1.CircSLC8A1_005 Inhibits the Fibrotic Phenotype of Cardiac Fibroblasts by Encoding Protein
Yating HU ; Yuan GAO ; Huayan WU ; Yu LIANG ; Hui LI ; Jindong XU ; Yupeng LIU ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):35-44
ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes, collagen type I alpha 1 chain (Col1a1), collagen type Ⅲ alpha 1 chain (Col3a1) and smooth muscle actin alpha 2 (Acta2), in mouse cardiac fibroblasts (mCFs) were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay, respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site (IRES) in circSLC8A1_005. CircSLC8A1_005-translated protein, SLC8A1-605aa, and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation (RIP) was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 (Sod2) mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs, and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku, which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 (Sod2) expression, but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA, and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein, and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.
2.Meta-analysis of the incidence and related factors for cervical spine instability in patients with rheumatoid arthritis
Chenghan XU ; Hanjie ZHUO ; Xubin CHAI ; Yong HUANG ; Bowen ZHANG ; Qin CHEN ; Yupeng HAO ; Lin LI ; Yingjie ZHOU
Chinese Journal of Tissue Engineering Research 2024;28(24):3922-3929
OBJECTIVE:At present,there are many reports on the related factors associated with the incidence of cervical spine instability in patients with rheumatoid arthritis,but there are problems such as small sample size and many confounding factors,and the research results of various studies on the same related factors are also different.This article analyzed the factors related to cervical spine instability in patients with rheumatoid arthritis by means of a systematic review. METHODS:Articles related to cervical spine instability in patients with rheumatoid arthritis were collected by searching both Chinese and English databases until March 2023.The outcome of cervical spine instability in patients with rheumatoid arthritis was used as the grouping criterion to abstract basic information,baseline patient characteristics,laboratory-related tests,medication use,and other relevant risk factors.Meta-analysis was done using Stata 14.0 software. RESULTS:(1)Sixteen relevant studies,all of moderate or above quality,were included,including seven studies with case-control studies and nine with cross-sectional studies.The overall incidence of cervical spine instability in patients with rheumatoid arthritis was 43.08%.(2)Meta-analysis showed:Related risk factors included female(OR=0.60,95%CI:0.44-0.82,P=0.002);age at disease onset(SMD=-0.52,95%CI:-0.86 to-0.18,P=0.003);duration of disease(SMD=0.58,95%CI:0.14-1.02,P=0.01);body mass index(OR=0.74,95%CI:0.63-0.88,P=0.001);rheumatoid factors positive univariate analysis subgroup(OR=1.33,95%CI:1.02 to 1.72,P=0.04),C-reactive protein(SMD=0.26,95%CI:0.16-0.35,P=0.00),erythrocyte sedimentation rate(SMD=0.15,95%CI:0.002-0.29,P=0.047),anti-cyclic-citrullinated peptide antibodies(OR=1.73,95%CI:1.19-2.51,P=0.004),28-joint Disease Activity Score(SMD=0.20,95%CI:0.04-0.37,P=0.02),destruction of peripheral joints(OR=2.48,95%CI:1.60-3.85,P=0.00),and corticosteroids(OR=1.91,95%CI:1.54-2.37,P=0.00)were strongly associated with the development of rheumatoid arthritis-cervical spine instability.Female and corticosteroid use were independently associated with the occurrence of rheumatoid arthritis-cervical spine instability. CONCLUSION:Based on clinical evidence from 16 observational studies,the overall incidence of rheumatoid arthritis-cervical spine instability was 43.08%.However,the incidence of cervical spine instability in rheumatoid arthritis patients varied greatly among different studies.Gender(female)and the use of corticosteroids were confirmed as independent correlation factors for the onset of cervical spine instability in patients with rheumatoid arthritis.The results of this study still provide some guidance for early clinical recognition,diagnosis,and prevention of rheumatoid arthritis-cervical spine instability.
