1.Application of Onlay bone grafts from mandibular lateral oblique line in implant restoration of bone defects in upper anterior teeth
Shencong XU ; Zifei FANG ; Mingyi JI ; Chengrui XU ; Binhong LI ; Jiayu CAO ; Junfeng XU
Chinese Journal of Tissue Engineering Research 2026;30(4):841-848
BACKGROUND:With the development of oral implantology,implant restoration has gradually become the first choice of restoration after missing teeth,and bone augmentation procedures have led to the expansion of implant indications and the improvement of the success rate of implant restoration.However,the long-term stability of bone height,width and volume after bone augmentation surgery has been one of the clinical difficulties for oral implantologists.OBJECTIVE:To measure and analyze the bone width,height,and volume of different sites in the bone augmentation area at different time points using cone-beam CT and an automatic image alignment program.METHODS:Seventeen patients with severe bone defects in the upper anterior region who underwent Onlay bone block grafting in the external oblique region were recruited from the Department of Stomatology,Zhejiang Tongde Hospital.There were 10 males and 7 females,with a mean age of(45.88±12.47)years.The cone-beam CT scans of the patients' Onlay bone grafts were taken at five time points:preoperatively,immediately postoperatively,6 months postoperatively,immediately post implantation,and 6 months post implantation,and then were statistically analyzed for alveolar bone volume,width,and height in the bone augmentation area,as well as for the difference in the alveolar bone volume of the bone incremental area between patients of different sexes and age.RESULTS AND CONCLUSION:(1)The alveolar bone volume in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P<0.05)as well as was higher immediately after bone grafting than 6 months after bone grafting(P<0.05).The alveolar bone height in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P<0.05).The horizontal width of the alveolar bone at various sites in the bone augmentation area immediately and 6 months after bone grafting was higher than that before bone grafting(P<0.05).(2)There was no significant difference in the volume of bone graft resorption at various sites in the bone augmentation area between males and females immediately and 6 months after bone grafting(P>0.05).Pearson correlation analysis showed a positive correlation between age and the change in bone augmentation area volume immediately and 6 months after bone grafting,but the difference was not statistically significant(P>0.05).(3)Twenty-five dental implants with completed implant restorations functioned normally,and the survival rate of the implants was 100%.To conclude,Onlay bone graft implant restoration in the upper anterior region can significantly improve insufficient bone with favorable outcomes.However,there is some amount of bone resorption in the bone augmentation area at 6 months after Onlay bone grafting and it is necessary to open up the second surgical area.Clinicians should consider different bone augmentation procedures in accordance with the specific circumstances.
2.Expert consensus on neoadjuvant PD-1 inhibitors for locally advanced oral squamous cell carcinoma (2026)
LI Jinsong ; LIAO Guiqing ; LI Longjiang ; ZHANG Chenping ; SHANG Chenping ; ZHANG Jie ; ZHONG Laiping ; LIU Bing ; CHEN Gang ; WEI Jianhua ; JI Tong ; LI Chunjie ; LIN Lisong ; REN Guoxin ; LI Yi ; SHANG Wei ; HAN Bing ; JIANG Canhua ; ZHANG Sheng ; SONG Ming ; LIU Xuekui ; WANG Anxun ; LIU Shuguang ; CHEN Zhanhong ; WANG Youyuan ; LIN Zhaoyu ; LI Haigang ; DUAN Xiaohui ; YE Ling ; ZHENG Jun ; WANG Jun ; LV Xiaozhi ; ZHU Lijun ; CAO Haotian
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(2):105-118
Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.
