1.Application of 5-point positioning point-contact pedicle navigation template in the case of scoliosis and complex pedicle
Lihang WANG ; Tingsheng LU ; Qiling CHEN ; Shudan YAO ; Xingwei PU ; Linsong JI ; Guoquan ZHAO ; Beiping OUYANG ; Bin ZHANG ; Zaisong YANG ; Chunshan LUO
Chinese Journal of Tissue Engineering Research 2024;28(18):2859-2864
BACKGROUND:The pedicle navigation template has many advantages,but there are still some problems.For example,poor soft tissue dissection leads to poor adhesion of the pedicle navigation template,resulting in screw path deviation;careful dissection of soft tissue to fit the pedicle navigation template leads to prolonged surgery time and increased bleeding;the design of the pedicle navigation template cannot predict the vertebral rotation and the impact of body position changes,resulting in the poor fitting. OBJECTIVE:To explore the utility of a new 5-point positioning point-contact pedicle navigation template in the case of scoliosis and complex pedicle. METHODS:A total of 20 patients with scoliosis and complicated pedicle admitted to the Department of Spinal Surgery,Guizhou Hospital,Beijing Jishuitan Hospital from February 2020 to February 2023 were selected for scoliosis orthopedics.During the operation,the 5-point positioning point-contact pedicle navigation template was used to guide the screws.According to the inclusion and exclusion criteria,34 cases were matched as the empirical nail placement group,and conventional barehanded nail placement was performed.The time of placement,the amount of bleeding,the number of fluoroscopies,the number of manual diversions,the level and accuracy of pedicle screws,the complications of placement,and the rate of correction of main curvature were compared between the two groups. RESULTS AND CONCLUSION:(1)There were no significant differences in sex,age,coronal Cobb's angle of the main curvature,bending Cobb's angle of the main curvature,pedicle variation,apex rotation,fusion segment,number of screws,level of screws,accuracy of screws,and rate of correction of main curvature between the navigation template group and the empirical nail placement group(P>0.05).(2)Compared with the empirical nail placement group,the navigation template group had more advantages in time of placement(P=0.034),amount of bleeding(P=0.036),number of fluoroscopies(P=0.000)and number of manual diversions(P=0.021).(3)There were 0 cases of screw-related complications in both groups.(4)In conclusion,the 5-point positioning point-contact 3D printing pedicle navigation template has a claw-like structure.It can firmly adapt to various deformities of the lamina articular process,avoid drift,and accurately place the screws.It has a point-like contact lamina structure to avoid extensive and complete dissection of the posterior structure,and reduce bleeding,operation time,and trauma.Pre-designed screw entry points and directions can reduce the number of fluoroscopy and operation time.Segmental design can avoid discomfort due to changes in anesthesia position.The operation is simple and the accuracy of screw placement is high.
2.Diabetes mellitus and the risk of sudden cardiac death: a meta-analysis
Xuhan TONG ; Qingwen YU ; Ting TANG ; Chen CHEN ; Jiake TANG ; Siqi HU ; Yao YOU ; Shenghui ZHANG ; Xingwei ZHANG ; Mingwei WANG
Chinese Journal of General Practitioners 2024;23(12):1307-1317
Objective:To assess the association between diabetes mellitus and the risk of sudden cardiac death (SCD), and to identify potential contributing factors.Methods:This meta-analysis was an updated version of the original study Diabetes mellitus and the risk of sudden cardiac death: a systematic review and meta-analysis of prospective studies. The original review included all eligible case-control and cohort studies published in PubMed and Embase up to 2017 that investigated the association between diabetes and SCD risk. In this updated study, newly published studies were added, including those available in PubMed, Embase, China National Knowledge Infrastructure (CNKI), and WANFANG MED ONLINE up to December 3, 2023. Search terms included "diabetes""glucose""sudden cardiac death" "cardiac arrest" and their Chinese equivalent. The primary outcome was the risk of SCD, while factors such as country, ethnicity, skin color, follow-up