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*

Objective To investigate the causal relationship between serum total bile acid (TBA) levels and gastric cancer (GC) using regression discontinuity design (RDD). Methods A total of 1244 GC patients and 1333 healthy controls were included in the study. Demographic characteristics, gallbladder disease history, tumor markers, and serum TBA levels were collected from both groups. Logistic regression was used to construct a risk prediction model to estimate the risk of GC. RDD was employed with serum TBA as the grouping variable and the individual risk of developing GC as the outcome variable. Results The predictive factors in the GC risk prediction model included age, sex, body mass index(BMI), serum TBA, carcinoembryoniv antigen(CEA), alpha fetoprotein(AFP), carbohydrate antigen 199(CA199), and CA125. Serum TBA was identified as an independent risk factor for GC (OR=1.054, 95% CI: 1.030 to 1.079). RDD analysis indicated that when serum TBA levels reached 8 μmol/L, the probability of developing GC increased sharply by 23.7%. The breakpoint remained statistically significant following validity and robustness assessments. Conclusion The study demonstrates a positive causal relationship between serum TBA levels and GC, when the serum TBA level reaches 8 μmol/L, the risk of an individual developing GC increases sharply.
Humans ; Stomach Neoplasms/etiology* ; Male ; Female ; Middle Aged ; Bile Acids and Salts/blood* ; Aged ; Adult ; Risk Factors ; Case-Control Studies ; Biomarkers, Tumor/blood* ; Logistic Models

AIM: To investigate the changes of retinal nerve fiber layer(RNFL)thickness, retinal thickness and blood flow density in different stages of diabetic retinopathy(DR)patients based on optical coherence tomography angiography(OCTA).METHODS: A retrospective analysis was conducted on 382 patients(382 eyes)diagnosed with DR in our hospital from February 2023 to February 2024. According to the staging criteria, the patients were divided into mild group(n=121), moderate group(n=133), severe group(n=72), and proliferative group(n=56). The general clinical data of the four groups of patients was compared; OCTA was used to scan and collect data from all patients, and the RNFL thickness, retinal thickness, and blood flow density were compared among the four groups of patients.RESULTS: There was no statistically significant difference in age, gender, hypertension, chronic kidney disease, and random blood glucose among patients in the mild, moderate, severe, and proliferative groups(all P>0.05). As the stage of DR worsened, the duration of the disease gradually prolonged(P<0.05). The thickness of the RNFL(superior, inferior, temporal, nasal, and average thickness)and retinal thickness significantly increased with the severity of DR(all P<0.001); however, there was no statistically significant difference in inferior RNFL thickness between the moderate and mild groups(P>0.05). The blood flow density in the superficial and deep retinal layers, as well as in the choroidal capillary layer, significantly decreased with the progression of DR(all P<0.05). Nevertheless, there was no statistically significant difference in superficial retinal blood flow density between the moderate and severe groups(P>0.05).CONCLUSION: OCTA can accurately observe the changes in RNFL thickness, retinal thickness, and blood flow density in patients with DR at different stages, which can serve as sensitive indicators for monitoring DR progression.

