1.Molecular Mechanism of Carbon Metabolism Inhibition in Spleen Tissues of Mice Under High Altitude Hypoxia Environment
Xiaochen CHEN ; Ying HU ; Yuzhen XU ; Qifu LONG ; Ruxue MA ; Sheng YONG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(5):806-817
[Objective]To explore the regulatory mechanism of hypoxia exposure on carbon metabolism pathway in spleen of mice.[Methods]C57BL/6 mice were raised at altitudes of 400 m and 4 200 m,with 5 mice in each group.After 30 days,spleen tissues were aseptically removed for analysis of differentially expressed genes,proteins,and metabolites using transcriptome sequencing,proteomics,and non-targeted metabolomics.GO and KEGG enrichment analysis were conducted to explore key pathways.The key genes and protein in the pathway were validated by RT-qPCR and Western blot.[Results]Transcriptome sequencing revealed a significant difference in the expression of 4 213 genes in hypoxic exposure,of which 1 947 were up-regulated and 2 266 were down-regulated.The analysis of differentially expressed proteins showed that 166 proteins were up-regulated and 39 proteins were down-regulated.The results of non-targeted metabolomics showed that 133 different metabolites were screened under high altitude hypoxia condition,of which 95 were up-regulated and 38 were down-regulated.KEGG enrichment analysis showed that differentially expressed genes,differentially expressed proteins and differentially expressed metabolites were enriched into the carbon metabolic pathway.Therefore,the key genes and proteins in the carbon metabolic pathway were verified.The mRNA and protein expressions of PGAM2、ENO3、PRPS2、PGLS、RPE、IDH3A、SUCLA2 and MDH2 were significantly down-regulated in the carbon metabolism pathway.[Conclusion]Low oxygen environment at high altitude weakens glycolysis,tricarboxylic acid cycle and pentose phosphate pathway by inhibiting the carbon metabolism pathway of the body,resulting in oxidative stress and energy metabolism imbalance.
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.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.
4.Effects of home hospice care team service model on fall risk in patients with end-stage malignant tumors and main caregivers
Fangping ZHOU ; Yuzhen HE ; Mingcai HU ; Lixia ZOU ; Rixia XIAO ; Xuejun HUANG ; Jun ZHOU
Chinese Journal of Practical Nursing 2024;40(28):2165-2172
Objective:To explore the effects of home hospice care team service model in patients with end-stage malignant tumors and main caregivers, so as to provide intervention programs for improving the quality of life of patients with end-stage malignant tumors.Methods:In the prospective and controlled study, 106 patients with malignant tumors who received end-stage hospice care in Yuebei People′s Hospital and main caregivers from May 2021 to July 2021 were selected by convenience sampling method, and divided into trial group (53 pairs) and control group (53 pairs) according to the random number table method. The control group was treated with routine nursing intervention, and the trial group was given home hospice care team service model intervention based on the control group. The occurrence of falls and negative emotions and quality of life of patients, psychological stress of primary caregivers before and after intervention were observed by using Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Relative Stress Scale (RSS) and European Organization for Research and Treatment of Cancer Quality of Life Scale (EORTC QLQ-C30).Results:Finally, 103 patients and main caregivers completed the study, with 52 pairs in the control group and 51 pairs in the trial group. In the control group, the patients were 29 males and 23 females, aged (54.33 ± 12.24) years old,and the main caregivers were 22 males and 30 females, aged (41.67 ± 8.14) years old. In the trial group,the patients were 27 males and 24 females,aged (55.17 ± 10.56) years old,and the main caregivers were 24 males and 27 females, aged (43.62 ± 7.39) years old. After intervention, the total incidence of falls and the total incidence of fall complications in the trial group were 7.84% (4/51) and 1.96% (1/51), respectively, which were lower than 25.00% (13/52) and 11.54% (7/52) in the control group, the differences were statistically significant ( χ2=5.50, 4.75, both P<0.05). There was no significant difference in the score of SAS, SDS, RSS, EORTC QLQ-C30 before intervention between the two groups (all P>0.05). After intervention, the scores of SAS and SDS in trial group were (32.66 ± 3.18), (31.19 ± 4.50) points,which lower than those in control group (34.54 ± 3.91), (34.31 ± 4.03) points, the differences were statistically significant ( t=2.67, 2.51, both P<0.05). After intervention, the RSS scores of psychological distress, life disruption, negative emotion and total score of the main caregivers in trial group were (3.52 ± 0.48), (3.66 ±0.56), (3.47 ± 0.82), (10.65 ± 0.67) points, which were lower than those in the control group (4.74 ± 2.75), (4.67 ± 2.64), (4.12 ± 2.13), (13.53 ± 2.26) points, the differences were statistically significant ( t values were 2.04-8.73, all P<0.05). After intervention, the EORTC QLQ-C30 score in the trial group was (74.14 ± 5.64) points, which was lower than that in the control group (70.54 ± 7.07) points, the difference was statistically significant ( t=2.85, P<0.05). Conclusions:The application of home hospice care team service model can effectively reduce the risk of falls in patients with malignant tumor chemotherapy, improve the negative emotions of patients and the psychological stress state of their main caregivers, and improve the quality of life of patients.