3.Application of Onlay bone grafts from mandibular lateral oblique line in implant restoration of bone defects in upper anterior teeth
Shencong XU ; Zifei FANG ; Mingyi JI ; Chengrui XU ; Binhong LI ; Jiayu CAO ; Junfeng XU
Chinese Journal of Tissue Engineering Research 2026;30(4):841-848
BACKGROUND:With the development of oral implantology,implant restoration has gradually become the first choice of restoration after missing teeth,and bone augmentation procedures have led to the expansion of implant indications and the improvement of the success rate of implant restoration.However,the long-term stability of bone height,width and volume after bone augmentation surgery has been one of the clinical difficulties for oral implantologists.OBJECTIVE:To measure and analyze the bone width,height,and volume of different sites in the bone augmentation area at different time points using cone-beam CT and an automatic image alignment program.METHODS:Seventeen patients with severe bone defects in the upper anterior region who underwent Onlay bone block grafting in the external oblique region were recruited from the Department of Stomatology,Zhejiang Tongde Hospital.There were 10 males and 7 females,with a mean age of(45.88±12.47)years.The cone-beam CT scans of the patients' Onlay bone grafts were taken at five time points:preoperatively,immediately postoperatively,6 months postoperatively,immediately post implantation,and 6 months post implantation,and then were statistically analyzed for alveolar bone volume,width,and height in the bone augmentation area,as well as for the difference in the alveolar bone volume of the bone incremental area between patients of different sexes and age.RESULTS AND CONCLUSION:(1)The alveolar bone volume in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P<0.05)as well as was higher immediately after bone grafting than 6 months after bone grafting(P<0.05).The alveolar bone height in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P<0.05).The horizontal width of the alveolar bone at various sites in the bone augmentation area immediately and 6 months after bone grafting was higher than that before bone grafting(P<0.05).(2)There was no significant difference in the volume of bone graft resorption at various sites in the bone augmentation area between males and females immediately and 6 months after bone grafting(P>0.05).Pearson correlation analysis showed a positive correlation between age and the change in bone augmentation area volume immediately and 6 months after bone grafting,but the difference was not statistically significant(P>0.05).(3)Twenty-five dental implants with completed implant restorations functioned normally,and the survival rate of the implants was 100%.To conclude,Onlay bone graft implant restoration in the upper anterior region can significantly improve insufficient bone with favorable outcomes.However,there is some amount of bone resorption in the bone augmentation area at 6 months after Onlay bone grafting and it is necessary to open up the second surgical area.Clinicians should consider different bone augmentation procedures in accordance with the specific circumstances.
4.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
5.Adhering to the purpose of academic journal establishment, and fulfilling the mission of scientific journals: discipline construction of digestive surgery in the new era
Peng JIANG ; Jiahong DONG ; Jia FAN ; Qiang LI ; Xiujun CAI ; Minhua ZHENG ; Jiafu JI ; Yinmo YANG ; Hui CAO ; Yajin CHEN ; Guoxin LI ; Guoyue LYU ; Leida ZHANG ; Min CHEN
Chinese Journal of Digestive Surgery 2025;24(8):1022-1026
On the occasion of the 110th Anniversary of the establishment of the Chinese Medical Association, the third conference of the Fourth Editorial Board of Chinese Journal of Digestive Surgery, and the Second Elite Group of Chinese Journal of Digestive Surgery, was successfully held in Kunming on July 4, 2025. This conference systematically summarizes the development experience of the journal over the past 20 years from three aspects: the role of ecological construction of thought in the discipline construction of digestive surgery, the display of the latest academic achievements in the field of digestive surgery, the development difficulties, and breakthrough paths of the discipline, and strategically plans the path of discipline construction in the new era.
