1.Analysis of serum differential proteomics in patients with acute cervical spondylotic radiculopathy
Xianzhong BU ; Baoxian BU ; Wei XU ; Chi ZHANG ; Yisheng ZHANG ; Yuanming ZHONG ; Zhifei LI ; Fubo TANG ; Wei MAI ; Jinyan ZHOU
Chinese Journal of Tissue Engineering Research 2024;28(4):535-541
BACKGROUND:The specific molecular mechanism of the transformation from normal healthy people to acute cervical spondylotic radiculopathy has not been clear,which needs to be further studied. OBJECTIVE:To investigate the differential expression of serum proteomics between normal healthy people and patients with acute cervical spondylotic radiculopathy,and to find and identify potential specific serum markers between them. METHODS:The serum samples of eight patients with acute cervical spondylotic radiculopathy and eight normal healthy people were collected,and the proteomic screening and analysis were performed by tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology,in order to explore and identify serum proteins differentially expressed in patients with acute cervical spondylotic radiculopathy. RESULTS AND CONCLUSION:A total of 183 significantly differential proteins were screened by tandem mass tag technology,and 11 significantly differential proteins were identified(P<0.05).Compared with normal healthy people,three differential proteins were significantly up-regulated,including human leukocyte antigen-A,secretoglobin family 1a member 1,and protein 4-hydroxyphenylpyruvate dioxygenase,and seven differential proteins were significantly down-regulated,such as immunoglobulin heavy constant gamma 3,skin factor,and myosin light chain 3,in patients with acute cervical spondylotic radiculopathy.Gene ontology enrichment analysis showed that these differential proteins participated in antigen binding,immunoglobulin receptor binding and other molecular functions.Protein-protein interaction analysis showed that among the common differential proteins between normal healthy people and patients with acute cervical spondylotic radiculopathy,HLA-A,HPD,PSMA3,DMKN,SCGB1A1,and MYL3 were located at the nodes of the functional network,and were closely related to the systems of body immunity,cellular inflammatory response,energy metabolism,and mechanical pressure.The significantly differential proteins HLA-A,HPD and MYL3 were verified by western blot,and the results were consistent with those of proteomics.To conclude,tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology can be used to find the differentially expressed proteins in serum between normal healthy people and patients with acute cervical spondylotic radiculopathy.It is preliminarily believed that HLA-A,HPD and MYL3 may be specific serum markers of acute cervical spondylotic radiculopathy,providing a new direction for further research on its pathogenesis.
2.Serum differential proteomics between developmental cervical spinal stenosis and cervical spondylotic myelopathy
Xianzhong BU ; Baoxian BU ; Wei XU ; Zhifei LI ; Hanli YANG ; Weiwei WANG ; Jinyan ZHOU ; Yuanming ZHONG
Chinese Journal of Tissue Engineering Research 2024;28(11):1704-1711
BACKGROUND:Previous studies have found that qi deficiency and blood stasis syndrome is the main syndrome among various TCM syndromes of cervical spondylotic myelopathy.However,there is no report on proteomic markers as early diagnosis indicators for the transformation of developmental cervical spinal stenosis with qi deficiency and blood stasis syndrome to cervical spondylotic myelopathy. OBJECTIVE:To explore serum proteomics difference between developmental cervical spinal stenosis and cervical spondylotic myelopathy and to find and identify the potential serum biomarkers between them. METHODS:Serum samples of nine patients with cervical spondylotic myelopathy of qi deficiency and blood stasis syndrome(experimental group)and nine patients with developmental cervical spinal stenosis of qi deficiency and blood stasis syndrome(control group)were collected.The proteomic analysis was carried