OBJECTIVE: To propose a new protocol for personalized mandibular reconstruction assisted by three-dimensional (3D) retrieval model based on fully connected neural network (FCNN) and a database of mandibles, and to verify clinical feasibility of the protocol. METHODS: A database of mandibles of 300 normal northern Chinese Han people was established. On the basis of cephalometry, the mandible landmarks with good stability were further screened. Mandibular landmarks were selected and geometric features of the mandible were extracted. A 3D retrieval algorithm was developed, which could retrieve the mandible most similar to a given mandible from the database. A FCNN was built to train the algorithm to improve accuracy of the 3D retrieval model. Using Geomagic Control 2014 software, matching accuracy of the 3D retrieval model was based on aforementioned mandible database and algorithm. From December 2019 to March 2021, a total of 5 patients underwent personalized mandibular reconstruction assisted by a 3D retrieval model based on mandible database and FCNN in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. The most similar mandible was retrieved from mandible database through 3D retrieval algorithm. It was used to restore the premorbid morphology of defect area and guide mandibular reconstruction. For the 5 patients, mandible was reconstructed with iliac flap. Virtual surgical plan was transformed using individual surgical guides. RESULTS: Through screening, mandibular landmarks with high reproducibility and stability were identified and composed of mandibular landmarker protocols. After training, the average deviation between most similar mandible retrieved from the 300-case mandible database through 3D retrieval model based on FCNN and given mandible was (1.77±0.44) mm. And the root-mean-square deviation between the most similar mandible retrieved from the database and given mandible was (2.58±0.86) mm. The mandibular reconstruction surgery was successful in all the 5 patients. Their facial symmetry and occlusion were restored. All the patients were satisfied with postoperative appearance. The mean deviation between postoperative mandible and preoperative design was (0.98±0.17) mm. The area with a deviation ≤1 mm accounted for 61.34%±14. 13%, ≤2 mm accounted for 83.82%±7.35%, and ≤3 mm accounted for 93.94%± 2.87%. CONCLUSION The personalized mandibular reconstruction assisted by 3D retrieval model based on the 300-case mandible database and FCNN is feasible clinically.
Humans ; Neural Networks, Computer ; Mandibular Reconstruction/methods* ; Mandible/diagnostic imaging* ; Imaging, Three-Dimensional/methods* ; Adult ; Databases, Factual ; Female ; Male ; Algorithms ; Middle Aged ; Cephalometry

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Purpose To investigate the incidence and risk of malignancy(ROM)of the Bethesda class Ⅰ/Ⅲ di-agnosis of thyroid nodules due to insufficient number of follicular cells,and to analyze the correlation between their in-sufficient cell volume and the characteristics of the nodules themselves from the perspective of ultrasound and histology.Methods Clinical data were collected from fine needle aspiration cytology(FNAC)of the thyroid gland.Review and statistical analysis was performed on cases with the Bethesda class Ⅰ/Ⅲ diagnosis due to insufficient cell volume.The incidence and the ROM of Bethesda class Ⅰ/Ⅲ diagnosis were calculated.BRAF V600E(+)or postoperative patho-logical indicating papillary thyroid carcinoma(PTC)was used as the criterion for malignancy.Then,we matched the Bethesda class Ⅱ/Ⅵ cases with sufficient cell volume as the control group.The ultrasound characteristics and histo-logical images of the two groups were compared and analyzed in order to reveal the correlation between the insufficient amount of penetrating cells and the objective characteristics of the nodule itself.Results There were 39 solid thyroid nodules with the Bethesda class Ⅰ diagnosis,with an incidence of 3.3％and a ROM of 38.5％,and 160 nodules with the Bethesda class Ⅲ diagnosis,with an incidence of 13.5％and a ROM of 59.4％.The incidence and ROM of nod-ules with C-TIRADS ≥4b(22.4％,67.6％)were higher than those of C-TIRADS ≤4a(12.7％,39.8％),and the differences were statistically significant(P＜0.001).Compared to the Bethesda class Ⅱ/Ⅵ nodules with sufficient cell volume,occurrence of the Bethesda class Ⅰ/Ⅲ nodules were significantly correlated with small nodules(maximal diameter＜5 mm),vertical growth(aspect ratio ≥ 1)and poor blood supply(no or little blood flow signals)(r=0.131,-0.230,0.237,P=0.008,＜0.001,＜0.001).They were also significantly correlated with the pathologic histologic structure of diffuse significant fibrosis of the interstitium and low parenchyma/interstitium composition ratio(about 1:1)(r=-0.269,-0.396,P=0.019,＜0.001).Conclusion Thyroid Bethesda class Ⅰ/Ⅲ nodules have a high ROM,and BRAF V600E detection is recommended as a tool of tiered management.Bethesda class Ⅰ/Ⅲ diagnosis of insufficient cell volume is more likely when the nodules are too small,grow vertically and lack blood sup-ply,presumably associated with extensive interstitial fibrosis and sparse parenchymal cells.

