1.Inhibitory effect of downregulating HMGB2 expression on epithelial-mesenchymal transition of liver cancer LM3 cells and its AKT/m TOR signaling pathway mechanism
Yanhong WEI ; Chenxue YANG ; Guangmin YANG ; Shuai SONG ; Ming LI ; Haijiao YANG ; Haifeng WEI
Journal of Jilin University(Medicine Edition) 2024;50(1):143-149
Objective:To discuss the effect of downregulating of high mobility group box protein 2(HMGB2)expression on the biological behavior of the liver cancer cells and the epithelial-mesenchymal transition(EMT)process,and to clarify its mechanism.Methods:The human liver cancer LM3 cells at logarithmic growth phase were divided into negative control group and HMGB2 RNA interference group(HMGB2 siRNA group);the cells in two groups were transfected with RNA oligonucleotides(RNA oligos)with irrelevant sequences and RNA oligos designed to knock down HMGB2,and the Lipofectamine 2000 was regarded as the vector.The expression levels of HMGB2 mRNA and protein in the cells in two groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods;cell scratch assay and Transwell chamber assay were used to detect the migration and invasion abilities of the cells in two groups;the expression levels of E-cadherin,N-cadherin,and Vimentin proteins and protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway related proteins in the cells in two groups were detected by Western blotting method.Results:Compared with negative control group,the expression levels of HMGB2 mRNA and protein in the cells in HMGB2 siRNA group were significantly decreased(P<0.05),the cell scratch healing rate was significantly decreased(P<0.01),the number of invasion cells was significantly decreased(P<0.01),and the expression level of E-cadherin protein in the cells was significantly increased(P<0.01),while the expression levels of N-cadherin,Vimentin,mTOR,AKT,and phosphorylated AKT(p-AKT)proteins in the cells were significantly decreased(P<0.05 or P<0.01).Conclusion:Downregulating the expression of HMGB2 can reduce the migration and invasion abilities of the liver cancer LM3 cells and inhibit the EMT,and its mechanism may be related to regulating the expression of the AKT/mTOR pathway related proteins.
2.Exploration and practice of smart hospital based on new diagnosis and treatment model
Hanliang DAN ; Zongyi LI ; Ning ZENG ; Rongrong NIE ; Haijiao ZHANG ; Fen TANG
Modern Hospital 2024;24(1):84-87
As the state vigorously promotes the high-quality development of hospitals and improves people's medical ex-perience,the patient-centered hospital should make full use of technological resources such as the Internet,5 G and artificial in-telligence,vigorously develop mobile medical services and artificial intelligence services,transform and optimize the diagnosis and treatment process,and streamline all links before,during and after diagnosis so as to provide better data services to the pa-tient to ensure that they can get things done with greater ease.The patients'medical experience and hospital management effi-ciency can be greatly improved.In this study,specific measures to create a new diagnosis and treatment model through the con-struction of smart hospital platform were expounded in order to provide references for related research and policy formulation of other Chinese medical institutions.
3.Bioequivalence Study of Minocycline Hydrochloride Capsules in A Healthy Chinese Population
Xincheng FENG ; Jiongxian LYU ; Chang SU ; Chaochao HUANG ; Hong SUN ; Haijiao CHENG ; Minlu CHENG ; Juefang DING ; Li DING ; Yuwen SU
Herald of Medicine 2024;43(10):1545-1551
Objective To evaluate the bioequivalence of two formulations of minocycline hydrochloride capsules administered orally after fasting administration and fed administration.Methods An open-label,randomized,two-period,self-crossover design was employed to assess the bioequivalence study.Twenty-eight healthy subjects were enrolled in both fasting and fed groups,with each period involving a single administration of either the reference formulation or the test formulation of 50 mg,separated by a washout period of 7 days.The concentration of minocycline in human plasma was determined by HPLC-MS/MS and was used for calculating pharmacokinetic parameters and evaluating the bioequivalence of the test formulation and reference formulation.Results After oral administration of test and reference formulations of minocycline under fasting condition,the Cmax Values of minocycline were(541±137)ng·mL-1 for the test formulation and(558±140)ng·mL-1for the reference formulation.The AUC0-t values were(8 347±1 986)h·ng·mL-1 for the test and(8 205±1 790)h·ng·mL-1 for the reference.The t1/2 values were(18.2±2.84)h for the test and(18.0±3.05)h for the reference.After oral administration of the test and reference formulations of minocycline under fed condition,the Cmax values of minocycline were(349±72.1)ng·mL-1 for the test and(352±73.2)ng·mL-1for the reference.The AUC0-twere(6 428±1 077)h·ng·mL-1 for the test and(6 588±1 118)h·ng·mL-1 for the reference.The t1/2values were(18.5±3.10)h for the test and(18.4±3.21)h for the reference.Under fasting condition,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test and reference formulations were(90.84%,101.46% ),(95.2%,102.8% ),and(95.31%,102.71% ),respectively.Under fed conditions,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test formulation and the reference formulation were(94.71%,103.42% ),(95.40%,99.83% ),and(95.79%,100.02% ),respectively.Conclusions Bioequivalence of the two minocycline formulations was demonstrated after fasting administration and fed administration in a healthy Chinese population.