out by Tandem Mass Tag combined with liquid chromatography tandem mass spectrometry,so as to find and identify differentially expressed proteins. RESULTS AND CONCLUSION:A total of 1027 significantly differential proteins were initially screened by TMT technology and 89 significantly differential proteins were finally identified(P<0.05).Compared with the control group,there were 45 up-regulated proteins in the experimental group,such as α-actinin-4,α-actinin-1,cell division control protein 42 homolog,integrin-linked protein kinase and B-actin.Conversely,there were 44 down-regulated proteins in the experimental group compared with the control group,such as fibronectin,fibrinogen γ chain,fibrinogen α chain,fibrinogen β chain.Gene ontology enrichment analysis indicated that these differential proteins were involved in signal receptor binding,kinase binding,protein kinase activity,integrin binding,actin filament binding and other molecular functions.Based on the Kyoto Encyclopedia of Genes and Genomes pathway analysis,20 common differential signal/metabolic pathways were identified,including Rap1 signaling pathway,adherens junction,tight junction,platelet activation,and regulation of actin cytoskeleton.Protein-protein interaction analysis showed that ILK,FGA,FGB,FGG,FN1,Cdc42,ACTN1,ACTN4 and ACTB were located at the nodes of protein-protein interaction network and were closely related to bone formation and destruction system,nervous system,coagulation system,cellular inflammation and other systems.To conclude,the serum differentially expressed proteins between developmental cervical spinal stenosis and cervical spondylotic myelopathy can be successfully screened by Tandem Mass Tag combined with liquid chromatography tandem mass spectrometry.ILK,FN1,CDC42 and ACTN 4 are identified as specific markers for the transformation of developmental cervical spinal stenosis with qi deficiency and blood stasis syndrome into cervical spondylotic myelopathy.These findings provide a basis for further clarifying the transformation mechanism.
3.Clinical analysis of 56 children with central sleep apnea
Li ZHENG ; Yunxiao WU ; Zhifei XU
Chinese Journal of Applied Clinical Pediatrics 2024;39(8):592-596
Objective:To explore the clinical characteristics and disease composition of pediatric patients with central apnea (CA) (classification by respiratory event type) and enhance the understanding of pediatric sleep-disordered breathing diseases.Methods:A cross section study was conducted.From March 2019 to March 2022, a total of 5 708 children underwent overnight polysomnography (PSG) at the Sleep Monitoring Center of Beijing Children′s Hospital, Capital Medical University.Among them, 56 patients (1.0%) had the central apnea index (CAI)≥5 times/h and the number of CA and/or central hypopneas>50% of the number of apneas and hypopneas.A retrospective analysis was conducted on the PSG and clinical data of the 56 pediatric patients with CA as the main manifestation.The disease composition and respiratory characteristics were summarized and analyzed.The factors related to central respiratory events were analyzed by multiple linear regression analysis.Results:Among the 56 children, 37 had concurrent obstructive sleep apnea (OSA), including 16 boys and 21 girls.CAI was positively correlated with the obstructive apnea-hypopnea index in central sleep apnea(CSA) patients with OSA ( r=0.673, P<0.001) and had no significant correlation with the body mass index or age.Among the 56 CSA patients, 4 had a CAI>20 times/h, including 1 case of Chiari malformation, 2 cases of brainstem tumors, and 1 case of inherited metabolic disease. Conclusions:The incidence of CA is lower compared to obstructive apnea.CSA patients often have concurrent OSA, and the severity of obstruction is the main factor affecting CAI.If CAI>20 times/h, it should be given high attention, and a comprehensive assessment of medical history and relevant imaging examinations are necessary to exclude underlying medical conditions causing CSA.
