1.Phillygenin ameliorates tight junction proteins reduction, fibrosis, and apoptosis in mice with chronic colitis via TGR5-mediated PERK-eIF2α-Ca2+ pathway.
Huanhuan XUE ; Peijie LI ; Jing GUO ; Tinggui CHEN ; Shifei LI ; Liwei ZHANG
Journal of Pharmaceutical Analysis 2025;15(1):101042-101042
Ulcerative colitis (UC) is an idiopathic, relapsing, and etiologically complicated chronic inflammatory bowel disease. Despite substantial progress in the management of UC, the outcomes of mucosal barrier repair are unsatisfactory. In this study, phillygenin (PHI) treatment alleviated the symptoms of chronic colitis in mice, including body weight loss, severe disease activity index scores, colon shortening, splenomegaly, oxidative stress, and inflammatory response. In particular, PHI treatment ameliorated the tight junction proteins (TJs) reduction, fibrosis, apoptosis, and intestinal stem cell activity, indicating that PHI exerted beneficial effects on the intestinal mucosal barrier in mice with chronic colitis. In the NCM460 cells damage model, dextran sulfate sodium triggered the sequential induction of TJs reduction, fibrosis, and apoptosis. Takeda G protein-coupled receptor-5 (TGR5) dysfunction mediated NCM460 cell injury. Moreover, PHI treatment enhanced TJs and suppressed fibrosis and apoptosis to maintain NCM460 cell function, depending on TGR5 activation. PHI promoted TGR5 activation and elevated intracellular cyclic adenosine monophosphate levels in HEK 293T cells transfected with TGR5 expression plasmids. Cellular thermal shift assay and molecular docking studies confirmed that PHI directly binds to TGR5, indicating that PHI is an agonist of TGR5. The process of PERK-eIF2α pathway-mediated endoplasmic reticulum Ca2+ release was involved in NCM460 cell injury as well, which was associated with TGR5 dysfunction. When NCM460 cells were pretreated with PHI, the PERK-eIF2α pathway and elevated Ca2+ levels were blocked. In conclusion, our study demonstrated a novel mechanism that PHI inhibited the PERK-eIF2α-Ca2+ pathway through TGR5 activation to against DSS-induced TJs reduction, fibrosis, and apoptosis.
2.Screening and analysis of ferroptosis related genes in peripheral blood mononuclear cells of patients with systemic lupus erythematosus
Kang TAO ; Yuan TIAN ; Shifei LI ; Bing NI ; Xiaoqiang CHEN ; Zhifang ZHAI
Chinese Journal of Rheumatology 2024;28(2):93-98
Objective:To analyze the differentially expressed genes in PBMCs of patients with systemic lupus erythematosus (SLE) by bioinformatics methods screening and analyzing the key genes related to ferroptosis, and explore the possible mechanism of ferroptosis involved in the pathogenesis of SLE at the transcription level.Methods:The data sets and samples of healthy people (HC) and SLE patients who met the screening criteria were retrieved from the Gene Expression Omnibus (GEO), a sub-database of the National Center for Biotechnology Information (NCBI). The differentially expressed genes, GO enrichment analysis and KEGG pathway enrichment analysis were analyzed by GEO2R, R language and related software packages. The protein interaction network (PPI) of differential genes was analyzed by STRING, Cytoscape and other tools to explore the key genes and pathways. In addition, real-time quantitative reverse transcription PCR (RT-qPCR) was used to verify the expression of key genes. Mann-Whitney U test was used to compare the expression of key genes in PBMCs between the two groups. Spearman rank correlation analysis was used to explore the relationship between SLE disease activity and the level of key genes. Results:Six data sets were included in this study. A total of 166 genes related to ferroptosis were differentially expressed between SLE and HC groups. The differential genes were specifically expressed in alveolar macrophages, neutrophils, CD49 + cells and CD31 + cells. GO enrichment analysis and KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly involved in multiple signaling pathways closely related to SLE, such as oxidative stress response, infection and TNF signaling pathway. Hub genes screened by different algorithms all suggested RELA as a key gene, and RT-qPCR confirmed that compared with the RELA gene expression level in the HC group [0.75(0.37,1.13)], the expression level in SLE group [2.02 (1.19,4.06)] was increased, the difference was statistically significant ( Z=-3.08, P=0.002), and was positively correlated with the corresponding SLEDAI score of SLE samples ( r=0.52, P=0.019). Conclusion:The ferroptosis of many immune cells, including alveolar macrophages and CD49 + NK cells, is involved in the pathogenesis of SLE. RELA may be involved in the ferroptosis of PBMCs in SLE through the NF-κB pathway.
