Objective To investigate the effect and potential molecular mechanism of PTGS2 on the prognosis of colon cancer patients.Methods The transcriptomic and proteomic data of pan-cancer were collected from TCGA,HPA,UALCAN and other databases,and the expression pattern and prognostic value of PTGS2 were analyzed by combining the clinical data such as staging,histology,survival time and so on.Based on GSEA,the biological functions which were significantly activated in patients with high expression of PTGS2 were iden-tified and the colon cancer cell line SW480 was used as an example for in vitro validation.PTGS2 over-expressing cell strains were constructed,and the effect on cell proliferation was determined by CCK8 method.Different concen-trations of H2O2 were used to form gradient oxidative stress,and the changes in cell antioxidant capacity were detected.The regulatory mechanism was preliminarily verified by Western blot.Results The transcription and expression of PTGS2 were found to be significantly up-regulated in colon cancer patients(P<0.05),and the increased expression of PTGS2 was associated with an increased mortality risk(P<0.05).Data analysis and in vitro experiments showed that over-expression of PTGS2 may promote the proliferation of colon cancer cells by activating the mTOR pathway.The antioxidant effect of cells was regulated by up-regulating oxidative stress regulatory proteins SOD2 and NRF2.Conclusions PTGS2 is a potential risk factor for colon cancer and its over-expression promotes cell proliferation,enhances cell antioxidant effect and is associated with poor progno-sis of colon cancer patients.

Humans ; COVID-19 ; SARS-CoV-2

Objective:To explore the potential of thrombus-targeted nanoprobes for ultrasound/near-infrared bimodal imaging and their synergistic therapeutic effects on thrombosis in vitro.Methods:Nanoprobes loaded with arginine-glycine-aspartate peptide (RGD), perfluoropentane (PFP) and indocyanine green (ICG) were prepared by ultrasonic vibration and carbodiimide method with mesoporous silica nanoparticle (MSN) as the carrier. The probe morphology was observed by scanning and transmission electron microscopy. The loading of RGD and ICG was detected by Bicinchoninic Acid Assay (BCA) and UV-Visible-NIR spectroscopy respectively. The imaging performance and photothermal response of the nanoprobe under near infrared light (NIR) irradiation were studied in vitro. Its biological safety was tested by cytotoxicity test and hemolysis test. The phase transformation was studied under ultrasound and NIR irradiation. The nanoprobe was incubated with fresh arterial thrombus, and its target-seeking ability was observed by frozen section. Ultrasound and NIR irradiation were used to evaluate its thrombolytic ability by the weight changes of thrombus before and after irradiation.Results:The prepared nanoprobe had regular morphology and uniform size. The particle diameter was (156.83±5.05)nm, and the surface potential was (11.47±0.25)mV. The RGD coupling rate was (77.67±4.50)%, which could mediate the targeting of nanoprobe to fresh extracorporeal arterial thrombus. UV-Visible-NIR spectroscopy confirmed the successful loading of ICG, and its encapsulation rate was (80.47±0.05)%. After ultrasound and NIR irradiation, the nanoprobe could undergo acoustically induced phase transition, thermally induced phase transition and enhance the ultrasonic development effect. With the increase of the concentration of the nanoprobe solution, the NIR signal gradually increased, and the temperature rose in a concentration-dependent and intensity-dependent manner after NIR irradiation. The cytotoxicity test and hemolysis test showed that the nanoprobe had good biological safety, and it could play a thrombolytic role under the combined irradiation of ultrasound and NIR, and the weight of thrombus was significantly reduced after the treatment ( P<0.01). Conclusions:In this study, the nanoprobe (RGD/ICG/PFP@MSN) were successfully prepared possesses excellent dual mode imaging capabilities of ultrasound and NIR, excellent phase transition ability and photothermal conversion efficiency, as well as efficient targeted penetration and therapeutic effects against thrombosis. This study provides strong in vitro experimental evidence and new strategies for the integration of diagnosis and treatment of thrombotic diseases under the cooperation of ultrasound and NIR.

Talaromycosis marneffei has been increasing in recent years. Our understanding of this disease has gradually deepened through extensive basic and clinical research, but there are still many limitations. In this article, by incorporating the latest research advancements, we discuss important issues in managing Talaromycosis marneffei trends, aiming to guide effective prevention and control of the disease, improving public health, and reducing the healthcare burden.

