1.The protective effect and mechanism of cornuside on diabetic nephropathy model mice
Wei WANG ; Xiaoyang GAN ; Huiqin XU ; Yihui ZHU ; Anmei SHU ; Yingxue FU ; Bin YU ; Gaohong LYU
China Pharmacy 2024;35(4):395-400
OBJECTIVE To investigate the protective effect and potential mechanism of cornuside on diabetic nephropathy (DN) model mice. METHODS Male KK-Ay mice were fed with high-fat and high-sugar diet for two weeks to reproduce the DN model. The successfully modeled mice were randomly grouped into model group, aminoguanidine group (positive control,100 mg/kg) and cornuside group (100 mg/kg), and male C57BL/6J mice were included as normal group, with 6 mice in each group. Administration groups were given relevant medicine intragastrically, and normal group and model group were given a constant volume of normal saline intragastrically, once a day, for 8 consecutive weeks. The levels of fasting blood glucose (FBG), 24 h urinary protein, serum interleukin-12 (IL-12), IL-10, blood urea nitrogen (BUN) and serum creatinine (Scr) were detected; the pathological injury, fibrotic change and glomerular microstructure of renal tissue were observed; the expressions of the receptor of advanced glycation end products (RAGE), collagen type Ⅳ (COL-Ⅳ) and inducible nitric oxide synthase (iNOS) in renal cortex were detected in each group. RESULTS Compared with normal group, the renal cortex of mice in model group showed obvious inflammatory cell infiltration and fibrotic changes; the mesangial hyperplasia of glomerulus was serious and the basement membrane had a large number of irregular dark dense deposits; the levels of FBG and 24 h urinary protein, the serum levels of IL- 12, BUN and Scr, and the expression levels of RAGE, COL-Ⅳ and iNOS in the renal cortex were significantly increased, while the serum level of IL-10 was significantly decreased (P<0.01). Compared with the model group, the renal pathological injuries, fibrotic changes and glomerular microstructure of mice in administration groups were improved significantly, and the above quantitative indexes were generally improved (P<0.05 or P<0.01). CONCLUSIONS Cornuside has a certain protective effect on DN model mice. It can inhibit the inflammatory response, reduce urinary protein excretion, and alleviate renal fibrosis, which may be related to the inhibition of the advanced glycation end products/RAGE signaling pathway.
2.Urinary Metabolomics Aanlysis of Differences in Effect of Aconiti Coreani Radix and Typhonii Rhizoma on Gerbils with Stroke
Liting ZHOU ; Wanting ZENG ; Ru JIA ; Huiying XU ; Yihui DING ; Hao DONG ; Haowen MA ; Yang QU ; Qian CAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):157-166
ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique, and then to clarify the mechanism of the two, as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group(CG), model group(MG), Aconiti Coreani Radix group(RA) and Typhonii Rhizoma group(RT). Except for the CG, ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG, rats in the other groups received whole powder suspension(0.586 mg·g-1) was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0, 3, 7 and 14. After the end of administration, the serum, brain tissue and urine of gerbils in each group were collected, and the rate of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TTC), and the levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH), and nitric oxide(NO) in serum and brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap-MS), and the data were processed by multivariate statistical analysis, and differential metabolites were screened based on value of variable importance in the projection(VIP) of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes(KEGG) database and Metaboanalyst 5.0. ResultCompared with the CG, the neurological deficit score was significantly increased in the MG(P<0.05), compared with the MG, the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d(P<0.05). Compared with the CG, the rate of cerebral infarction was significantly increased in the MG(P<0.05), compared with the MG, the rates of cerebral infarction in the RA and RT were significantly reduced(P<0.05). Compared with the CG, the levels of IL-6, TNF-α, and MDA in the serum and brain tissue of gerbils from the MG were significantly increased(P<0.05), and the levels of SOD, GSH and NO were significantly reduced(P<0.05). Compared with the MG, Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6, TNF-α and MDA, and up-regulated the levels of SOD, GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics, of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma, and could be used as potential biomarkers for both treatments in stroke gerbils, respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism, pyrimidine metabolism, and aminoacyl-tRNA biosynthesis. In addition, Aconiti Coreani Radix could also regulate riboflavin metabolism, Typhonii Rhizoma could also regulate purine metabolism, glycine, serine and threonine metabolism, arachidonic acid metabolism, biosynthesis of pantothenate and coenzyme A, and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke, with Aconiti Coreani Radix having stronger effects. From the metabolomics results, the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism, oxidative stress and so on, while Typhonii Rhizoma mainly involve amino acid metabolism, lipid metabolism, energy metabolism, etc.