6.Multimodal investigation of stress-induced RNA-brain covariance and its association with depression vulnerability
Yun LIU ; Xijuan XIA ; Kehan YAN ; Yang JI ; Yifeng LUO ; Zhihong CAO ; Yuefeng LI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(9):790-797
Objective:To explore the RNA expression and alterations in brain structure in individuals who have experienced stressful life events (SLE), as well as the correlation patterns between them and their association with the occurrence of depression.Methods:Prospectively, a total of 80 SLE subjects were recruited from the psychiatry and psychology clinic of the Jiangsu University Affiliated Yixing Hospital between January 2021 and December 2022, with 16 normal controls (NC) enrolled concurrently. The 17 items Hamilton depression scale (HAMD-17) and social readjustment rating scale (SRRS) were used to assess depressive symptoms and stress levels. RNA sequencing information of peripheral blood and imaging data at baseline were collected. Based on whether depression occurred during the 2-year follow-up period, SLE subjects were divided into the SLE-depression group ( n=15) and the SLE-non-depression group ( n=65). Differentially expressed genes (DEGs) were screened using differential analysis and protein-protein interaction (PPI) networks. Fractional anisotropy (FA) of white matter tracts and gray matter volume (GMV) were extracted using tract-based spatial statistics and voxel-based morphometry.Using analysis of variance compared inter-group differences in gene expression, GMV and white matter FA values. Partial correlation analysis was used to explore correlations between DEGs, altered GMV and white matter microstructure. Gene set enrichment analysis (GSEA) was performed on key genes to identify potential biological pathways. Propensity score matching constructed sensitivity subgroups to verify result robustness. Results:The SLE-depression group showed significantly higher SRRS and HAMD-17 scores at baseline and at the end of follow-up compared to the SLE-non-depression group and the NC group ( H=47.773, 35.427, 41.114, all P<0.05). Expression levels of IL-10 (2.12±0.28, 2.43±0.44), EZH2 (2.11±0.43, 2.45±0.51), NCAM1 (3.60±0.30, 3.03±0.39), CD3E (4.95±0.37, 4.57±0.48), CCK (3.29±0.28, 3.02±0.42), and CX3CR1 (5.55±0.40, 5.91±0.34) were significantly different between the SLE-depression group and SLE-non-depression group( F=5.549~28.371, all P<0.05). Compared with the SLE-non-depression group, the SLE-depression group exhibited significantly lower FA values in the genu of the corpus callosum (0.29±0.04, 0.31±0.04) and the left uncinate fasciculus (0.31±0.02, 0.33±0.02), as well as significantly smaller GMV in the right hippocampus (0.29±0.07, 0.33±0.06), bilateral middle frontal gyrus (left: 0.27±0.05, 0.31±0.05; right: 0.28±0.06, 0.32±0.06), right insula (0.36±0.03, 0.38±0.04), and left precentral gyrus (0.19±0.04, 0.24±0.05) ( F=4.593-12.064, all P<0.05, FDR correction). GMV in the right anterior cingulate and paracingulate gyri was significantly larger than that in the SLE-non-depression group (0.34±0.05, 0.29±0.06) ( F=6.704, P=0.034, FDR correction). Partial correlation analysis revealed significantly stronger correlations between hub DEGs and altered brain regions in the SLE-depression group ( r=0.017-0.801) compared to the SLE-non-depression group ( r=0.002-0.382), with a statistically significant difference ( U=629, P<0.001; Cliff's Delta=0.454). GSEA indicated that the aforementioned genes were primarily involved in pathways including the ribosome, spliceosome, ribosome biogenesis in eukaryotes, and neuroactive ligand-receptor interaction. Sensitivity analysis confirmed that the above results remained statistically significant after balancing sample sizes (all P<0.05). Conclusion:The SLE-depression group showed specific RNA expression and brain structure alterations compared to the SLE-non-depression group, and the correlation between RNA and brain structure was significantly enhanced in the SLE-depression group. This suggests that the correlation between genes and brain structure in the SLE population may be related to their susceptibility to depression.
