ABSTRACT
Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.
ABSTRACT
Objective:To explore the effect of sports training guidance based on Internet platform on the limb function and quality of life in home rehabilitation of stroke hemiplegic patients.Methods:Eighty patients with stroke and hemiplegia admitted to Beijing Rehabilitation Hospital Affiliated to Capital Medical University from June 2018 to December 2019 were selected and divided into observation group and control group with 40 cases in each group by random digits table method. The control group was given routine rehabilitation training. In addition to the regular rehabilitation training, the observation group was supplemented with home rehabilitation based on the WeChat platform for modified constraint-induced movement therapy. The limb motor function Fugl-Meyer Assessment (FMA) score, Upper Extremity Function Test (UEFT) score, Stroke-Specific Quality of Life scale (SS-QOL) score before and after intervention, and patients′ satisfaction and cares′ satisfaction score were compared between the two groups.Results:There was no significant difference in the score of FMA, UEFT, SS-QOL before intervention between the two groups( P>0.05). After discharge, the FMA score, UEFT score and physical function, physiological function, mental health, social function of SS-QOL score were (68.87±6.64),(72.38±7.33), (35.28±4.13), (36.55±4.23), (37.22±3.84), (38.23±3.44) points in the observation group and (55.25±6.20), (61.24±6.47), (28.72±4.56), (30.85±5.30), (31.28±4.63), (31.02±5.16) points in the control group, and the differences were statistically significant between the two groups( t values were 5.316-9.482, P<0.01). During the nursing period, the patients′ satisfaction and cares′ satisfaction score were 92.50%(37/40), 87.50%(35/40) in the observation group and 72.50%(29/40), 67.50%(27/40) in the control group, and the differences were statistically significant between the two groups( χ 2 values were 5.541, 4.588, P<0.05). Conclusions:The home rehabilitation based on the Internet platform for modified constraint-induced movement therapy helps to promote the recovery of limb motor function in stroke hemiplegic patients, improve the nursing satisfaction of patients and their families, and has a positive effect on improving the quality of life of patients.
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OBJECTIVE:To study the effect of EGCG-Zn chelated by epigallocatechin gallate (EGCG) and Zn ion on learn-ing,memory and antioxidant abilities in vascular dementia(VD)rats. METHODS:Rats were randomly divided into sham group, model group,zinc gluconate group (positive control,70 mg/kg),EGCG group (5 mg/kg),and EGCG-Zn low-dose,mid-dle-dose,high-dose groups (2,5,10 mg/kg),10 in each group. The VD models were induced by middle cerebral artery occlu-sion. The rats were intragastrically given relevant medicines after 7 d of modeling,once a day,for 28 d. Morris water maze were used to evaluate learning and memory abilities of rats. Spectrophotometric method was adopted to detect the superoxide dismutase (SOD),catalase(CAT),glutathione peroxidase(GSH-Px)activities and malondialdehyde(MDA)content in brain tissue of rats. RESULTS:Compared with sham group,escape latency was extended in model group,percentage of platform quadrant swimming distance(dP/dT)was reduced(P<0.01);SOD,CAT,GSH-Px activities in brain tissue were reduced,and MDA content was in-creased (P<0.01). Compared with model group,escape latency on 4th d of recording was obviously shortened in EGCG group and EGCG-Zn dose groups,dP/dT was obviously increased and dose-depended(P<0.05 or P<0.01);SOD,CAT,GSH-Px activi-ties in brain tissue were increased,MDA content was decreased(P<0.05 or P<0.01)and dose-depended. Compared with EGCG group and zinc gluconate group,escape latency was obviously shortened in EGCG-Zn dose groups,dP/dT was increased;SOD, CAT,GSH-Px activities in brain tissue were increased,MDA content was decreased;and the effects in high-dose,medium-dose groups were more obvious(P<0.05 or P<0.01). CONCLUSIONS:EGCG-Zn can improve the learning,memory and antioxidant abilities in VD rats,and the effect is superior to EGCG.
ABSTRACT
Background The objective of this study was to assess the clinical safety and efficacy of vena cava filter (VCF) placement,with particular emphasis on the incidence and risk factors of inferior vena cava thrombosis (VCT) after VCF placement.Methods Clinical data of patients with venous thromboembolism (VTE),with or without placement of VCF,were analyzed in a retrospective single-center audit of medical records from January 2005 to June 2009.The collected data included demographics,procedural details,filter type,indications,and complications.Results A total of 168 cases of VTE (82 with VCF; 86 without VCF) were examined.Over a median follow-up of 24.2months,VCT occurred in 18 of 82 patients with VCFs (11 males,7 females,mean age 55.4 years).In 86 patients without VCFs,VCT occurred in only 6 individuals (4 males,2 females) during the study period.VCT was observed more frequently in patients fitted with VCFs than in those without VCFs (22% vs.7.0%).Conclusions The incidence of VCT in patients with VTE after VCF implantation was 22% approximately.Anticoagulation therapy should be continued for all patients with VCF placement,unless there is a specific contraindication.Almost all instances of VCT in patients with VCF implants in our study occurred after stopping anticoagulation treetment.The use of VCFs is increasing,and more trials are needed to confirm their benefit and accurately assess their safety.