3.circMYO9A_006 inhibits expression of cardiac hypertrophy-related pro-teins in cardiomyocytes by translating protein MYO9A-208aa
Jiaxue JIANG ; Jinfeng SU ; Ya WANG ; Tao OU ; Hui LI ; Jindong XU ; Yupeng LIU ; Xianhong FANG ; Zhixin SHAN
Chinese Journal of Pathophysiology 2024;40(1):1-8
AIM:To investigate the effect of circular RNA MYO9A-006(circMYO9A_006)on hypertrophic phenotype of cardiomyocytes and the underlying mechanism.METHODS:The effect of adenovirus-mediated overexpres-sion of circMYO9A_006 on the expression of hypertrophy-related proteins,including β-myosin heavy chain(β-MHC),skeletal muscle actin alpha 1(ACTA1)and atrial natriuretic peptide(ANP),was evaluated in neonatal mouse ventricular cardiomyocytes(NMVCs).Moreover,a neonatal rat ventricular cardiomyocyte(NRVC)model of phenylephrine(PE)-in-duced hypertrophy was established.The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method.Dual-luciferase reporter assay was employed to measure the activity of potential in-ternal ribosome entry sites(IRES)in circMYO9A_006.The translation and intracellular location of the circMYO9A_006-translated protein,MYO9A-208aa,were verified using Western blot.To investigate the role of MYO9A-208aa in the ef-fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype,we prepared and used the following adenoviruses:the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa,the recombinant circMYO9A_006-ATG-mut adenovirus that does not express MYO9A-208aa,the recombinant circMYO9A_006 adenovirus,and the adenovirus vector control.These were then employed to infect NRVCs.RESULTS:Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs.The increased expression of circMYO9A_006 notably reduced the expres-sion of hypertrophy-related proteins in NMVCs(P<0.01).Concurrently,overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs(P<0.05).Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006.Western blot results indicated that circ-MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs,primari-ly found in the cytoplasm.Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex-pression of hypertrophy-associated proteins(P<0.01),and counteracted the enlarged size of PE-induced NRVCs(P<0.05).However,increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe-notype of NRVCs.CONCLUSION:circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe-sizing the MYO9A-208aa protein.
4.A novel nomogram-based model to predict the postoperative overall survival in patients with gastric and colorectal cancer
Siwen WANG ; Kangjing XU ; Xuejin GAO ; Tingting GAO ; Guangming SUN ; Yaqin XIAO ; Haoyang WANG ; Chenghao ZENG ; Deshuai SONG ; Yupeng ZHANG ; Lingli HUANG ; Bo LIAN ; Jianjiao CHEN ; Dong GUO ; Zhenyi JIA ; Yong WANG ; Fangyou GONG ; Junde ZHOU ; Zhigang XUE ; Zhida CHEN ; Gang LI ; Mengbin LI ; Wei ZHAO ; Yanbing ZHOU ; Huanlong QIN ; Xiaoting WU ; Kunhua WANG ; Qiang CHI ; Jianchun YU ; Yun TANG ; Guoli LI ; Li ZHANG ; Xinying WANG
Chinese Journal of Clinical Nutrition 2024;32(3):138-149
Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.
5.Factors affecting target volume in adaptive radiotherapy for locally advanced nasopharyngeal carcinoma
Shuhui DONG ; Wenyan YAO ; Mengxue HE ; Ziyue ZHONG ; Yupeng ZHOU ; Senkui XU ; Weixiong XIA
Chinese Journal of Medical Physics 2024;41(7):798-802
Objective To investigate the relationships of pre-radiotherapy body weight,gender,age,EBVDNA,hemoglobin,plasma albumin,and induction chemotherapy regimen with the changes of target area and lymph node volume in adaptive radiotherapy,so as to provide a reference for the timing and population selection of adaptive radiotherapy.Methods A retrospective analysis was conducted on 34 patients who received the first course of radiotherapy at Sun Yat-sen University Cancer Center from January 2022 to November 2022.All patients underwent CT scans again after 20 sessions of radiotherapy for developing the secondary radiotherapy plans.The body weight,gender,age,tumor stage,hemoglobin,plasma albumin,induction chemotherapy regimen,and EBVDNA were collected.Results The tumor volume reduction in the primary focus was more evident in patients with pre-treatment plasma albumin≥40 g/L than in those with pre-treatment plasma albumin<40 g/L(t=3.971,P=0.001),and in patients with pretreatment EBVDNA≤4000 copies/mL than in those with pretreatment EBVDNA>4000 copies/mL(t=4.080,P=0.001).Pearson analysis showed that GTVnx volume difference was positively correlated with pre-radiotherapy GTVnx volume(r=0.444,P=0.009),right parotid gland volume difference(r=0.737,P<0.001),left parotid gland volume difference(r=0.435,P=0.010),and hemoglobin(r=0.722,P<0.001).Conclusion The reduction in tumor volume during radiotherapy is more pronounced in nasopharyngeal cancer patients with normal plasma albumin level and those with pretreatment EBVDNA≤4000 copies/mL.The pre-radiotherapy treatment volume of primary focus,parotid gland volume change before and after radiotherapy,and pre-radiotherapy EBVDNA,hemoglobin and plasma albumin levels can be used to predict the degree of tumor volume shrinkage during radiotherapy,providing a reference for the selection of the timing of adaptive radiotherapy for nasopharyngeal carcinoma.
