1.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.
2.Autosomal recessive complete signal transducer and activator of transcription 1 deficiency in a newborn: a case report
Ya DONG ; Yumei HUANG ; Huai JIANG ; Yihui LEI ; Jianghu ZHU ; Shangqin CHEN
Chinese Journal of Perinatal Medicine 2023;26(5):426-429
We reported the clinical data of a neonate admitted to the Second Affiliated Hospital (Yuying Children's Hospital) of Wenzhou Medical University in November 2021 with autosomal recessive complete signal transducer and activator of transcription 1 ( STAT1) deficiency identified by whole exome sequencing. The baby boy received bacillus of calmette-guerin (BCG) vaccine 2 d after birth and presented with persistent high fever, increased white blood cell count and increased level of C-reactive protein (CRP) on 21 d after birth. Human cytomegalovirus (HCMV) was detected in both blood and bone marrow specimens. The patient improved after comprehensive treatment with antiviral agents, antibiotics and intravenous gammaglobulin. Oral anti-viral drugs were prescribed on discharge. However, the baby was rehospitalized due to a fever at 55 days. HCMV and Mycobacterium tuberculosis complex were detected in blood samples. The infant was transferred to the Children's Hospital of Fudan University due to persistent high fever even after active management and died after treatment withdrawal at 69 d after birth because of worsening infections and multiple organ failure. A homozygous mutation in the STAT1 gene was detected [c.1011_1012del, NM_007315: exon11: c.1011_1012del (p.V339Pfs*18)] and the child was diagnosed as autosomal recessive complete STAT1 deficiency. We concluded that the clinical manifestations of autosomal recessive complete STAT1 deficiency are bacterial infections caused by lethal low-pathogenic mycobacteria and life-threatening virus infections. Whole exome sequencing is of great value for early diagnosis and timely treatment. The prognosis of this disease is very poor, but the condition of the patients might be improved in a short period with early anti-tuberculosis and anti-viral treatment.
3.Effect of Polysaccharides and n-Butanol Fractions of Atractylodis Rhizoma Stir-fried with Bran on Metabonomics in Rats with Spleen Deficiency
Huiying XU ; Yihui DING ; Hao DONG ; Xuecen ZHAO ; Yang BAI ; Qian CAI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):112-120
ObjectiveTo explore the regulatory effect of polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran on the plasma metabolites of spleen-deficient rats, and then to elucidate their mechanisms of spleen-enhancing effects. MethodForty male SD rats were randomly divided into the blank group, model group, polysaccharide group (FD group, 0.075 6 g·mL-1·d-1), n-butanol fractions group (FZ group, 0.012 1 g·mL-1·d-1), with 10 rats in each group. Except the blank group, the other three groups used the compound factors of overwork, dietary disorders and intragastric administration of Sennae Folium decoction to replicate the rat model of spleen deficiency. After the end of modeling, the FD group and FZ group were given the corresponding medicinal solution by gavage for 7 d, meanwhile, the blank group and model group were given an equal volume of saline. The plasma samples from rats in the blank, model, FZ and FD groups were analyzed by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS), multivariate statistical methods were used to process the data and screen differential metabolites, and metabolic pathway enrichment analysis of the screened differential metabolites was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG))database and MetaboAnalyst 5.0. ResultThe results of multivariate statistical analysis showed that there were significant differences in plasma metabolites between the model group and blank group, FZ group and model group, FD group and model group. There were 380 differential metabolites between the blank group and the model group, of which 78 and 57 were called back by polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran, respectively. Metabolic pathway enrichment results showed that the n-butanol fractions mainly affected glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, D-arginine and D-ornithine metabolism, which were summarized as amino acid metabolism, while the polysaccharides mainly affected glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, tricarboxylic acid cycle, biotin metabolism and thiamine metabolism. ConclusionBoth of polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran have significant regulating effects on the metabolic abnormalities in spleen-deficient rats, in which the n-butanol fractions is mainly involved in amino acid metabolism, and the polysaccharides are involved in energy metabolism and cofactor and vitamin metabolism in addition to regulating amino acid metabolism.
4.Research advance on the role of pro-inflammatory cytokines in sepsis
Yihui CHEN ; Peng DONG ; Xiyang ZHANG
Chinese Critical Care Medicine 2023;35(2):212-216
Sepsis, a series of pathophysiological abnormalities caused by infection, is also one of the most important factors of death and disability in infected patients all over the world, so it has always been the focus of the medical community. Cytokines are small molecule proteins secreted by cells with biological activity, involved in the immune and inflammatory regulation of sepsis. Many studies using cytokine targeting to treat sepsis have achieved beneficial effects, and the level of cytokines is also believed to be related to the development, severity of sepsis, so they are reliable biomarkers of sepsis. Among them, pro-inflammatory cytokines such as interferon-β (IFN-β) and interleukins (IL-1β, IL-3, IL-6, and IL-7) are the focus of the discussion in this review. IFN-β and IL-1β are double-sided in the treatment of sepsis, namely early low-dose treatment can reduce sepsis by restoring the function of immune cells and play a protective effect, but they are also related to severe inflammatory response of sepsis and can aggravate the mortality of sepsis patients. IL-3 and IL-6 focus more on enhancing inflammatory factors and play a damage role. IL-7 mainly participates in immune regulation, promoting lymphocyte activation and protecting sepsis.