duration, left ventricular ejection fraction (LVEF), baseline comorbidities, and other relevant variables were analyzed as potential influencing factors. Relative risk ( RR) was used as the summary measure. A random-effects model was used when significant heterogeneity was detected, otherwise a fixed-effects model was used. Cochran′s Q test was used for subgroup analysis to assess the influence of factors such as region, baseline diseases, LVEF, and ethnicity (based on skin color) on the outcomes. Results:A total of 32 cohort/case-control studies with a combined sample size of 3 252 954 individuals were included. The meta-analysis showed that the risk of SCD in patients with diabetes was double that of non-diabetics ( RR=2.00, 95% CI: 1.83-2.19, P<0.001). In Asian populations, the risk of SCD in diabetic patients was 1.78 times that of non-diabetic individuals ( RR=1.78, 95% CI: 1.51-2.10), 2.05 times that of in European populations ( RR=2.05, 95% CI: 1.79-2.34), and 2.12 times that of in American populations ( RR=2.12, 95% CI: 1.82-2.47), with no statistically significant heterogeneity between regions ( P=0.287). Among individuals without other baseline comorbidities, the risk of SCD was 2.12 times higher in diabetic patients than in those without diabetes ( RR=2.12, 95% CI: 1.89-2.38). In patients with baseline coronary heart disease, the risk was 1.75 times that of non-diabetics ( RR=1.75, 95% CI: 1.45-2.11). In those with baseline heart failure, the risk was 1.92 times that of non-diabetics ( RR=1.92, 95% CI: 1.51-2.43). In patients with baseline atrial fibrillation, the risk was 4.00 times that of non-diabetic individuals ( RR=4.00, 95% CI: 1.38-11.56). In patients undergoing hemodialysis due to renal failure, the risk was 1.76 times that of non-diabetic individuals ( RR=1.76, 95% CI: 1.25-2.48), with no statistically significant heterogeneity between groups ( P=0.262). In cardiac patients with LVEF>50%, the risk of SCD in diabetic patients was 2.08 times that of non-diabetic individuals ( RR=2.08, 95% CI: 1.57-2.75), and in those with LVEF<50%, the risk was 1.69 times that of non-diabetic individuals ( RR=1.69, 95% CI: 1.30-2.18), with no statistically significant heterogeneity between groups ( P=0.277). In yellow-skinned populations, the risk of SCD in diabetic patients was 1.80 times that of healthy individuals ( RR=1.80, 95% CI: 1.73-1.87), and in white-skinned populations, it was 2.18 times that of healthy individuals ( RR=2.18, 95% CI: 1.88-2.54), with statistically significant heterogeneity between groups ( P=0.014). Conclusions:Diabetes mellitus significantly increased the risk of SCD, and this effect may be more pronounced in white-skinned populations, while region, baseline comorbidities, and LVEF had no further effect.
3.Clinical observation of Tuina plus Chinese medication hot compress for lumbar muscle strain
Ji MA ; Fei GU ; Yupu ZHANG ; Xingwei CHEN ; Yumin LIU ; Zhengcai YU ; Cheng WANG ; Jue HONG
Journal of Acupuncture and Tuina Science 2024;22(5):387-392
Objective:To discuss the clinical efficacy of treating lumbar muscle strain(LMS)with Tuina(Chinese therapeutic massage)plus Chinese medication hot compress. Methods:A total of 147 LMS patients were randomized into a Tuina group,a Chinese medication hot compress group,and a combined group,each consisting of 49 cases.The Tuina group received Tuina treatment;the Chinese medication hot compress group received Chinese medication hot compress treatment;and the combined group received the forementioned two therapies alternately.The three groups of patients were assessed using the visual analog scale(VAS)and Oswestry disability index(ODI)before treatment and after 2 weeks of treatment.A 2-month follow-up was also conducted to observe the relapse rate. Results:The VAS and ODI scores dropped significantly after treatment in all three groups compared with their baseline(P<0.05),and the combined group surpassed the other two groups in comparing the ODI score(P<0.05).The 2-month follow-up showed that the combined group had the lowest relapse rate among the three groups(P<0.05). Conclusion:Compared to each therapy used alone,Tuina plus Chinese medication hot compress can relieve pain,improve daily living function,and reduce the short-term relapse rate better in treating LMS patients.