Objective To explore the application effect of ultrasound-assisted localization in spinal anesthesia for elderly patients with hip fractures.Methods A total of 114 elderly patients undergoing hip fracture surgery with spinal anesthesia in our hospital from September 2022 to June 2024 were enrolled.The random number table method was applied to allocate participants into two groups:surface anatomical landmark localization group and ultrasound-assisted localization group,with 57 patients in each group.Both groups of patients underwent spinal anesthesia via the paramedian approach for puncture.The first-attempt puncture success rate,success rate of the initial puncture site,number of skin punctures,number of adjusted epidural needle direction,positioning time of the puncture point,puncture time(puncture success time,anesthesia time,and total time),adverse events during the puncture process(nerve hypersensitivity and accidental puncture of the dura mater),spinal anesthesia related complications(back pain,headache,and nerve injury),patient satisfaction and hospital stay were observed and compared between the two groups.The quality of early postoperative recovery was evaluated by using the 15-Item Quality of Recovery(QOR-15)scale at 24 h after surgery.Results The first-attempt puncture success rate in the ultrasound-assisted localization group was 71.9％(41/57),which was significantly higher than that in the surface anatomical landmark localization group[28.1％(16/57),x2=21.930,P=0.000].The success rate of the initial puncture site in the ultrasound-assisted localization group was 87.7％(50/57),which was significantly higher than that in the surface anatomical landmark localization group[54.4％(31/57),x2=15.396,P=0.000].The number of skin punctures and adjusted epidural needle direction in the ultrasound-assisted localization group were 1(1,1)and 0(0,1)times,while in the surface anatomical landmark localization group were 2(1,3)and 3(0,5)times,with statistically significant differences(all P=0.000).The puncture positioning time in the ultrasound-assisted localization group was 2.2(1.7,3.2)min,which was significantly longer than that in the surface anatomical landmark localization group[0.8(0.5,1.2)min,Z=-8.418,P=0.000].The puncture success time,anesthesia time,and total time of the ultrasound-assisted localization group were 1.9(1.7,2.3),4.9(4.3,5.3),and 7.1(6.3,8.7)min,while of the surface anatomical landmark localization group were 5.1(2.3,8.0),7.9(5.7,11.0),and 8.6(6.6,12.0)min,with statistically significant differences(all P＜0.05).There were no statistically significant differences in the incidence of nerve hypersensitivity during operation(3.5％vs.7.0％,x2=0.176,P=0.675),accidental puncture of the dura mater by epidural needles(0％vs.3.5％,P=0.496),postoperative headache(0％vs.3.5％,P=0.496),and back pain(1.8％vs.10.5％,x2=2.435,P=0.119)between the two groups.Both groups of patients showed no symptoms of nerve injury after surgery.There were no statistically significant differences in QOR-15 scores at 24 h postoperatively[119(115,124)points vs.116(112,121)points,Z=-1.858,P=0.063]and length of hospital stay[10.0(9.0,12.5)dvs.10.0(8.0,13.0)d,Z=-0.043,P=0.966]between the two groups.The satisfaction of patients in the ultrasound-assisted localization group was significantly higher than that in the surface anatomical landmark localization group(P=0.004).Conclusion Application of ultrasound-guided localization in spinal anesthesia for elderly patients with hip fractures significantly improves the first-attempt puncture and initial puncture site success rates,reduces skin puncture attempts and adjustments of the epidural needle direction,shortens time of anesthetic procedure,and enhances patient satisfaction,making it highly recommendable for clinical use.

Objective To investigate the levels of hypoxia-inducible factor 1α(HIF-1α)and lipopolysaccha-ride signal receptor(CD14)in gingival crevicular fluid of preschool children with dental caries and their clini-cal significance.Methods A total of 468 preschool children(aged 3-6 years)who underwent oral examina-tions in the hospital from April 2022 to May 2024 were selected as the research objects and were divided into the observation group(with dental caries,n=107)and the healthy group(without dental caries,n=361)based on the presence or absence of dental caries.The observation group was further divided into three sub-groups according to the degree of caries activity test(CAT)score:low activity group(n=29),moderate activ-ity group(n=46),and high activity group(n=32).The children in the observation group were followed up for 6 months,and then divided into the occurrence group(n=36)and the non-occurrence group(n=71)based on whether chronic apical periodontitis occurred during the follow-up period.The levels of HIF-1α and CD14 in gingival crevicular fluid in the research objects were detected.The relationship between the levels of HIF-1α and CD14 in gingival crevicular fluid of preschool children with dental caries and CAT score was ex-plored by Pearson correlation analysis.The predictive value of HIF-1α and CD14 levels in gingival crevicular fluid for chronic apical periodontitis in preschool children with dental caries was explored by receiver operating characteristic(ROC)curve.Results The levels of HIF-1α and CD14 in gingival crevicular fluid in the obser-vation group were higher than those in the healthy group(P＜0.05).With the increase of CAT score,the lev-els of HIF-1α and CD14 in gingival crevicular fluid gradually increased(high activity group＞moderate activi-ty group＞low activity group),and the differences were statistically significant(P＜0.05).The levels of HIF-1α and CD14 in gingival crevicular fluid of preschool children with dental caries were positively correlated with CAT score(r=0.526,0.634,P＜0.001).The levels of HIF-1α and CD14 in gingival crevicular fluid in the occurrence group were significantly higher than those in the non-occurrence group(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of combined prediction of HIF-1α and CD14 levels in gingival crevicular fluid for chronic apical periodontitis in preschool children with dental caries was 0.902(95％CI:0.857-0.952),which was higher than 0.709(95％CI:0.664-0.759)and 0.825(95％CI:0.775-0.870)of individual prediction of HIF-1α and CD14 levels in gingival crevicular fluid.Conclusion HIF-1α and CD14 are highly expressed in gingival crevicular fluid of preschool children with dental caries,and their levels are related to the activity of dental caries and the occurrence of chronic apical periodontitis in preschool chil-dren with dental caries.The combined detection of the two can be used as effective indicators for predicting the occurrence of chronic apical periodontitis in preschool children with dental caries.