5.Relationship between serum BMP9 and SMAD3 expression and growth and bone age in children with idiopathic short stature
Yihui DONG ; Lihua SUN ; Lili SUN
International Journal of Laboratory Medicine 2023;44(24):3045-3049
Objective To investigate the relationship between serum levels of bone morphogenetic protein(BMP)9,Drosophila mother anti-cerebral palsy protein(SMAD)3 and growth and bone age in children with idiopathic short stature(ISS).Methods A total of 110 children with ISS admitted to the Qingdao Eighth Peo-ple's Hospital from September 2020 to September 2022 were selected as the ISS group,and 110 healthy chil-dren who underwent physical examination in the hospital during the same period were selected as the control group.The serum BMP9 and SMAD3 levels were compared between the two groups.Pearson correlation analysis was used to analyze the correlation between BMP9,SMAD3 and sexual development status,height,weight,body mass index(BMI),osteocalcin(Ost),Leptin,bone age index(BAI),bone age difference(BAD)in children with ISS.Re-ceiver operating characteristic(ROC)curve was used to analyze the diagnostic value of BMP9 and SMAD3 in ISS.Multivariate Logistic regression was used to analyze the risk factors of ISS.Results Compared with the control group,the level of BMP9 was significantly increased and the level of SMAD3 was significantly de-creased in the ISS group(P<0.05).There were significant differences in sexual development status,BMI,BAI,BAD,Ost and Leptin levels between the control group and ISS group(P<0.05).Correlation analysis showed that the serum level of BMP9 was negatively correlated with SMAD3,sexual development status,height,weight,BMI,Ost,Leptin,BAI,and BAD in children with ISS(r=-0.497,-0.523,-0.447,-0.486,-0.501,-0.465,-0.502,-0.434,-0.520,P<0.05).Serum SMAD3 level was positively corre-lated with sexual development status,height,weight,BMI,Ost,Leptin,BAI,and BAD(r=0.432,0.458,0.431,0.465,0.503,0.467,0.515,0.527,P<0.05).ROC curve analysis showed that BMP9,SMAD3 joint in-spection ISS area under curve was higher than the two separate detection(Z=2.774,2.958,P<0.05).Multi-variate Logistic regression analysis showed that serum BMP9 level was an independent risk factor for ISS,and SMAD3 level was an independent protective factor(P<0.05).Conclusion The serum level of BMP93 is in-creased and SMAD3 is decreased in children with ISS,and they are closely related to the growth and bone age of children with ISS,which can be used as molecular markers to evaluate the condition of children with ISS.
6.Clinical and cardiac MR characteristics of heart involvement in patients with Fabry disease
Yangfei XU ; Kai YANG ; Xiaofeng LIU ; Xiuyu CHEN ; Yanyan SONG ; Yihui WANG ; Yucong ZHENG ; Shiqin YU ; Shujuan YANG ; Jiaxin WANG ; Zhixiang DONG ; Minjie LU ; Shihua ZHAO
Chinese Journal of Radiology 2022;56(2):168-174
Objective:To investigate the clinical and cardiac magnetic resonance (CMR) characteristics of heart involvement in patients with Fabry disease (AFD).Methods:From January 2018 to March 2021, eight AFD patients [3 males and 5 females, mean age (50±11) years old, range 26-60 years old] confirmed by genetic testing or pathology in Fuwai Hospital were retrospectively included in this study. At the same time, sixteen patients with hypertrophic cardiomyopathy (HCM) [6 males and 10 females, mean age (46±15) years old] and 16 healthy individuals [6 males and 10 females, mean age (51±11) years old] were included as controls. The clinical baseline data and CMR data of the patients were collected and analyzed. The CMR data were analyzed using the software CVI42, with the corresponding parameters automatically generated. One-way ANOVA or Kruskal-Wallis test was used to compare the differences in the parameters among the three groups. Independent-samples t test, Fisher precise test or Mann-Whitney U test were used for the comparison between each two groups. Results:Statistically significant difference was found in renal insufficiency between the HCM group and the AFD group; No other significant difference was found in other clinical factors and ECG results (all P>0.05). CMR results showed that in the AFD group, there were 5 cases with symmetric or roughly symmetric