BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Home enteral nutrition(HEN)has demonstrated advantages in improving patients'quality of life and reducing medical costs.It is widely embraced in the United States,Europe,and other regions.Due to individual differences in the characteristics of HEN preparations,drug interactions,and variations in patient nutritional status,patients need pharmaceutical supervision from a nutritional support pharmacist(NSP)when using HEN.HEN in China is still in its infancy.There are no corresponding norms and guidelines for NSP participation in HEN and a need for specific operating standards.This article delves into the current situation of NSP participation in HEN management,the content of pharmaceutical care,and the value of pharmaceutical services.It aims to offer valuable reference evidence for future practice and research.

Objective:To investigate the effects of extracts of Rhizoma Sparganii and Rhizoma Curcumae on cartilage damage in osteoarthritis rats and NADPH oxidase 2 (NOX2)/reactive oxygen species (ROS)/nuclear factor-κB (NF-κB) signaling pathways. Methods:Rats (50 cases) were divided into the sham group, and model group, as well as the low, medium, and high dose groups of extracts of Rhizoma Sparganii and Rhizoma Curcumae, with 10 rats in each group. Except for sham group, the rat model of cartilage damage in knee osteoarthritis was established. On the second day after modeling, the rats in the low, medium, and high dose groups received intragastric extracts perfusion of Rhizoma Sparganii and Rhizoma Curcumae at the doses of 5, 10, and 20 g/kg respectively. The rats in the sham and model groups received intragastric equivalent 0.9% sodium chloride solution perfusion, once daily, for 20 days by continuous administration. The knee joint behavior, bone metabolism indicators, serum superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) levels, inflammatory factors, NOX2, and NF-κB levels of each group were observed. Results:Compared with the model group, the behavioral abnormality scores, cartilage oligomeric matrix protein (COMP), MDA, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), NOX2, and NF-κB levels in the low, medium, and high dose groups were all gradually decreased (all P < 0.05), while proteoglycan, SOD, GSH, and interleukin-10 (IL-10) levels in the low, medium, and high dose groups were all gradually increased (all P < 0.05), and it was dose-dependent. Conclusions:Rhizoma Sparganii and Rhizoma Curcumae extracts can effectively improve cartilage damage in osteoarthritis rats, and it may be related to the inhibition of the NOX2/ROS/NF-κB signaling pathway.

Objective To observe the efficacy of different dosage of midazolam oral solution in re-lieving anxiety in children undergoing laparoscopic high ligation of the hernia sac with oblique inguinal her-nia.Methods A total of 120 children,93 males and 27 females,aged 2-6 years,78-120 cm in height and 11-25 kg in weight,ASA physical statusⅠ orⅡ,were selected to perform laparoscopic high ligation of inguinal oblique hernia sac under general anesthesia.According to random number table method,the chil-dren were divided into three groups:the oral midazolam 0.25 mg/kg group(group M1),0.5 mg/kg group(group M2),and 0.75 mg/kg group(group M3)30 minutes before anesthesia,40 children in each group.Modified Yale preoperative anxiety scale-short form(mYPAS-SF)was recorded at premedication,parental separation,and immediate induction of anesthesia.Induction compliance checklist(ICC)score,recovery time,extubation time,PACU residence time,pediatric anesthesia emergence delirium scale(PAED)and the modified face,legs,activity,cry and consolability scale(FLACC)30 minutes after operation were also recorded.Results Compared with before taking medication,mYPAS-SF scores in groups M2 and M3 at parental separation and immediate induction of anesthesia were significantly decreased(P＜0.05).Com-pared with group M1,mYPAS-SF scores at parental separation and immediate induction of anesthesia and ICC scores at immediate induction of anesthesia were significantly lower in groups M2 and M3(P＜0.05),the recovery time,extubation time and PACU resident time in groups M2 and M3 were significantly pro-longed,PAED score was decreased significantly within 30 minutes after operation(P＜0.05).Compared with group M2,the awakening time and extubation time in group M3 were significantly prolonged.(P＜0.05).Conclusion Oral midazolam 0.5 mg/kg or 0.75 mg/kg 30 minutes before anesthesia can effectively alleviate the preoperative anxiety of children,improve the degree of cooperation in anesthesia in-duction,and reduce the occurrence of postoperative agitation,the recovery time and extubation time pro-longed in children with oral midazolam 0.75 mg/kg.Therefore,an oral solution of midazolam 0.5 mg/kg was a more appropriate dose for preoperative antianxiety regimen in children.