AIM:To investigate the effects of microRNA-200a(miR-200a)on the formation of primary cilia and the apoptosis in X-ray-injured cardiac fibroblasts.METHODS:Hearts were isolated from neonatal Wistar rats and di-gested with trypsin.Cardiac fibroblasts were isolated,irradiated with 1 Gy of X-ray,and subsequently transfected with miR-200a-3p mimic or si-IFT88.Primary cilia were detected by immunofluorescence staining,and tranfoming growth fac-tor-β1(TGF-β1)in the culture medium was detected by ELISA.The viability of cardiac fibroblasts was detected by CCK-8.The mRNA expression of tumor necrosis factor-α(TNF-α)and caspase-3 was detected by RT-qPCR,and the protein expression of TNF-α,caspase-3,collagen type I α1 chain(Col1α1)and TGF-β1 was detected by Western blot.RE-SULTS:Compared with control group,X-ray irradiation significantly decreased the expression of miR-200a-3p and the level of apoptosis,but increased the proportion of cells with primary cilia,the length of primary cilia and the viability of cardiac fibroblasts.Compared with X-ray group,the percentage of apoptotic cardiac fibroblasts in si-IFT88 group was in-creased.Compared with X-ray group,the proportion of cells with primary cilia and the TGF-β1 content in cardiac fibro-blasts were reduced,and the proportion of apoptotic cells increased in miR-200a-3p overexpression group.CONCLU-SION:X-ray-induced down-regulation of miR-200a-3p in neonatal rat cardiac fibroblasts drives the formation of primary cilia and suppresses the apoptosis.

AIM:To investigate the effects of microRNA-200a(miR-200a)on the formation of primary cilia and the apoptosis in X-ray-injured cardiac fibroblasts.METHODS:Hearts were isolated from neonatal Wistar rats and di-gested with trypsin.Cardiac fibroblasts were isolated,irradiated with 1 Gy of X-ray,and subsequently transfected with miR-200a-3p mimic or si-IFT88.Primary cilia were detected by immunofluorescence staining,and tranfoming growth fac-tor-β1(TGF-β1)in the culture medium was detected by ELISA.The viability of cardiac fibroblasts was detected by CCK-8.The mRNA expression of tumor necrosis factor-α(TNF-α)and caspase-3 was detected by RT-qPCR,and the protein expression of TNF-α,caspase-3,collagen type I α1 chain(Col1α1)and TGF-β1 was detected by Western blot.RE-SULTS:Compared with control group,X-ray irradiation significantly decreased the expression of miR-200a-3p and the level of apoptosis,but increased the proportion of cells with primary cilia,the length of primary cilia and the viability of cardiac fibroblasts.Compared with X-ray group,the percentage of apoptotic cardiac fibroblasts in si-IFT88 group was in-creased.Compared with X-ray group,the proportion of cells with primary cilia and the TGF-β1 content in cardiac fibro-blasts were reduced,and the proportion of apoptotic cells increased in miR-200a-3p overexpression group.CONCLU-SION:X-ray-induced down-regulation of miR-200a-3p in neonatal rat cardiac fibroblasts drives the formation of primary cilia and suppresses the apoptosis.

