1.Molecular mechanism of high-altitude hypoxia-induced lipid metabolism disorder in mouse spleen tissue
Chengling CUI ; Yuzhen XU ; Chaoqun TANG ; Jiaying JIANG ; Ying HU ; Jie SHUANG
Journal of Southern Medical University 2024;44(10):2024-2032
Objective To investigate the molecular mechanism of lipid metabolism disorder in mouse spleen tissues due to high-altitude hypoxia.Methods Ten C57BL/6 male mice were randomly divided into normoxia group(maintained at an altitude of 400 m)and high-altitude hypoxia group(maintained at 4200 m)for 30 days(n=5).Lipidomics and metabolomics analyses of the spleen tissue of the mice were conducted using liquid chromatography-mass spectrometry(LC-MS)to identify the differential metabolites,which were further analyzed by KEGG enrichment and pathway analyses,and the differential genes were screened through transcriptome sequencing.Bioinformatics analysis was conducted to identify the upstream target genes of the differential metabolites in specific metabolic pathways.RT-qPCR and Western blotting were used to detect mRNA expressions of 11β-hydroxysteroid dehydrogenase 1(HSD11B1),steroid 5α reductase 1(SRD5A1),prostaglandin-endoperoxide synthase 1(PTGS1),hematopoietic prostaglandin D synthetase(HPGDS),xanthine dehydrogenase(XDH),purine nucleoside phosphorylase(PNP),hypoxanthine guanine-phosphoribosyltransferase(HPRT)and extracellular 5'-nucleotidase(NT5E)and protein expressions of HSD11B1,SRD5A1,XDH,PNP and HPRT in the mouse spleens.Results We identified a total of 41 differential lipid metabolites in the mouse spleens,and these metabolites and the differential genes were enriched in steroid hormone biosynthesis,arachidonic acid metabolism,and purine metabolism pathways.Compared to the mice kept in normoxic conditions,the mice exposed to high-altitude hypoxia showed significantly upregulated expressions of adrenosterone,androsterone,prostaglandin D2,prostaglandin J2,xanthine,xanthosine,and uric acid in the spleen with also changes in the expression levels of HSD11B1,SRD5A1,PTGS1,HPGDS,XDH,PNP,HPRT,and NT5E.Conclusion High-altitude hypoxia can result in lipid metabolism disorder in mouse spleen tissue by affecting steroid hormone biosynthesis,arachidonic acid metabolism,and purine metabolism pathways.
2.Molecular mechanism of high-altitude hypoxia-induced lipid metabolism disorder in mouse spleen tissue
Chengling CUI ; Yuzhen XU ; Chaoqun TANG ; Jiaying JIANG ; Ying HU ; Jie SHUANG
Journal of Southern Medical University 2024;44(10):2024-2032
Objective To investigate the molecular mechanism of lipid metabolism disorder in mouse spleen tissues due to high-altitude hypoxia.Methods Ten C57BL/6 male mice were randomly divided into normoxia group(maintained at an altitude of 400 m)and high-altitude hypoxia group(maintained at 4200 m)for 30 days(n=5).Lipidomics and metabolomics analyses of the spleen tissue of the mice were conducted using liquid chromatography-mass spectrometry(LC-MS)to identify the differential metabolites,which were further analyzed by KEGG enrichment and pathway analyses,and the differential genes were screened through transcriptome sequencing.Bioinformatics analysis was conducted to identify the upstream target genes of the differential metabolites in specific metabolic pathways.RT-qPCR and Western blotting were used to detect mRNA expressions of 11β-hydroxysteroid dehydrogenase 1(HSD11B1),steroid 5α reductase 1(SRD5A1),prostaglandin-endoperoxide synthase 1(PTGS1),hematopoietic prostaglandin D synthetase(HPGDS),xanthine dehydrogenase(XDH),purine nucleoside phosphorylase(PNP),hypoxanthine guanine-phosphoribosyltransferase(HPRT)and extracellular 5'-nucleotidase(NT5E)and protein expressions of HSD11B1,SRD5A1,XDH,PNP and HPRT in the mouse spleens.Results We identified a total of 41 differential lipid metabolites in the mouse spleens,and these metabolites and the differential genes were enriched in steroid hormone biosynthesis,arachidonic acid metabolism,and purine metabolism pathways.Compared to the mice kept in normoxic conditions,the mice exposed to high-altitude hypoxia showed significantly upregulated expressions of adrenosterone,androsterone,prostaglandin D2,prostaglandin J2,xanthine,xanthosine,and uric acid in the spleen with also changes in the expression levels of HSD11B1,SRD5A1,PTGS1,HPGDS,XDH,PNP,HPRT,and NT5E.Conclusion High-altitude hypoxia can result in lipid metabolism disorder in mouse spleen tissue by affecting steroid hormone biosynthesis,arachidonic acid metabolism,and purine metabolism pathways.