4. Baicalein promotes laryngeal cancer cell death and inhibits invasion via miR-125b-5p/IRF4 axis
Jian WANG ; Yongdong SUN ; Xingwei ZHOU ; Lei LIU ; Long CHEN ; Xingke TONG ; Jiali ZHU
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(11):1209-1218
AIM: To investigate the mechanism of baicalin-induced apoptosis in human laryngeal cancer cells. METHODS: AMC-HN-8 cells were selected for the study, and baicalin was applied to the cells at different concentrations (0, 10, 30, 100, and 300 μmol/L), and the half-inhibitory concentration (IC50) was measured by the CCK-8 method. Bax, cleaved-caspase-3, Cyto-c, IRF4 protein expression by protein blotting (Western blot); miR-125b-5p and IRF4 expression by RT-qPCR. Dual-luciferase reporter gene validation of Targetscan prediction (binding of miR-125b-5p to IRF4-3'UTR); apoptosis and necrosis inhibitors explore the way baicalein induces death in laryngeal cancer cells. AMC-HN-8 was then divided into blank group, baicalein (IC50), miR-125b-5p inhibitor group, baicalein + inhibitor NC group, baicalein+miR-125b-5p inhibitor group, and cell invasion and clone formation assays to detect cell invasion and proliferation ability, respectively. Apoptosis was detected by flow cytometry. RESULTS: Baicalein inhibited the proliferation of AMC-HN-8 cells in a dose-dependent manner with an IC50 value of 47.31 μmol/L. Compared with the blank group, 47.31 μmol/L baicalin induced apoptosis and inhibited cell invasion, while upregulating the expression of miR-125b-5p and suppressing the mRNA and protein levels of IRF4. The luciferase results showed that the miR-125b-5p mimic was able to inhibit the activity of the IRF4-3'UTR promoter relative to the NC mimic (mimic) group. Baicalein induces laryngeal cancer cell death in an apoptotic manner. In addition, the combination of 47.31 μmol/L baicalin and miR-125b-5p inhibitor affected the behavior of AMC-HN-8 cells, showing that compared with the blank group, the baicalin group showed a decrease in the number of cell clones, weakened invasion ability, and increased apoptosis; the miR - 125b-5p inhibitor group showed an increase in the number of cell clones, enhanced invasion ability and decreased apoptosis. The baicalin+ inhibitor NC group was consistent with baicalin, with no significant effect of inhibitor NC on cell behavior. The cloning, invasion, and apoptosis of cells in the baicalin+miR-125b-5p inhibitor group were intermediate between the baicalin and miR-125b-5p inhibitor groups. CONCLUSION: Baicalin inhibits the proliferation of AMC-HN-8 cells, and the mechanism may be related to miR-125b-5p targeting to inhibit the expression of IRF4, inducing the pro-apoptotic proteins Bax, cleaved-caspase3, and Cyto-c, and inhibiting the apoptosis suppressor protein Bcl-2 thereby inducing apoptosis.
