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*

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

OBJECTIVES: To explore the association between GPSM2 expression level and gastric cancer progression and analyze the functional pathways and action mechanism of GPSM2. METHODS: We analyzed GPSM2 expression levels in gastric cancer tumors based on data from the GEPIA database and the clinical data of 109 patients. Public databases enrichment analysis were used to assess the impact of GPSM2 expression level on survival outcomes and the functional pathways and action mechanism of GPSM2. We further observed the effects of GPSM2 knockdown and overexpression on proliferation, migration and apoptosis of MGC803 cells using CCK-8 assay, colony formation assay, flow cytometry and immunoblotting and on the growth of MGC803 cell xenografts in nude mice. RESULTS: Bioinformatic analysis and immunohistochemical staining of the clinical specimens both revealed high GPSM2 expressions in gastric cancer (P<0.01). A high GPSM2 expression was significantly correlated with T3-4 stages, N2-3 stages, a carcinoembryonic antigen (CEA) level ≥5 μg/L, and a carbohydrate antigen (CA) 19-9 level ≥37 kU/L (P<0.05). Cox regression analysis identified high GPSM2 expression as an independent risk factor affecting 5-year survival of the patients (P<0.05). Gene ontology (GO) analysis suggested that GPSM2 was involved in cell cycle regulation. In MGC803 cells, GPSM2 overexpression significantly promoted cell proliferation and G1/S transition and xenograft growth in nude mice. KEGG pathway enrichment analysis indicated that GPSM2 executed its biological functions by regulating the p53 signaling pathway, which was confirmed by the results of immunoblotting experiments showing suppression of p53 signaling pathway activity in GPSM2-over expressing MGC803 cells. CONCLUSIONS GPSM2 is highly expressed in gastric cancer to affect patient prognosis by promoting tumor cell proliferation and G1/S transition possibly via inhibiting the p53 pathway.
Stomach Neoplasms/metabolism* ; Humans ; Cell Proliferation ; Prognosis ; Animals ; Mice, Nude ; Cell Line, Tumor ; Mice ; Apoptosis ; Tumor Suppressor Protein p53/metabolism* ; Cell Movement

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

Aim To investigate the protective poten-tial of paeoniflorin 6-oxy-benzenesulfonate(CP-25)in preserving knee cartilage integrity in osteoarthritis mice through inhibition of GRK2 activity.Methods The posttraumatic osteoarthritis model was established fol-lowing DMM surgery.The experiment consisted of a sham operation group,a model group,a CP-25 admin-istration group,and a paroxetine positive control group.Intragastric administration commenced after the surgery.After 12 weeks of administration,the animals were euthanized.Micro-CT imaging was used to ob-serve the knee cartilage degeneration and abnormal bone remodeling,and the joint histopathology of mice was observed by staining with ferrubens solid green.Immunohistochemistry and immunofluorescence were used to detect the expression level of related molecules in cartilage tissue.Furthermore,Western blot was em-ployed to determine GRK2 and EP4 membrane protein expression levels as well as total protein levels of GRK2 and MMP13 following CP-25 treatment.Results Compared with the sham operation group,the articular cartilage in the model group was significantly degrad-ed,with the cartilage surface calcifying and osteo-phytes forming.CP-25 could significantly reduce the number of osteophytes and the thickness of the sub-chondral plate of articular cartilage,promote the regen-eration of the cartilage matrix,reduce the expression of cartilage matrix degradation protein,and have a signifi-cant protective effect on knee cartilage.Immunohisto-chemical and immunofluorescence results showed that compared with the model group,CP-25 treatment sig-nificantly decreased the expressions of GRK2,AD-AMTS5 and MMP13 in knee tissue and increased the expressions of Col Ⅱ and Aggrecan in knee tissue.The results of in vitro experiments showed that CP-25 ad-ministration could significantly reduce the expression levels of GRK2 membrane protein and total protein,in-crease the level of EP4 membrane protein,and de-crease the level of MMP13.Conclusions The ad-ministration of CP-25 can significantly promote the re-generation of articular cartilage matrix in OA mice,re-duce the degradation of cartilage matrix,and exhibit therapeutic effects on OA.The mechanism behind this is related to the inhibition of GRK2-mediated cartilage matrix metabolism.