3.Research progress of microRNA-mediated immune function of CD4+T cells subsets in immune thrombocytopenia
Hui SONG ; Yihui GUO ; Jiawei XU ; Qing ZENG ; Weimin CHENG
Chinese Journal of Immunology 2024;40(3):663-667
MicroRNA(miRNA)is a kind of small non-coding single stranded RNA that can participate in multiple biological processes.It also plays an important role in regulating the immune function of the body.Immune thrombocytopenia(ITP)is an autoim-mune disease,whose cause and deterioration are closely related to miRNA regulates immune function of CD4+T cells subsets.In ITP patients,different expression of miRNA can affect the immune function of CD4+T cells subsets,which causes not only unbalanced ex-pression of Th1/Th2,Th17/Treg and excessive differentiation of TFH,but also abnormal cytokine secretion furthermore.This paper summarizes the unbalanced mechanism of miRNA regulating immune function of CD4+T cells subsets in ITP,so as to provide inspira-tion for exploring the immunology and immunotherapy of ITP.
4.Development of a prognostic risk marker of colon adenocarcinoma based on a weighted gene co-expression network and its clinical significance
Yihui LI ; Hao PENG ; Yuchun XU ; Rong GUO ; Wei GONG
Chinese Journal of Comparative Medicine 2024;34(1):69-79
Objective Because of the poor prognosis of colon adenocarcinoma(COAD),it is necessary to screen prognosis-related genes in COAD patients and establish a new prognostic risk assessment model.Methods COAD-related data from the cancer genome atlas(TCGA)and gene expression omnibus(GEO)were used as training and validation sets,respectively.Weighted gene co-expression network analysis(WGCNA),a Cox regression model and least absolute selection and shrinkage operator(LASSO)regression analysis were used to screen prognosis-related genes of COAD and establish a prognostic model.A receiver operating characteristic(ROC)curve was combined with a survival curve to verify the model accuracy,and a nomogram was constructed.Patients were divided into two groups by the median risk score.The immune cell proportion score(IPS)was used to evaluate the immunotherapy response of the two groups.Results A total of 15 feature genes were screened.The area under the ROC curve in the predictive model of COAD patients was>0.6,and the survival rate of the high-risk group was significantly lower than that of the low-risk group(P<0.05),suggesting a good distinguishing ability for high-and low-risk COAD patients.Patients in the low-risk group had a higher IPS(P=0.026),indicating a better response to immunotherapy.Conclusions The model developed for COAD in this study has a good ability to predict the survival of patients at high and low risk of COAD.
5.Impact of ERCC1 C8092A gene polymorphism on the efficacy of platinum-based chemotherapy for lung cancer
LI Yixuan ; WANG Yiwei ; FU Yihui ; MENG Chong ; KUANG Shicheng ; LYU Pengfei ; ZHOU jing ; XU Qiongjun ; HUANG Hairong ; XIAO Sha
China Tropical Medicine 2024;24(1):65-
Objective To explore the relationship between the polymorphism of excision repair cross-complementation group 1 (ERCC1) C8092A locus and the efficacy and prognosis of platinum-based chemotherapy for lung cancer (LC), and to provide a theoretical basis for precision treatment of LC. Methods From January 2014 to October 2017, 120 patients from two tertiary hospitals in Haikou City, and with pathologically confirmed lung cancer treated with platinum-based chemotherapy were selected as the research objects. After informed consent was obtained, peripheral blood samples were collected for DNA extraction, and the genotype of ERCC1 C8092A locus was detected by mass spectrometry. WHO's Response Evaluation Criteria in Solid Tumours (RECIST) was used to judge patients' chemotherapy efficacy and patients' survival status was obtained by telephone follow-up and other means. Results Among the 120 LC patients, the genotype frequencies of ERCC1 C8092A locus were 67 cases of CC wildtype (55.8%), 45 cases of CA heterozygous type (37.5%), and 8 cases of AA rare mutation type (6.7%), which conformed to Hardy-Weinberg equilibrium (χ2=0.140, P>0.05). The total effective rate of chemotherapy was 32.5%, with the highest effective rate in patients with the CA genotype (42.2%) at the ERCC1 C8092A locus and the lowest in patients with the CC genotype (25.4%). The overall one-year survival rate was 68.3% and the three-year survival rate was 35.8%. The patients with ERCC1 C8092A AA genotype had the lowest survival rate, with a one-year survival rate of 50.0% and three-year survival rate of only 25.0%. However, there were no statistical differences in the overall survival rate among the three genotypes of carriers of ERCC1 C8092A (χ2=0.328, P=0.849). Conclusions The polymorphism of ERCC1 C8092A locus is associated with the efficacy of platinum-based chemotherapy for LC, and patients with CA genotype have the highest efficacy. The one-year and three-year survival rates of patients with CC genotype are significantly higher than those of CA and AA genotypes.
