OBJECTIVES: To investigate YEATS2 expression in gastric cancer (GC), its prognostic value, and its regulatory role in epithelial-mesenchymal transition (EMT) of GC cells. METHODS: YEATS2 expression in GC was analyzed using publicly available databases. Paired GC and adjacent tissues were collected from 100 patients undergoing radical surgery for immunohistochemical detection of YEATS2 expression, and its correlations with the patients' clinicopathological parameters and Ki67 expression were analyzed. The prognostic value of YEATS2 was assessed using Kaplan-Meier analysis, Cox regression and ROC curves, and its regulatory mechanisms were analyzed using KEGG enrichment analysis. In cultured GC cell lines (HGC-27 and AGS), the effect of YEATS2 knockdown and overexpression on migration, invasion and EMT of the cells were examined with scratching assay, Transwell assay and Western blotting. RESULTS: YEATS2 was significantly overexpressed in GC tissues with a positive correlation with Ki67 (P<0.05). High YEATS2 expression was associated with elevated CEA (≥5 μg/L), CA19-9 (≥37 kU/L), T3-4 stage, and N2-3 stage (all P<0.05). Patients with high YEATS2 expression had significantly reduced 5-year survival (P<0.001); ROC analysis showed that YEATS2 expression levels had a sensitivity of 80.00% and a specificity of 66.67% for predicting patient survival (P<0.05). Cox regression identified high YEATS2 as an independent risk factor for poor postoperative 5-year survival outcome of GC patients (HR: 1.675, 95%CI: 1.013-2.771; P=0.045). KEGG enrichment analysis suggested involvement of YEATS2 in EMT in GC and Wnt/β-catenin signaling. In cultured GC cells, YEATS2 overexpression significantly promoted cell migration and invasion, upregulated the expressions of vimentin, N-cadherin, Wnt and active β-catenin, and downregulated E-cadherin expression, and these changes were obviously suppressed by treatment with XAV-939 (a Wnt/β-catenin inhibitor). CONCLUSIONS High YEATS2 expression activates Wnt/β-catenin signaling to promote EMT in GC and is correlated with poor prognosis of GC patients.
Humans ; Stomach Neoplasms/pathology* ; Epithelial-Mesenchymal Transition ; Wnt Signaling Pathway ; Cell Line, Tumor ; Prognosis ; Cell Movement ; Male ; Female ; beta Catenin/metabolism*

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function

OBJECTIVE: To explore the clinical features, lysosomal enzymatic [acid α-glucosidase (GAA)] activities and genetic variants in a child with late-onset Pompe disease (LOPD). METHODS: Clinical data of a child who had presented at the Genetic Counseling Clinic of West China Second University Hospital in August 2020 was retrospectively analyzed. Blood samples were collected from the patient and her parents for the isolation of leukocytes and lymphocytes as well as DNA extraction. The activity of lysosomal enzyme GAA in leukocytes and lymphocytes was analyzed with or without addition of inhibitor of GAA isozyme. Potential variants in genes associated with neuromuscular disorders were analyzed, in addition with conservation of the variant sites and protein structure. The remaining samples from 20 individuals undergoing peripheral blood lymphocyte chromosomal karyotyping were mixed and used as the normal reference for the enzymatic activities. RESULTS: The child, a 9-year-old female, had featured delayed language and motor development from 2 years and 11 months. Physical examination revealed unstable walking, difficulty in going upstairs and obvious scoliosis. Her serum creatine kinase was significantly increased, along with abnormal electromyography, whilst no abnormality was found by cardiac ultrasound. Genetic testing revealed that she has harbored compound heterozygous variants of the GAA gene, namely c.1996dupG (p.A666Gfs*71) (maternal) and c.701C>T (p.T234M) (paternal). Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1996dupG (p.A666Gfs*71) was rated as pathogenic (PVS1+PM2_Supporting+PM3), whilst the c.701C>T (p.T234M) was rated as likely pathogenic (PM1+PM2_Supporting+PM3+PM5+PP3). The GAA in the leukocytes from the patient, her father and mother were respectively 76.1%, 91.3% and 95.6% of the normal value without the inhibitor, and 70.8%, 112.9% and 128.2% of the normal value with the inhibitor, whilst the activity of GAA in their leukocytes had decreased by 6 ~ 9 times after adding the inhibitor. GAA in lymphocytes of the patient, her father and mother were 68.3%, 59.0% and 59.5% of the normal value without the inhibitor, and 41.0%, 89.5% and 57.7% of the normal value with the inhibitor, the activity of GAA in lymphocytes has decreased by 2 ~ 5 times after adding the inhibitor. CONCLUSION The child was diagnosed with LOPD due to the c.1996dupG and c.701C>T compound heterozygous variants of the GAA gene. The residual activity of GAA among LOPD patients can range widely and the changes may be atypical. The diagnosis of LOPD should not be based solely on the results of enzymatic activity but combined clinical manifestation, genetic testing and measurement of enzymatic activity.
Humans ; Child ; Male ; Female ; Glycogen Storage Disease Type II/pathology* ; Retrospective Studies ; alpha-Glucosidases/genetics* ; Mothers ; Lysosomes/pathology* ; Mutation

