Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Neoantigen pulsed dendritic cell vaccine(Neo-DCVac)is a new type of tumor immunotherapy.Neoantigen is strong immunologic and tumor-specific mutated peptides expressed in a tumor.Neo-DCVac is a therapeutic modality based on the uptake and processing of neoantigens by dendritic cells and their delivery and activation of T cells to trigger the body's immune response for anti-tumor effects.The development of individualized Neo-DCVac based on high-throughput sequencing is expected to be a new direction for precision immunotherapy of tumors.In this review,we discuss construction of individualized Neo-DCVac,clinical application of combination therapy in solid tumors,suitable population for vaccination and the current limitations of Neo-DCVac,aiming to provide a theoretical reference for research on tumor immunotherapy.

Objective To investigate the application value of spectral computed tomography venography(CTV)in the display and staging of deep venous thrombosis(DVT)in the lower extremity.Methods Eighty-two patients with CTV were selected and ran-domly divided into group A(42 patients)and group B(40 patients).Group A:tube voltage 120 kVp.Group B:gemstone spectral ima-ging(GSI)mode,reconstruction of 50 keV and iodine(water)maps.The CT and standard deviation(SD)values of the veins were measured,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated in 120 kVp images of group A and in 50 keV images of group B.Two observers scored the image quality of the 2 groups subjectively,and Kappa test was used to examine the con-sistency.Based on the duration from the occurrence of clinical symptoms,the DVTs were classified.The CT values and iodine con-centration(IC)of DVT were measured in the 120 kVp images of group A and in the iodine(water)maps of group B,respectively.The receiver operating characteristic(ROC)curve was drawn to compare the effectiveness of CT values and IC in diagnosing DVT staging.Results CT values,SNR,and CNR of veins in group B were higher than those in group A(P<0.05).The subjective scores of the two groups were consistent(Kappa=0.926-0.955,P<0.05).The score for the display of veins and thrombus clarity in group B was 5(4,5),which was better than the score of 4(3,4)in group A(P<0.05).The efficiency of IC in diagnosing DVT staging[area under the curve(AUC)=0.973]was better than that of CT values(AUC=0.891).Conclusion The spectral CTV can improve the contrast of lower extremity deep veins and the clarity of thrombus,and can provide more objective indicators for the diagnosis of thrombus staging,which is conducive to accurate clinical diagnosis and treatment.