Objective To explore the preoperative assessment of the differentiation degree of hepatocellular carcinoma(HCC),based on the imaging features observed on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI HCC.Methods A retrospective analysis was conducted on the data of 198 patients with HCC confirmed by surgery or biopsy pathology,all of whom underwent Gd-EOB-DTPA enhanced examination before operation.According to pathological results,HCC patients were divided into poorly-differentiated group(group A,69 cases),moderately-differentiated group(group B,97 cases)and well-differentiated group(group C,32 cases).The signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),relative intensity ratio(RIR,,RIR2),and enhancement ratio(ER)of hepatobiliary phase HCC were calculated and analyzed.Results The CNR was the high-est in the group A and the lowest in the group C.Conversely,the SIHCC unenhanced,SIHCC hepatobiliary phase,and RIR1,RIR2 all were the highest in the group C and the lowest in the group A.There were statistically significant differences between the group C and the group B,as well as the group C and the group A(P＜0.05).Regarding signal characteristics during the hepatobiliary phase,the group A had the highest proportion of low/slightly low signal,while the group C had the lowest proportion.A statistically significant difference was observed between the group C and the group A(P＜0.05).Conclusion The Gd-EOB-DTPA enhanced MRI is helpful to preoperative assessment the differentiation degree of HCC.The higher the signal in the hepatobiliary phase,the smaller the CNR,the larger val-ues for the SIHCCunenhanced,SIHCC hepatobiliaryphase and RIR1,RIR2 are associated with the better the differentiation degree of HCC.

Oral squamous cell carcinoma(OSCC)accounts for over 90％of oral malignancies,with more than 370 000 new cases and approximately 188 000 deaths annually worldwide.In China,there are roughly 65 000 new cases and 35 000 deaths each year,showing a significant upward trend compared with 2015 statistics.Despite continuous advancements in treatment modalities,the 5-year survival rate remains stagnant at 50％-60％,where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology.To address these critical challenges,this study established a standardized bioban-king protocol for OSCC patient-derived organoids(PDOs)(Patent:Method for constructing an oral squa-mous cell carcinoma organoid bank,ZL202311378598.3).Through groundbreaking optimization of cul-ture media,enzymatic digestion kinetics,and stepwise cryopreservation,we achieved a biobanking suc-cess rate exceeding 95％and pioneered synchronous cultivation of matched primary tumors,lymph node metastases,and adjacent normal mucosa from individual patients,preserving spatial heterogeneity and stromal interactions.Leveraging this platform,we developed high-throughput drug screening:Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate(ATP)-based viability as-says;We discovered resistance mechanisms:Identified sialylated cancer IgG(SIA-cIgG)-mediated cis-platin resistance(primary/secondary)through PTPN13 suppression,with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy.Besides,we elucidated metastatic drivers:CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming,activating epithelial-mesenchymal plasticity(EMP)and inducing partial epithelial-mesenchymal transi-tion(pEMT).This"holographic patient-mirroring"platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Techni-cal Guidelines(Technical guideline for establishing patient-derived oral squamous cell carcinoma or-ganoid banks,CHSA 2024-08).Future integration of immune-competent organoids,3D-bioprinted vas-culature,and multi-omics-AI systems will accelerate personalized oncology.These innovations will accelerate clinical translation of personalized therapeutic regimens,ultimately bridging the gap between bench research and bedside application.

Objective To explore the preoperative assessment of the differentiation degree of hepatocellular carcinoma(HCC),based on the imaging features observed on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI HCC.Methods A retrospective analysis was conducted on the data of 198 patients with HCC confirmed by surgery or biopsy pathology,all of whom underwent Gd-EOB-DTPA enhanced examination before operation.According to pathological results,HCC patients were divided into poorly-differentiated group(group A,69 cases),moderately-differentiated group(group B,97 cases)and well-differentiated group(group C,32 cases).The signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),relative intensity ratio(RIR,,RIR2),and enhancement ratio(ER)of hepatobiliary phase HCC were calculated and analyzed.Results The CNR was the high-est in the group A and the lowest in the group C.Conversely,the SIHCC unenhanced,SIHCC hepatobiliary phase,and RIR1,RIR2 all were the highest in the group C and the lowest in the group A.There were statistically significant differences between the group C and the group B,as well as the group C and the group A(P＜0.05).Regarding signal characteristics during the hepatobiliary phase,the group A had the highest proportion of low/slightly low signal,while the group C had the lowest proportion.A statistically significant difference was observed between the group C and the group A(P＜0.05).Conclusion The Gd-EOB-DTPA enhanced MRI is helpful to preoperative assessment the differentiation degree of HCC.The higher the signal in the hepatobiliary phase,the smaller the CNR,the larger val-ues for the SIHCCunenhanced,SIHCC hepatobiliaryphase and RIR1,RIR2 are associated with the better the differentiation degree of HCC.