5.Predictive value of diaphragm thickening fraction and intra-abdominal pressure monitoring-oriented risk prediction model for weaning failure in patients with severe acute pancreatitis
Xingwei DI ; Xiaodong LI ; Tian LI ; Haiyan FU ; Yonghao JIN ; Xi CHEN ; Xuexing TANG
Chinese Critical Care Medicine 2023;35(2):177-181
Objective:To establish a risk prediction model dominated by diaphragm thickening fraction (DTF) and intra-abdominal pressure (IAP) monitoring, and to explore the predictive value of the model for weaning failure in patients with severe acute pancreatitis (SAP).Methods:A prospective research was conducted. Sixty-three patients undergoing invasive mechanical ventilation treatment who diagnosed with SAP admitted to intensive care unit of the First Affiliated Hospital of Jinzhou Medical University from August 2020 to October 2021 were enrolled. The spontaneous breathing trial (SBT) was carried out when the clinical weaning criteria was met. The stable cardiovascular status, good pulmonary function, no chest and abdominal contradictory movement, and adequate oxygenation were defined as successful weaning. Otherwise, it was defined as failure weaning. The clinical indicators such as SBT 30-minure DTF, IAP, tidal volume (VT), respiratory rate (RR), body mass index (BMI), and blood lactic acid (Lac) were compared between the weaning success group and the weaning failure group. The indicators with statistically significant differences in the single-factor analysis were included in the secondary multivariable Logistic regression analysis to establish a risk prediction model. The correlation between the DTF and IAP at 30 minutes of SBT was analyzed. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of the risk prediction model for SAP patient withdrawal failure at 30 minutes of SBT.Results:Finally, 63 patients with SAP were enrolled. Among the 63 patients, 42 were successfully weaned and 21 failed. There were no significant differences in age, gender, and oxygenation index (PaO 2/FiO 2), sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score at admission between the two groups, indicating that the data in the two groups were comparable. Compared with the weaning success group, IAP, RR, BMI and Lac at 30 minutes of SBT in the weaning failure group were significantly increased [IAP (mmHg, 1 mmHg≈0.133 kPa): 14.05±3.79 vs. 12.12±3.36, RR (times/min): 25.43±8.10 vs. 22.02±5.05, BMI (kg/m 2): 23.71±2.80 vs. 21.74±3.79, Lac (mmol/L): 5.27±1.69 vs. 4.55±1.09, all P < 0.05], while DTF and VT were significantly decreased [DTF: (29.76±3.45)% vs. (31.86±3.67)%, VT (mL): 379.00±98.74 vs. 413.60±33.68, both P < 0.05]. Secondary multivariable Logistic regression analysis showed that DTF [odds ratio ( OR) = 0.758, 95% confidence interval (95% CI) was 0.584-0.983, P = 0.037], IAP ( OR = 1.276, 95% CI was 1.025-1.582, P = 0.029), and RR ( OR = 1.145, 95% CI was 1.014-1.294, P = 0.029) were independent risk factors for SBT withdrawal failure in 30 minutes in SAP patients. The above risk factors were used to establish the risk prediction model of aircraft withdrawal failure at 30 minutes of SBT: Logit P = -0.237-0.277×DTF+0.242×IAP+0.136×RR. Pearson correlation analysis showed that SBT 30-minute DTF was significantly correlated with IAP in SAP patients, and showed a significant positive correlation ( r = 0.313, P = 0.012). The ROC curve analysis results showed that area under the ROC curve (AUC) of the risk prediction model for SAP patient withdrawal failure at 30 minutes of SBT was 0.716, 95% CI was 0.559-0.873, P = 0.003, with the sensitivity of 85.7% and the specificity of 78.6%. Conclusions:DTF, IAP and RR were independent risk factors for SBT withdrawal failure in 30 minutes in SAP patients. The DTF and IAP monitoring-oriented risk prediction model based on the above three variables has a good predictive value for weaning failure in patients with SAP.
6.Psychosocial crisis intervention for coronavirus disease 2019 patients and healthcare workers.
Li ZHANG ; Lingjiang LI ; Wanhong ZHENG ; Yan ZHANG ; Xueping GAO ; Liwen TAN ; Xiaoping WANG ; Qiongni CHEN ; Junmei XU ; Juanjuan TANG ; Xingwei LUO ; Xudong CHEN ; Xiaocui ZHANG ; Li HE ; Jin LIU ; Peng CHENG ; Lizhi XU ; Yi TIAN ; Chuan WEN ; Weihui LI
Journal of Central South University(Medical Sciences) 2023;48(1):92-105
OBJECTIVES:
Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model.
METHODS:
The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention.
RESULTS:
The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful.
CONCLUSIONS
Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.