Objective:To investigate the predictive value of a clinical imaging model based on multi-slice helical computer tomography (MSCT) examination in predicting prognosis of advanced gastric adenocarcinoma.Methods:The retrospective cohort study was conducted. The clinicopatho-logical data of 88 patients with advanced gastric adenocarcinoma who were admitted to the Ningbo Yinzhou No.2 Hospital from January 2019 to January 2021 were collected. There were 62 males and 26 females, aged (60±15)years. All patients underwent preoperative MSCT examination. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Univariate and multivariate analyses were conducted using the Logistic regression model. The receiver opera-ting characteristic curve was used to analyze the predictive efficacy of prognosis, and the area under the curve (AUC), sensitivity, and specificity were calculated. Results:(1) Surgical situations and follow-up. All 88 patients underwent radical gastrectomy for gastric cancer and were diagnosed with advanced gastric adenocarcinoma through postoperative pathological examination. All 88 patients were followed up after surgery for 41(range, 36?48)months, with a 3-year overall survival rate of 69.32%. (2) Analysis of factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. Results of multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) and extramural venous invasion (EMVI) were independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery ( odds ratio=1.10, 7.72, 95% confidence interval as 1.01?3.82, 1.42?15.42, P<0.05). (3) Construction and evaluation of predictive model. The AUC of predictive efficacy of prognosis for advanced gastric adenocarcinoma of preoperative CEA and EMVI were 0.90 (95% confidence interval as 0.82?0.97) and 0.80 (95% confidence intervalas 0.71?0.89), respectively, with sensitivity of 85.25% and 78.69% and specificity of 100.00% and 81.48%, respec-tively. A predictive model was constructed by combining preoperative CEA and EMVI based on the results of multivariate analysis, and the AUC of the predictive model was 0.93 (95% confidence interval as 0.87?0.98), with sensitivity and specificity of 86.89% and 96.30%. Conclusions:CEA and EMVI are independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. The predictive model constructed by combining preoperative CEA and EMVI has good predictive efficacy for patient prognosis.

Epstein-Barr virus (EBV) is generally susceptible in human beings and multi-organ systems can be involved in EBV infection, such as blood, respiratory, urinary, digestive and nervous systems. EBV infection also plays an important role in the pathogenesis of related tumors, autoimmune diseases and other diseases, posing a great threat to human health. As a DNA virus, EBV can be sensed by DNA recognition receptors to trigger a series of downstream immune responses. A DNA-sensing pathway consists of DNA sensors, adaptor molecules and downstream effector signals. Double-stranded DNA sensors mainly include absent in melanoma 2-like receptors (ALRs) and cyclic GMP-AMP synthase (cGAS). Adaptors were mainly stimulator of interferon genes (STING) and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Downstream immune responses mainly involve typeⅠIFN, inflammasomes and proinflammatory cytokines. As a double-stranded DNA virus of the Herpesviridae family, EBV triggers complex innate and adaptive immune responses in the host, especially the sensing pathways mediated by a variety of DNA recognition receptors, which play a key role in host immune defense and pathogen immune evasion. This review made the DNA sensor as the clue to comprehensively summarize the progress in the activation, regulatory mechanism and clinical relevance of DNA-sensing pathways in EBV infection in recent years, aiming to achieve a better understanding of the host innate immune responses during EBV infection and provide an immunological basis for the prevention and treatment of EBV infection-related diseases.