Peritoneal adhesion (PA) is a high morbidity complication after surgical procedures, with serious clinical consequences and requiring substantial medical expenditure. The pathogenesis of PA is complex and is still not very clear. Clinically, it is mainly treated by optimizing surgical protocols, using anti-adhesion drugs and biomaterial barriers. Although these methods have shown certain preventive effects, the effectiveness needs to be further improved. Elucidating the mechanism of PA formation is the basis and premise for preventing its occurrence. In the process of PA formation, a variety of inflammatory cells, inflammatory factors play important roles. In this paper, the mechanism of inflammation and immunoregulatory responses in the formation of adhesions in the peritoneal cavity was reviewed, in order to provide a reference for the improvement of PA prevention strategies.

Objective ToexploretheclinicalvalueofMSCTcombinedwithultrasonographyinthediagnosisofacuteappendicitis. Methods 238patientswithsuspiciousappendicitisunderwentMSCTandultrasonographybeforesurgery.Allpatientsweredivided intoappendicitisgroupandnormalappendixgroupaccordingtoCTappearances.TheefficacyofMSCTcombinedwithultrasoundin diagnosingappendicitiswasanalyzedbycomparisonofsurgicalpathologicalfindings.Results Therewere220casesinappendicitis group,whichhad165casesofappendicitisconfirmedbypathology,and55casesofnormalappendix.Therewere18casesinnormal group,2caseswereconfirmedappendicitisbypathology,and16caseswerenormalappendix.Theoveralldiagnosticperformancesof theCTscanwere98.8%ofsensitivity,22.5%ofspecificity,82.5%ofpositivepredictivevalue,88.9%ofnegativepredictivevalue, and76.1%ofaccuracy.TheperformancesofMSCTcombinedwithultrasonographywere90.4%ofsensitivity,93.0%ofspecificity, 96.8%ofpositivepredictivevalue,80.5%ofnegativepredictivevalue,and91.2%ofaccuracy.Thedifferencewasstatisticallysignificant indiagnosisperformancesbeforeandafterMSCTcombinedwithultrasonography (P＜0.001).Conclusion MSCTcombinedwith ultrasonographyexaminationcouldimprovethediagnosticaccuracyofappendicitis,andmayreducethenegativerateofappendectomy.

Objective: To investigate the regulation of emodin on microRNA expressions in mouse model with sepsis by GeneChip microRNA array. Methods: Forty two c57 mice were randomly (random number) divided into 3 groups: sham operation group (sham group, n=14),sepsis group(n=14) and emodin group (n=14). The sepsis model of the mouse was subjected to cecal ligation and puncture (CLP). Mice in emodin group received intraperitoneal injection of emodin (40 mg/kg) half an hour before operation and every 12 hours after CLP. All mice were sacrificed 48 h after surgery and part of the ileum were removed for intestine tissue stained with hematoxylin eosin. The levels of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and intestinal fatty acid binding protein (I-FABP) in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). Total RNA of ileum tissues was extracted from the sepsis group and emodin group, and then subjected to miRNA microarray. The results of microarray were further verified by quantitative real-time PCR (qRT-PCR). Target genes of differentially expressed miRNAs were predicted and subjected to gene ontology (GO) and KEGG pathway enrichment analysis. Data of multi-groups were analyzed by one way variance (ANOVA) and inter-group comparisons were made by SNK-q tests. Mann-Whitney U test was used when homogeneity of variance were not met. The value of P<0.05 was considered statistically significant. Results: Compared to the sepsis group, the levels of serum TNF-α, IL-6 and I-FABP in the emodin group were decreased significantly. MiRNA microarray showed that 23 miRNAs were differentially expressed in the emodin group as compared to the sepsis group, among which 17 miRNAs were up-regulated and 6 miRNAs were down-regulated. qRT-PCR results were consistent with miRNA array data. Target genes of 10 selected miRNAs were predicted and subjected to bioinformatic analysis. A total of 3 410 target genes were significantly enriched in 2 072 GO biological process terms, 246 GO cellular component items and 277 GO molecular function terms. Moreover, KEGG pathway analysis showed that these differential miRNAs were involved in the regulation of PI3K-Akt signaling pathway, MAPK signaling pathway, and TNF signaling pathway. Conclusions Emodin can regulate the expression of multiple microRNAs, and play an important role in protecting the intestinal mucosal barrier via a variety of targets and pathways.