Objective To explore the application effect of ultrasound-assisted localization in spinal anesthesia for elderly patients with hip fractures.Methods A total of 114 elderly patients undergoing hip fracture surgery with spinal anesthesia in our hospital from September 2022 to June 2024 were enrolled.The random number table method was applied to allocate participants into two groups:surface anatomical landmark localization group and ultrasound-assisted localization group,with 57 patients in each group.Both groups of patients underwent spinal anesthesia via the paramedian approach for puncture.The first-attempt puncture success rate,success rate of the initial puncture site,number of skin punctures,number of adjusted epidural needle direction,positioning time of the puncture point,puncture time(puncture success time,anesthesia time,and total time),adverse events during the puncture process(nerve hypersensitivity and accidental puncture of the dura mater),spinal anesthesia related complications(back pain,headache,and nerve injury),patient satisfaction and hospital stay were observed and compared between the two groups.The quality of early postoperative recovery was evaluated by using the 15-Item Quality of Recovery(QOR-15)scale at 24 h after surgery.Results The first-attempt puncture success rate in the ultrasound-assisted localization group was 71.9％(41/57),which was significantly higher than that in the surface anatomical landmark localization group[28.1％(16/57),x2=21.930,P=0.000].The success rate of the initial puncture site in the ultrasound-assisted localization group was 87.7％(50/57),which was significantly higher than that in the surface anatomical landmark localization group[54.4％(31/57),x2=15.396,P=0.000].The number of skin punctures and adjusted epidural needle direction in the ultrasound-assisted localization group were 1(1,1)and 0(0,1)times,while in the surface anatomical landmark localization group were 2(1,3)and 3(0,5)times,with statistically significant differences(all P=0.000).The puncture positioning time in the ultrasound-assisted localization group was 2.2(1.7,3.2)min,which was significantly longer than that in the surface anatomical landmark localization group[0.8(0.5,1.2)min,Z=-8.418,P=0.000].The puncture success time,anesthesia time,and total time of the ultrasound-assisted localization group were 1.9(1.7,2.3),4.9(4.3,5.3),and 7.1(6.3,8.7)min,while of the surface anatomical landmark localization group were 5.1(2.3,8.0),7.9(5.7,11.0),and 8.6(6.6,12.0)min,with statistically significant differences(all P＜0.05).There were no statistically significant differences in the incidence of nerve hypersensitivity during operation(3.5％vs.7.0％,x2=0.176,P=0.675),accidental puncture of the dura mater by epidural needles(0％vs.3.5％,P=0.496),postoperative headache(0％vs.3.5％,P=0.496),and back pain(1.8％vs.10.5％,x2=2.435,P=0.119)between the two groups.Both groups of patients showed no symptoms of nerve injury after surgery.There were no statistically significant differences in QOR-15 scores at 24 h postoperatively[119(115,124)points vs.116(112,121)points,Z=-1.858,P=0.063]and length of hospital stay[10.0(9.0,12.5)dvs.10.0(8.0,13.0)d,Z=-0.043,P=0.966]between the two groups.The satisfaction of patients in the ultrasound-assisted localization group was significantly higher than that in the surface anatomical landmark localization group(P=0.004).Conclusion Application of ultrasound-guided localization in spinal anesthesia for elderly patients with hip fractures significantly improves the first-attempt puncture and initial puncture site success rates,reduces skin puncture attempts and adjustments of the epidural needle direction,shortens time of anesthetic procedure,and enhances patient satisfaction,making it highly recommendable for clinical use.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.