5.Hypoxia at high altitude induces inflammation in the spleen of mice through NOD⁃like receptor signaling pathway
Jiayang Wang ; Ying Hu ; Yuzhen Xu ; Qifu Long ; Chaoqun Tang ; Sheng Yong
Acta Universitatis Medicinalis Anhui 2023;58(9):1498-1506
Objective :
Based on metabolomics and transcriptomics analysis , to explore the molecular mechanism of
spleen inflammation induced by high altitude hypoxia in mice through NOD⁃like receptor signaling pathway .
Methods :
C57BL/6 mice were raised at an altitude of 400 m and 4 200 m respectively , with five mice in each group , and spleen tissues were collected after 30 days . Differential metabolites and differentially expressed genes in key pathways were screened by metabolomics and transcriptome analysis and correlation KEGG enrichment analysis , and the related network interaction diagram of differential metabolites and differentially expressed genes in key pathways was constructed and verified by RT⁃qPCR .
Results :
Metabolomics analysis showed that 133 differential metabolites were screened from in the plain spleen control group (PSC group) and the plateau spleen test group (HST group) , 95 of which were up⁃regulated while 38 of which were down⁃regulated . KEGG enrichment analysis showed that they were mainly involved in NOD⁃like receptor signaling pathway , HIF⁃1 signaling pathway , cholesterol metabolism and other metabolic pathways . The results of transcriptome analysis showed that a total of 4213 differentially expressed genes were identified in PSC group and HST group , including 1947 up⁃regulated genes and 2266 down⁃regulated genes . KEGG was enriched in 173 signaling pathways , including NOD⁃like receptor signaling pathway , MAPK signaling pathway , NF⁃κB signaling pathway and other pathways . Comprehensive analysis showed that the differential metabolites and differentially expressed genes were obviously enriched in NOD⁃like receptor signaling pathway . Therefore , the correlation network interaction map was constructed for the differential metabolites ATP and differentially expressed genes in NOD⁃like receptor signaling pathway . RT⁃qPCR results showed that compared with PSC group , the expression levels of DEGs related to NOD1 and NOD2 (CHUK , TAB3 , MAPK8) in the signaling pathway of NOD⁃like receptor and NLRP1 ⁃CASP1 pathway (NLRP1b , CASP1) in HST group were significantly enhanced . The mRNA expression levels of downstream inflammatory factors IL⁃6 , IL⁃1 β , IL⁃18 , INF⁃γ and TNF⁃α were up⁃regulated and differentially expressed .
Conclusion
Based on the combined analysis of metabolomics and transcriptomics , it was found that hypoxia stimulation at high altitude may affect the NOD⁃like receptor signaling pathway in vivo , and the differential metabolite ATP is positively correlated with the differential key genes in the pathway . ATP mediates the release of downstream inflammatory factors by activating NOD1 , NOD2 pathways and NLRP1 inflammable⁃CASP1 pathways . Inflammatory response occurred in spleen tissue of mice.
6.Study on Pharmacokinetics and Bioavailability of Naproxen Choline Ionic Liquid in Rat
TANG Yimei ; HU Benquan ; ZHANG Bo ; XIN Nina ; HE Maofang ; ZHANG Yuzhen
Chinese Journal of Modern Applied Pharmacy 2023;40(18):2506-2511
OBJECTIVE To investigate the pharmacokinetics and bioavailability of naproxen choline ionic liquid in rats after intragastric administration. METHODS Naproxen choline ionic liquid was given to rats by intragastric administration. Blood samples were collected at different time points after administration. The blood samples were precipitated by methanol and then centrifuged, and then an Extend-C18 column(4.6 mm×250 mm, 5 μm) was used. Methanol(A)-0.3% phosphoric acid aqueous solution(B) (74:26) was used as the mobile phase, the flow rate was 0.8 mL·min-1, and the detection wavelength was 230 nm. Indomethacin and naproxen were used as internal standard and tested object in determination of naproxen choline ionic liquid in rat plasma. Pharmacokinetic parameters were calculated using DAS 2.0 software. RESULTS After intragastric administration of naproxen suspension to rats, its t1/2α was 5.12 h, t1/2β was 10.13 h, Tmaxwas 2 h, Cmax was 112.92 mg·L-1, and AUC(0-t) was 1 091.01 mg·L-1·h. After intragastric administration of naproxen choline, its t1/2α was 5.64 h, t1/2β was 69.32 h, Tmax was 1 h, Cmax was 135.97 mg·L-1, AUC(0-t) was 1 305.79 mg·L-1·h, and the relative bioavailability was 119.686%. CONCLUSION After intragastric administration of naproxen choline to rats, the peak concentration and bioavailability of the naproxen in vivo are higher than those of the common suspension, and the peak time is earlier.