4.The mid-term and long-term efficacy of cement augmentation of pedicle screws in the treatment of thoracolumbar osteoporotic vertebral compression fractures complicated with spinal kyphosis deformity
Yuwei LI ; Xiuzhi LI ; Haijiao WANG
Chinese Journal of Spine and Spinal Cord 2024;34(8):812-818
Objectives:To evaluate the safety and mid-term clinical efficacy of cement augmentation of pedicle screws in the treatment of thoracolumbar osteoporotic vertebral compression fractures complicated with spinal kyphosis deformity.Methods:A retrospective study was conducted to analyze the clinical data of el-derly patients with osteoporotic vertebral compression fractures complicated with spinal kyphosis deformity ad-mitted and treated from January of 2017 to October of 2020.According to whether pedicle augmentation us-ing bone cement was used,the patients were divided into a cement-augmented group(22 cases,cement-augmented pedicle screws)and a control group(23 cases,pedicle screws without cement augmentation).In the reinforced group,there were 9 males and 13 females;age ranged from 70 to 91 years,with a mean of 78.68±7.12 years;disease duration ranged from 1.1 to 3.8 years,with a mean of 2.39±0.71 years.In the control group,there were 10 males and 13 females;age ranged from 70 to 89 years,with a mean of 77.73±5.83 years,and disease duration ranged from 0.8 to 3.3 years,with a mean of 2.38±0.67 years.The follow-up period was 36-69 months.The incidence of pedicle screw loosening,correction rate of kyphosis,and improvement rate of visual analogue scale(VAS)and Oswestry disability index(ODI)at final follow-up were compared between the two groups.Results:In the cement-augmented group,1-2 segments of surgical decompression were performed,6-9 segments were fixed and fused,and 14 cases underwent SPO and 8 cases underwent PSO.The operational time was 221±32mins,and the volume of blood loss was 939±113mL.In the control group,1-3 segments of surgical decompression were performed,6-8 segments were fixed and fused,and 16 cases underwent SPO and 7 cases underwent PSO.The operative time was 209±36mins,and the vol-ume of blood loss was 979±111mL.One case in the cement-augmented group and two cases in the control group complicated with cerebrospinal fluid leakage,which were treated with intraoperative repair of the dura mater,tight suturing of the incision,and postoperative Trendelenburg's position.There was no statistical differ-ence in the comparison of decompression segments(t=1.785,P=0.081),fusion segments(t=0.922,P=0.362),oper-ative time(t=1.162,P=0.252),bleeding(t=1.193,P=0.239),and CSF leak complications(x2=0.311,P=0.577)be-tween the two groups.There were no complications of incision infection or leakage of bone cement into the spinal canal causing neurological symptoms.At final follow-up,the screw loosening rate was 0%in the ce-ment-augmented group(0/268)and 18.6%in the control group(45/242).The difference in screw loosening rate between the two groups was statistically significant(x2=54.657,P=0.000).The correction rate of kyphosis defor-mity was(73.27±9.78)%in the cement-augmented group and(55.96±11.31)%in the control group.There was a significant difference in the correction rate of kyphosis between the two groups(t=5.480,P=0.000).The im-provement rate of VAS in the cement-augmented group was(67.94±14.72)%,while in the control group was(74.29±13.18)%.There was no significant difference in the improvement rate of VAS between the two groups(t=1.526,P=0.134).The improvement rate of ODI in the cement-augmented group was(82.01±3.11)%,while in the control group it was(81.96±3.58)%,there was no significant difference in the improvement rate of ODI between the two groups(t=0.41,P=0.968).Conclusions:The application of cement augmentation of pedicle screws in decompression,osteotomy,and long segment fixation fusion for the treatment of thoracolumbar osteo-porotic vertebral compression fractures with spinal kyphosis deformity can effectively reduce the loosening rate of pedicle screws and improve the correction rate,resulting in satisfactory clinical outcomes.
5.UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL
Renyu ZHANG ; Can LI ; Shuai ZHANG ; Lingmin KONG ; Zekun LIU ; Yixiao GUO ; Ying SUN ; Cong ZHANG ; Yule YONG ; Jianjun LV ; Meng LU ; Man LIU ; Dong WU ; Tianjiao ZHANG ; Haijiao YANG ; Ding WEI ; Zhinan CHEN ; Huijie BIAN
Clinical and Molecular Hepatology 2024;30(4):771-792
Background/Aims:
Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking.