6.The evidence summary for nutrition management in breast cancer patients
Chen PAN ; Beibei WANG ; Yan YANG ; Jiehui XU ; Yihui HU
Chinese Journal of Practical Nursing 2024;40(13):1015-1021
Objective:To systematically search, evaluate and integrate the relevant evidence of nutrition management in breast cancer patients, and summarize the best evidence, so as to provide evidence for the clinical practice of nutrition management in breast cancer patients.Methods:Evidence-based nursing method was adopted. The BMJ Best Practice, Cochrane Library, etc. and websites were systematically searched for relevant clinical decisions, guidelines, expert consensus,etc. on nutrition management in breast cancer patients. The search period was from the establishment of the database to June 21, 2023. Three researchers independently evaluated the quality of the included literature and the level of evidence and recommendation.Results:A total of 17 pieces of literature were included, including 2 clinical decisions, 6 guidelines, 1 expert consensus and 8 systematic reviews. A total of 33 pieces of best evidence were summarized on 8 aspects, including objective, nutrition screening and assessment, nutrition management population, body mass index management, nutrient structure, diet type and quantity, the use of health products and nutritional supplements, and nutritional monitoring and follow-up.Conclusions:The study summarized the best evidence on nutrition management in breast cancer patients, and provided evidence-based basis for healthcare professionals to better manage nutrition in breast cancer patients. In the practical application of evidence, the differences in dietary habits, structures and religious beliefs of different regions and cultures should be considered, and the best evidence appropriate for individuals should be reasonably selected, taking patients′ own wishes and preferences into account, so as to provide more scientific and comprehensive nutrition management for breast cancer patients.
7.Newborn screening, clinical features and genetic analysis for Citrin deficiency in Henan province
Xinyun ZHU ; Yizhuo XU ; Jie ZHANG ; Xiaole LI ; Jingwen HE ; Chenlu JIA ; Shubo LYU ; Suna LIU ; Yanbo GAO ; Kun MA ; Yunjia OUYANG ; Yihui REN ; Dehua ZHAO
Chinese Journal of Medical Genetics 2024;41(4):461-466
Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.
8.Investigation on the particle size determination method of elemene emulsion injection
Dongxue MEI ; Youjian YANG ; Xiaodan LIU ; Yihui WANG ; Wenshu XU
Drug Standards of China 2024;25(5):489-494
Objective:To investigate the influence of different test conditions on the particle size distribution of elemene emulsion injection measured by laser light scattering method.Methods:The method of particle size deter-mination of elemene emulsion injection was explored.The test conditions were as follows:shading rate 5%-10%,absorption rate 0.000 1-0.1,refractive index1.52-1.54,mixing speed 800-1 600 r·min-1,balance time 0.5-1 min.After the methodology verification,3 batches of elemene emulsion injection were taken and deter-mined on the Bettersize 2600 laser particle size distribution instrument(wet method).Results:Measurement results of 3 batches of samples:d(0.1),d(0.5),d(0.9),d(0.99)were 252,251,213 nm;354,351,316 nm;543,532,476 nm;979,953,887 nm.Conclusion:This test method can be used to determine the particle size distribution of elemene emulsion injection with good reproducibility.