Objective:To explore the influence of social capital at work on anxiety of medical staff, and the mediating role of resilience.Methods:From March to May 2022, a total of 201 medical staff in the Affiliated Hospital of Jining Medical University were investigated with the General Information Questionnaire, Workplace Social Capital Scale, Connor-Davidson Resilience Scale (CD-RISC-10) and Generalized Anxiety Disorder-7 (GAD-7) . K-S method was used for normdity test of econometic voriobles, and normal distribution data were represented by Mean± SD, Pearson correlation analysis and linear regression analysis were used to test correlation between variables and mediating effect, and Bootstrap method was carried out by SPSS macro program PROCESS v3.5 to verify the mediating effect. Results:The detection rate of anxiety was 59.20% (119/201) in medical staff. The scores of social capital at work (28.90±5.83) and resilience (31.55±4.98) were negatively correlated with the score of anxiety (7.20±2.06) ( r=-0.338, -0.510, P<0.001) , while the score of social capital at work was positively correlated with resilience ( r=0.392, P<0.001) . Workplace social capital positively predicted resilience (β=0.392, P<0.001) , and both workplace social capital (β=-0.222, P=0.001) and resilience at work (β=-0.423, P<0.001) negatively predicted anxiety score. The direct effect of social capital in the workplace of medical staff on anxiety was -0.222 (95% CI: -0.349~-0.095, P=0.001) , and the indirect effect of resilience on anxiety was -0.166 (95% CI: -0.265~-0.080) . The resilience of medical staff had a partial mediating effect between workplace social capital and anxiety, which accounted for 42.78% of the total effect. Conclusion:The resilience of medical staff has a partial mediating effect between workplace social capital and anxiety. Workplace social capital can not only directly affect the anxiety of medical staff, but also indirectly affect it through resilience.

Halogenated sesquiterpenes are important derivatives of sesquiterpenes, referring to chemical components of sesquiterpenes that contain halogens such as chlorine, bromine, and iodine. Halogenated sesquiterpenes have attracted attention from researchers in China and abroad because of their diverse structures, unique halogen elements, and extensive pharmacological activities. Studies have shown that halogenated sesquiterpenes exhibit significant antimicrobial, anti-inflammatory, anticancer, insecticidal, hypoglycemic, and enzyme inhibitory activities. In order to better explore the potential pharmaceutical value of halogenated sesquiterpenes, this paper reviewed the structural characteristics and pharmacological activities of halogenated sesquiterpenes in the past two decades, aiming to provide references for further research and development of this class of compounds.
Sesquiterpenes/chemistry* ; Anti-Inflammatory Agents/pharmacology* ; China

Objective:To explore the influence of social capital at work on anxiety of medical staff, and the mediating role of resilience.Methods:From March to May 2022, a total of 201 medical staff in the Affiliated Hospital of Jining Medical University were investigated with the General Information Questionnaire, Workplace Social Capital Scale, Connor-Davidson Resilience Scale (CD-RISC-10) and Generalized Anxiety Disorder-7 (GAD-7) . K-S method was used for normdity test of econometic voriobles, and normal distribution data were represented by Mean± SD, Pearson correlation analysis and linear regression analysis were used to test correlation between variables and mediating effect, and Bootstrap method was carried out by SPSS macro program PROCESS v3.5 to verify the mediating effect. Results:The detection rate of anxiety was 59.20% (119/201) in medical staff. The scores of social capital at work (28.90±5.83) and resilience (31.55±4.98) were negatively correlated with the score of anxiety (7.20±2.06) ( r=-0.338, -0.510, P<0.001) , while the score of social capital at work was positively correlated with resilience ( r=0.392, P<0.001) . Workplace social capital positively predicted resilience (β=0.392, P<0.001) , and both workplace social capital (β=-0.222, P=0.001) and resilience at work (β=-0.423, P<0.001) negatively predicted anxiety score. The direct effect of social capital in the workplace of medical staff on anxiety was -0.222 (95% CI: -0.349~-0.095, P=0.001) , and the indirect effect of resilience on anxiety was -0.166 (95% CI: -0.265~-0.080) . The resilience of medical staff had a partial mediating effect between workplace social capital and anxiety, which accounted for 42.78% of the total effect. Conclusion:The resilience of medical staff has a partial mediating effect between workplace social capital and anxiety. Workplace social capital can not only directly affect the anxiety of medical staff, but also indirectly affect it through resilience.