Objective:To construct a self-management intervention program for patients with adenocarcinoma chemotherapy based on chronic disease trajectory model, and to provide reference for clinical nursing intervention.Methods:From October 2021 to June 2022, a research team was established. Based on the chronic disease trajectory model and self-management theory, through preliminary quantitative research, literature review and semi-structured interview, the first draft of the intervention plan was prepared. 24 experts were selected for two rounds of Delphi expert correspondence consultation to determine the self-management intervention plan for breast cancer patients undergoing chemotherapy based on the trajectory model of chronic disease.Results:The effective questionnaire recovery rates of the two rounds of expert letter consultation were 100%, and the coefficient of expert authority degree was 0.805 and 0.863, respectively. The mean values of importance were 4.21- 4.96 and 4.46 - 5.00, the coefficients of variation were 0.00 - 0.19 and 0.00-0.17, and the Kendall concordant coefficients were 0.123 and 0.149 ( both P<0.01). Finally, the self-management intervention scheme for breast cancer chemotherapy patients based on the trajectory model of chronic disease was constructed, including 3 first-level indicators, 6 second-level indicators and 27 third-level indicators. Conclusions:The self-management intervention program for patients with adenocarcinoma chemotherapy based on chronic disease trajectory model constructed in this study can provide a certain reference for clinical nurses to carry out targeted self-management interventions.

Objective: To analyze the electrocardiographic (ECG) characteristics in patients with primary hyperparathyroidism (PHPT) and meanwhile, to explore the relationship between ECG abnormality and serum calcium level in relevant patients. Methods: Our study included 2 groups: Observation group,n=84 PHPT patients treated in our hospital from 2010-01 to 2014-04 and Control group,n=80 normal subjects from regular physical examination at the same period. The ECG manifestation was compared between 2 groups. Meanwhile, according to tertile levels of serum calcium, PHPT patients were further divided into 3 subgroups:①Ca2+ level (2.0-2.8) mmol/L,②Ca2+ level (2.8-3.1) mmol/L,③Ca2+ level >3.1 mmol/L andn=28 in each subgroup. The ECG abnormalities were compared among 3 subgroups and the relationship between ECG changes and serum calcium levels were studied. Results: The ECG abnormality rates in Observation group and Control group were as 83.3% vs 18.8%, P<0.001. Compared with Control group, Observation group presented more frequent ST-T changes, QRS duration widening, high left ventricular pressure and QT interval shortening,P<0.001 orP<0.05. In observation group, with the rising of serum calcium, the incidences of ST-T changes and high left ventricular pressure were increased accordingly, the ST-T changes among 3 subgroups were significant,P<0.05; while with the rising of serum calcium, the QT interval was shortened and QRS duration was widened accordingly, the differences were obvious among 3 subgroups, allP<0.05.Conclusion: PHPT patients have the higher incidence with abnormal ECG, while ECG abnormality has beenrelated to serum calcium level in relevant patients.

Objective To predict the length of peripherally inserted central venous catheters(PICC) with electronic chest radiograph scale measurement techniques, and observe its clinical effect. Methods A total of 185 breast cancer patients from October 2012 to December 2013 who were treated by PICC combined with MST guided by ultrasonic technology were as control group. A total of 192 breast cancer patients from January to November 2014 were as observation group. Control group adopted from the puncture point to right sternoclavicular joints impreaaion nip down again to the third floor of PICC in vitro measurement method. Observation group used to right sternoclavicular joints from the puncture point plus right sternoclavicular joints to subcarinal 1 vertebral body length, right sternoclavicular joints to subcarinal 1 vertebral body length measurement by electronic chest radiograph scale technology directly measured from the electronic chest radiographs. The accuracy rates and complications between the two measurement methods were compared. Results The accuracy rate in observation group was 97.92%(188/192), which was higher than that in control group (68.11%,126/185 ),and there was significant differencek,χ2=60.15, P<0.01. The complication rate in observation group was 6.77%(13/192), which was lower than that in control group (20.54%, 38/185) ,and there was significant difference,χ2=9.58, P<0.01. Conclusions The electronic chest radiograph scale measurement techniques could effectively improve the accuracy of PICC catheter placed, improve the quality of venipuncture, decrease the complications .