7.Preoperative MRI radiomics models for predicting risk stratification of endometrial cancer
Wei KONG ; Yuzhen YU ; Kang WANG ; Long CHEN ; Yunxiang HU ; Weiguo CHEN
Chinese Journal of Medical Imaging Technology 2023;39(12):1857-1861
Objective To observe the value of preoperative MRI radiomics models for predicting risk stratification of endometrial cancer(EC).Methods Data of 219 EC patients who underwent pelvic MR examination before surgery were retrospectively analyzed.The patients were divided into high risk group(n=104)or low risk group(n=115)according to postoperative pathological findings,also assigned into training set(n=153)or test set(n=66)according to examination time and further divided into high or low risk subgroups in each set.ROI was manually sketched on MRI using 3D Slicer,and each 1 130 features were extracted from axial and sagittal fat suppression(FS)T2WI as well as axial and sagittal enhanced FS-T1WI,respectively.Then the least absolute shrinkage and selection operator(LASSO)was used to select a total of 54 merged MRI features,including 12,14,16 and 12 features,respectively.Finally,25 merged LASSO features were reduced dimensionality and selected by reusing LASSO.Extremely randomized trees algorithm was used to construct radiomics models based on each single sequence features,merged MRI features and merged LASSO features,respectively.Receiver operating characteristic curves were drawn,the area under the curve(AUC),the accuracy and F1 score were obtained to evaluate the predicting efficacy of each model.AUC was used to evaluate the predictive efficacy of the models and subjective diagnosis of test set.Results In training set,the accuracy(0.784,0.777),F1 score(0.730,0.731)and AUC(0.835,0.855)of modelmerged MRI and modelmerged LASSO were both higher than those of each single sequence model,while in test set,the sensitivity(0.794,0.882),specificity(0.909,0.969)and AUC(0.904,0.934)of modelmerged MRI and modelmerged LASSO were both higher than those of subjective diagnosis and each single sequence model.The predictive effiency of modelmerged LAsSo was better than that of modelmerged MRI,which was the best model.Conclusion Preoperative MRI radiomics model was effective for predicting risk stratification of endometrial cancer.Modelmerged LASSO had the best performance.
8.Molecular biological characteristics of the 2019 novel Coronavirus in Shijiazhuang
Huixia GAO ; Lin YANG ; Yun GUO ; Yicong WANG ; Yuzhen LIU ; Yue TANG ; Zhang HE ; Xinming LIANG ; Shunkai HUANG ; Peng GAO ; Ying HUANG ; Muwei DAI ; Zhi ZHANG ; Qian HU ; Yuling WANG ; Fang CHEN ; Erhei DAI ; Ping JIANG ; Yutao DU
Chinese Journal of Laboratory Medicine 2022;45(6):637-641
Objective:To analyze the molecular epidemiological characteristics of the Corona virus disease 2019 (COVID-19) cases in Shijiazhuang, which can reveal the origin of the outbreak and provide a scientific basis for COVID-19 prevention and control.Methods:From January 2 to January 8, 2021, a total of 404 samples from 170 COVID-19 cases were collected from the Shijiazhuang Fifth Hospital. The consensus sequence of 2019 novel Coronavirus(2019-nCoV) was obtained through multiplex polymerase chain reaction-based sequencing. The sequences of 170 COVID-19 cases were analyzed by the PANGOLIN, and the data were statistically analyzed by T-test.Results:Among the 404 COVID-19 samples, a total of 356 samples obtained high quality genome sequences (>95%,100×sequencing depth). The whole genome sequences of 170 COVID-19 cases were obtained by eliminating repeated samples. All 170 sequences were recognized as lineage B1.1 using PANGOLIN. The number of single nucleotide polymorphism arrange from 18-22 and most of the single nucleotide polymorphism were synonymous variants. All of 170 genomes could be classified into 48 sub-groups and most of the genomes were classified into 2 sub-groups (66 and 31, respectively).Conclusions:All cases in this study are likely originated from one imported case. The viruses have spread in the community for a long time and have mutated during the community transmission.