6.Anatomical characteristics of femoral intercondylar notch of knee joint for predicting non-contact anterior cruciate ligament tear
Yupeng ZHU ; Jun XU ; Qizheng WANG ; Yongye CHEN ; Siyuan QIN ; Ruixin YAN ; Peijin XIN ; Ning LANG
Chinese Journal of Medical Imaging Technology 2024;40(6):902-906
Objective To observe the value of anatomical characteristics of femoral intercondylar notch of knee joint for predicting non-contact anterior cruciate ligament tear(NC-ACLT).Methods MRI data of knee joint of 55 patients with NC-ACLT(NC-ACLT group)and 55 controls(control group)were retrospectively analyzed.The parameters of intercondylar notch,including depth,width,depth/width ratio,opening width,opening width index,area and width of the femoral condyle's outer edge at the same level were measured between groups,and the types of intercondylar notch(type A,U and W)were recorded.Univariate and multivariate logistic regression analysis were used to screen the independent impact factors of NC-ACLT.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each intercondylar notch parameter for predicting NC-ACLT.Results The depth and depth/width ratio of intercondylar notch in NC-ACLT group were both higher,while the opening width and opening width index of intercondylar notch in NC-ACLT group were both lower than those in control group(all P<0.05).Multivariate logistic regression analysis revealed that the depth of intercondylar notch was an independent impact factors of NC-ACLT(P<0.05).Taken 29.55 mm in depth of intercondylar notch,1.45 in depth/width ratio of intercondylar notch,21.15 mm in opening width of intercondylar notch and 0.29 in opening width index as the optimal cut-off value,respectively,the sensitivity of the above parameters for predicting NC-ACLT was 74.55%,58.18%,67.27%and 67.27%,the specificity was 69.09%,80.00%,61.82%and 78.18%,and the AUC was 0.720,0.713,0.652 and 0.710,respectively.Conclusion The anatomical characteristics of femoral intercondylar notch of knee joint could be used to predict NC-ACLT.The depth,depth/width ratio,opening width and opening width index of intercondylar notch could be used as predictive indicators.
7.Application of the rotational arch method of revealing the spinal canal and implanting back in resection of benign intravertebral tumors
Yingjie ZHOU ; Yanjin WANG ; Hanjie ZHUO ; Xubin CHAI ; Chenghan XU ; Yupeng HAO
Chinese Journal of Orthopaedics 2024;44(10):669-675
Objective:To investigate the efficacy and safety of the rotational arch method of revealing the spinal canal and implanting back in resection of benign intravertebral tumours.Methods:A total of 17 patients with benign intravertebral tumors of the thoracolumbar spine who underwent a rotational arch method of revealing the spinal canal and implantation back in combination with tumor resection in Luoyang Orthopaedic-Traumatological Hospital of Henan Province from April 2017 to October 2022 were retrospectively analyzed. There were 9 males and 8 females, aged 58.59±13.57 years (range, 29-75 years). There were 7 cases of thoracic intravertebral tumors, 2 cases of thoracolumbar intravertebral tumors, and 8 cases of lumbar intravertebral tumors. The operated segments were 6 cases of single-segment, 8 cases of double-segment, and 3 cases of triple-segment. The disease duration was 20.35±16.58 months (range, 3-60 months). Histopathology showed 9 cases of schwannoma, 5 cases of meningioma, 2 cases of teratoma, and 1 case of dermoid cyst. The operation time, intraoperative blood loss, postoperative spinal canal volume, stability of internal fixation, and lamina healing were recorded. The Cobb angle, American Spinal Injury Association (ASIA) classification and Oswestry disability index (ODI) were compared before and after operation.Results:All patients were successfully operated and followed up for an average of 10.5±2.4 months (range, 6-20 months). The operation time was 156.76±26.81 min (range, 120-210 min) and intraoperative bleeding was 338.24±97.68 ml (range, 200-600 ml). There was no neurovascular injury during the operation. Incomplete spinous process fracture occurred in 1 case due to excessive exertion, which healed well without special treatment. Postoperative drainage volume was 147.06±31.58 ml (range, 100-210 ml). The patient's local Cobb angle was 