👤 Qiang Jie

To analyse the effects of noise exposure in emergency resuscitation rooms (ERRs) on cognitive function and hyperalgesia in patients with trauma. Clinical data from 110 patients with trauma who were treated in the ERR of Suizhou Central Hospital between June 2022 and July 2023 were retrospectively analysed. Participants were divided into the following two groups on the basis of real-time noise monitoring: the high-noise-exposure (n = 85) and low-noise-exposure (n = 25) groups. Neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), homocysteine (Hcy), the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA) were used to measure cognitive performance. Mechanical pain threshold and serum nerve growth factor (NGF), substance P (SP), calcitonin gene-related peptide (CGRP) and 5-hydroxytryptamine (5-HT) levels were applied to assess hyperalgesia. Pearson correlation was employed to investigate the connections between noise levels and outcome factors. The high-noise-exposure group demonstrated significantly lower MMSE scores, MoCA scores and serum BDNF levels but higher serum NSE and Hcy levels compared with the low-noise-exposure group (P < 0.05). Additionally, compared with the low-noise-exposure group, the high-noise-exposure group exhibited larger mechanical hyperalgesia areas around incisions and on the volar forearm, as well as elevated serum CGRP, NGF and SP levels, while showing reduced mechanical pain thresholds and lower serum 5-HT levels (P < 0.05). Pearson analysis revealed that noise exposure values had negative correlations with mechanical pain threshold, MMSE and MoCA scores and serum BDNF and 5-HT levels (r < 0, P < 0.05) but positive correlations with mechanical hyperalgesia area and serum CGRP, NSE, Hcy, NGF and SP levels (r > 0, P < 0.05). High noise exposure in ERRs may be associated with cognitive dysfunction and hyperalgesia in patients with trauma. Clinical management should recognise and control noise levels in these settings. Show less

Colorectal cancer (CRC) is the leading cause of cancer deaths worldwide, wherein distant metastasis is the main reason for death. The non-psychoactive phytocannabinoid cannabidiol (CBD) effectively induces the apoptosis of CRC cells. We investigated the role of CBD in the migration and metastasis of CRC cells. CBD significantly inhibited proliferation, migration, and invasion of colon cancer cells in a dose- or time-dependent manner. CBD could also inhibit epithelial-mesenchymal transition (EMT) by upregulating epithelial markers such as E-cadherin and downregulating mesenchymal markers such as N-cadherin, Snail, Vimentin, and HIF-1α. CBD could suppress the activation of the Wnt/β-catenin signaling pathway, inhibit the expression of β-catenin target genes such as APC and CK1, and increase the expression of Axin1. Compared to the control group, the volume and weight of orthotopic xenograft tumors significantly decreased after the CBD treatment. The results demonstrated that CBD inhibits invasion and metastasis in CRC cells. This was the first study elucidating the underlying molecular mechanism of CBD in inhibiting EMT and metastasis via the Wnt/β-catenin signaling pathway in CRC cells. The molecular mechanism by which CBD inhibits EMT and metastasis of CRC cells was shown to be through the Wnt/β-catenin signaling pathway for the first time. Show less

It has been reported that LXR agonist can inhibit Aβ generation and alleviate Aβ-induced various adverse reactions in vivo and in vitro experiments, but the mechanisms have not been clarified. The study aimed to observe the effect of LXR agonist TO901317 on the cognitive function of AD transgenic mice fed with cholesterol-rich diet (CRD), and to explore the possible mechanism. Methods: 32 male 6-month-old double transgenic AD mice were enrolled and randomly divided into 4 groups: control (normal diet) group, CRD treatment group, TO901317 treatment group and GSK2033 treatment group. After 3 month, Morris water maze was for the changes of spatial exploration and memory ability; ELISA was for detecting the production of Aβ42 in the brain; the concentration of total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) in serum were detected by cholesterol enzyme colorimetry; Finally, the expression of LXR-β, RXR-α, ABCA1, caveolin-1, BACE1 and APP at protein level in the brains was measured by Western blotting. Compared with the control group, the learning, memory ability and spatial exploration ability of the mice were more significantly serious in the CRD group (P<0.05); The contents of TC and LDL in the serum and the production of Aβ42 in the brains were significantly increased (P<0.05), but HDL was remarkably decreased (P<0.05); The protein levels of LXR-β, RXR-α and ABCA1 were also significantly decreased (P<0.05); The expression of caveolin-1, APP and BACE1 were evidently increased (P<0.05). However, after treatment with TO901317, the impaired learning and memory and spatial exploration ability of the mice were significantly improved (P<0.05); The contents of TC and LDL in serum and the production of Aβ42 in the brains were significantly decreased (P<0.05), but HLD was increased (P<0.05); The protein levels of LXR-β, RXR-α, ABCA1were all significantly increased (P<0.05), while, the expression of caveolin-1, APP and BACE1 were all significantly decreased (P<0.05). All the changes were reversed by GSK2033 (P<0.05). TO901317 attenuated the more serious impairment of spatial exploration, learning and memory in transgenic AD mice induced by CRD, and the mechanism may be that TO901317 could activate the LXR-β/RXR-α/ABCA1 transmembrane transport system, promote the cholesterol efflux, and decreased caveolin-1, APP and BACE1, further reduce Aβ42 in the brains. Show less