Objective: To observe the different imaging manifestations of condylar sclerosis in temporomandibular joint osteoarthrosis and explore the imaging significance of condylar sclerosis. Methods: From January 2018 to December 2020, 50 patients with temporomandibular joint condylar sclerosis were examined by cone-beam CT (CBCT) and underwent spiral CT, MRI and radionuclide bone imaging at the Department of Oral and Maxillofacial Surgery in General Hospital of Chinese PLA. There were 15 males and 35 females aged from 16 to 65 years with age of (42.7±14.5) years. The imaging manifestations of CBCT, spiral CT, MRI and radionuclide bone imaging, joint disc displacement and abnormal bone metabolism of condylar sclerosis were analyzed. And the area of condylar sclerosis was graded according to the image of CBCT. Results: A total of 50 patients were included, including 38 unilateral condylar sclerosis, 12 patients with bilateral condylar sclerosis, the total condylar sclerosis were 66. There was no significant difference between the detection rate of further spiral CT (95.5%, 63/66) and CBCT (100.0%, 66/66) (corrected χ²=1.36,P=0.244). The area of condylar sclerosis was (35.5±4.5) mm², ranged from 1 to 100 mm². In addition, spiral CT showed more clearly condylar sclerosis than CBCT. Sclerosis can occur in all parts of condyle, mainly in the upper middle region (68.2%,45/66) in coronal position and in the upper front region (71.2%,47/66) in sagittal position. Fifty-seven condylar sclerosis were detected by MRI, including 4(4/19) condylar sclerosis less than 4 mm². There was significant difference in the displacement of temporomandibular joint disc between the sclerotic side and the non sclerotic side (χ²=10.09, P=0.006). MRI display the condylar sclerosis showed low signal (56/62), followed by high signal (5/62) and medium signal (1/62). Radionuclide bone imaging showed that 4 of the 38 patients with unilateral condyle sclerosis had symmetrical bone metabolism, 34 had abnormal bone metabolism, and 21 patients had concentrated on the non-sclerotic side. Radionuclide bone imaging showed that 4 of the 38 patients with unilateral condyle sclerosis had symmetrical bone metabolism and 34 had abnormal bone metabolism. Conclusions: Spiral CT is more accurate than CBCT in terms of condyle sclerosis through different imaging analysis, and the detection rate of both is higher than MRI. Most of condylar sclerosis showed different degrees of low signal on MRI. The condylar sclerosis side is usually manifested by abnormal bone metabolism.
Male ; Female ; Humans ; Mandibular Condyle/diagnostic imaging* ; Sclerosis/diagnostic imaging* ; Temporomandibular Joint/diagnostic imaging* ; Temporomandibular Joint Disorders/etiology* ; Temporomandibular Joint Disc/diagnostic imaging* ; Cone-Beam Computed Tomography ; Temporomandibular Joint Dysfunction Syndrome ; Osteoarthritis/etiology* ; Magnetic Resonance Imaging

Objective: To investigate the clinical and pathological features, treatments and prognosis of laryngeal neuroendocrine carcinoma (LNEC). Methods: We conducted the retrospective analysis of the clinical data of 12 patients with LNEC admitted to the Department of Otorhinolaryngology Head and Neck Surgery, Second Hospital of Shanxi Medical University from May 2014 to December 2021, including 9 males and 3 females, aged 50-77 years. There were 4 cases of typical carcinoid tumour (highly differentiated), 5 cases of atypical carcinoid tumour (moderately differentiated) and 3 cases of neuroendocrine small cell carcinoma (hypofractionated). The clinical features, diagnosis, treatment and prognosis of LNEC were analysed. Results: The clinical manifestations of LNEC varied according to the tumour type but did not correlate with the pathological types. The supraglottic type was characterized by sore throat, foreign body sensation in the pharynx, coughing, obstructive sensation when eating and choking on water. The treatments were determined according to the pathological types, lesion location and invasion scope. Of 12 patients 4 underwent horizontal partial laryngectomy plus elective lymphatic dissection plus postoperative radiotherapy/chemotherapy, 4 underwent vertical partial laryngectomy (3 of them with cervical lymphatic dissection), 3 underwent supported laryngoscopic plasma laryngectomy for laryngeal cancer, and 1 abandoned for treatment. With the follow-up of 8 -78 months, 5 patients were alive, 1 died from chemotherapy reactions, 3 died from other diseases, 1 died from lung metastasis, 1 died from lung infection and 1 was lost to follow-up. Conclusion: LNEC is clinically rare, the clinical manifestations are less specificity, diagnosis relies on pathological and immunohistochemical examinations, and treatment modalities and prognoses are closely related to the pathological subtypes of LNEC.
Humans ; Male ; Female ; Laryngeal Neoplasms/pathology* ; Retrospective Studies ; Carcinoma, Neuroendocrine/pathology* ; Laryngectomy ; Carcinoid Tumor/pathology*