Identification of differentially expressed mRNAs as novel predictive biomarkers for gastric cancer diagnosis and prognosis.

BACKGROUND: Gastric cancer (GC) has a high mortality rate worldwide. Despite significant progress in GC diagnosis and treatment, the prognosis for affected patients still remains unfavorable. AIM: To identify important candidate genes related to the development of GC and identify potential pathogenic mechanisms through comprehensive bioinformatics analysis. METHODS: The Gene Expression Omnibus database was used to obtain the GSE183136 dataset, which includes a total of 135 GC samples. The limma package in R software was employed to identify differentially expressed genes (DEGs). Thereafter, enrichment analyses of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the gene modules using the clusterProfile package in R software. The protein-protein interaction (PPI) networks of target genes were constructed using STRING and visualized by Cytoscape software. The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram. The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase (GPT) in GC and normal immortalized cell lines. In addition, cell viability, cell cycle distribution, migration and invasion were evaluated by cell counting kit-8, flow cytometry and transwell assays. Furthermore, we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital, Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020. The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients. RESULTS: We selected 19214 genes from the GSE183136 dataset, among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P-value < 0.05. In addition, GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction, whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion, vascular smooth muscle contraction and biosynthesis of the different cofactors. Furthermore, PPI networks were constructed based on the various upregulated and downregulated genes, and there were a total 15 upregulated and 10 downregulated hub genes. After a comprehensive analysis, several hub genes, including runt-related transcription factor 2 (RUNX2), salmonella pathogenicity island 1 (SPI1), lysyl oxidase (LOX), fibrillin 1 (FBN1) and GPT, displayed prognostic values. Interestingly, it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells. Furthermore, the expression level of GPT was found to be associated with age, lymph node metastasis, pathological staging and distant metastasis (P < 0.05). CONCLUSION: RUNX2, SPI1, LOX, FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis. GPT was significantly associated with the prognosis of GC, and its upregulation can effectively inhibit the proliferative, migrative and invasive capabilities of GC cells.

Rectal sensitivity and associated factors in patients with different subtypes of functional defecation disorder.

OBJECTIVE: To investigate rectal sensitivity and associated factors in patients with different subtypes of functional defecation disorder (FDD). METHODS: We segregated individuals diagnosed with FDD into two groups based on their defecation patterns: those with dyssynergic defecation and those with inadequate defecatory propulsion. We gathered general information through questionnaires and assessed rectal sensitivity using anorectal manometry. The rectal sensitivity performances of the two groups were compared; the factors related to rectal sensitivity were analyzed to determine the factors associated with rectal sensitivity, and the effect of biofeedback therapy on rectal sensitivity was clarified. RESULTS: Rectal sensitivity in different subtypes of FDD decreased, and the difference between the two groups was not statistically significant ( P  > 0.05). There were no statistically significant differences in the first constant sensation volume, defecatory desire volume, and maximum tolerable volume between the different subtypes of FDD ( P  > 0.05). Multi-factor binary logistic regression analysis showed that age, constipation symptom score, and diabetes were all independent risk factors for decreased rectal sensitivity ( P  < 0.05). There were no statistically significant differences between the prior- and post-biofeedback therapy in the first constant sensation volume, defecatory desire volume, and maximum tolerable volume ( P  > 0.05). CONCLUSION: Rectal sensitivity in different subtypes of FDD decreased. Age, constipation symptom score, and diabetes were independent risk factors for decreased rectal sensitivity. Short-term biofeedback therapy did not improve rectal hyposensitivity in patients with FDD.

[Effect of acupuncture combined with moxibustion on serum matrix metalloproteinase-9 and matrix metalloproteinase inhibitor-1 in patients with knee osteoarthritis].