Objective:To evaluate the influence of Helicobacter pylori ( H. pylori) infection on anxiety and depression in patients with chronic gastritis. Methods:From December 1 2020 to June 30 2021, 387 patients with chronic gastritis who visited the outpatient Department of Gastroenterology, the First Hospital Affiliated to Air Force Medical University were continuously recruited. According to the status of current H. pylori infection, the patients were divided into H. pylori uninfected group and H. pylori infected group. The general demographic information of patients was collected. Hamilton anxiety scale, Hamilton depression rating scale-24, Pittsburgh sleep quality index (PSQI) and gastrointestinal symptom rating scale (GSRS) were filled in. The detection rates of anxiety and depression were compared between the H. pylori uninfected group and the H. pylori infected group according to demographic characteristics. Chi-square test and multiple logistic regression analysis were used for statistical analysis. Results:Finally, 360 patients with chronic gastritis were enrolled, including 200 patients in H. pylori uninfected group and 160 patients in H. pylori infected group. The detection rates of anxiety and depression of the H. pylori infected group were both higher than those of the H. pylori uninfected group (48.1%, 77/160 vs. 30.0%, 60/200; 25.0%, 40/160 vs. 12.5%, 25/200), and the differences were statistically significant ( χ2=12.39 and 9.39, P<0.001 and=0.002). The detection rate of anxiety of male patients in the H. pylori infected group was higher than that in the H. pylori uninfected group (45.1%, 32/71 vs. 24.5%, 27/110); the detection rate of depression of female patients in the H. pylori infected group was higher than that in the H. pylori uninfected group (30.3%, 27/89 vs. 11.1%, 10/90), and the differences were statistically significant ( χ2=8.27 and 10.09, P=0.004 and 0.001). The detection rates of anxiety and depression of patients less than 48 years old in the H. pylori infected group were both higher than those in the H. pylori uninfected group (46.2%, 37/80 vs. 21.9%, 21/96; 20.0%, 16/80 vs. 7.3%, 7/96), and the differences were statistically significant ( χ2=11.73 and 6.20, P=0.001 and 0.013). The detection rates of anxiety and depression of the patients with high school education and below in the H. pylori infected group were higher than those in the H. pylori uninfected group (56.5%, 48/85 vs. 31.7%, 38/120; 32.9%, 28/85 vs. 14.2%, 17/120), and the differences were statistically significant ( χ2=12.57 and 10.24, P<0.001 and =0.001). The results of multivariate analysis showed that H. pylori infection, history of hypertension, PSQI score ≥8, GSRS score ≥7, chronic superficial gastritis and chronic atrophic gastritis were independent risk factors of anxiety in patients with chronic gastritis( P<0.001, =0.013, =0.001, <0.001, =0.036, =0.021), and the risk of anxiety of patients with H. pylori infection was 2.509 times as much as that in uninfected patients (95% confidence interval 1.512 to 4.163). H. pylori infection, PSQI score ≥8, GSRS score≥7, and having overnight dish ≥3 times per week all were independent risk factors of depression in patients with chronic gastritis( P=0.004, =0.002, <0.001, =0.001). The risk of depression in patients with H. pylori infection was 2.563 times as much as that in uninfected patients (95% confidence interval 1.356 to 4.846). Conclusion:H. pylori infection is correlated to anxiety and depression in patients with chronic gastritis, and it is an independent risk factor of anxiety and depression in patients with chronic gastritis.

