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*

OBJECTIVES: As early as the Apollo 11 mission, astronauts experienced ocular, skin, and upper airway irritation after lunar dust (LD) was brought into the return cabin, drawing attention to its potential biological toxicity. However, the biological effects of LD exposure through the digestive system remain poorly understood. This study aimed to evaluate the impact of digestive exposure to lunar dust simulant (LDS) on gut microbiota and on the intestine, liver, kidney, lung, and bone in mice. METHODS: Eight-week-old female C57BL/6J mice were used. LDS was used as a substitute for lunar dust, and Shaanxi loess was used as Earth dust (ED). Mice were randomly divided into a phosphate buffered saline (PBS) group, an ED group (500 mg/kg), and a LDS group (500 mg/kg), with assessments at days 7, 14, and 28. Mice were gavaged once every 3 days, with body weight recorded before each gavage. At sacrifice, fecal samples were analyzed by 16S ribosomal RNA (rRNA) sequencing; inflammatory cytokine expression [interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α)] in intestinal, liver, and lung tissues was measured by real-time reverse transcription PCR (real-time RT-PCR); hematoxylin and eosin (HE) staining was performed on lung, liver, and intestinal tissues; Periodic acid-Schiff (PAS) staining was used to assess the integrity of the intestinal mucus barrier, and immunohistochemical staining was performed to evaluate the expression of mucin-2 (MUC2). Serum biochemical tests assessed hepatic and renal function. Femoral bone mass was analyzed by micro-computed tomography (micro-CT); osteoblasts and osteoclasts were assessed by osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) staining. Bone marrow immune cell subsets were analyzed by flow cytometry. RESULTS: At day 10, weight gain was slowed in ED and LDS groups. At days 22 and 28, body weight in both ED and LDS groups was significantly lower than controls (both P<0.05). LDS exposure increased microbial species richness and diversity at day 7. Compared with the PBS and ED groups, mice in the LDS group showed increased relative abundance of Deferribacterota, Desulfobacterota, and Campylobacterota, and decreased Firmicutes, with increased Helicobacter typhlonius and reduced Lactobacillus johnsonii and Lactobacillusmurinus. HE and PAS staining of the colon showed that mucosal structural disruption and goblet cell loss were more severe in the LDS group. In addition, immunohistochemistry revealed a significant downregulation of MUC2 expression in this group (P<0.05). No obvious pathological alterations were observed in liver HE staining among the 3 groups, and none of the groups exhibited notable hepatic or renal dysfunction. HE staining of the lungs in the ED and LDS groups showed increased perivascular inflammatory cell infiltration (both P<0.05). CONCLUSIONS LDS exposure via the digestive route induces gut dysbiosis, intestinal barrier disruption, pulmonary inflammation, bone loss, and bone marrow immune imbalance. These findings indicate that LD exposure poses potential health risks during future lunar missions. Targeted restoration of beneficial gut microbiota may represent a promising strategy to mitigate LD-related health hazards.
Animals ; Dust ; Mice ; Mice, Inbred C57BL ; Dysbiosis/etiology* ; Female ; Gastrointestinal Microbiome/drug effects* ; Moon ; Liver/metabolism* ; Digestive System/microbiology* ; Lung/metabolism* ; Kidney