3.Analysis of the diagnostic efficiency of wrist joint ulnar deviation supination 45° palmar oblique position for scaphoid waist fracture and displacement
Shifei CHEN ; Jun ZHANG ; Shuman HAN ; Wenjuan WU ; Zhiwei ZHONG ; Jing LI ; Zhe GUO ; Huizhao WU ; Ziyi QIAO
Journal of Practical Radiology 2024;40(5):805-808
Objective To investigate the clinical application value of wrist joint ulnar deviation supination 45° palmar oblique posi-tion in the diagnosis of scaphoid waist fracture and displacement.Methods The imaging and clinical data such as digital radiography(DR),CT of 93 wrist joint trauma patients were analyzed.The four position views including wrist joint anteroposterior+lateral view,scaphoid position,wrist joint ulnar deviation supination 45° palmar oblique position,scaphoid position+wrist joint ulnar devia-tion supination 45° palmar oblique position were analyzed by three readers.The consistency of the evaluation among different readers and the diagnostic efficiency of the diagnosis of scaphoid fracture and displacement were compared.Results The inter-observer agreement,sensitivity,specificity,accuracy,and other diagnostic efficiency of scaphoid waist fracture and displacement was evaluated,wrist joint ulnar deviation supination 45° palmar oblique position+scaphoid position and wrist joint ulnar deviation supination 45° palmar oblique position were better than those of scaphoid position and wrist joint anteroposterior+lateral view.The combination of wrist joint ulnar deviation supination 45° palmar oblique position+scaphoid position obtained the best diagnostic efficiency.Conclusion The wrist joint ulnar deviation supination 45° palmar oblique position shows the long axis of the scaphoid,which has a high diagnostic efficiency in the diagnosis of scaphoid waist fracture and displacement and would be used as a useful supplement to other scaphoid imaging.
4.Radiation dose optimization in nasal bone cone beam CT
Jun ZHANG ; Xiaonan HAN ; Shifei CHEN ; Hongyu ZHAO ; Yan SONG ; Zhiwei ZHONG ; Wenjuan WU ; Huizhao WU
Journal of Practical Radiology 2024;40(10):1702-1706
Objective To investigate the optimal scanning parameters for cone beam computed tomography(CBCT)of the nasal bone,to achieve low-dose scanning of the nasal bone CBCT.Methods Utilizing Prangmerka CBCT 3D single-tooth sequence,nasal bone scans were performed on two human-equivalent phantoms using two dose protocols,five body types,and five resolutions,resul-ting in 50 scanning sequences.The dose area product(DAP)and volume CT dose index(CTDIvol)were recorded.Objective image quality assessment was conducted by calculating the contrast-to-noise ratio(CNR),signal-to-noise ratio(SNR),noise,and figure of merit(FOM)in region of interest(ROI)set on sagittal images.Subjective scoring was performed using a five-point Likert scale.Differences in radiation dose and image quality among various scanning parameters were compared and analyzed.Results(1)Signifi-cant differences in DAP were observed among different dose modes,body types,and resolutions(P<0.05),with the lowest DAP values recorded for the XS body type.(2)Statistically significant differences in CNR,SNR,noise,and FOM were found among differ-ent dose modes and resolutions(P<0.05).The XS body type exhibited the highest SNR and FOM values and the lowest noise.The 200 μm resolution demonstrated the higher CNR value and the highest SNR value,with moderate noise and FOM value.(3)Signifi-cant differences in image quality,contrast,sharpness,and noise were observed among different dose modes,body types,and resolu-tions(P<0.05).Higher subjective scores were assigned to the 200 μm and 150 μm resolutions,indicating clear anatomical details.Conclusion The scanning parameters of 200 μm resolution combined with an ultra-low-dose protocol for the XS body type achieve a balance between low radiation dose and high image quality,making them suitable for low-dose nasal bone CBCT examinations.