3.Effect of Liangxue Huoxue decoction on intestinal flora and NLRP3/caspase-1/GSDMD signaling pathway in mice model of sepsis-induced acute kidney injury
Min ZHOU ; Lei YANG ; Yuzhen ZHUO ; Dihua LI ; Lanqiu ZHANG ; Lingzhi CUI ; Jiarui LI
Chinese Critical Care Medicine 2023;35(3):250-255
Objective:To investigate the effect of Liangxue Huoxue decoction on intestinal flora, intestinal barrier and NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pyroptosis signaling pathway in mice model of sepsis-induced acute kidney injury (AKI).Methods:The model of AKI was established by cecal ligation and perforation (CLP). Thirty male C57BL/6 mice were randomly divided into sham operation group (Sham group), sepsis group (CLP group) and sepsis+Liangxue Huoxue decoction (CLP+LXHX group), with 10 mice in each group. Mice in Sham group only underwent laparotomy. Two hours before model establishment, mice in CLP+LXHX group were treated with Liangxue Huoxue decoction (6 g/kg) by gavage; mice in Sham group and CLP group were given equal volume of normal saline by gavages. After 24 hours of modeling, all mice were sacrificed under anesthesia, and the colon and kidney tissues and fresh feces in the colon were taken. The pathological changes of kidney and colon were observed by hematoxylin-eosin (HE) staining under light microscope. Real-time polymerase chain reaction (RT-PCR) was used to detect inflammatory factors (interleukins, IL-1β and IL-18) in renal tissue. The expressions of NLRP3, caspase-1 and GSDMD were detected by Western blotting. The changes of intestinal flora in mice were detected by 16S rDNA high-throughput sequencing.Results:Compared with the Sham group, the inflammatory cell infiltration of the kidney tissue was increased and the kidney became vacuolated in CLP group, the mRNA expressions of IL-1β, IL-18, and the protein expressions of NLRP3, caspase-1 and GSDMD were significantly increased in CLP group, the species richness of intestinal microflora decreased significantly, the relative abundance of Enterococcus and Escherichia-Shigella increased significantly, and the relative abundance of Ileibacterium, Alloprevotella, Lachnospiraceae, Klebsiella and Parasutterella increased significantly in CLP group. Compared with CLP group, Liangxue Huoxue decoction can significantly reduce the pathological changes of kidney and colon tissue, reduce the pathological score (1.75±0.43 vs. 3.50±0.50 for kidney tissue, 1.25±0.43 vs. 4.50±0.50 for colon tissue, both P < 0.05), improve the composition of intestinal flora, reduce the relative abundance of Enterococcus and Escherichia-Shigella, and significantly increase the relative abundance of Lactobacillus and Akkermansia. In addition, Liangxue Huoxue decoction can significantly reduce mRNA expressions of IL-1β and IL-18 in kidney tissue [IL-1β mRNA (2 -ΔΔCt): 1.59±0.05 vs. 4.61±0.88, IL-18 mRNA (2 -ΔΔCt): 1.69±0.17 vs. 2.86±0.63, both P < 0.05] and the protein expressions of NLRP3, caspase-1 and GSDMD (NLRP3/GAPDH: 0.71±0.04 vs. 0.89±0.01, caspase-1/GAPDH: 1.04±0.04 vs. 1.48±0.04, GSDMD/GAPDH: 0.90±0.01 vs. 1.41±0.02, all P < 0.05). Conclusions:Liangxue Huoxue decoction has obvious protective effect on AKI induced by sepsis. It can improve intestinal barrier by regulating intestinal flora, thereby inhibiting the activation of NLRP3/caspase-1/GSDMD signaling pathway in kidney tissue and reducing the expression of proptosis-related inflammatory factors.
4.Revealing the role of gut microbiota in immune regulation and organ damage in sepsis using 16s rRNA and untargeted metabolomics.
Ping ZHANG ; Lei YANG ; Yuzhen ZHUO ; Lingzhi CUI ; Qiaoying GAO ; Min ZHOU ; Lixiu GE ; Jiarui LI
Chinese Critical Care Medicine 2023;35(9):927-932
OBJECTIVE:
To analyze the composition and metabolites of gut microbiota in septic rats by fecal 16s rRNA sequencing and untargeted metabolomics, and to preliminarily explore the effect and potential mechanism of gut microbiota and its metabolites on inflammatory response and multiple organ damage in sepsis.