7.Incidence and Mortality of Liver Cancer in Fusui County of Guangxi Zhuang Autonomous Region in 2019 and Trend from 2011 to 2019
Yuman FAN ; Yunxi LI ; Jiangshi ZHAO ; Ji CAO ; Zihan ZHOU ; Qiulin LI ; Minhua RONG ; Lianying GE ; Chenglei YANG ; Xiumei LIANG ; Yingchun LIU ; Hongping YU
China Cancer 2025;34(3):195-202
[Purpose]To analyze the incidence and mortality of liver cancer in Fusui County of Guangxi Zhuang Autonomous Region in 2019 and the trend of change from 201 1 to 2019.[Meth-ods]Based on the incidence and mortality data of liver cancer in Fusui County from 2011 to 2019,the crude incidence rate,crude mortality rate,age-standardized rate by Chinese standard population(ASIRC/ASMRC),age-standardized rate by world standard population(ASMRW/ASM-RW),disability-adjusted life years(DALY),years of life lost(YLL),years of lived with disability(YLD)were calculated.The Joinpoint linear regression model was used to calculate the average annual percentage change(AAPC)of the ASIRC/ASMRC and DALY rate of liver cancer in Fusui County from 2011 to 2019.[Results]In 2019,there were 345 new cases and 298 deaths of liver cancer in Fusui County,accounting for 28.49%and 35.86%of all new cases and death cases of malignant tumors in Fusui County,respectively.The crude incidence rate,ASIRC and ASIRW were 74.71/105,67.55/105 and 65.63/105,respectively;the crude mortality rate,ASMRC and ASMRW were 64.53/105,58.78/105 and 56.88/105,respectively.In 2019,ASIRC/ASMRC of men were higher than those of women(105.32/105 and 95.67/105 for men;27.26/105 and 19.11/105 for women).The peak incidence and mortality rates were in the 65~69 and 80~84 age groups,re-spectively.The incidence rate of liver cancer in Fusui County declined from 82.50/105 in 2011 to 67.55/105 in 2019,with an AAPC of-3.01%(P=0.024),but the mortality rate did not have sig-nificant changes(AAPC=-1.44%,P=0.224).The rate of DALY decreased from 14.51/105 to 10.36/105,with an AAPC of-2.82%(P=0.050).[Conclusion]The incidence rate and DALY rate of liv-er cancer in Fusui County showed an overall decreasing trend from 2011 to 2019,but still re-mained at a high level.It is necessary to further strengthen the prevention,screening and early treatment of liver cancer in this region,especially for men and the elderly.
8.Effects of Liangxue Heying Formula-medicated serum on the activation of LPS-induced human umbilical vein endothelial cells via JAK2/STAT3 signaling pathway
Chun-lan XIA ; Xia FENG ; Ye-min CAO ; Zhi-qiang LIANG ; Yi LE ; Hong-tao XU ; Fei QI ; Ji LI
Chinese Traditional Patent Medicine 2025;47(4):1150-1156
AIM To investigate the effects of Liangxue Heying Formula-medicated serum(LXHY-MS)on human umbilical vein endothelial cells(HUVECs)induced by lipopolysaccharide(LPS).METHODS CCK-8,DCFH-DA fluorescence probe and Western blot method were used to screen the LPS concentration in modeling and the serum LXHY concentration for treatment.The HUVECs divided into the normal group,the model group and the LXHY-MS group had their SOD activity detected by automatic biochemical analyzer;their MDA level detected by colorimetry;their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 detected by Western blot;and their mROS expression and recruitment effect on THP-1 photographed with high connotation.With the use of JAK2/STAT3 pathway inhibitor(AG490),the HUVECs divided into the normal group,the AG490 group,the LPS group,the LPS+AG490 group,the LPS+LXHY-MS group,and LPS+LXHY-MS+AG490 group were subjected to the corresponding treatment,followed by the detection of their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 by Western blot.RESULTS Compared with the normal group,the model group displayed decreased SOD activity(P<0.01),increased MDA level(P<0.05),increased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P<0.05,P<0.01),and increased mROS expression and THP-1 cells recruitment.Compared with the model group,the LXHY-MS group shared increased SOD activity(P<0.05),decreased MDA level(P<0.01),decreased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P<0.05,P<0.01),reduced mROS expression and THP-1 cells recruitment.Given the use of AG490,the model group displayed increased protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 in contrast to the normal group(P<0.05,P<0.01);each intervened group showed decreased expressions of related proteins in contrast to the model group(P<0.05,P<0.01).CONCLUSION LXHY-MS may protect the injury due to the activation of HUVECs by inhibiting the JAK2/STAT3 signaling pathway.