OBJECTIVES: Due to prolonged exposure to cosmic radiation and meteorite impacts, lunar surface dust forms nanoscale angular particles with strong electrostatic adsorption properties. These dust particles pose potential inhalation risks, yet their pulmonary toxicological mechanisms remain unclear. Given the need for dust exposure protection in future lunar base construction and resource development, this study established an acute exposure model using lunar soil simulant (LSS) and used Earth soil (ES; Loess from Shaanxi, China) as a comparison to investigate lung injury mechanisms. METHODS: C57BL/6 mice were randomly assigned to 3 groups: Phosphate buffered saline (PBS), LSS, and ES, with 5 to 7 mice per group. Mice in the LSS and ES groups received a single intratracheal instillation to induce acute inhalation exposure. Body weight was monitored for 28 days. Mice were euthanized at days 3, 7, 14, and 28 post-exposure, and peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected. Immune cell subsets in BALF were analyzed using flow cytometry. Hematoxylin-eosin (HE) staining assessed lung structure and inflammation; periodic acid-Schiff (PAS) staining evaluated airway mucus secretion; Masson staining examined collagen deposition. Real-time reverse transcription PCR (real-time RT-PCR) was used to measure the mRNA expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and epithelial barrier genes (Occludin, Cadherin-1, and Zo-1). Lung tissues at day 7 were subjected to transcriptomic sequencing, followed by immune infiltration and pathway enrichment analyses to determine immunoregulatory mechanisms. RESULTS: Body weight in the ES group progressively declined after day 18 (all P<0.05), while the LSS group showed no significant changes compared with the control group. HE staining showed both LSS and ES induced inflammatory cell infiltration around airways and vasculature, which persisted for 28 days but gradually lessened over time. PAS staining revealed marked mucus hypersecretion in the LSS group at day 3, followed by gradual recovery; no significant mucus changes were observed in the ES group. Masson staining indicated no obvious pulmonary fibrosis in either group within 28 days. Real-time RT-PCR demonstrated significant upregulation of IL-1β and TNF-α in both LSS and ES groups, peaking on day 7, accompanied by downregulation of epithelial barrier genes (Occludin, Cadherin-1, and Zo-1)(all P<0.05). Transcriptomic analysis showed that both LSS and ES activated chemokine-related pathways and enriched leukocyte migration and neutrophil recruitment pathways. Further validation revealed upregulation of CXCL2 and MMP12 in the LSS group, whereas CXCL3 and MMP12 were predominantly elevated in the ES group. CONCLUSIONS Both LSS and ES can induce sustained lung injury and neutrophil infiltration in mice, though the underlying molecular mechanisms differ. Compared with ES, exposure to LSS additionally triggers a transient eosinophilic response, suggesting that lunar dust particles possess stronger immunostimulatory potential and higher biological toxicity.
Animals ; Mice ; Mice, Inbred C57BL ; Soil ; Lung Injury/etiology* ; Dust ; Bronchoalveolar Lavage Fluid ; Moon ; Lung/pathology* ; Inhalation Exposure/adverse effects* ; Male

Objective:To analyze the clinical features and genetic characteristics of a patient with Shwachman-Diamond syndrome (SDS) due to compound heterozygous variants of SBDS gene.Methods:A female child with SDS who was admitted to the Children's Hospital Affiliated to Zhengzhou University in February 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her elder sister and parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a 1-year-and-1-month-old girl, had mainly manifested with diarrhea, hematochezia, growth retardation and malnutrition, along with increased transaminases and decreased neutrophils and hemoglobin. The anteroposterior X-ray of her left wrist indicated significantly delayed bone age. Colonoscopy revealed that her colorectal mucosa was erosive with oily food residues attached to the intestinal lumen. Genetic testing revealed that she has harbored c. 258+ 2T>C and c. 100A>G compound heterozygous variants of the SBDS gene. The c. 258+ 2T>C variant has derived from her father and known to be pathogenic, whilst the other has derived from her mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 100A>G variant was classified as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PM5+ PP3). Conclusion:The compound heterozygous variants of c. 258+ 2T>C and c. 100A>G probably underlay the SDS in this child. For children with refractory diarrhea, liver damage and growth retardation, SDS should be suspected, and genetic testing can facilitate the diagnosis and treatment.

Objective:To clarify the genetic diagnosis of two children with ring chromosome 18 and explore their mechanisms and clinical phenotypes.Methods:Two patients treated at the Children′s Hospital of Henan Province respectively in June 2022 and March 2023 were selected as the study subjects. Genetic testing and diagnosis were carried out through copy number variation sequencing (CNV-seq), G-banded chromosomal karyotyping, and whole exome sequencing (WES). This study was approved by the Children′s Hospital of Henan Province (Ethics No. 2023-K-075).Results:Child 1 had mainly manifested developmental delay, white matter hypoplasia, type 1 diabetes mellitus, and micropenis. He was found to have a chromosomal karyotype of 46, XY, r(18)(p11.21q22.1)[40]/46, XY[7], and CNV-seq results showed that he has a 14.86 Mb deletion at 18p11.21p11.32 and a 14.02 Mb deletion at 18q22.1q23. Child 2 had peculiar facial features, delayed white matter myelination, developmental delay, atrial septal defect, severe sensorineural deafness, and congenital laryngeal stridor. He was found to have a chromosomal karyotype of 46, XY, r(18)(p11.2q23). CNV-seq result proved that he had a 14.86 Mb deletion at 18p11.21p11.32 and a 20.74 Mb deletion at 18q21.32q23. WES has failed to detect single nucleotide variants (SNVs) in either child, but revealed a large segmental deletion at chromosome 18 in both of them.Conclusion:Both children were diagnosed with ring chromosome 18 syndrome. The different size of the deletional fragments in the 18q region and mosaicism of ring chromosome 18 in child 1 may underlay the variation in their clinical phenotypes. The type 1 diabetes mellitus and micropenis noted in both children are novel features for ring chromosome 18 syndrome.