14.15°±6.58° preoperatively and 14.73°±6.34° postoperatively, with no statistically significant difference ( t=1.810, P=0.089). The patient's ODI was 63.65%±6.57% preoperatively and decreased to 23.88%±4.21% at the final follow-up, with statistically significant difference ( t=53.359, P<0.001). In 17 patients, there were 2 cases of ASIA grade B, 9 cases of grade C, and 6 cases of grade D before operation, and 1 case of ASIA grade B, 4 cases of grade C, 8 cases of grade D, and 4 cases of grade E at the final follow-up, which was a significant improvement compared with the preoperative period, and the difference was statistically significant ( Z=2.587, P=0.010). All patients' incisions healed at stage I, and none of them had complications such as cerebrospinal fluid leakage and epidural haematoma. Three-dimensional CT of the spine at 6 months after operation showed that none of the patients had displacement of the vertebral plate, loosening of the internal fixation, infection or fracture. Conclusion:The rotational arch method of revealing the spinal canal and implantation back in combination with tumor resection for the treatment of benign intravertebral canal tumors has good postoperative neurological function recovery and a low complication rate, which is a safe and effective surgical procedure for the treatment of benign intravertebral canal tumours.
8.Association between serum uric acid concentration and radiographic axial spondylarthritis: a cross-sectional study of 202 patients.
Yupeng LAI ; Yanpeng ZHANG ; Zhihao LEI ; Yihong HUANG ; Tongxin NI ; Pin HE ; Xiaoling LI ; Chiduo XU ; Jun XIA ; Meiying WANG
Chinese Medical Journal 2023;136(9):1114-1116
9.Research status and progress on the influence of high myopia on ocular structure and visual function
Shang LIU ; Yupeng XU ; Xun XU
Chinese Journal of Ocular Fundus Diseases 2023;39(8):690-695
High myopia has a high genetic tendency, it not only shows in the excessive elongation of the axial length, but also lends to the formation and progression of various eye lesions, such as peripheral retinopathy, optic disc changes, posterior staphyloma, and myopic maculopathy, due to the mechanical stretching of the axial length to the ocular structure. In addition, high myopia increases the risk of several complications, such as glaucoma, cataract, and corneal disease. All these pathological changes will affect visual function and lead to irreversible vision impairment and blindness in the future. Therefore, it is important to pay attention to screening for optic disc abnormalities and posterior staphyloma, and regular monitor the changes of fundus, intraocular pressure, and lens. At the same time, high myopia has an impact on personal life such as study, psychology, sport, and work, and can reduce the quality of life as well as increase the cost of health care. The clinic should pay more attention to high myopia, prevent and control the development of high myopia from an early stage, in order to minimize its impact on ocular structure and visual function as well as its hazard to personal life and society.
10.LncRNA SBF2-AS1 Regulates Invasion and Proliferation of Hepatocellular Carcinoma Cells Through miR-372-3p/CDK6 Axis
Wei SONG ; Rong XU ; Yupeng LI ; Zhide LI ; Jinguo WANG ; Chao MA ; Yuan MENG ; Xiong CHEN
Cancer Research on Prevention and Treatment 2023;50(7):666-674
Objective To investigate the effects of lncRNA SBF2-AS1 on the proliferation and invasion of hepatoma cells by regulating the miR-372-3p/CDK6 pathway. Methods Bel7402 and SK-hep1 cells were selected as research objects. The expression levels of SBF2-AS1, miR-372-3p, and CDK6 were up- or down-regulated according to different experimental stages, while the expression levels of miR-372-3p and CDK6 in cells were detected by real-time fluorescence quantitative PCR and Western blot. Dual luciferase reporter assay verified the targeting relationships between SBF2-AS1 and miR-372-3p as well as miR-372-3p and CDK6, respectively. CCK-8, colony formation assay, Transwell, cell cycle assay, and flow cytometry were used to analyze cell proliferation, colony formation, migration/invasion ability, cell cycle activity, and apoptosis. Results SBF2-AS1 was highly expressed in hepatocellular carcinoma cells (

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