4.Research of the construction of comprehensive material management system based on multi-campus development model of public hospital
Heng XU ; Tu TU ; Huaiying ZHANG ; Guo ZHAO ; Pan ZHAO ; Zhifei DENG ; Yuxin LI
China Medical Equipment 2024;21(8):127-131
Objective:To construct a comprehensive material management system for public hospitals to meet the needs of material homogeneity and refined management under the hospital's multi-campus development model.Methods:By systematically sorting out the process and each link of the whole life cycle of hospital material management,using Java programming language,browser and server(B/S)architecture,setting up the integrated management platform module of medical equipment,the process module of each link of the material management system and the authority management module,the comprehensive material management system of public hospitals was constructed.The information call,mutual connection and restriction mechanism between the component modules were determined,and the dynamic real-time usage data and status of hospital materials were uniformly supervised.The homogeneity and fine management effects of hospital materials in Beijing Children's Hospital Capital Medical University before and after the application of the system were compared.Results:The integrated material management system of public hospitals realized full lifecycle coverage of hospital materials,the collaboration between various business modules and the smooth operation of the system,and realized the coordination of basic information,business and resources of hospital materials,as well as the homogeneity,refinement and integrated management of cross-campus materials.After the application of the system,seamless real-time data docking between different hospital campuses was realized,the average time of receiving materials in clinical departments was shortened by 2 hours compared with that before the application of the system,the review efficiency of material warehousing data,consumption data and inventory data was increased by 30%,and the backtracking error rate of the whole process of materials was reduced to 0.2%.Conclusion:The comprehensive material management system of public hospitals can improve the efficiency of material management in the operation of multiple hospital campuses,reduce management costs,and realize the homogeneity,refinement and scientificization of hospital material management.
5.The Combination of Gefitinib and Acetaminophen Exacerbates Hepatotoxicity via ROS-Mediated Apoptosis
Jiangxin XU ; Xiangliang HUANG ; Yourong ZHOU ; Zhifei XU ; Xinjun CAI ; Bo YANG ; Qiaojun HE ; Peihua LUO ; Hao YAN ; Jie JIN
Biomolecules & Therapeutics 2024;32(5):647-657
Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.
6.Clinical and prognostic characteristics of REM sleep related obstructive sleep apnea in children
Yunxiao WU ; Guoshuang FENG ; Zhifei XU ; Xin NI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(8):765-772
Objective:To analyze the clinical and prognostic characteristics of rapid eye movement sleep related obstructive sleep apnea (REM-OSA) in children.Methods:A retrospective analysis was performed on the clinical data of 62 children aged from 2 to 14 years who were admitted to Beijing Children′s Hospital, Capital Medical University from December 2017 to April 2021, diagnosed with moderate to severe OSA by polysomnography monitoring (PSG), underwent adenoid tonsillectomy, and completed follow-up 6 months after surgery. There were 45 males (72.6%) and 17 females (27.4%). The age range was 2.0-12.3 years. All children completed the clinical data collection, PSG, OSA-18 quality of life questionnaire and Children′s Sleep questionnaire-sleep related breathing disorder subscale at baseline. PSG and OSA-18 quality of life questionnaire were reexamined at 6 months after surgery. Children were divided into REM-OSA group (33 cases) and non-REM-OSA group (29 cases) according to whether the obstructive apnea-hypopnea index (OAHI) during rapid eye movement sleep and OAHI during non-rapid eye movement sleep ratio was≥2. Baseline PSG parameters and scale scores, 6-month postoperative cure rate and OSA-18 quality of life questionnaire scores of the 2 groups were compared, and statistical analysis was performed using SPSS 23.0 software.Results:There were no significant differences in age, sex, body mass index, neck circumference/height ratio, overweight or obesity, history of disease, tonsil and adenoid size between the two groups (all P>0.05). Compared with non-REM-OSA group, REM-OSA group had higher oxygen desaturation index and proportion of SpO2<90% of total sleep time ( Z=-2.723, P=0.006; Z=-3.414; P=0.001 respectively), and lower SpO 2 nadir ( Z=-3.957, P<0.001). The proportion of obstructive apnea in total respiratory events (related to anatomical factors) in REM-OSA group was higher than that in non-REM-OSA group ( t=2.840, P=0.006). However, the proportion of central apnea in total respiratory events and arousal index (related to functional factors) in REM-OSA group was lower than that in non-REM-OSA group ( t=-2.597, P=0.012; Z=-2.956, P=0.003), and there were no significant differences in other PSG parameters between the two groups (all P>0.05). There was an interaction effect between the two groups in the change trend of OSA cure rate at 6 months after surgery under different baseline OAHI (χ 2=4.282, P=0.039). Conclusions:The weight of anatomic factors and functional factors in the etiology of children with REM-OSA and non-REM OSA was different, and the postoperative OSA cure rate of children with different baseline OAHI changed in reverse trend.