9.Identification and Quality Evaluation of Dendrobium flexicaule and Its Related Species
Ting SUN ; Yuzhen YANG ; Shuxiao HU ; Yao LU ; Cun ZHANG ; Rushan HU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(20):128-134
ObjectiveTo identify Dendrobium flexicaule and its related species, and analyze the differences in polysaccharide composition and D-mannose content, so as to provide theoretical basis for the accurate identification and quality control of Dendrobium medicinal materials. MethodNine samples of Dendrobium (S1-S9) were identified by DNA barcoding and infrared spectroscopy, and the contents of polysaccharides and D-mannose were determined by ultraviolet spectrophotometry (UV) and high performance liquid chromatography (HPLC), respectively. UV detection condition was 488 nm, HPLC detection conditions were the mobile phase of 20 mmol·L-1 ammonium acetate solution-acetonitrile (81.5∶18.5) and the detection wavelength at 250 nm. ResultDNA barcoding results showed that samples S1-S3 were D. nobile, samples S4-S5 were D. officinale, sample S6 was D. huoshanense, and S7-S9 were D. flexicaule. One-dimensional infrared spectroscopy showed that only D. nobile had stable characteristics at the wavenumber of 1 570-1 467 cm-1, showing a "W" shape, while no absorption peak was found at the wavenumber of 842-740 cm-1, but the other Dendrobium samples had stable absorption peaks at the wavenumber of 842-740 cm-1. In the first derivative spectrum, at the wavenumber of 785 cm-1, D. huoshanense presented a "V" shape, while the rest of Dendrobium presented a "W" shape. At the wavenumber of 1 110 cm-1, D. flexicaule had a stable characteristic peak. In the second derivative spectrum, at the wavenumber of 1 125 cm-1, D. officinale presented an "M" shape, and the rest of Dendrobium was approximately "W" shape. The results of determination showed that the contents of polysaccharides in samples S1-S9 were 9.35%, 9.12%, 32.78%, 49.38%, 48.97%, 32.48%, 32.95%, 39.41% and 25.32%, and their contents of D-mannose were 1.39%, 0.47%, 13.57%, 3.04%, 33.85%, 23.57%, 16.64%, 17.47% and 19.49%, respectively. Among them, D. flexicaule had high polysaccharide and D-mannose contents. ConclusionBoth DNA barcoding and infrared spectroscopy can be used to identify D. flexicaule and its related species, and infrared spectroscopy is cost-effective and easy to operate. At the same time, D. flexicaule has high contents of polysaccharides and D-mannose, which can provide a scientific basis for rapid identification of D. flexicaule and its relatives, and provides a reference for its quality control, and resource development and utilization.
10.Effect of affected side upper limb pillow position on hemodynamic and safety of patients undergoing cerebellopontine angle tumor resection
Weiling ZHU ; Yuzhen XIE ; Sufen HU ; Dahao CHEN ; Dongdong CHEN
Chinese Journal of Practical Nursing 2021;37(1):26-30
Objective:To investigate the effect of upper limb pillow position on hemodynamic and safety of patients undergoing cerebellopontine angle tumor resection.Methods:Eighty-four patients receiving cerebellopontine angle tumor resection in our hospital from January 2016 to December 2019 were randomly divided into the experimental group (42 cases) and the control group (42 cases). Patients in the control group were placed in routine upper limb position, while patients in the experimental group were placed in upper limb pillow position. The data including systolic pressure, diastolic pressure, heart rate, saturation of blood oxygen were recorded on admission of operation room, completing placing body position, 30 minutes and 60 minutes after operation and after finishing the operation. The numbness/soreness of upper limbs and pressure injury rate was compared between the experimental group and the control group.Results:The rate of numbness/soreness of upper limbs were 2.4% (1/42) in the experimental group, 19.1%(8/42) in the control group, the differences were statistically significant ( χ2 value was 6.098, P<0.05). The stage 1 pressure injury were 2 cases in the experimental group, stage 1 and 2 pressure injury were 6 cases and 2 cases, respectively in the control group, the differences were statically significant ( Z value was 2.039, P<0.05). Conclusion:Upper limb pillow position of the operation side can reduce postoperative complication of patients undergoing cerebellopontine angle tumor resection, but will not increase the risk of abnormal hemodynamic fluctuation.


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