9.Harmonization of 18F-FDG PET brain imaging based on ComBat method: a pilot study
Fangyang JIAO ; Dan WANG ; Yuhua ZHU ; Jiaying LU ; Zizhao JU ; Qian XU ; Jingjie GE ; Tao HUA ; Ping WU ; Kuangyu SHI ; Yihui GUAN ; Chuantao ZUO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(7):412-416
Objective:To perform harmonization based on the ComBat method for PET brain imaging scanned by different types of scanners from the same manufacturer and explored its effect on center effect.Methods:The three-dimensional (3D) Hoffman brain model was scanned by two different PET/CT instruments (Siemens Biograph64 TruePoint and Biograph128 mCT). Fourteen healthy subjects (8 males, 6 females, age: (57.7±9.5) years) underwent 18F-FDG PET/CT on Siemens Biograph64 TruePoint and 12 healthy subjects (9 males, 3 females, age: (55.8±10.5) years) underwent 18F-FDG PET/CT on Siemens Biograph128 mCT (all from Huashan Hospital, Fudan University; from November 2020 to March 2023). The whole brain was divided into 116 brain regions based on the anatomical automatic labeling (AAL) brain template. The ComBat method was applied to harmonized the PET data from brain model and healthy subjects. Mann-Whitney U test was performed on the radioactive counts and SUV ratios (SUVR) before and after homogenization acquired by both PET/CT instruments. Voxel-based statistical parametric mapping (SPM) independent-sample t test was also performed on data of healthy subjects. Results:In 3D Hoffman brain model, radioactivity counts (5 590.33(4 961.67, 6 102.95) vs 6 116.03(5 420.97, 6 660.66); z=-9.35, P<0.001) and SUVR (1.35(1.19, 1.47) vs 1.37(1.21, 1.49); z=-3.63, P<0.001) were significantly different between the two PET/CT scanners before harmonization and not after harmonization (radioactivity counts: 5 845.95(5 192.68, 6 378.63) vs 5 859.17(5 193.84, 6 380.52); SUVR: 1.35(1.20, 1.48) vs 1.36(1.20, 1.49); both z=-0.68, both P=0.498). In the healthy subjects, radioactive counts in 19 brain regions (12 422.78(11 181.60, 13 424.28)-18 166.40(15 882.80, 18 666.27); z values: from -3.24 to -2.06, all P<0.05) and SUVR in 40 brain regions (1.46(1.41, 1.52)-2.28(2.16, 2.36); z values: from -3.65 to -1.70, all P<0.05) were significantly different between the two scanners before harmonization, while after homogenization there were no statistical differences for all 116 brain regions (radioactivity counts: 9 243.55(8 502.38, 9 854.87)-20 419.60(19 931.51, 21 179.43); z values: from -0.72 to 0, all P>0.05; SUVR: 1.04(1.01, 1.09)-2.32(2.24, 2.40); z values: from -0.82 to 0, all P>0.05). SPM showed that significant differences of glucose metabolism in the cerebral cortex, basal ganglia, midbrain and cerebellum were found in healthy subjects between the two PET/CT scanners before homogenization, and brain regions with obvious differences reduced after homogenization. Conclusion:ComBat harmonization method is efficient at removing the center effect among different types of PET/CT scanners from the same manufacturer and may provide a simple and easy-to-implement homogenization for multicenter brain imaging studies.
10.Status quo of research on herb-induced liver injury
Yihui LIU ; Yan GUO ; Hong XU ; Hui FENG ; Qingqing LU ; Dawei QI ; Feng PAN
Chinese Journal of General Practitioners 2024;23(11):1225-1231
Herb-induced liver injury (HILI) is a type of drug-induced liver injury (DILI) caused by Chinese herb medicines, natural medicines or their related preparations. With the increasing number of reports on HILI events in recent years, traditional Chinese medicine is facing great challenges and controversies. Compared to other types of DILI, HILI is more complicated in terms of diagnosis and risk factors.This article reviews the current research status on the herb-induced liver injury.

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