METHODS:
Ten males healthy male Wistar rats were randomly divided into a sham operated group (Sham group) and sepsis model group (CLP group) using a random number table method, with 5 rats in each group. A rat sepsis model was established by cecal ligation and perforation (CLP) method. The animals were sacrificed 24 hours after modeling, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung and kidney tissues, and the pathological scores were evaluated. Fecal samples were collected, and 16s rRNA high-throughput sequencing and non-targeted metabolomics were used to screen microbiota, metabolites and potential signal pathways that may play an important role in disease outcomes. Spearman correlation analysis was conducted to jointly analyze the gut microbiota and non-targeted metabolism.
RESULTS:
Compared with the Sham group, the degree of pathological damage to lung and kidney tissues in the CLP group was significantly increased (lung tissue score: 3.60±0.80 vs. 0.00±0.00, kidney tissue score: 2.40±0.80 vs. 0.00±0.00, both P < 0.01), the level of IL-6 and TNF-α in peripheral blood significantly increased [TNF-α (ng/L): 248.12±55.98 vs. 143.28±36.57, IL-6 (ng/L): 260.26±39.47 vs. 116.01±26.43, both P < 0.05], the species diversity of intestinal flora of rats in the CLP group was significantly reduced, the relative abundance of Morganella, Bacteroides and Escherichia-Shigella were significantly increased, and the relative abundance of Lachnospiraceae NK4A136, Ruminococcus, Romboutsia and Roseburia were significantly reduced. In addition, the biosynthesis and bile secretion of phenylalanine, tyrosine, and tryptophan in the gut microbiota of the CLP group were significantly increased, while the biosynthesis of secondary bile acids was significantly reduced. There was a significant correlation between differential metabolites and differential microbiota.
CONCLUSIONS
Sepsis can cause significant changes in the characteristics of gut microbiota and fecal metabolites in rats, which provides a basis for translational research to seek new targets for the treatment of sepsis.
Rats
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Male
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Animals
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Tumor Necrosis Factor-alpha
;
RNA, Ribosomal, 16S
;
Gastrointestinal Microbiome
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Interleukin-6
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Rats, Wistar
;
Sepsis
5.Effect of Vitamin D Supplementation in Early Pregnancy on High-risk Women with Gestational Diabetes Mellitus
Yuzhen ZHANG ; Zhirui CAO ; Qiaoting CUI
Journal of Medical Research 2023;52(12):61-64
Objective To investigate the effect of vitamin D supplementation in early pregnancy on the incidence and glucose metab-olism of high-risk women with gestational diabetes mellitus.Methods Pregnant women who had regular prenatal examination in Hefei First People's Hospital from December 2019 to May 2022 with serum 25(OH)D level<30ng/ml,expected date of delivery ≥ 35 years or pre-pregnancy body mass index(BMI)≥24kg/m2were selected.They were randomly divided into intervention group(86 cases)and control group(94 cases).The intervention group,took 1200IU/d vitamin D3 capsules orally from the first trimester of pregnancy to the second trimester of pregnancy[the date of oral glucose tolerance test(OGTT)examination for pregnant women];the control group was not given vitamin D3 capsules,and pregnant women with vitamin D deficiency or insufficient were recommended to take vitamin D3 cap-sules or calcium tablets containing vitamin D.Results The levels of vitamin D in the first and second trimester of pregnancy were 12.986± 5.654ng/ml and 31.277±9.856ng/ml in the intervention group,and the difference was statistically significant(P<0.001).The inci-dence of gestational diabetes mellitus in control group and intervention group was 24.5%and 20.9%,and the difference was not statisti-cally significant(P>0.05).There were no significant difference in fasting blood glucose,fasting insulin,1h blood glucose,2h blood glucose and homeostasis model assessment insulin resistance index(HOMR-IR)between the intervention group and the control group in the second trimester of pregnancy(P>0.05).Conclusion Vitamin D supplementation in early pregnancy can only significantly improve the level of vitamin D in pregnant women,and almost make it reach sufficient state,but has no obvious effect on the risk of gestational dia-betes mellitus and glucose metabolism.