Humans
;
COVID-19
;
Sleep Initiation and Maintenance Disorders
;
Crisis Intervention
;
Psychosocial Intervention
;
SARS-CoV-2
;
Mental Health
;
Depression/epidemiology*
;
Health Personnel/psychology*
;
Anxiety/etiology*
7.An image classification method for arrhythmias based on Gramian angular summation field and improved Inception-ResNet-v2.
Xiangkui WAN ; Jing LUO ; Yang LIU ; Yunfan CHEN ; Xingwei PENG ; Xi WANG
Journal of Biomedical Engineering 2023;40(3):465-473
Arrhythmia is a significant cardiovascular disease that poses a threat to human health, and its primary diagnosis relies on electrocardiogram (ECG). Implementing computer technology to achieve automatic classification of arrhythmia can effectively avoid human error, improve diagnostic efficiency, and reduce costs. However, most automatic arrhythmia classification algorithms focus on one-dimensional temporal signals, which lack robustness. Therefore, this study proposed an arrhythmia image classification method based on Gramian angular summation field (GASF) and an improved Inception-ResNet-v2 network. Firstly, the data was preprocessed using variational mode decomposition, and data augmentation was performed using a deep convolutional generative adversarial network. Then, GASF was used to transform one-dimensional ECG signals into two-dimensional images, and an improved Inception-ResNet-v2 network was utilized to implement the five arrhythmia classifications recommended by the AAMI (N, V, S, F, and Q). The experimental results on the MIT-BIH Arrhythmia Database showed that the proposed method achieved an overall classification accuracy of 99.52% and 95.48% under the intra-patient and inter-patient paradigms, respectively. The arrhythmia classification performance of the improved Inception-ResNet-v2 network in this study outperforms other methods, providing a new approach for deep learning-based automatic arrhythmia classification.
Humans
;
Arrhythmias, Cardiac/diagnostic imaging*
;
Cardiovascular Diseases
;
Algorithms
;
Databases, Factual
;
Electrocardiography
8.Application of a new point contact pedicle navigation template as an auxiliary screw implant in scoliosis correction surgery.
Lihang WANG ; Qian TANG ; Qiling CHEN ; Tingsheng LU ; Shudan YAO ; Xingwei PU ; Linsong JI ; Chunshan LUO
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(6):700-705
OBJECTIVE:
To explore the effectiveness of a new point contact pedicle navigation template (referred to as "new navigation template" for simplicity) in assisting screw implantation in scoliosis correction surgery.
METHODS:
Twenty-five patients with scoliosis, who met the selection criteria between February 2020 and February 2023, were selected as the trial group. During the scoliosis correction surgery, the three-dimensional printed new navigation template was used to assist in screw implantation. Fifty patients who had undergone screw implantation with traditional free-hand implantation technique between February 2019 and February 2023 were matched according to the inclusion and exclusion criteria as the control group. There was no significant difference between the two groups ( P>0.05) in terms of gender, age, disease duration, Cobb angle on the coronal plane of the main curve, Cobb angle at the Bending position of the main curve, the position of the apical vertebrae of the main curve, and the number of vertebrae with the pedicle diameter lower than 50%/75% of the national average, and the number of patients whose apical vertebrae rotation exceeded 40°. The number of fused vertebrae, the number of pedicle screws, the time of pedicle screw implantation, implant bleeding, fluoroscopy frequency, and manual diversion frequency were compared between the two groups. The occurrence of implant complications was observed. Based on the X-ray films at 2 weeks after operation, the pedicle screw grading was recorded, the accuracy of the implant and the main curvature correction rate were calculated.
RESULTS:
Both groups successfully completed the surgeries. Among them, the trial group implanted 267 screws and fused 177 vertebrae; the control group implanted 523 screws and fused 358 vertebrae. There was no significant difference between the two groups ( P>0.05) in terms of the number of fused vertebrae, the number of pedicle screws, the pedicle screw grading and accuracy, and the main curvature correction rate. However, the time of pedicle screw implantation, implant bleeding, fluoroscopy frequency, and manual diversion frequency were significantly lower in trial group than in control group ( P<0.05). There was no complications related to screws implantation during or after operation in the two groups.