AIM:We investigated how AT 1-R stimulated by mechanical stresses induces cardiac fibrosis .METHODS:We produced in vivo cardiac pressure overload model in angiotensinogen knockout ( ATG-/-) mice and in vitro mechanically-stretched cell model in cultured neonatal cardiac cells of ATG-/-mice both lack the participation of Ang II .RESULTS: Pressure overload for 4 weeks in ATG-/-mice induced myocardial hypertrophy accompanied by the significant interstitial fibrosis , however , the TGF-β, a key regulatory factor of fibrosis, was not significantly increased in these ATG-/-mice.Meanwhile, the inhibitor for AT1-R significantly inhibited mechani-cal stress-induced cardiac fibrosis in these ATG-/-models whereas inhibition of TGF-βdid not.CONCLUSION:The results showed that mechanical stress-induced fibrotic responses through AT 1-R required the phosphorylation of Smad 2 but not the involvement of TGF-β.

Objective To explore the relations ofnicotinamide adenine dinucleotide phosphate (NAD [P]H) oxidase p22phox C242T gene polymorphism with hyperlipidemia and cerebral infarction.Methods A case-control association study containing 207 hyperlipidemia patients (collected from Physical Examination Center from March 2014 to March 2015),185 cerebral infarction patients (collected from Department of Neurology from March 2014 to March 2015) and 183 controls (collected from Physical Examination Center from March 2014 to March 2015) was carried out.The genetypes and allele frequency were compared;the clinical data,lipoprotein oxidation level and NAD (P)H oxidase activity were performed correlation analysis between different patient groups and different genetypes.Results There were no differences in low-density lipoprotein (LDL),oxidized LDL and malondialdehyde levels,NAD (P)H oxidase activity,and frequencies of CT+TT genotype and T allelic gene between patients with hyperlipidemia and controls (P＞0.05).Group of cerebral infarction had significantly higher serum levels of oxidized high-density lipoprotein (HDL) and malondialdehyde,and NAD(P)H oxidase activity than the controls (P＜0.05);the frequencies of CT+TT genotype and T allelic gene in patients with cerebral infarction were significantly higher than those in the controls (P＜0.05).There was no difference between CC genotype patients and CT+TT genotype patients in the serum levels of triglyceride,cholesterol and HDL (P＞0.05),but CC genotype patients had significantly higher serum levels of oxidized HDL,oxidized LDL and malondialdehyde,and NADPH oxidase activity than CT+TT genetype patients (P＜0.05).Logistic regression analysis indicated that smoking,hypertension,serum levels oflipoprotein (a),oxidized HDL and malondialdehyde,NADPH oxidase activity and T allelic gene (OR=0.299,95％CI:0.102-1.879,P=0.028) were independent risk factors for cerebral infarction.Conclusion C242T polymorphism is associated with lipoprotein oxidation and cerebral infarction in Han people from Shanghai Songjiang of China,and T allelic gene and lipoprotein oxidation are independent risk factors for cerebral infarction.

Aims To synthesize acetylated low molecu-lar weight heparin( ALMWH) and to detect its physico-chemical properties and antineoplastic activity. Meth-ods LMWH was prepared by degradation of UFH with sodium periodate oxidation and sodium borohydride re-duction, then the LMWH was acetylated by acetic an-hydride where N, N′, -dicyclohexylcarbodiimide ( DCC ) and 4-dimethylaminopyridine ( DMAP ) were used as catalysts. X-ray diffraction(XRD)and Differ-ential Scanning Calorimetry ( DSC ) of ALMWH were obtained. The antiproliferative activity and anti-inva-sive activity were determined on MDA-MB-231 and MCE-7 human breast cancer cells. Results XRD a-nalysis showed that the LMWH degraded from UFH and ALMWH synthesized by acetylation of LMWH be-longed to amorphous structure, however, their DSC curves were significantly different. Compared with LM-WH, ALMWH had more powerful capacity for binding water and lowering anticoagulant activity, more signifi-cantly ALMWH exhibited stranger anti-proliferative and anti-invasive activity than LMWH, especially when it was used in low concentrations. Conclusion The syn-thesized ALMWH possesses a low anticoagulant activi-ty, certain anti-proliferative, anti-invasive and anti-metastatic activity. This study provides a basic method for screening of antineoplastic drug with low toxicity.