Axin1 is a key regulator of canonical Wnt signaling pathway. Roles of Axin1 in skeletal development and in disease occurrence have not been fully defined. Here, we report that Axin1 is essential for lower limb development. Specific deletion of Show less

Metastasis is the dominant cause of cancer-related mortality. Metastasis-associated with colon cancer protein 1 (MACC1) has been proven to play a critical role in cancer metastasis. However, the prometastatic role of MACC1 in regulating the pancreatic cancer (PC) metastatic phenotype remains elusive. Here, we report that MACC1 is highly expressed in The Cancer Genome Atlas (TCGA) and tissue microarray (TMA) and identified as a good indicator for poor prognosis. Overexpression or knockdown of MACC1 in PC cells correspondingly promoted or inhibited pancreatic cancer cell migration and invasion in a MET proto-oncogene receptor tyrosine kinase (MET)-independent manner. Notably, knockdown of MACC1 in PC cells markedly decreased the liver metastatic lesions in a liver metastasis model. Mechanistically, MACC1 binds to the epithelial-mesenchymal transition (EMT) regulator snail family transcriptional repressor 1 (SNAI1) to drive EMT via upregulating the transcriptional activity of SNAI1, leading to the transactivation of fibronectin 1 (FN1) and the trans-repression of cadherin 1 (CDH1). Collectively, our results unveil a new mechanism by which MACC1 drives pancreatic cancer cell metastasis and suggest that the MACC1-SNAI1 complex-mediated mesenchymal transition may be a therapeutic target in pancreatic cancer. Show less

To explore the genetic basis and phenotypic correlation with disease severity in a large cohort of Chinese patients with hypertrophic cardiomyopathy (HCM). A total of 179 unrelated Chinese HCM patients admitted to our department from 2002 to 2011 were enrolled in this study. Direct gene sequencing of β-myosin heavy chain (MYH7), myosin binding protein-C ( MYBPC3), and cardiac troponin T (TNNT2) were performed and clinical data were obtained in these patients. A total of 34 mutations were identified in 40 patients (22.3%), 79.4% (27/34) mutations occurred only once and a possible hot spot, A26 in MYH7, was found. Distribution of mutations was 52.9% (18/34) (MYBPC3), 35.3% (12/34) ( MYH7) and 11.8% (4/34) (TNNT2) respectively. Double mutations were identified in 2.2% (4/179) patients. Genotype-positive patients were associated with an earlier symptom onset, severer left ventricular hypertrophy, a higher incidence of syncope, and were more likely to have positive family history of HCM or sudden cardiac death (SCD) , and were more likely to progress into heart failure (24.2% vs. 5.0%, P = 0.002) and at a higher risk of SCD (9.1% vs. 0, P = 0.009) during the 6.5-year follow-up. No statistical difference in any clinical parameters and outcomes was found between patients carrying MYBPC3 and MYH7 mutations. Double mutations were associated with malignant clinical progression in this cohort. Different phenotype severity could be seen in HCM patients with same genotype (e. g. MYH7-1736T, TNNT2-R92W). MYBPC3 is the most predominant gene mutation in this HCM cohort. The presence of a sarcomere mutation in patients with HCM is associated with poor clinical outcome, although no specific genes or mutations can exactly predict the severity of clinical phenotypes. Show less

Multiple osteochondromas (MO) is an autosomal-dominant disorder and mutations in EXT1 and EXT2 account up to 78% of the cases studied, including missense, nonsense, frameshift, and splice-site mutations. EXT1 and EXT2 encode glycosyltransferases required for the synthesis of heparan sulfate (HS) chains. The molecular pathogenesis underlying these mutations is still largely unknown. A heterozygous c.1173 + 1G > T (EXT2) mutation was identified in a three-generation 34-member MO family and is present in all 19 affected members. The consequence of this mutation is exon 7 being spliced out, and the result is a shift in the codon-reading frame from position 360 (R360) of the amino acid sequence leading to a premature termination codon, and the mutant mRNA is degraded to an undetectable level. Interestingly, HS glycosaminoglycans were also undetectable in the cartilage cap of the tumors by immunostaining. Full penetrance of this mutation in all affected members ranging from 5 to 70 years of age suggests this primary defect in EXT2 mRNA level, in conjunction with other cellular changes such as enhanced heparanase expression, can produce profound effect on the synthesis of HS chains in cartilage, the consequence of which impacts on the regulation of chondrocyte proliferation and differentiation. Show less