hypertrophy, and 3 with asymmetric hypertrophy. The late gadolinium enhancement (LGE) showed myocardial enhancement in 5 patients, mainly presenting as multiple intermural enhancement, and partially as local subendocardial enhancement. In the HCM group, fourteen cases suffered mainly asymmetric ventricular septal thickening, with or without thickening of other parts of left ventricular wall; and 2 cases had thickening of middle and distal part of the left ventricle. The LGE showed myocardial enhancement in 14 patients, which manifested as focal or patchy enhancement in hypertrophic myocardium, including focal enhancement in the right ventricular insertion of ventricular septum (more common) and subendocardial enhancement in the middle and far segments of left ventricle. Statistically significant difference was found in the differences between the left atrial anterior posterior diameter, the maximum wall thickness of left ventricular, the left ventricular myocardial mass index (LVMI) and the native T 1 value among the three groups (all P<0.001). However, there was no statistically significant difference in the left atrial anterior posterior diameter and the maximum wall thickness of left ventricular between AFD group and HCM group ( P>0.05). The LVMI in AFD group was higher than that in healthy group and HCM group (all P<0.05). Significant difference was found in the native T 1 value among the three groups, with the native T 1 value of the AFD group [(1 177.4±46.0) ms] was significantly lower than that of the healthy group [(1 244.5±34.3) ms] and the HCM group [(1 278.8±41.6) ms], with ( F=13.10, P<0.001). Conclusions:The clinical characteristics of AFD and HCM are quite similar. When AFD is suspected, CMR imaging should be the first choice for imaging examination. Especially, T 1 mapping imaging can provide important information for the diagnosis of AFD.
7.Efficacy of internal fixation with common intramedullary nail versus bone cement reinforced antirotation intramedullary nail in the treatment of femoral intertrochanteric fracture
Xiaoming WANG ; Wei DONG ; Xinwei LI ; Luchao ZHANG ; Yihui SUN
Chinese Journal of Primary Medicine and Pharmacy 2022;29(9):1375-1379
Objective:To investigate the efficacy of internal fixation with common intramedullary nail versus bone cement reinforced antirotation intramedullary nail in the treatment of femoral intertrochanteric fracture. Methods:A total of 106 patients with femoral trochanteric fractures who were surgically treated in Weihaiwei People's Hospital from January 2018 to January 2019 were selected and divided into a control group and an observation group with 53 patients in each group. The control group received internal fixation with common intramedullary nails. The observation group was fixed with bone cement reinforced anti-rotation intramedullary nails. The therapeutic effects were compared between the two groups.Results:There were no significant differences in the amount of blood loss, postoperative Visual Analogue Scale score, amount of fluid drainage, postoperative time to get out of bed, and postoperative hospital stay between the two groups ( t = 1.33, 0.19, 0.34, 0.58, 0.37, all P > 0.05). Operative time in the observation group was significantly longer than that in the control group [(80.21 ± 6.52) minutes vs. (75.92 ± 8.15) minutes, t = 2.99, P < 0.05]. Time to fracture healing in the observation group was significantly shorter than that in the control group [(9.25 ± 1.12) weeks vs. (10.05 ± 1.31) weeks, t = 3.37, P < 0.05]. The incidence of complications in the observation group was significantly lower than that in the control group [3.77% (2/53) vs. 16.98% (9/53), χ2 = 4.97, P = 0.025]. At 6 and 12 months after surgery, Harris hip scores in the observation group were (82.84 ± 6.58) points and (85.55 ± 7.91) points, respectively, which were significantly higher than (78.35 ± 7.54) points and (79.92 ± 9.94) points in the control group ( t = 3.26, 3.22, both P < 0.05). Conclusion:Internal fixation with bone cement-reinforced anti-rotation intramedullary nails for treatment of femoral trochanteric fractures can shorten the time to fracture healing, reduce complications, and improve hip joint function.