Methods:
Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth.
Results:
Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy.
Conclusions
UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.
6.Posterior atlantoaxial non-fusion fixation versus anterior cervical odontoid screw fixation in treatment of odontoid fracture of Anderson-D'Alonzo type Ⅱ
Yuwei LI ; Haijiao WANG ; Xiaoyun YAN
Chinese Journal of Orthopaedic Trauma 2023;25(10):847-852
Objective:To compare the curative effects of posterior atlantoaxial non-fusion fixation and anterior cervical odontoid screw fixation in the treatment of odontoid fracture of Anderson-D'Alonzo type Ⅱ.Methods:A retrospective study was conducted to analyze the clinical data of 21 patients with odontoid type II fracture who had been treated at Department of Spine Surgery, The Central Hospital of Luohe from January, 2015 to January, 2020. The patients were divided into a posterior group subjected to posterior atlantoaxial non-fusion fixation and an anterior group subjected to anterior cervical odontoid screw fixation. In the posterior group of 12 patients, there were 7 males and 5 females with an age of (42.2±11.8) years. In the anterior group of 9 patients, there were 5 males and 4 females with an age of (40.0±9.1) years. The 2 groups were compared in terms of operation time, bleeding volume, intraoperative fluoroscopy, fusion time, cervical rotation and neck dysfunction index (NDI).Results:The differences in the preoperative general information were not statistically significant between the 2 groups, indicating comparability ( P>0.05). The implants were successfully inserted in all patients. Intraoperative fracture reduction was satisfactory and no arteriovenous or spinal cord injuries occurred. The mean follow-up time was (24.5±11.3) months. The operation time [(108.5±15.9) min] and bleeding volume [(48.3±12.2) mL] in the anterior group were significantly less than those in the posterior group [(153.9±34.2) min and (275.8±56.0) mL], and the intraoperative fluoroscopy [(13.0±2.1) times] in the anterior group was significantly higher than that in the posterior group [(7.2±1.4) times] ( P<0.05). There was no statistically significant difference in fracture healing time between the 2 groups ( P>0.05). There was no statistically significant difference either in total cervical rotation or NDI between the 2 groups at the last follow-up ( P>0.05). Conclusions:Posterior atlantoaxial non-fusion fixation can preserve the range of rotation of the cervical spine and reduce the dysfunction of the cervical spine. The anterior screw fixation may result in shorter operation time and less intraoperative bleeding, but more intraoperative X-ray fluoroscopy. Therefore, the 2 internal fixation methods should be adopted on the basis of each individual in the treatment of odontoid type Ⅱ fracture to achieve good curative results.
7.Effects of different moxibustion time on knee cartilage morphology and the expression of TNF-α and IL-10 in rats with knee osteoarthritis
Qing LI ; Pingju XUE ; Xiaoqin ZHANG ; Yejuan JIA ; Jing XU ; Zilong CHEN ; Chunsheng JIA ; Haijiao XING ; Yanping YANG
Journal of Acupuncture and Tuina Science 2023;21(3):187-196
Objective:To observe the effects of different moxibustion time on cartilage morphology,tumor necrosis factor(TNF)-α and interleukin(IL)-10 of the knee joint in rats with knee osteoarthritis(KOA),and to explore the best treatment time of moxibustion for KOA.Methods:Healthy male Wistar rats were randomly divided into a blank group,a model group,a 15-minute-moxibustion group,a 30-minute-moxibustion group,and a 60-minute-moxibustion group,with 10 rats in each group.Except for the blank group,the KOA model was established in all groups by injecting sodium iodoacetate solution into the knee joint cavity of rats.Rats in the 15-minute-moxibustion group,the 30-minute-moxibustion group,and the 60-minute-moxibustion group were all treated with mild moxibustion intervention for 15 min,30 min,and 60 min,respectively at Neixiyan(EX-LE4)and Dubi(ST35)points near the patella,3 times a week for 4 weeks,12 times in total.Rats in the blank group and the model group were fixed for 30 min without moxibustion intervention.Macroscopic observation for the smoothness of knee cartilage surface was performed after the intervention.Hematoxylin-eosin staining,toluidine blue staining,and Mankin score were used to evaluate the pathological changes in the cartilage.The expression levels of TNF-α and IL-10 in the serum were detected by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the articular cartilage surface in the model group was rough,the chondrocyte arrangement was irregular,the Mankin score and the serum TNF-α expression were significantly increased(P<0.05),while the expression of serum IL-10 was significantly decreased(P<0.05).Compared with the model group,the articular cartilage surface was smoother,the chondrocytes were arranged neatly,the Mankin score and serum TNF-α expression level were significantly lower in the three moxibustion intervention groups(P<0.05);the serum IL-10 level in the 30-minute-moxibustion group and the 60-minute-moxibustion group was increased significantly(P<0.05).Compared with the 15-minute-moxibustion group,the articular cartilage surface in the 30-minute-moxibustion group and the 60-minute-moxibustion group was smoother,the chondrocyte arrangement was more regular,the Mankin score and the serum TNF-α level were decreased significantly(P<0.05),and the serum IL-10 level was increased(P<0.05).There was no significant difference in the serum TNF-α or IL-10 level between the 30-minute-moxibustion group and the 60-minute-moxibustion group(P>0.05).Conclusion:Moxibustion can obviously improve the morphology and structure of KOA articular cartilage,protect articular cartilage,inhibit cartilage inflammation,and delay KOA cartilage degeneration.Moxibustion's effect is closely related to moxibustion time;the therapeutic effect of the 30-minute-moxibustion and the 60-minute-moxibustion is better than that of the 15-minute-moxibustion.