Objective:To investigate the effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats.Methods:This study was an experimental study. Eighteen 8-week-old male Sprague Dawley rats were divided into control group, diabetes group, and diabetes+metformin group according to complete random grouping method, with 6 rats in each group. The latter two groups of rats were used to create diabetic models, and then four circular full-thickness skin defect wounds with a diameter of 5 mm were made on the back of 18 rats. Metformin F-127 hydrogel was applied only to the wounds of rats in diabetes+metformin group. The wound healing status on post injury day (POD) 7 and 13 was observed and the wound healing rate was calculated. The wound tissue on POD 7 and 13 was collected for hematoxylin-eosin staining to measure the length of re-epithelialized epidermis and calculate the change rates in diameters of epidermal and dermal wounds, for immunohistochemical staining to detect the relative expressions of keratin 10 and proliferating cell nuclear antigen (PCNA), and for Western blotting to detect the protein expressions of keratin 10 and PCNA. The sample size in all the above experiments was 8 except that in the last experiment was 3. The correlations between the relative expressions of keratin 10 and PCNA in wound tissue in three groups of rats and their wound healing rates, and the correlation between the relative expressions of keratin 10 and PCNA in wound tissue were analyzed.Results:On POD 7, the wound healing rates of rats in diabetes group and diabetes+metformin group were 81.48% (77.89%, 85.53%) and 93.04% (92.51%, 94.24%), which were significantly lower than 100% (97.17%, 100%) in control group (with Z values of 2.37 and -3.36, respectively, P<0.05); the wound healing rate of rats in diabetes+metformin group was significantly higher than that in diabetes group ( Z=3.45, P<0.05). On POD 13, the wound healing rates of rats in control group and diabetes+metformin group were both 100% (100%, 100%), which were significantly higher than 94.47% (90.68%, 99.82%) in diabetes group (with Z values of 2.90 and -2.90, respectively, P<0.05). On POD 7, the change rates in epidermal wound diameter of rats in control group and diabetes+metformin group were significantly higher than that in diabetes group (with Z values of 3.36 and -2.74, respectively, P<0.05). The change rates in dermal wound diameter of rats in the three groups were similar on POD 7 and 13 ( P>0.05). The lengths of re-epithelialized epidermis of rats in control group and diabetes+metformin group on POD 13 were significantly longer than that in diabetes group (with Z values of 3.34 and -2.64, respectively, P<0.05). The relative expressions of keratin 10 in wound tissue of rats in diabetes group on POD 7 and 13 were significantly higher than those in control group (with Z values of -3.36 and -3.26, respectively, P<0.05) and diabetes+metformin group (with Z values of 3.36 and 3.15, respectively, P<0.05), and the relative expression of keratin 10 in wound tissue of rats in diabetes+metformin group on POD 7 was significantly lower than that in control group ( Z=3.05, P<0.05); the relative expressions of PCNA in wound tissue of rats in diabetes group on POD 7 and 13 were significantly lower than those in control group (with both Z values of 3.36, P<0.05) and diabetes+metformin group (with both Z values of -3.36, P<0.05). The protein expressions of keratin 10 in wound tissue of rats in control group and diabetes+metformin group on POD 7 as well as that in diabetes+metformin group on POD 13 were significantly lower than those in diabetes group ( P<0.05), and the protein expressions of PCNA in wound tissue of rats in control group and diabetes+metformin group on POD 7 were significantly higher than that in diabetes group ( P<0.05). There was a significant positive correlation between the relative expression of keratin 10 in wound tissue and the wound healing rate in control group and diabetes+metformin group of rats (with r values of 0.78 and 0.71, respectively, P<0.05), there was a significant negative correlation between the relative expression of PCNA in wound tissue and the wound healing rate in diabetes+metformin group of rats ( r=-0.60, P<0.05), and there was a significant negative correlation between the relative expressions of PCNA and keratin 10 in wound tissue of rats in diabetes group and diabetes+metformin group (with r values of -0.41 and -0.49, respectively, P<0.05). Conclusions:The diabetic rats with full-thickness skin defect wound exhibit delayed healing, accompanied by up-regulation of keratin 10 and down-regulation of PCNA in keratinocytes in the wound tissue. Metformin can promote wound healing in diabetic rats with full-thickness skin defects by down-regulating keratin 10 expression and up-regulating PCNA expression in keratinocytes in the wound tissue, and the wound healing rate was positively correlated with the expression of keratin 10 and negatively correlated with the expression of PCNA.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.