Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.

The relationship between self-esteem and happiness of college students in China:A moderated mediation model.

The objective of the study is to explore the influence of self-esteem on the happiness levels of college students and the mediating roles of social avoidance and loneliness. 1021 college students between 18 and 24 years of age completed the Self-esteem Scale, General Well-being Scale, Social Avoidance and Distress Scale, UCLA Loneliness Scale and Interpersonal Trust Scale.And descriptive statistical analysis and correlation analysis, structural equation model analysis were conducted. The result turns out that Self-esteem negatively predicted the happiness levels of college students. Self-esteem indirectly predicted happiness through three paths: mediating the roles of social avoidance, mediating the roles of loneliness and the chain-mediated roles of social avoidance and loneliness in college students.Interpersonal Trust moderated the relationship between loneliness and happiness.The higher the self-esteem levels of the college students, the less happiness they experienced.

[Medical Institution's Multiple Role in the Collaborative Innovation Transformation Mode of "Industry-University-Research-Medicine" on Domestic Surgical Robots].

In recent years, with the rapid development of Chinese domestic surgical robot technology and the expansion of the application market, the "industry-university-research-medicine" collaborative innovation transformation mode has gradually developed and formed. Medical institutions play an important role in multi-party cooperation with enterprises, universities, and research institutes, as well as in product planning, technology research and development, achievement transformation, and personnel training. On the basis of reviewing the current situation of the development of the "industry-university-research-medicine" collaborative innovation transformation mode of domestic surgical robots, this study explores the multiple roles played by medical institutions in this mode and challenges, further putting forward corresponding recommendations.

Advances in Exosome Research in the Management of Lung Cancer.

Lung cancer is one of the most common malignant tumors, and its death rate is much higher than that of colon, kidney, breast, and prostate cancers, and its 5-year survival rate is only 18%. Lung cancer has no specific clinical symptoms in its early stages and lacks effective detection, making early detection difficult. The survival rate for advanced lung cancer is meager, with a median survival of only 12 months for stage IIIB/IV non-small cell lung cancer treated with platinumbased chemotherapy. Exosomes could provide vital information for the early diagnosis of lung cancer and have the potential to become a tumor marker for lung cancer. In addition, scientists have proposed encouraging ways to treat lung cancer by loading drugs, proteins, microRNAs, and siRNAs into exosomes. Therefore, studying lung cancer exosomes and exosomal nano drugs will provide new ideas and approaches for the diagnosis and treatment of lung cancer. This paper reviews the progress of research on the biological functions of exosomes and exosomal nanomedicines and their applications in clinical practice.

Cold spells linked with respiratory disease hospitalization, length of hospital stay, and hospital expenses: Exploring cumulative and harvesting effects.

BACKGROUND: Previous studies have revealed the relationship between cold spells and morbidity and mortality due to respiratory diseases, while the detrimental effects of cold spells on the length of hospital stay and hospitalization expenses remain largely unknown. METHODS: We collected hospitalization data for respiratory diseases in 11 cities of Shanxi, China during 2017-2019. In each case, exposure to meteorological variables and air pollution was estimated by the bilinear interpolation approach and inverse distance weighting method, respectively, and then averaged at the city level. Cold spells were defined as the daily mean temperature below the 10th, 7.5th, or 5th percentiles for at least 2 to 5 consecutive days. We applied distributed lag non-linear models combined with generalized additive models to assess cumulative effects and harvesting effects. RESULTS: There were significant associations between cold spells and hospital admissions, length of hospital stay, and hospital expenses for respiratory diseases. Compared with the non-cold spell period, the overall (lag 0-21) cumulative risk of hospitalization for total respiratory diseases was 1.232 (95 % CI: 1.090, 1.394) on cold spell days, and the increased length of hospital stay and hospitalization expenses were 112.793 (95 % CI: 10.755, 214.830) days and 127.568 (95 % CI: 40.513, 214.624) thousand Chinese yuan. The overall cumulative risks of cold spells on total respiratory diseases and pneumonia were statistically significant. We further observed harvesting effects in the associations between cold spells and hospital admission, length of hospital stay, and hospitalization expenses for respiratory diseases. CONCLUSIONS: Cumulative cold-spell exposure for up to three weeks is associated with hospitalization, length of hospital stay, and hospital expenses for respiratory diseases. The observed harmful effects of cold spells on respiratory diseases can be partly attributable to harvesting effects.