Objective To investigate the application value of energy spectral CT low energy(keV)targeted reconstruction tech-niques combined with adaptive statistical iterative reconstruction-Veo(ASIR-V)algorithm in lower extremity computed tomography venography(CTV).Methods Forty patients with lower extremity CTV examination were retrospectively selected.Gemstone spec-tral imaging(GSI)mode was used with a transient tube voltage of 80 kVp/140 kVp and tube current in GSI Assist mode.Group A(conventional group):70 keV combined with 40％ASIR-V mono-energy images,conventional display field of view(DFOV)inclu-ding both lower extremity.Group B(low keV group):50 keV combined with 50％ASIR-V mono-energy images,DFOV as in group A.Group C(low keV targeted reconstruction group):50 keV combined with 50％to 80％ASIR-V mono-energy images(10％interval,called as groups C1-C4),targeted reconstruction(small DFOV,covered one lower extremity with left and right femurs as the center).The CT and standard deviation(SD)values of the bilateral lower extremity veins were measured on each axial image and the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated.Two observers scored the venous images and the sharpness of embolus display subjectively using a 5-point scale and Kappa test was used to examine the consistency.Results In terms of vein dis-play,the score of groups B and C was better than that of group A(P＜0.05).In terms of embolus display sharpness,the scores of large and small embolus in group C increased with the increase of ASIR-V percentage initially and then gradually decreased(P＜0.05).The scores in group C2 were the highest which were superior to the scores of group B and group A(P＜0.05).The CT values of each venous segment in groups B and C were higher than those in group A(P＜0.05).In groups C1 to C4,with the increasing weight of ASIR-V,the SNR and CNR increased gradually(P＜0.05),but slightly lower than those in group B(P＜0.05).Conclusion 50 keV targeted reconstruction techniques combined with 60％ASIR-V algorithm significantly improves the contrast of lower extremity veins and the embolus display sharpness,providing more accurate clinical imaging information.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Chromosome karyotyping is a critical way to diagnose various hematological malignancies and genetic diseases, of which chromosome detection in raw metaphase cell images is the most critical and challenging step. In this work, focusing on the joint optimization of chromosome localization and classification, we propose ChromTR to accurately detect and classify 24 classes of chromosomes in raw metaphase cell images. ChromTR incorporates semantic feature learning and class distribution learning into a unified DETR-based detection framework. Specifically, we first propose a Semantic Feature Learning Network (SFLN) for semantic feature extraction and chromosome foreground region segmentation with object-wise supervision. Next, we construct a Semantic-Aware Transformer (SAT) with two parallel encoders and a Semantic-Aware decoder to integrate global visual and semantic features. To provide a prediction with a precise chromosome number and category distribution, a Category Distribution Reasoning Module (CDRM) is built for foreground-background objects and chromosome class distribution reasoning. We evaluate ChromTR on 1404 newly collected R-band metaphase images and the public G-band dataset AutoKary2022. Our proposed ChromTR outperforms all previous chromosome detection methods with an average precision of 92.56% in R-band chromosome detection, surpassing the baseline method by 3.02%. In a clinical test, ChromTR is also confident in tackling normal and numerically abnormal karyotypes. When extended to the chromosome enumeration task, ChromTR also demonstrates state-of-the-art performances on R-band and G-band two metaphase image datasets. Given these superior performances to other methods, our proposed method has been applied to assist clinical karyotype diagnosis.
Humans ; Metaphase ; Karyotyping/methods* ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Chromosomes, Human/genetics*

OBJECTIVES: To investigate genotype-phenotype characteristics and long-term prognosis of neonatal carbamoyl phosphate synthetase 1 (CPS1) deficiency among children through newborn screening in Zhejiang province. METHODS: The clinical and follow-up data of children with CPS1 deficiency detected through neonatal screening and confirmed by tandem mass spectrometry and genetic testing in Zhejiang Province Newborn Disease Screening Center from September 2013 to August 2023 were retrospectively analyzed. RESULTS: A total of 4 056 755 newborns were screened and 6 cases of CPS1 deficiency were diagnosed through phenotypic and genetic testing. Ten different variations of CPS1 genewere identified in genetic testing, including 2 known pathogenic variations (c.2359C>T and c.1549+1G>T) and 8 unreported variations (c.3405-1G>T, c.2372C>T, c.1436C>T, c.2228T>C, c.2441G>A, c.3031G>A, c.3075T>C and c.390-403del). All patients had decreased citrulline levels (2.72-6.21 μmol/L), and varying degrees of elevated blood ammonia. The patients received restricted natural protein intake (special formula), arginine and supportive therapy after diagnosis, and were followed-up for a period ranging from 9 months to 10 years. Three patients experienced hyperammonemia, and one patient each had attention deficit hyperactivity disorder, transient facial twitching and increased muscle tone. One patient died, while the other five surviving patients had normal scores of the Ages & Stages Questionnaires (ASQ) and Griffiths Development Scales up to the present time; 4 cases had combined height or weight lag and one case was normal in height and weight. CONCLUSIONS Low citrulline levels and hyperammonemia are common in CPS1 deficiency patients in Zhejiang. Most gene variants identified were specific to individual families, and no hotspot mutations were found. Early diagnosis through newborn screening and following standardized treatment can significantly improve the prognosis of the patients.
Child ; Humans ; Infant, Newborn ; Carbamoyl-Phosphate Synthase I Deficiency Disease/therapy* ; Neonatal Screening ; Follow-Up Studies ; Hyperammonemia ; Citrulline/genetics* ; Retrospective Studies ; Mutation

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*