicles , Liver Neoplasms , Colorectal Neoplasms/pathology , Extracellular Vesicles/metabolism , Humans , Liver Neoplasms/metabolism , Prognosis , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tumor Microenvironment
3.
J Thorac Dis ; 9(7): 1891-1902, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28839987

ABSTRACT

BACKGROUND: The incidence of venous thromboembolism (VTE) is about 4-10% in lung cancer patients. Huisheng oral solution (HSOS) has been previously demonstrated to inhibit carageenan induced acute thrombosis in rats, reduce the incidence of thrombosis in the lungs and mesentery of tumor-bearing mice and inhibit tumor cell metastasis. The purpose of this study was to assess the anticoagulant effect of HSOS in lung cancer patients in the perioperative period. METHODS: This study was a multicenter, randomized, single-blind, blank-controlled clinical trial. A total of patients at five hospitals in Hebei Province, China were included. The patients were randomly divided into study group or control group according to random number table. The primary outcome was the blood test indices in both groups. The study group was given oral HSOS (20 mL, bid) from admission until 24 h before surgery. If no active bleeding was observed, the patients were given oral HSOS (20 mL, tid) from 24 h to 24 d postoperatively. The patients in the study group did not receive any other anticoagulation therapy during the study period and the control group only underwent surgery. The study protocol was approved by the local ethics committee of principal investigator hospital. Blood samples were taken at admission (before therapy), 24 h, 72 h, 10 d (before discharge) and 24 d (first visit after discharge) after surgery. Routine blood tests [red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin (HGB), and platelet (PLT) count] and coagulation function test [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and plasma D-dimer] were performed. The changes in outcome measures over time were analyzed by repeated measures analysis of variance to compare the differences between groups and between different time points and assess the impact of tumor stage and mode of surgery on them. All tests were two-tailed, and P values <0.05 were considered statistically significant. RESULTS: The results differed between different tumor stage groups. In stage III-IV group, there was no significant difference in various indices between the study group and control group. In stage I-II group, there was significant difference in hemoglobin (P=0.004), platelet count (P=0.007), fibrinogen (P=0.046), and plasma D-dimer (24 d: P=0.032) between two groups. Fibrinogen reach the peak 72 h after surgery, and other indices reach the peak 7-10 d postoperatively and declined one month after surgery, and the decline tendency was different between two groups. In addition, no adverse drug reaction was observed in both the study group and control group. CONCLUSIONS: HSOS (20 mL, tid) is of good safety profile and does not increase the risk of bleeding. With its unique characteristic of convenience for being taken, HSOS (20 mL, tid) could be a proper treatment for lung cancer patients in the perioperative period.

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