Associations of Ambient NO2 with Daily Hospitalization, Hospitalization Expenditure and Length of Hospital Stay of Cause-Specific Respiratory Diseases - Shanxi, China, 2017-2019.

What is already known about this topic?: Numerous epidemiological studies have documented the association between ambient nitrogen dioxide (NO2) and mortality and morbidity of respiratory diseases, however, research on the effect of NO2 on the length of hospital stay (LOS) and hospitalization expenditure is limited. What is added by this report?: This study collected the respiratory hospitalization, hospital expenditure, and LOS for respiratory diseases from 2017-2019 in Shanxi, China, and comprehensively evaluated the association between ambient NO2 exposure and respiratory hospitalization, expenditure, and LOS. What are the implications for public health practice?: This study provides evidence on the association between ambient NO2 and respiratory burden, suggesting that continuously reducing the NO2 concentrations could prevent respiratory disease-associated hospital admissions and decrease the relative burden in Shanxi Province and other similar regions.

Ambient sulfur dioxide and hospital expenditures and length of hospital stay for respiratory diseases: A multicity study in China.

BACKGROUND: Ambient sulfur dioxide (SO2) has been associated with morbidity and mortality of respiratory diseases, however, its effect on length of hospital stays (LOS) and cost for these diagnoses remain unclear. METHODS: We collected hospital admission information for respiratory diseases from all 11 cities in the Shanxi Province of China during 2017-2019. We assessed individual-level exposure by using an inverse distance weighting approach based on geocoded residential addresses. A generalized additive model was built to delineate city-specific effects of SO2 on hospitalization, hospital expenditure, and length of hospital stay for respiratory diseases. The overall effects were obtained by random-effects meta-analysis. We further estimated the respiratory burden attributable to SO2 by comparing different reference concentrations. RESULTS: We observed significant effects of SO2 exposure on respiratory diseases. At the provincial level, each 10 µg/m3 increase in SO2 on lag03 was associated with a 0.63% (95% CI: 0.14-0.11) increase in hospital admission, an increase of 4.56 days (95% CI: 1.16-7.95) of hospital stay, and 3647.97 renminbi (RMB, Chinese money) (95% CI: 1091.05-6204.90) in hospital cost. We estimated about 6.13 (95% CI: 1.33-11.10) thousand hospital admissions, 65.77 million RMB (95% CI: 19.67-111.87) in hospital expenditure, and 82.13 (95% CI: 20.87-143.40) thousand days of hospital stay could have potentially been avoided had the daily SO2 concentrations been reduced to WHO's reference concentration (40 µg/m3). Variable values in correspondence with this reference concentration could reduce the hospital cost and LOS of each case by 52.67 RMB (95% CI: 15.75-89.59) and 0.07 days (95% CI: 0.02-0.117). CONCLUSION: This study provides evidence that short-term ambient SO2 exposure is an important risk factor of respiratory diseases, indicating that continually tightening policies to reduce SO2 levels could effectively reduce respiratory disease burden in Shanxi Province.

Transcriptome Analysis of Ivosidenib-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer.

Ivosidenib is an isocitrate dehydrogenase mutant inhibitor that the US Food and Drug Administration recently approved for the treatment of leukemia. Studies suggested that ivosidenib may inhibit the progression of non-small cell lung cancer (NSCLC). In the present study, we explored RNAs and their potential regulatory mechanisms by which ivosidenib treats NSCLC cells. We used MTT assays, Transwell assays, and flow cytometry to measure the anti-tumor effects of ivosidenib in NSCLC cells. We performed whole transcriptome sequencing to determine differentially expressed mRNAs (DE-mRNAs) and non-coding RNAs (ncRNA). We used GO and KEGG pathway enrichment analyses to identify the functions and potential mechanisms. According to miRNA target interactions, we constructed a competing endogenous network. Ivosidenib inhibited the proliferation, invasion, and migration of NSCLC cells and inhibited tumor growth in vivo. We identified 212 DE-mRNAs, four DE-miRNAs, and 206 DE-lncRNAs in ivosidenib-treated NSCLC cells compared to untreated NSCLC cells. DE-mRNAs were significantly enriched in the cancer-associated pathways, including the TGF-ß signaling pathway, the PI3K-Akt signaling pathway, the Jak-STAT signaling pathway, the MAPK signaling pathway, the Rap1 signaling pathway, and cell adhesion molecules. Based on the competing endogenous RNA hypothesis, we constructed lncRNA-miRNA-mRNA networks to elucidate the regulatory relationships between mRNA and ncRNA. We found that qRT-PCR results showed corresponding expression trends of differential genes with sequencing data. Our results provide insights into the molecular basis of ivosidenib suppression of NSCLC.