Objective:To screen key genes of renal clear cell carcinoma based on bioinformatics methods, identify possible microRNA (miRNA)-mRNA action axis, and explore the expression of related genes in clear cell renal cell carcinoma tissues and cells.Methods:Gene expression profiles of GSE40435 and GSE71302 datasets were obtained from the Gene Expression Omnibus (GEO) database. TCGA-KIRC datasets were obtained from The Cancer Genome Atlas (TCGA) database. R software was used to identify the differentially expressed mRNA and miRNA, and the functional enrichment analysis was performed. STRING database and Cytoscape software were used to perform the protein interaction analysis. The prognosis-related differentially expressed miRNA was evaluated by the Oncomir database. The potential targeted genes regulated by miRNA were determined by using TargetScan and miRDB targeted gene prediction tools. The tissue samples and clinicopathological features of 34 patients with clear cell renal cell carcinoma in the First Hospital of Shanxi Medical University from June to December 2021 were collected, and normal renal cell line 293T and clear cell renal cell carcinoma cell line 786O were selected. The real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), was used to detect the relative expression of genes; Western blotting and immunohistochemical staining were used to detect the expression levels of the targeted proteins. The dual luciferase reporter gene assay was carried out to verify the targeting relationship between genes.Results:A total of 1 351 differentially expressed mRNA and 50 differentially expressed miRNA were screened and identified. The result of functional enrichment analysis suggested that the fatty acid metabolism pathway and xenobiotic metabolism pathway were suppressed in clear cell renal cell carcinoma, while the apoptosis and immune response pathways were activated. Protein interaction analysis suggested that the signal transduction and protein ubiquitination pathways might play a key role in clear cell renal cell carcinoma. The screening results showed that miRNA-224-5p (miR-224-5p) was most closely associated with clear cell renal cell carcinoma progression and was highly expressed in tumor tissues, and its prognosis-related target gene was NEDD4L. The relative expression of NEDD4L mRNA in clear cell renal cell carcinoma tissues and paraneoplastic tissues were 0.138±0.103 and 1.000±0.026 ( t = 46.23, P < 0.05), and the relative expression of miR-224-5p was 1.000±0.043 and 0.129±0.108 ( t = 45.28, P < 0.05). The differences of NEDD4L mRNA and miR-224-5p expressions in different grades and stages of clear cell renal cell carcinoma tissues were statistically significant (all P < 0.05). The expression of NEDD4L protein was decreased in clear cell renal cell carcinoma. The relative expression of NEDD4L gene in 293T and 786O cells were 1.000±0.125 and 0.210±0.044 ( t = 17.52, P < 0.05); the relative expressions of miR-224-5p gene were 0.209±0.049 and 1.000±0.234 ( t = 10.61, P < 0.05). The relative expressions of NEDD4L mRNA in miRNA mimic group and negative control group were 0.236±0.062 and 1.000±0.024, and the difference was statistically significant ( t = 43.56, P < 0.05). NEDD4L protein expression was reduced in the miRNA mimic group. Dual luciferase reporter gene assay suggested that NEDD4L was a direct target gene of miR-224-5p. Conclusions:In clear cell renal cell carcinoma, miR-224-5p targets and regulates NEDD4L expression, and this mechanism may be related to carcinogenesis and progression of clear cell renal cell carcinoma.

Objective:To investigate the value of a cuproptosis-related differential long non-coding RNA (lncRNA) scoring formula related to the prognosis of clear cell renal cell carcinoma (ccRCC) patients in the clinical diagnosis, prognosis prediction and treatment options based on bioinformatics.Methods:Gene matrix and clinical data of ccRCC patients were obtained from the Cancer Genome Atlas (TCGA) database (update to 29 March, 2022). The expression data of 539 ccRCC tissues and 72 paracancerous normal tissues were collected from gene matrix; the data of 530 ccRCC were collected from clinical data. Pearson correlation analysis, Wilcoxon signed rank test and univariate Cox proportional risk model were used to analyze the screened cuproptosis-related differential lncRNA related to the prognosis. R software was used to randomly divide 530 ccRCC patients with survival data into training set (266 cases) and validation set (264 cases) according to approximate 1∶1 ratio. LASSO regression analysis was used to construct a cuproptosis-related differential lncRNA scoring formula and cross-validation was performed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the specificity and sensitivity of cuproptosis-related differential lncRNA scoring formula, and the area of the curve (AUC) was calculated. According to the median risk value, all patients were divided into the low-risk group and high-risk group; Kaplan-Meier method was used to analyze the difference in the overall survival (OS) of patients in the low-risk group and high-risk group. T test was used to detect the differences in the risk value of patients with different clinicopathological characteristics. R package rms was used to construct the nomogram for predicting 1-year, 3-year, 5-year OS rates of ccRCC patients, R package pRRophetic was used to predict the half-inhibitory concentration ( IC50) of common targeted drugs such as sorafenib and sunitinib in clinical treatment of ccRCC patients, and IC50 value of patients in low-risk group and high-risk group was compared by using Wilcoxon signed rank test. Tissue samples of 20 ccRCC patients who underwent radical nephrectomy and were diagnosed with pathology and the matched paracancerous normal tissues were collected from the First Hospital of Shanxi Medical University between June 2021 and December 2021. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of key lncRNA in ccRCC tissues. Results:Based on the expression matrix of 10 cuproptosis genes (FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, CDKN2A) of ccRCC patients in TCGA database, 153 cuproptosis-related differential lncRNA related to the prognosis were identified. According to LASSO regression analysis, a scoring formula of 4 cuproptosis-related differential lncRNA related to the prognosis was obtained, risk value was calculated as 0.020×AC015912.3+0.011×AC026401.3+0.063×AC103706.1+(-0.076)×EPB41L4A-DT. All patients were divided into high-risk group (≥0.76) and low-risk group (<0.76) based on the median value (0.76). ROC curve analysis showed that the scoring formula had good prediction accuracy in 1-year, 3-year, 5-year OS rates. In training set, validation set, the total cohort, the OS of patients in the high-risk group was worse than that in the low-risk group (all P < 0.001). The age, pathological degree, tumor staging, risk value calculated by cuproptosis-related differential lncRNA were independent influencing factors of OS (all P < 0.001). There were statistically significant differences in the risk value calculated by cuproptosis-related differential lncRNA scoring formula among patients with different pathological degree, tumor staging, T staging, N staging, M staging (all P < 0.01), while there were no statistically significant differences among patients with different gender and age (all P > 0.05). The established nomogram had good prediction accuracy in the 1-year, 3-year, 5-year OS rates. Sunitinib and sirolimus showed higher sensitivity in the high-risk group; axitinib, sorafenib and pazopanib showed higher sensitivity in the low-risk group. qRT-PCR results showed that relative expression level of AC015912.3 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.04 vs. 0.68±0.24, t = 6.37, P < 0.01); the relative expression level of AC026401.3 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.05 vs. 0.64±0.22, t = 7.29, P < 0.01); the relative expression level of AC103706.1 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.04 vs. 0.64±0.21, t = 7.49, P < 0.01); the relative expression level of EPB41L4A-DT in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.06 vs. 0.73±0.10, t = 10.68, P < 0.01). Conclusions:Cuproptosis-related differential lncRNA scoring formula based on TCGA database can be used as a new marker for clinical diagnosis and prognosis prediction of ccRCC patients, which can help guide the clinical drug treatment of patients and facilitate accurate diagnosis and treatment.

Objective: To analyze the current status of work-related musculoskeletal disorders (WMSDs), work fatigue and musculoskeletal pain in Chinese occupational population, and to study the relationship between work fatigue and musculoskeletal pain and WMSDs. Methods: A total of 66 961 employees from 323 enterprises in 15 key industries in China were selected as the study subjects using stratified cluster sampling method. The incidence of WMSDs in the past year was investigated using the Chinese version of the Musculoskeletal Disorders Questionnaire, and the work fatigue and musculoskeletal pain were investigated using Borg 6-20 Rating of Perceived Exertion Scale and visual analogue scale. The data were standardized using the age composition data of 18 to 60 years from the seventh national population census. Results: The standardized annual incidence of WMSDs was higher in the front-line workers than that in the administrative and other supportive staff (38.82% vs 36.30%). The detection rates of work fatigue and musculoskeletal pain in the study subjects were 44.54% and 63.08%, respectively. The result of S-curve fitting showed that the risk of WMSDs increased with the level of work fatigue (P<0.01). Among the front-line workers, the average of monthly fatigue frequency in the neck, shoulder, lower back, upper back, wrist/hand, foot and ankle, knee, leg, and elbow were higher in the group with WMSDs compared to those without WMSDs (all P<0.01). The pain degree of musculoskeletal pain was higher in all nine sites in the fatigued group than in the no-fatigue group (all P<0.01). The standardized detection rate of musculoskeletal pain was higher in the fatigued group than in the non-fatigued group (80.38% vs 25.71%). The work fatigue was moderate and positively correlated with musculoskeletal pain in all seven sites except the lower back and elbow, with Kendall Tau-b correlation coefficients ranging from 0.423 to 0.546 (all P<0.01). Conclusion: There is a good correlation between work fatigue and local musculoskeletal pain, work fatigue and WMSDs in Chinese occupational population. Implementing ergonomic interventions to control the development of work fatigue can be an effective measure for preventing WMSDs.