5.Application value of dual-energy CT in removing artifacts of metal implants in different parts
Shifei CHEN ; Huizhao WU ; Ping ZHANG ; Lin BAI ; Ming WANG ; Ranxu ZHANG ; Yali WANG
Journal of Practical Radiology 2024;40(11):1888-1891
Objective To investigate the removal of metal artifacts caused by different metal implants in different parts of the human body using dual-energy CT and to select the best method for metal artifacts reduction.Methods Forty-three patients with metal implants underwent dual-energy CT scans.Reconstructed images were obtained to produce eight sets of imaging data:conventional image(CI),120 keV,140 keV,160 keV,180 keV,200 keV,Orthopedic metal artifact reduction algorithm(O-MAR),200 keV+O-MAR.The optimal spectral monoenergetic images was selected based on the trend of changes in artifact index(AI)values with different keV monoenergetic images and subjective evaluation.One-way ANOVA was used to analyze and compare objective image evaluation indi-cators and subjective evaluations of image quality among different groups.The intraclass correlation coefficient(ICC)was used to evaluate the consistency and reliability of subjective evaluations of image quality among different observers.Results The AI values of differ-ent keV monoenergetic images showed a decreasing trend with increasing keV,and the virtual monoenergetic images at the 200 keV level had the smallest AI value.There were statistically significant differences in objective indicators for the removal of high-density artifacts and low-density artifacts among the groups(P<0.05).Pairwise comparison showed statistical differences between CI and O-MAR,CI and O-MAR+200 keV,200 keV and O-MAR,200 keV and O-MAR+200 keV(P<0.05),with O-MAR+200 keV demon-strating the best objective indicators.The ICC for subjective evaluation among different observers was 0.97%,and the ICC within observers was 0.91%.There were statistically significant differences in subjective image scores among the groups(P<0.05),with the CI had the lowest score[(1.04±0.24)points]and the O-MAR+200 keV combination had the highest score[(4.57±0.78)points].Conclusion Dual-energy CT virtual monoenergetic 200 keV spectroscopy combined with O-MAR technique can be used as the best technique for removing metal implant artifacts and achieving better contrast in the surrounding soft tissue of prostheses.
6.Analysis of the Symptoms of Jaundice Formula"Ma-Huang Lian-Yao Chi-Xiao-Dou Tang",Examination of Lian-Yao,and Insight into the Medicinal Value and Research of Forsythiae Fructus
Tao WANG ; Qilei CHEN ; Baifang WANG ; Jiankai TANG ; Xuejian GUO ; Shifei LI ; Hubiao CHEN ; Liwei ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(9):2909-2913
Ma-huang Lian-yao Chi-xiao-dou Tang is one of the three formulas for typhoid jaundice.But it has not received much attention,and the source of Lian-yao in the formula is unknown and the status and role are difficult to identify.In this paper,we first analyzed the functions of Ephedra and the symptoms of the whole formula.The formula was mainly used to"clear damp-heat"in order to remove jaundice.On this basis,it is proved that Lian-yao is the root of Forsythia,not"Qiao-gen".Today,the use of Forsythia instead of Lian-yao has the same effect.Then,the indispensable and important position of Forsythia in the formula was analyzed.It also pointed out some valuable directions for the medicinal use and research and development of Forsythia based on its wide range of effects but the lack of main symptoms.This paper provides insights for in-depth theoretical and practical research on Forsythiae Fructus.
7.Protective mechanism of tetramethylpyrazine on pancreatic tissue in rats with acute necrotizing pancreatitis based on network pharmacology
Jie CHEN ; Shifei HUANG ; Yehong HAN
Chinese Journal of Pancreatology 2022;22(3):171-177
Objective:To explore the core targets and potential molecular mechanisms of tetramethylpyrazine in the treatment of rats with acute necrotizing pancreatitis (ANP) based on network pharmacology.Methods:The related co-targets of tetramethylpyrazine and ANP were screened out by traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and human disease information-related databases (CTD, DisGeNET, GeneCards, OMIM); Uniprot data were used to co-link and put into the STRING database to build protein-protein interaction (PPI) networks; the Cytoscape software was used for further analysis and the key targets were obtained by using the cytoHubba plug-in. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on these key targets, and finally the molecular docking models were constructed by using PyMol and AutoDockTools software. 