Systematic Transcriptome Analysis Reveals the Inhibitory Function of Cinnamaldehyde in Non-Small Cell Lung Cancer.

Cinnamaldehyde (CA) is the main component extracted from the traditional Chinese medicine cinnamon. Recent studies revealed that CA has antiviral and anti-tumor effects. However, the effect and mechanism of CA on non-small cell lung cancer (NSCLC) through whole transcriptome sequencing integrated analysis have not been systematically investigated. In this study, whole transcriptome sequencing was used to identify differentially expressed messenger RNAs (mRNAs), micro RNAs (miRNAs), and long non-coding RNAs (lncRNAs) that were influenced by CA and screen regulatory pathways. The results showed that CA significantly inhibited proliferation, invasion, and migration, whereas it induced the apoptosis of NSCLC cells. CA inhibited tumor growth in vivo. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that these differentially expressed mRNAs were potentially implicated in the CA-suppressing malignant phenotypes of NSCLC. According to the competing endogenous RNA (ceRNA) hypothesis, a ceRNA network was constructed, including 13 mRNAs, 6 miRNAs, and 11 lncRNAs. Kyoto Encyclopedia of Genes and Genomes analysis of the 13 mRNAs in the ceRNA network showed that suppressors of cytokine signaling 1 (SOCS1), BTG anti-proliferation factor 2 (BTG2), and Bruton tyrosine kinase (BTK) were significantly enriched in the JAK/STAT signaling pathway, RNA degradation, and nuclear factor-κB (NF-κB) signaling pathway related to cancer. These findings indicated that SOCS1, BTG2, and BTK play an essential role in CA against NSCLC. Meanwhile, based on the ceRNA network, three lncRNAs (long intergenic non-protein coding RNA 1504 [LINC01504], LINC01783, and THUMPD3 antisense RNA 1 [THUMPD3-AS1]) and three miRNAs (has-miR-155-5p, has-miR-7-5p, and has-miR-425-5p) associated with SOCS1, BTG2, and BTK may be important in CA against NSCLC. Taken together, the present study demonstrated the activity of CA against lung cancer and its potential use as a therapeutic agent.

[Clinical analysis of eosinophilic gastroenteritis in six children].

OBJECTIVE: To analyze the clinical characteristics and treatment of eosinophilic gastroenteritis (EG) in children. METHOD: A retrospective analysis of the clinical manifestation, laboratory test, endoscopy, biopsy, bone marrow examination and treatment of 6 children diagnosed with EG in Beijing Children's Hospital seen from Jun. 2005 to May 2009 was performed. RESULT: Five of the cases were boys and 1 was girl, the range of age was from 2 to 13 years; food allergy test was positive in 4 cases. Clinical manifestations included:abdominal pain, diarrhea, vomiting, digestive tract hemorrhage, and ascites was found in 4 children. The eosinophilic cell count in blood increased in 5 cases [(160 - 13,560) × 10(6)/L]. The percentage of eosinophilic cell in bone marrow increased in 6 cases (0.18 - 0.41). Beside stomach and duodenum, anatomical foci were found in mesentery (5 cases), small intestine (4 cases), colon (3 cases), and esophagus (2 cases). Endoscopy and imaging showed edema, congestion, erosion, ulcer, bile reflux and gastric juice retention. Stomach and duodenum pathological changes included epithelial erosion, large quantities of eosinophilic cell infiltration in lamina propria and scattered lymphoid cells, which were more obvious in duodenum. In the group received glucocorticoid therapy, clinical symptoms disappeared 3 days later, the eosinophilic cell count in blood returned to normal one-week later;in the group of non-glucocorticoid therapy, most of the clinical symptoms disappeared after two weeks. The eosinophilic cell count in blood was still high 5 weeks later. CONCLUSION: Compared to the common gastroenteritis, gastrointestinal symptoms in EG cases were nonspecific, the increase of blood eosinophilic cells can suggest the possibility of EG, but biopsy is the key to the diagnosis of EG. The therapeutic effect of glucocorticoid seemed to be better than non-glucocorticoid therapies in the improvement of clinical symptoms and the decrease of blood eosinophilic cell.