CONCLUSION
The new navigation template is suitable for all kinds of deformed vertebral lamina and articular process, which not only improves the accuracy of screw implantation, but also reduces the difficulty of operation, shortens the operation time, and reduces intraoperative bleeding.
Humans
;
Orthopedic Procedures
;
Pedicle Screws
;
Retrospective Studies
;
Scoliosis/surgery*
;
Spinal Fusion/methods*
;
Spine
;
Surgery, Computer-Assisted/methods*
9.Single-cell transcriptomic analysis of tumor heterogeneity and intercellular networks in human urothelial carcinoma
Xingwei JIN ; Qizhang WANG ; Fangxiu LUO ; Junwei PAN ; Tingwei LU ; Yang ZHAO ; Xiang ZHANG ; Enfei XIANG ; Chenghua ZHOU ; Baoxing HUANG ; Guoliang LU ; Peizhan CHEN ; Yuan SHAO
Chinese Medical Journal 2023;136(6):690-706
Background::Heterogeneity of tumor cells and the tumor microenvironment (TME) is significantly associated with clinical outcomes and treatment responses in patients with urothelial carcinoma (UC). Comprehensive profiling of the cellular diversity and interactions between malignant cells and TME may clarify the mechanisms underlying UC progression and guide the development of novel therapies. This study aimed to extend our understanding of intra-tumoral heterogeneity and the immunosuppressive TME in UC and provide basic support for the development of novel UC therapies.Methods::Seven patients with UC were included who underwent curative surgery at our hospital between July 2020 and October 2020. We performed single-cell RNA sequencing (scRNA-seq) analysis in seven tumors with six matched adjacent normal tissues and integrated the results with two public scRNA-seq datasets. The functional properties and intercellular interactions between single cells were characterized, and the results were validated using multiplex immunofluorescence staining, flow cytometry, and bulk transcriptomic datasets. All statistical analyses were performed using the R package with two-sided tests. Wilcoxon-rank test, log-rank test, one-way analysis of variance test, and Pearson correlation analysis were used properly.Results::Unsupervised t-distributed stochastic neighbor embedding clustering analysis identified ten main cellular subclusters in urothelial tissues. Of them, seven urothelial subtypes were noted, and malignant urothelial cells were characterized with enhanced cellular proliferation and reduced immunogenicity. CD8 + T cell subclusters exhibited enhanced cellular cytotoxicity activities along with increased exhaustion signature in UC tissues, and the recruitment of CD4 + T regulatory cells was also increased in tumor tissues. Regarding myeloid cells, coordinated reprogramming of infiltrated neutrophils, M2-type polarized macrophages, and LAMP3 + dendritic cells contribute to immunosuppressive TME in UC tissues. Tumor tissues demonstrated enhanced angiogenesis mediated by KDR + endothelial cells and RGS5 +/ACTA2 + pericytes. Through deconvolution analysis, we identified multiple cellular subtypes may influence the programmed death-ligand 1 (PD-L1) immunotherapy response in patients with UC. Conclusion::Our scRNA-seq analysis clarified intra-tumoral heterogeneity and delineated the pro-tumoral and immunosuppressive microenvironment in UC tissues, which may provide novel therapeutic targets.
10.Anticarin-β shows a promising anti-osteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis.
Gan WANG ; Min ZHANG ; Ping MENG ; Chengbo LONG ; Xiaodong LUO ; Xingwei YANG ; Yunfei WANG ; Zhiye ZHANG ; James MWANGI ; Peter Muiruri KAMAU ; Zhi DAI ; Zunfu KE ; Yi ZHANG ; Wenlin CHEN ; Xudong ZHAO ; Fei GE ; Qiumin LV ; Mingqiang RONG ; Dongsheng LI ; Yang JIN ; Xia SHENG ; Ren LAI
Acta Pharmaceutica Sinica B 2022;12(5):2268-2279
Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

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