OBJECTIVE: To observe the effect of acupuncture combined with moxibustion on serum bone metabolism indexes in patients with knee osteoarthritis (KOA), so as to evaluate its clinical efficacy on KOA. METHODS: Ninety-six patients with KOA were randomly divided into control and observation groups, with 48 cases in each group. The patients in the control group were treated with acupuncture at Zusanli(ST36), Neixiyan(EX-LE4), Heding(EX-LE2) and Xuanzhong(GB39) etc. on the affected side for 30 min once daily. Patients in the observation group were given moxibustion on the above-mentioned acupoints on the basis of treatment in the control group. The course of treatment for both groups was 4 weeks. The Western Ontario and MacMaster University Osteoarthritis Index (WOMAC) scores were compared before and after treatment and the clinical efficacy of the two groups were calculated according to the WOMAC scores after treatment. Ultrasound examination of the knee joint was used to analyze the thickness of joint effusion and synovial membrane thickness of the patients. Enzyme-linked immunoassay was used to detect the serum type Ⅰ collagen C-terminal foreign body peptide (CTX-Ⅰ), insulin-like growth factor (IGF), bone gla protein (BGP), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase inhibitor-1 (TIMP-1) levels. RESULTS: Compared with those before treatment, WOMAC score, knee joint synovial thickness and joint effusion thickness, serum CTX-Ⅰ, MMP-9, TIMP-1 levels, and MMP-9/TIMP-1 ratio were all down-regulated (P<0.05), while the levels of serum IGF and BGP up-regulated (P<0.05) in the two groups after treatment. The improvements of the above indexes in the observation group were superior to those in the control group (P<0.05). The total effective rate in the observation group was 95.83% (46/48), which was higher than 81.25% (39/48) in the control group(P<0.05). CONCLUSION: Acupuncture combined with moxibustion can regulate bone metabolism and effectively improve the symptoms of KOA patients, which may be related to its effect in regulating the dynamic balance of MMP-9 and TIMP-1 in serum.

Clinical phenotypes, hemodynamic characteristics and prognosis of Chinese patients with systemic sclerosis-associated precapillary pulmonary hypertension: a retrospective study.

INTRODUCTION: Systemic sclerosis (SSc) is associated with interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). This study aimed to explore the prevalence, clinical features, hemodynamic characteristics and prognosis of different severity of ILD in a cohort of patients with SSc-associated precapillary pulmonary hypertension (SSc-PH) and investigate the differences between SSc-PAH and idiopathic pulmonary arterial hypertension (IPAH) patients. METHOD: SSc-PH patients and IPAH patients, admitted to Shanghai Pulmonary Hospital (August 1, 2008-January 31, 2020) and diagnosed by right-sided heart catheterization (RHC) or echocardiography, were retrospectively included. SSc-PH patients had a baseline chest high-resolution computed tomography (HRCT), and PH classification was based on the extent of ILD. Clinical, pulmonary function, hemodynamic characteristics and survival data were extracted. RESULTS: The study included 45 SSc-PH patients (60% had coexisting ILD and 77.8% were SSc-Group 1 PH/SSc-PAH [without ILD or with mild ILD], 22.2% were SSc-Group 3 PH/SSc-PH with severe ILD) and 52 IPAH patients. SSc-PH with ILD had lower arterial oxygen partial pressure (PaO2) than those without ILD. Hemodynamic characteristics and survival rates were comparable between SSc-PAH with mild ILD and those without ILD. SSc-Group 3 PH had lower pulmonary vascular resistance (PVR) and more severe restrictive ventilatory dysfunction than SSc-Group 1 PH, but the survival rate was equally poor. SSc-PAH had a poorer prognosis than IPAH patients despite the better hemodynamic characteristics. CONCLUSIONS: ILD was common in SSc-PH patients. Careful phenotyping of PH in SSc-PH patients is very important as it is imperative to recognize its impact on clinical course, treatment and survival. KEY POINTS: • ILD was common in Chinese SSc-PH patients. • SSc-PH patients with ILD had lower PaO2 than those without ILD. • Hemodynamic characteristics and survival rates were similar in SSc-PAH patients with mild ILD and those without ILD. • Patients in SSc-Group 3 PH had lower pulmonary vascular resistance (PVR) and more severe restrictive ventilatory dysfunction than those in SSc-Group 1 PH, but the survival rate was equally poor. SSc-PAH patients had a poorer prognosis than IPAH patients despite their better hemodynamic characteristics.