[Expression pattern of tumor-associated antigen MG7-Ag in gastric cancer: difference between Tibetans and Hans].

OBJECTIVE: To investigate the difference of the expression pattern of tumor-associated antigen MG(7)-Ag in gastric carcinoma between Hans and Tibetans. METHODS: Avidin-biotin peroxidase complex immunohistochemical methods were adapted to examine the expression pattern of MG(7)-Ag in 200 patients with gastric carcinoma, including 100 Tibetan patients and 100 Hans patients, 10 patients with chronic artrophic gastritis, 18 with gastric mucosal dysphasia and 10 subjects with normal gastric mucosa served as control. RESULTS: The positive rate for MG(7)-Ag was 92.4% and 88.7% in Tibetan and Han gastric carcinoma patients, 55.6% and 38.9% in Tibetan and Han gastric mucosal dysplasia patients, 20.0% and 10.0% in Tibetan and Han chronic atrophic gastritis patients, respectively. There was no positive expression in normal gastric mucosa of both Hans and Tibetans. >From normal gastric mucosa, chronic artrophic gastritis and gastric mucosal dysplasia to gastric carcinoma, expression of MG(7)-Ag showed an ascending tendency in the same group of subjects or patients (P < 0.01). However between Hans and Tibetans there was no significantly different expression of MG(7)-Ag. In gastric carcinoma, the expression pattern of MG(7)-Ag was not related to tumor cell differentiation and metastasis of lymph nodes in Hans and Tibetans (P > 0.05), but in the same group the expression of MG(7)-Ag was related to metastasis of lymph nodes. CONCLUSIONS: The expression pattern of MG(7)-Ag displayed no significant difference between Hans and Tibetans, The tumor associated antigen MG(7)-Ag in gastric carcinoma can be used in Tibetans as a reliable marker to predict early gastric cancer.

SOX7 and GATA-4 are competitive activators of Fgf-3 transcription.

Fgf-3 is expressed in a dynamic and complex spatiotemporal pattern during mouse development. Previous studies identified GATA-4 as a transcription factor that binds the key regulatory element PS4A of the Fgf-3 promoter and stimulates transcription. Here we show that members of the SOX family of transcription factors also bind PS4A and differentially modulate transcription. At least five SOX genes, Sox2, Sox6, Sox7, Sox13, and Sox17, were expressed in F9 cells, and of these, Sox7 and Sox17 were dramatically induced in parallel with Fgf-3 following differentiation into parietal endoderm-like cells with retinoic acid and dibutyryl cAMP. Complexes could be detected on PS4A with SOX2, SOX7, and SOX17 by using nuclear extracts from differentiated F9 cells. However, only Sox7 expression markedly activated the Fgf-3 promoter in these cells. By contrast, SOX2 was a poor activator of Fgf-3 transcription, and when Sox2 was coexpressed with Gata4, it negatively modulated the strong activation mediated by GATA-4. More detailed analyses showed that SOX7 competes with GATA-4 for PS4A occupancy and to activate the Fgf-3 promoter. In situ hybridization analysis showed that Sox7 is co-expressed with Fgf-3 and Gata4 in the parietal endoderm of E7.5 mouse embryos. In culture, GATA-4-deficient embryonal stem cells were shown to express Fgf-3 upon differentiation into embryoid bodies, although at lower levels than were found in wild type embryonal stem cells. This Fgf-3 expression was virtually abolished when Sox7 expression was suppressed by RNA interference. These results show that SOX7 is a potent activator of Fgf-3 transcription.