9.Research hotspots and trends of functional cure of hepatitis B based on bibliometric analysis
Qi-ran ZHANG ; Bing CAO ; Ji-bin XIN ; Li-jun WU ; Yu-lei SUN ; Jun YING ; Wen-hong ZHANG
Fudan University Journal of Medical Sciences 2025;52(2):159-170
Objective To analyze the global literature related to functional cure of hepatitis B from 2019 to 2023 by using bibliometric analysis methods,so as to help researchers understand the research hotspots and trends in this field.Methods The literature related to the topic of functional cure of hepatitis B included in the Science Citation Index Expanded(SCI-Expanded)of the Web of Science Core Collection from 2019 to 2023 was searched.By using VOSviewer and CiteSpace visual analysis tools,analyses were conducted from the perspectives of publication trends,international research cooperation networks,and keyword emergence,and were elaborated with the specific contents of the related literature to elucidate research hotspots and trends.Results A total of 600 eligible papers in this field were included.Keyword co-occurrence and thematic clustering suggested that the main research directions of functional cure were:serum biomarkers for prediction and monitoring of functional cure,functional cure and immunity,nucleoside analog discontinuation,interferon therapy,and long-term prognosis of functional cure.The research contents of the ESI highly cited original research papers were similar to the clustering of the above,but showed more attention on the novel agents for functional cure.The content of the keyword emergence map showed that hotspots of interest changed from virologic mechanisms and serum markers,to nucleoside analog discontinuation and interferon therapy,and finally to immunologic mechanisms and new drug.Conclusion The research hotspots and trends of functional cure of hepatitis B were focused on virological mechanism,serum markers,immunological mechanism,nucleoside analog discontinuation,interferon therapy,and long-term prognosis after cure.
10.Current status,hotspots and prospects of research on liver failure caused by viral hepatitis:a bibliometric and visualization-based analysis
Xiang-yu QIN ; Bing CAO ; Ji-bin XIN ; Li-jun WU ; Jian-ming ZHENG ; Jun YING
Fudan University Journal of Medical Sciences 2025;52(2):180-189
Objective To conduct a bibliometric analysis of relevant literature on liver failure caused by viral hepatitis from the past five years,and to help researchers understand the current status and hotspots in this field,and to provide insights into future research trends.Methods Based on the Science Citation Index Expanded(SCI-Expanded)data from Web of Science Core Collection,visualization analysis and mapping were conducted through VOSviewer and CiteSpace software to generate visual representations of international research collaboration networks,keyword co-occurrence clustering,and keyword bursts.Results From 2019 to 2023,a total of 873 relevant literature were included,with a total citation frequency of 7 364 and an average citation frequency of 8.44.Among them,China had the highest number of publications(458 articles,52.46%)and had the most cooperation with the United States.The research hotspots of viral hepatitis induced liver failure were mainly divided into three categories:basic and clinical research on liver failure caused by non-hepatitis B virus(HBV),the pathogenesis of HBV related liver failure,and treatment and prediction models of liver failure.The keyword time overlay map and burst map showed that the research hotspots had gradually shifted from the prevention and control of new infections to the treatment and prognosis assessment of patients with chronic infection.Conclusion China is a major international research entity in liver failure caused by viral hepatitis and actively participates in international scientific collaborations.The research hotspots on liver failure caused by viral hepatitis have gradually shifted from preventing viral hepatitis infections and expanding treatment options to the treatment of chronic infection patients and prognostic prediction.


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