7.Progress of comorbidities of asthma in children
Yuliang LIU ; Shanshan LIU ; Zhifei XU ; Ju YIN ; Kunling SHEN
International Journal of Pediatrics 2023;50(9):575-579
As a common respiratory disease in children, asthma affects children′s physical and mental health and increases the burden on families and society.Patients with asthma can have one or more comorbidities, and these asthma comorbidities not only make the diagnosis of asthma more difficult, but also affect the control and treatment and outcome of the disease.However, asthma comorbidities are often under-recognized and poorly-managed.Therefore, it is important to improve the understanding of asthma comorbidities and to correctly identify, diagnose and treat them.Asthma in children contains a variety of comorbidities.This article reviews the research progress of epidemiology, impact on asthma and the treatment of these common comorbidities of asthma in children.
8.N-acetyl-D-glucosamine inhibits oxidative stress and promotes M2 macrophage polarization to alleviate acute pancreatitis in rats
Zuzhi XU ; Liang ZHANG ; Xin HUANG ; Lei YU ; Pengfei CHEN ; Xuewen XIE ; Zhifei CHEN ; Kaihan FANG ; Shuke FEI
Acta Laboratorium Animalis Scientia Sinica 2023;31(11):1389-1398
Objective To investigate the effects of N-acetyl-D-glucosamine(GlcNAc)on acute pancreatitis in rats.Methods Twenty male SD rats were randomly divided into a control group,AP group,low GlcNAc + AP group and high GlcNAc + AP group,with five rats in each group.Acute pancreatitis was induced in AP group,low GlcNAc + AP group and high GlcNAc + AP group by two intraperitoneal injections of 2.5 g/kg L-arginine with a 1 hour interval.Among them,low GlcNAc + AP group and high GlcNAc + AP group were administered 50 and 200 mg/kg GlcNAc,respectively,by intraperitoneal injection at 24 hours before the first intraperitoneal injection of L-arginine.Group control and AP were intraperitoneally injected with the same volume of normal saline.After 24 h,the rats were sacrificed,and serum and pancreatic tissues were collected.Pancreatic tissue morphology was observed by HE staining,and serum levels of amylase(AMY),lipase(LPS),interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD)and malondialdehyde(MDA)were measured by enzyme-linked immunosorbent assay.Protein expression of nuclear factor E2-related factor 2(NRF2),heme oxygenase-1(HO-1),and peroxisome proliferator-activated receptor-γ(PPAR-γ)in pancreatic tissue was detected by Western Blot.Cluster of differentiation(CD)86,CD206 and macrophage markers(F4/80)were detected by immunofluorescence.Expression of CD86 and CD206 in pancreatic tissue was detected by immunohistochemistry.Results(1)Compared with control group,AMY,LPS,IL-1β,IL-6,TNF-α,and MDA levels and pancreatic CD86 expression in AP group were significantly increased(P<0.05),while SOD activity,protein expression levels of NRF2,HO-1,and PPAR-γ,and pancreatic CD206 expression were significantly decreased(P<0.05).(2)Compared with AP group,serum IL-1β,IL-6,TNF-α,MDA,and LPS and the pancreatic CD86 expression in low GlcNAc + AP group were significantly decreased(P<0.05).The PPAR-γ protein level in the pancreas was significantly increased(P<0.05).(3)Compared with AP group,serum AMY,LPS,IL-1β,IL-6,TNF-α,and MDA and pancreatic CD86 expression in high GlcNAc + AP group were significantly decreased(P<0.05),while serum SOD,and NRF2,HO-1,PPAR-γ,and pancreatic CD206 expression were significantly increased(P<0.05).(4)Compared with low GlcNAc + AP group,serum LPS,IL-1β and IL-6 in high GlcNAc + AP group were significantly decreased(P<0.05).Pancreatic expression of HO-1,PPAR-γ,and pancreatic CD206 were significantly increased(P<0.05).Conclusion GlcNAc treatment attenuates acute pancreatitis injury in AP rats,possibly by activating the NRF2/HO-1 signaling pathway to inhibit oxidative stress and promoting M2 macrophage polarization to attenuate pancreatic injury in AP rats.