8.Clinical prediction model of moderate and severe obstructive sleep apnea hypopnea in snoring patients
Huiru LIU ; Chaoxin WANG ; Jie JIN ; Hanqiong XIAO ; Yihui QIU ; Dachuang SONG ; Zhiwen CHEN ; Jing DONG
Chinese Journal of Postgraduates of Medicine 2021;44(6):523-527
Objective:To establish a simple and efficient clinical prediction model of moderate and severe obstructive sleep apnea hypopnea (OSAHS) in snoring patients based on the clinical data and morphological measurement data in order to increase the early diagnosis and then early intervention of OSAHS. The prediction model is evaluated by external validation.Methods:A total of 299 subjects from January 2015 to December 2018 were selected to perform polysomngraphy (PSG) in Yangpu Hospital, Tongji University School of Medicine. According to the PSG results, they were divided into moderate and severe OSAHS groups (143 cases) and control groups (156 cases). Clinical complications data and morphological measurement data were collected. The regression equation and ROC curve were established according to the Logistic regression method. Then, another 110 subjects from January 2019 to October 2019 were chosen as verified data group, and used to verify the accuracy of the prediction model. The data of 110 subjects were put into the equation according to risk factors and assignment. The ROC curve was drawn and the area under the curve was calculated. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were calculated.Results:The predicted equation was: y = -10.707 86+0.589 60 × sex+ 0.141 61 × BMI+ 1.281 62 × tonsil size degree+ 1.807 43 × modified Mallampati degree′tongue position. The AUC of the ROC curve of prediction model in training set was 0.851(95% CI 0.807-0.895), the sensitivity was 83.9%, the specificity was 79.5%, and the cut-off value was 0.634.The AUC of the ROC curve in validation set was 0.827(95% CI 0.751-0.904) with a sensitivity of 73.3% and a specificity of 86.0%, and an accuracy of 79.1%. Its positive predictive value was 5.238, and negative predictive value was 0.310. Conclusions:The predictive model constructed by the combination of clinically accessible data (sex) and morphological measurement (BMI, tonsil size degree, modifiedMallampatidegree) has a relatively high predictive efficiency for screening snoring patients with moderate and severe OSAHS. The predictive model is proved with good forecast accuracy by the external verification method.
9.Effects of ROI-C Cervical Implantation on Biomechanics of Cervical Vertebra
Yanmei SONG ; Gaiping ZHAO ; Pengxiang LI ; Feiyi XIA ; Ziqiang DONG ; Houhai BI ; Nanxin CHEN ; Tong MA ; Yihui TU
Journal of Medical Biomechanics 2018;33(2):E114-E120
Objective To investigate the influence of ROI-C cervical implantation in the C5-6 segment on the C3-7 range-of-motion (ROM), biomechanical properties of the intervertebral disc and the vertebral body, and the mode of force transmission. Methods Two types of surgeries, ROI-C implantation and autograft fusion with plate fixation, were considered to establish the finite element model of cervical C5-6 segment degeneration. The ROM of C3-7 during flexion, extension, lateral bending, and axial rotation, as well as stress distributions on the adjacent discs, vertebral body, and implanted devices under two procedures, were analyzed. Results ROI-C implantation had a relatively small influence on the ROM of the adjacent segment. The stress on the vertebral discs was reduced, but the stress on the vertebral body increased significantly, with the C5 vertebral body stress increasing by 251%. In the fusion surgery model, the ROM of the surgical segment was reduced by 86%-91%, while the ROM of the adjacent segments and the stress on the vertebral disc and vertebral body increased significantly. Conclusions ROI-C implantation surgery has a relatively small influence on the cervical ROM and the intervertebral disc, and it has a greater impact on the vertebral body. The research findings provide a theoretical basis for the design of operation plans and clinical studies on ROI-C implantation and autograft fusion with plate fixation.
10.The role of D-dimer in detection and diagnosis of mycoplasma pneumonia
Xianwen YUAN ; Qingfeng WANG ; Yihui DONG
Chinese Journal of Primary Medicine and Pharmacy 2017;24(16):2449-2452
Objective To investigate the role of D-dimer in the diagnosis and evaluation of mycoplasma pneumonia.Methods The positive rate and concentration of D-dimer in mycoplasma pneumonia,bacterial pneumonia,viral pneumonia and healthy controls were detected and compared.The positive rate and concentration of D-dimer in patients with systemic inflammatory response syndrome(SIRS)and without SIRS were observed.Changes of D-dimer concentration in patients with mycoplasma pneumonia before and 2 weeks after treatment were observed.Results Compared with bacterial pneumonia group(16.7%),the viral pneumonia group(20.0%)and healthy control group(0.0%),the positive rate of D-dimer in mycoplasma pneumonia group(41.6%)was significantly higher(x2=5.625,4.158,17.308,all P<0.05).The positive rate of mycoplasma pneumonia group with SIRS(64.0%)was significantly higher than that in other groups(x2=17.308,P<0.05).The D-dimer levels of the mycoplasma pneumonia group [(324.4±125.3)μg/L],bacterial pneumonia group[(282.3±95.4)μg/L] and viral pneumonia group[(293.1±92.3)μg/L]were significantly higher than that in the healthy controls[(72.9±22.4)μg/L](t=10.878,11.704,12.698,all P<0.05).The concentration of D-dimer[(381.4±129.4)μg/L] in the mycoplasma pneumonia group with SIRS was significantly higher than that in the other groups(t=2.668,P<0.05).Compared with before treatment,the concentration of D-dimer after treatment in the two groups was significantly lower[(129.3±65.3)μg/L,(89.7±28.6)μg/L](t=2.582,P<0.05).Conclusion The level of D-dimer in children with mycoplasma pneumonia was significantly increased,and the severity of the disease could be reflected.

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