6.Analysis and discussion on practical activities of standardized residency training in the department of radiology
Ming LIU ; Yuzhen ZHANG ; Xue′e CUI ; Shijian LI ; Dengbin WANG
Chinese Journal of Medical Education Research 2022;21(1):74-77
Based on the characteristics of medical imaging specialty, this paper introduces in detail several features of standardized residency training in the Department of Radiology in our hospital, from the aspects of teaching purpose, preliminary preparation and specific implementation, namely, the morning reading and analysis of difficult cases, the analysis of postoperative cases and missed diagnosis cases, and the teaching reading. At the same time, it also deeply analyzes the advantages, existing problems and solutions of this teaching practice. In order to provide reference for improving the teaching quality of the standardized residency training in the Department of Radiology.
7.Value of albumin-bilirubin score combined with neutrophil count and procalcitonin in ascites in predicting spontaneous bacterial peritonitis in patients with cirrhotic ascites
Ping JIANG ; Rencheng DOU ; Zijin CUI ; Yinni TONG ; Chen LI ; Shanshan JIANG ; Yun BAI ; Jimin ZHENG ; Cunkai WANG ; Yuzhen WANG
Journal of Clinical Hepatology 2021;37(9):2097-2101
Objective To investigate the risk factors for spontaneous bacterial peritonitis (SBP) in patients with cirrhotic ascites, and to establish a new model for predicting the development of SBP. Methods A total of 215 patients who were diagnosed with cirrhotic ascites in Hebei General Hospital from September 2016 to September 2020 were enrolled, and according to the presence or absence of SBP, they were divided into SBP group with 55 patients and non-SBP group with 160 patients. Related clinical data were collected and albumin-bilirubin (ALBI) score, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, and Child-Pugh score were calculated. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; a multivariate logistic regression analysis was used to screen out independent risk factors, and the receiver operating characteristic (ROC) curve was plotted to evaluate the performance of ALBI score, procalcitonin (PCT), polymorphonuclear neutrophil (PMN) count in ascites, and the ALBI-PMN-PCT combined model in the diagnosis of SBP. Results Compared with the SBP group, the non-SBP group had a significantly higher concentration of Na + ( Z =-3.414, P =0.001) and significantly lower total bilirubin ( Z =-2.720, P =0.007), creatinine ( Z =-1.994, P =0.046), urea nitrogen ( Z =-2.440, P =0.015), C-reactive protein ( Z =-9.137, P < 0.001), PCT ( Z =-8.096, P < 0.001), prothrombin time ( Z =-1.969, P =0.049), international normalized ratio ( Z =-2.073, P =0.038), PMN ( Z =-8.292, P < 0.001), MELD score ( Z =-2.736, P =0.006), MELD-Na score ( Z =-3.188, P =0.001), Child-Pugh score ( Z =-3.419, P =0.001), and ALBI score ( t =-5.010, P < 0.001), and there were also significant differences between the two groups in the presence or absence of gastrointestinal bleeding or hepatic encephalopathy ( χ 2 =16.551 and 8.142, P < 0.001 and P =0.004). The multivariate logistic regression analysis showed that ALBI score (odds ratio [ OR ]=3.460, 95% confidence interval [ CI ]: 1.296-9.240, P =0.013), PMN ( OR =1.012, 95% CI : 1.007-1.017, P < 0.001), and PCT ( OR =6.019, 95% CI : 2.821-12.843, P < 0.001) were independent risk factors for SBP in patients with cirrhotic ascites. The ROC curve showed that ALBI, PCT, PMN, and ALBI-PMN-PCT had areas under the ROC curve of 0.711, 0.866, 0.875, and 0.934, respectively, in the diagnosis of SBP, with sensitivities of 50.91%, 73.36%, 72.73%, and 89.09%, respectively, and specificities of 86.87%, 81.25%, 100.00%, and 91.87%, respectively. The patients with ALBI-PMN-PCT > 0.272 had an increased risk of developing SBP. Conclusion The ALBI-PMN-PCT combined model has a high value in predicting the onset of SBP in patients with cirrhotic ascites.