30 male SD rats were randomly divided into the control group, ANP group, and tetramethylpyrazine treatment group (tetramethylpyrazine group). ANP rats were induced by retrograde infusion of 4% sodium taurocholate into the biliary-pancreatic duct, and the tetramethylpyrazine group rats were injected with 10 ml/kg tetramethylpyrazine through the abdominal cavity after ANP was induced. After 12 h, pancreatic tissue was taken, a pathological examination was performed routinely, and immunohistochemical staining was performed to observe the protein expression of key targets in pancreatic tissue. Blood was taken from orbits, and then the serum IL-6 and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay (ELISA).Results:The drug platform screened 137 tetramethylpyrazine action targets, and the disease database screened out 513 ANP-related targets; then 25 targets were obtained through intersection, finally resulting in a total of 5 key targets: albumin (ALB), epidermal growth factor receptor (EGFR), caspase 3 (CASP3), mitogen-activated protein kinase 1 (MAPK1) and B-cell lymphoma-2-like protein 1 (BCL2L1). GO functional enrichment analysis of biological processes mainly involved reproductive structure or system development, response to antibiotics, chemical stress and reactive oxygen species, and the cellular components were mainly vesicle lumen, membrane raft, membrane microdomain, and secretory granule lumen; molecular functions mainly included SH2 domain, phosphotyrosine residue, protease binding, protein tyrosine kinase and nuclear receptor activity; KEGG pathway enrichment analysis were mainly enriched in Ras signaling pathway, PI3K-Akt signaling pathway, platinum drug resistance, phospholipase D signaling pathway, and EGFR tyrosine kinase inhibitor resistance. The average binding energy of the 5 key targets molecule docking was -4.20 kcal/mol. After hematoxylin-eosin staining, it could be seen that the gland structure of rats in the ANP group was disordered, the interlobular space was significantly increased, and neutrophil infiltration was observed in the acinar, perivascular and gland space. The pancreatic lobule space of tetramethylpyrazine group rats was slightly increased, with mild neutrophil infiltration. The protein expressions of EGFR, CASP3 and MAPK1 in the ANP group were significantly higher compared with those in the control group, and EGFR, CASP3 and MAPK1 expression in tetramethylpyrazine group was significantly lower than those in ANP group ( P<0.01); the protein expression of BCL2L1 in the ANP group were significantly higher than that in control group, and the protein expression of BCL2L1 in tetramethylpyrazine group were significantly higher than that in ANP group (all P value <0.05). The serum levels of IL-6 and TNF-α in the ANP group were significantly higher than those in the control group, and IL-6 and TNF-α in tetramethylpyrazine group were significantly lower than those in the ANP group (all P value <0.01). Conclusions:Tetramethylpyrazine could reduce the inflammatory response and oxidative stress injury after ANP by activating a variety of signaling pathways, enhancing the expression of anti-apoptotic genes, and blocking the enzymatic cascade reaction of apoptotic caspase, thus playing a protective role in pancreatic tissues of rats with ANP.
8.Effectiveness of health education provided by general practice team in standardizing insulin administration and blood glucose control for diabetic patients
Shifei ZHU ; Xin HUANG ; Fayu CHEN
Chinese Journal of General Practitioners 2021;20(8):910-913
The general practice team of the Affiliated Hospital of Hangzhou Normal University and its medical consortium conducted health education for 73 diabetic patients from January to December 2019. The education was dealing with the knowledge and techniques of standardizing insulin administration, including the manipulations, rotation of injection sites and replacement of injection needles, etc. The questionnaire surveys on the knowledge of diabetic management and insulin administration were conducted before and after education. After education the number of patients who knew the injection site and skin disinfection increased from 68 and 69 to 73 and 73, respectively ( P>0.05); the number of patients who knew the injection depth and length of the needle used increased from 33 and 24 to 73 and 73, respectively ( P<0.05); the number of patients who knew pinching the skin, the angle of needle insertion increased from 30 and 44 to 73 and 73 ( P<0.05). After education the number of patients with pinch time>10 sec increased from 0 to 68 cases ( P<0.05); with needle stay>10 sec increased from 0 to 71 ( P<0.05); with rotation in the same area increased from 58 to 73 ( P<0.05); with repeated needle use decreased from 73 to 70 ( P>0.05). After education the blood glucose control of diabetic patients was improved: the glycosylated hemoglobin [(8.3±1.3)% vs. (6.8±0.5)%, t=9.00, P<0.05], fasting blood glucose [(7.7±0.8)mmol/L vs. (6.9±0.5)mmol/L, t=7.90, P<0.05] and 2-hour postprandial blood glucose[(11.4±2.1)mmol/L vs. (9.6±0.8)mmol/L, t=7.00, P<0.05] were significantly decreased. It is suggested that health education provided by the general practice team can standardize the insulin administration in diabetic patients and improve blood sugar control.
9.Possibility of women treated with fertility-sparing surgery for non-epithelial ovarian tumors to safely and successfully become pregnant-a Chinese retrospective cohort study among 148 cases.