Purpose To investigate the incidence and risk of malignancy(ROM)of the Bethesda class Ⅰ/Ⅲ di-agnosis of thyroid nodules due to insufficient number of follicular cells,and to analyze the correlation between their in-sufficient cell volume and the characteristics of the nodules themselves from the perspective of ultrasound and histology.Methods Clinical data were collected from fine needle aspiration cytology(FNAC)of the thyroid gland.Review and statistical analysis was performed on cases with the Bethesda class Ⅰ/Ⅲ diagnosis due to insufficient cell volume.The incidence and the ROM of Bethesda class Ⅰ/Ⅲ diagnosis were calculated.BRAF V600E(+)or postoperative patho-logical indicating papillary thyroid carcinoma(PTC)was used as the criterion for malignancy.Then,we matched the Bethesda class Ⅱ/Ⅵ cases with sufficient cell volume as the control group.The ultrasound characteristics and histo-logical images of the two groups were compared and analyzed in order to reveal the correlation between the insufficient amount of penetrating cells and the objective characteristics of the nodule itself.Results There were 39 solid thyroid nodules with the Bethesda class Ⅰ diagnosis,with an incidence of 3.3％and a ROM of 38.5％,and 160 nodules with the Bethesda class Ⅲ diagnosis,with an incidence of 13.5％and a ROM of 59.4％.The incidence and ROM of nod-ules with C-TIRADS ≥4b(22.4％,67.6％)were higher than those of C-TIRADS ≤4a(12.7％,39.8％),and the differences were statistically significant(P＜0.001).Compared to the Bethesda class Ⅱ/Ⅵ nodules with sufficient cell volume,occurrence of the Bethesda class Ⅰ/Ⅲ nodules were significantly correlated with small nodules(maximal diameter＜5 mm),vertical growth(aspect ratio ≥ 1)and poor blood supply(no or little blood flow signals)(r=0.131,-0.230,0.237,P=0.008,＜0.001,＜0.001).They were also significantly correlated with the pathologic histologic structure of diffuse significant fibrosis of the interstitium and low parenchyma/interstitium composition ratio(about 1:1)(r=-0.269,-0.396,P=0.019,＜0.001).Conclusion Thyroid Bethesda class Ⅰ/Ⅲ nodules have a high ROM,and BRAF V600E detection is recommended as a tool of tiered management.Bethesda class Ⅰ/Ⅲ diagnosis of insufficient cell volume is more likely when the nodules are too small,grow vertically and lack blood sup-ply,presumably associated with extensive interstitial fibrosis and sparse parenchymal cells.

Objective:To explore the function of LIM and calponin homology domains 1(LIMCH1)in the development and progression of oral squamous cell carcinoma(OSCC),along with their potential clinical applications.Methods:By utilizing transcriptome sequencing data from two groups of oral squa-mous cell carcinoma patients,along with bioinformatics analytical techniques such as Gene Ontology(GO)and gene co-expression networks,we identified genes that might play a pivotal role in the patho-genesis of oral squamous cell carcinoma.We employed real-time quantitative PCR and Western blotting to validate the expression patterns of these genes across twelve patient tissue samples.Furthermore,we con-ducted CCK-8 assays,flow cytometry analyses,and scratch wound healing assays to assess the impact of key genes on the biological behaviors of both the Ca127 oral squamous cell carcinoma cell line and the po-tentially malignant DOK oral lesion cell line.Additionally,we examined correlations between these key genes and clinical disease parameters in 214 oral squamous cell carcinoma patients using The Cancer Ge-nome Atlas(TCGA)data;gene set enrichment analysis(GSEA)analysis results were also incorporated to enhance our findings from real-time quantitative PCR and Western blotting regarding potential mecha-nisms underlying the action of these key genes.Results:The integrated analysis of sequencing data and bioinformatics revealed that LIMCH1 exhibited significantly reduced mRNA(P＜0.001)and protein levels(P＜0.01)in the oral squamous cell carcinoma tissues compared with normal control tissues.In the Ca127 cells,the low LIMCH1 level group demonstrated a larger wound healing area within 24 hours than the control group(P＜0.01),enhanced proliferation capacity over 72 hours relative to the control group(P＜0.01),and an increased apoptosis rate within 24 hours compared with the high expression group(P＜0.05).However,no significant differences were observed between the low and high level groups in DOK cells.Furthermore,it was determined that low LIMCH1 level correlated with poor prognosis in the patients(P=0.013)and a higher lymph node metastasis rate(P＜0.05).Investigations into the poten-tial mechanisms of action indicated that LIMCH1 did not influence the onset or progression of oral squa-mous cell carcinoma via the epithelial-mesenchymal transition pathway.Conclusion:LIMCH1 level may function as a promising biomarker to aid in the prognostic assessment of oral squamous cell carcinoma;however,its precise mechanistic role requires further investigation.