8.Study on 4 cases of mushroom poisoning with amanita and identification of poison
Jie HU ; Haijiao LI ; Qingfeng MENG ; Fuping LAI ; Ruilie WANG ; Yuanlan LU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(8):622-625
Different kinds of poisonous mushrooms contain different toxic components. Acute liver injury caused by amanita mushroom is the main cause of death from poisonous mushroom poisoning in China. Consumption of poisonous mushrooms has an incubation period, there is a false recovery period in the clinical process, and the early performance is slight and does not attract enough attention from doctors, and it is easy to miss the treatment opportunity. The clinical characteristics, treatment and identification of mushrooms containing amanita in 4 patients were analyzed in order to improve clinicians' understanding of the diagnosis and treatment of mushroom poisoning and early species identification.
9.Study on 4 cases of mushroom poisoning with amanita and identification of poison
Jie HU ; Haijiao LI ; Qingfeng MENG ; Fuping LAI ; Ruilie WANG ; Yuanlan LU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(8):622-625
Different kinds of poisonous mushrooms contain different toxic components. Acute liver injury caused by amanita mushroom is the main cause of death from poisonous mushroom poisoning in China. Consumption of poisonous mushrooms has an incubation period, there is a false recovery period in the clinical process, and the early performance is slight and does not attract enough attention from doctors, and it is easy to miss the treatment opportunity. The clinical characteristics, treatment and identification of mushrooms containing amanita in 4 patients were analyzed in order to improve clinicians' understanding of the diagnosis and treatment of mushroom poisoning and early species identification.
10.Treatment of benign tumors in the lumbar spinal canal by recapping laminoplasty preserving the continuity of superior spinous ligament
Yuwei LI ; Haijiao WANG ; Wei CUI ; Peng ZHOU ; Fan LI ; Yuanhao LIU ; Jingyi XU ; Tiantian TANG
Chinese Journal of Neuromedicine 2022;21(5):469-473
Objective:To investigate the efficacy of recapping laminoplasty preserving the continuity of superior spinous ligament in the treatment of benign tumors in the lumbar spinal canal.Methods:A retrospective analysis was performed. The clinical data of 23 patients with benign tumors in lumbar spinal canal, admitted to our hospital from March 2018 to March 2020, were collected. Follow up was performed for 12-23 months; Japanese Orthopaedic Association (JOA) scores were used for efficacy evaluation. X-ray, CT and MRI were used for imaging evaluation.Results:The number of replanted lamina was 1-4, with an average of 2.2. The surgical duration was (77.2±22.7) min, ranged from 67 min to 146 min; and the amount of intraoperative bleeding was (127±32.6) mL, ranged from 90-290 mL. The tumors were completely removed in all patients, and there were 2 patients complicated with cerebrospinal fluid leakage, and the wound healed after electrolyte supplement and local pressure treatment. No spinal cord injury, epidural hematoma, infection or other related complications were noted. The JOA scores increased from 11.85±1.38 before surgery to 23.22±2.47 at the last follow-up, with significant difference ( t=18.505, P<0.001). Of them, 10 had excellent efficacy, 9 had good efficacy, and 4 had medium efficacy, enjoying an excellent and good rate of 82.6%. Lumbar lordosis angle (LLA) was (51.58±2.39)°at the last follow-up, which showed no significant difference as compared with the preoperative LLA ([52.24±3.17]°, t=0.672, P=0.505). Imaging results showed that there was no spondylolisthesis or instability of lumbar spine, no recurrence of tumors was noted, and no displacement of lamina or secondary reduction of spinal canal volume were noted. Conclusion:The treatment of benign tumors in lumbar spinal canal by modified recapping laminoplasty preserving the continuity of superior spinous ligament can restore the normal anatomical structure of lumbar spinal canal, achieve no bone loss and maintain lumbar curvature well.

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