Bin YANG ; Yan YU ; Jing CHEN ; Yan ZHANG ; Ye YIN ; Nan YU ; Ge CHEN ; Shifei ZHU ; Haiyan HUANG ; Yongqun YUAN ; Jihui AI ; Xinyu WANG ; Kezhen LI
Frontiers of Medicine 2018;12(5):509-517
This study was performed to evaluate the oncological and reproductive outcomes of childbearing-age women treated with fertility-sparing surgery (FSS) for non-epithelial ovarian tumors in China. One hundred and forty eight non-epithelial ovarian tumor women treated with FSS between January 1, 2000 and August 31, 2015 from two medical centers in China were identified. Progression-free survival (PFS) was 88.5%, whereas overall survival (OS) was 93.9%. Univariate analysis suggested that delivery after treatment is related to PFS (P = 0.023), whereas histology significantly influenced OS. Cox regression analysis suggested that only histology was associated with PFS and OS (P < 0.05). Among the 129 women who completed adjuvant chemotherapy (ACT), none developed amenorrhea. Among the 44 women who desired pregnancy, 35 (79.5%) successfully had 51 gestations including 35 live births without birth defects. Non-epithelial ovarian tumors can achieve fulfilling prognosis after FSS and chemotherapy. Histology might be the only independent prognostic factor for PFS and OS. FSS followed by ACT appeared to have little or no effect on fertility. Meanwhile, postoperative pregnancy did not increase the PFS or OS. Use of gonadotropin-releasing hormone agonist was not beneficial for fertility.
Adolescent
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Adult
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Chemotherapy, Adjuvant
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adverse effects
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Child
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China
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Female
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Humans
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Infertility, Female
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etiology
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prevention & control
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Neoplasm Staging
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Organ Sparing Treatments
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Ovarian Neoplasms
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drug therapy
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surgery
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Pregnancy
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Pregnancy Rate
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Prognosis
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Retrospective Studies
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Survival Analysis
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Young Adult
10.A randomized controlled clinical trial on the effects of wearing orthokeratology and spectacles on ocular peripheral refraction in myopic children
Shifei WEI ; Shiming LI ; Yunyun SUN ; Mengtian KANG ; Bo MENG ; Anran RAN ; Ran YAN ; Yawen BAI ; Chen ZHUO ; Ningli WANG
Chinese Journal of Experimental Ophthalmology 2017;35(10):930-935
Background It has been reported that orthokeratology has the effects of slowing down myopia progression and axial elongation.However,the affecting mechanism of orthokeratology wearing on ocular peripheral refraction is still not elucidated.Objective This study was to observe and compare the changes of ocular peripheral refraction and relative peripheral refraction (RPR) in low to moderate myopic eyes of children after wearing orthokeratology lens and spectacles for 6 months.Methods A randomized controlled clinical trial was carried out after approval of Ethic Committee of Beijing Tongren Hospital and informed consent of guardians of the children.One hundred myopic children aged (ll.0±1.9) years were recruited in Beijing Tongren Hospital from June 2014 to January 2015,with the diopter of-0.50 to-6.00 D.The subjects were randomized into orthokeratology group and spectacles group by the process PLAN PROC of software SAS 9.1.3,50 for each group.The subjects in the orthokeratology group wore orthokeratology lens for 6 months and those in the spectacles group wore spectacles for the same period.An infrared open-field autorefractor was employed to measure the refraction at central 0°,temporal 15°,temporal 30°,nasal 15°and nasal 30° radial lines before and after wearing lens for the assessment and comparison of the changes of peripheral refraction and RPR.Results There was no significant difference in spherical equivalent between the orthokeratology group and the spectacles group before wearing lens ([-3.35±1.31] D versus [-3.01± 1.15] D,P =0.20).The peripheral refraction values in the orthokeratology group were (-2.28 ± 1.60),(-3.28±1.41),(-3.40±1.23),(-3.38±1.12) and (-2.09±1.29)D at nasal 15°and nasal30°,central,temporal 15° and temporal 30°radial lines before wearing lens,and reduced by (0.29±1.67),(0.85±1.66),(0.92±1.76) and (0.66±1.66) D at nasal 30°,nasal 15°,central and temporal 15° after wearing lens,respectively,with significant differences at nasal 15°,central and temporal 15°(all at P<0.05).The peripheral refraction values in the spectacles group were (-1.88±1.30),(-2.66±1.18),(-2.89±1.27) and (-1.94±1.31)D at nasal 15°,nasal 30°,temporal 15 ° and temporal 30°,radial lines before wearing lens and increased by (-0.25±0.80),(-0.43 ±0.67),(-0.32±0.64) and (-0.22±0.75)D after wearing lens,respectively,with significant differences between before and after wearing lens (all at P<0.05).The RPR shifted from hyperopia defocus to myopia defocus before and after wearing lens in temporal 15° and 30° radial lines in the orthokeratology group,and at various radial lines in the spectacles group,the RPR showed gradually worsening of hyperopia defocus.Conclusions Long-term wearing of orthokeratology results in a hyperopia shifting in myopic children by exposing the peripheral retina towards relative myopia defocus,whereas wearing spectacles leads to a relative hyperopia defocus on retina.Thus,orthokeratology may slow down the myopia progression.

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