Objective:To evaluate the clinical outcomes and define the indications for a one-stage mandibular reconstruction technique that combines iliac bone flaps with immediate implant-based den-tures,and to assess both the accuracy of surgical planning and the long-term success of the procedure.Methods:A total of ten patients underwent the procedure at Peking University Hospital of Stomatology between June 2020 and August 2023.The preoperative biopsy pathology of all the patients confirmed a benign tumor.In this technique,iliac bone flaps were used for mandibular reconstruction,and immediate implant-based dentures were placed during the same surgical session.Various outcome measures were evaluated,including the accuracy of the surgical reconstruction,implant placement deviations(entry point,apical point,depth,and angle),and long-term outcomes,such as cervical bone resorption,im-plant survival,and the cumulative survival rate.Results:Thirty-eight implants were successfully inserted into the iliac flaps of the ten patients.The median follow-up duration was 23.5 months,and no signifi-cant complications occurred during the follow-up period,such as infections,titanium plate exposure,im-plant loosening,or damage to the implants and dentures.The accuracy of preoperative virtual surgical planning(VSP)was highly reliable.The repeatability of the VSP model compared to the postoperative reconstructed mandible was as follows:67.82％±10.16％within 1 mm,82.14％±6.58％within 2 mm,and 90.61％±4.62％within 3 mm.The average maximum deviation from the plan was(6.10±0.89)mm,with an average overall deviation of(1.14±0.31)mm.For the implants,deviations in critical pa-rameters were as follows:entry point deviation was(2.02±0.58)mm,apical point deviation was(2.25±0.66)mm,depth deviation was(1.26±0.51)mm,and angular deviation was 1.84°±1.10°.The im-plant survival rate remained 100％during the follow-up,with a cumulative survival rate of 97.37％from 1 to 4 years.Average cervical bone resorption was 0.94 mm.Conclusion:The combination of iliac bone flaps with immediate implant-based dentures for one-stage mandibular reconstruction demonstrated pro-mising clinical outcomes,including high implant survival and minimal complications.This technique proved to be safe and reliable for mandibular reconstruction.However,further studies with larger sample sizes and longer follow-up periods are necessary to confirm the long-term efficacy and optimal indications for this procedure.

Objective To investigate the relationship between Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma viral oncogene RAS homolog(NRAS),V-raf murine sarcoma viral oncogene homo-log B(BRAF),human epidermal growth factor receptor 2(HER2)gene mutations and microsatellite instabili-ty(MSI)status and clinicopathological features in patients with colorectal cancer.Methods The clinical data of 226 patients with colorectal cancer treated in the hospital from October 2019 to March 2022 were collected.Next-generation sequencing technology was used to detect KRAS,NRAS,BRAF,HER2 gene mutations and MSI status.Immunohistochemistry was used to evaluate the mismatch repair system(MMR)status.Multiva-riate Logistic regression analysis was used to analyze the relationship between KRAS,NRAS,BRAF,HER2 gene mutations and clinicopathological features.Results Among 226 colorectal cancer patients,the mutation frequencies of KRAS,NRAS,BRAF and HER2 were 54.89％,5.3％,8.4％and 1.8％,respectively.The fre-quency of KRAS mutation in mucinous adenocarcinoma was higher than that in common adenocarcinoma(P＜0.05).The risk of KRAS mutation in right colon cancer was increased(OR=2.145,P=0.012).NR AS gene mutation was more frequent in left colon and rectal cancer(P＜0.05).The frequency of BRAF gene mu-tation was higher in poorly differentiated and microsatellite instability-high(MSI-H)colorectal cancer(P＜0.05),and the risk of BRAF gene mutation in the right colon was increased(OR=2.844,P=0.042).HER2 gene amplification mutation showed distant metastasis(P＜0.05).KRAS mutations were mutually exclusive with NRAS,BRAF and HER2 amplification mutations(P＜0.05).MSI-H was more frequent in the right co-lon(P＜0.05).Of the 226 cases,10 cases were defective mismatch repair(dMMR)/MSI-H,8 cases were dM-MR/microsatellite stable,and 5 cases were proficient mismatch repair/MSI-H.There was a moderate agree-ment between dMMR and MSI-H(Kappa=0.575).Conclusion KRAS,NRAS,BRAF,HER2 and MSI sta-tus are associated with clinicopathological features in patients with colorectal cancer.Combined detection of KRAS,NRAS,BRAF,HER2 and MSI can provide more accurate and effective data to guide the treatment and prognosis of patients.