8.Early clinical experience of transcatheter aortic valve implantation via apical approach for high-risk aortic valve disease in single-center
ZHANG Li ; WANG Pingfan ; WANG Fengling ; LI Yuzhen ; LIU Haixia ; LIU Jianhua ; LIU Xuping ; XIAO Changbo ; GAO Xia ; WU Gang ; ZHANG Xianghui ; CUI Cong ; CHEN Yuxin ; ZHENG Yi
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2019;26(12):1194-1198
Objective To summarize the clinical experience in the treatment of high-risk patients with severe aortic valve disease by transcatheter aortic valve implantation (TAVI) via heart apex approach and to evaluate the early efficacy. Method Five patients who underwent TAVI via heart apex approach from September 2017 to February 2019 in Henan Thoracic Hospital were retrospectively analyzed, including 3 males and 2 females, aged 65-84 (74.6±4.5) years. Result All operations were performed through a small left incision into the thoracic cavity (3-5 cm), and then through the J-Valve transport system, the aortic valve was successfully released via heart apex after precise positioning under digital subtraction angiography. One patient developed ventricular fibrillation during the operation, and the operation was completed with the assistance of emergency femoral arteriovenous catheterization cardiopulmonary bypass; one patient underwent percutaneous coronary intervention first because of severe coronary stenosis; one patient had paroxysmal atrial fibrillation during the perioperative period, and had hepatorenal insufficiency and thrombocytopenia after the operation, and was improved after medical treatment; one patient had perivalvular leak during the operation, and was improved after re-implantation of the valve; one patient was in stable condition during operation and recovered smoothly after operation. Surgery was successful in all 5 patients. The follow-up time was 2-19 months, and the early clinical effect was good. Conclusion The short-term clinical efficacy of TAVI via heart apex approach in the treatment of high-risk severe aortic valve disease is definite and safe, but the long-term and medium-term effects need to be further evaluated.
9.Research progress of functional exercise in patients with catheterization by PICC
Feng DAI ; Xun SU ; Lei WANG ; Yuzhen ZHANG ; Kechun HU ; Li'na CUI
Chinese Journal of Modern Nursing 2019;25(14):1845-1848
his article reviews the research status of functional exercise in patients with catheterization by peripherally inserted central catheters (PICC). This study describes the functional exercise method, exercise start time, exercise frequency and duration, exercise intensity and intervention effect, and provides references for guiding health education, discharge guidance and nursing intervention for patients with catheterization.
10.Clinical significance of serum CEA, CA125 and CA72-4 in gastric carcinoma with peritoneal metastasis
Liqiu SUN ; Hai CUI ; Yan CUI ; Wenbiao JIN ; Yuzhen CUI ; Aihua GAO ; Xionghu SHEN
China Oncology 2017;27(3):191-196
Background and purpose: Peritoneal metastasis of gastric cancer is mainly discovered in the ad-vanced cancer. Nonetheless, the clinical applicability of each tumor biomarker in peritoneal metastasis of gastric cancer is still ambiguous. Therefore, this study investigated the diagnostic value and clinical significance of CEA, CA125 and CA72-4 in gastric carcinoma patients with peritoneal metastases. Methods: A total of 108 gastric carcinoma patients with peritoneal metastases from Jan. 2008 to Dec. 2013 were studied. All patients were diagnosed by imaging, operations and pathological examination, and also received intravenous or intraperitoneal chemotherapy. Serum tumor markers such as CEA, CA125 and CA72-4 were determined during diagnosis and before each chemotherapy. The diagnostic sensitivity of single marker and combined detection with 2 or 3 markers were analyzed. The correlations among the serum tumor markers and clinical pathological factors, chemotherapeutic effects and survival time were analyzed. Results: Positive rates of CEA, CA125 and CA72-4 were 20.4%, 46.3% and 45.4% in gastric cancer patients with peritoneal metastases, respectively. For these patients, the positive rates of CEA/CA125, CEA/CA72-4, CA125/CA72-4 and CEA/CA125/CA72-4 were 54.7%, 52.8%, 69.5% and 79.6%, respectively. The combined detection of 3 tumor markers was much better than single marker detection (P<0.05). Positive rates of CEA, CA125 and CA72-4 were correlated with the ECOG scale (P<0.05). Positive rate of CA125 was associated with ascites (P<0.001), while positive rate of CA72-4 was associated with ovarian metastasis (P<0.05). Median survival time of patients with positive rates of CEA, CA125 and CA72-4 was significantly lower than that of the patients with normal levels of these markers (P<0.05). Compared with pre-treatment, the levels of all three tumor markers significantly declined after three cycles of chemo-therapy (P<0.05). The decline in CA125 level after chemotherapy was significantly correlated with decreased amount of ascites (P<0.05). The tumor markers turned negative after 3 cycles chemotherapy in patients with positive markers upon initial diagnosis, their survival was significantly prolonged (P<0.001). Conclusion: Combined detection of serum CEA, CA125 and CA72-4 can significantly promote diagnostic rate of gastric cancer with peritoneal metastasis, and may be helpful in evaluating chemotherapeutic effects and predicting prognosis.

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