9.Development and application of a new type of assisted micro implant anchorage 3D guide plate
Yufeng GAO ; Yu MA ; Zhifei CHEN ; Yanhua XU ; Fangyong ZHU ; Xiangbing WU ; Deqiang HOU
Journal of Chinese Physician 2023;25(9):1325-1328
Objective:To establish a computer-aided design and 3D printing system for precise implantation of micro implant anchorage, and accurately calibrate the position and direction of micro implant implantation.Methods:A retrospective selection was conducted on 15 patients (30 in total) who underwent micro implant implantation surgery from the Department of Stomatology, the Affiliated Hospital of Jiangnan University from November 2019 to November 2021, including 6 males and 9 females, aged (17.1±6.3)years old. The preoperative patient was photographed with cone beam computed tomography (CBCT) and the collected DICOM data format was output. A 3D scan was performed on the patient′s preoperative analysis model to obtain the STL file of the model scan. The CBCT data and model data were fitted and matched using 3Shape Implant Studio software, and the thickness of the guide plate, the amount of undercut compensation, and the size of the key component collar were designed. The 3D printer was used for printing after resizing. Using the assist method to implant micro implants, CBCT was taken postoperatively to compare the preoperative design with the postoperative results.Results:After fitting the postoperative CBCT with the designed CBCT of the micro implant, it was found that the micro implant was consistent with the preoperative design, maintained a safe distance and parallel to the adjacent tooth root, and did not damage the maxillary sinus and other areas. No detachment of the micro implant anchorage was observed 1 or 3 months after surgery. The application of assisted micro implant anchorage 3D guide plate was reliable, with accurate implantation position and direction, and can be implanted in most parts of the oral cavity.Conclusions:The use of computer-aided design and 3D printing system to create an assistive micro implant anchorage 3D guide plate can accurately locate the position and direction of the micro implant, which is worthy of clinical promotion and application.
10.Comparative analysis of the temporal characteristics of plasma metabolites in glioma mice after ultra-high dose rate radiation and conventional radiation
Jun ZHANG ; Wentao HU ; Zhiming XU ; Xinyang CHENG ; Yongsheng ZHANG ; Zhifei CAO
Chinese Journal of Radiological Medicine and Protection 2023;43(10):759-765
Objective:To investigate the effects of ultra-high dose rate radiation (FLASH-RT) and conventional radiation (CONV-RT) on plasma metabolites in glioma mice.Methods:Tocally 21 male C57BL/6J mice bearing intracranial glioma xenograft were randomly divided into healthy control group ( n=3), CONV-RT group ( n=9) and FLASH-RT group ( n=9). The CONV-RT group was administered a single dose of 24 Gy radiation on the head of mice at a dose rate of 0.4 Gy/s, and the FLASH-RT group was administered a single dose of 24 Gy radiation on the head of mice at a dose rate of 60 Gy/s, and the healthy control group was given 0 Gy pseudoradiation under the same condition. Mice blood was collected through the inner canthus vein for plasma separation at 1, 3 and 7 d after radiation in the two radiation groups, and the blood plasma of healthy control group was collected at 7 days after sham radiation. The changes in plasma metabolites were detected by the non-targeted metabolomics based on liquid chromatography mass spectrometry tandem platform. Results:After irradiation, the metabolites in plasma of two irradiation groups had significant difference. Compared with the healthy control group, 12 and 5 differential metabolites were screened out in the FLASH-RT group and CONV-RT group at three time points, respectively. The difference of plasma metabolites had the largest value at 1 day and decreased at 3 and 7 d after radiation. The arachidonic acid and isovaleric acid, involving arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, and tyrosine metabolism pathways were screened in both FLASH-RT group and CONV-RT group, and the 10 differential metabolites, mainly involving energy metabolism and redox reactions, only existed in the FLASH-RT group.Conclusions:Arachidonic acid and isovaleric acid may be the common sensitive biomarkers to different radiation patterns, which provides ideas for further exploring the molecular mechanism of FLASH-RT in the treatment of glioma.

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