Human NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavoenzyme expressed at high levels in multiple solid tumors, making it an attractive target for anticancer drugs. Bioactivatable drugs targeting NQO1, such as β-lapachone (β-lap), are currently in clinical trials for the treatment of cancer. β-Lap selectively kills NQO1-positive (NQO1⁺) cancer cells by inducing reactive oxygen species (ROS) via catalytic activation of NQO1. In this study, we demonstrated that cryptotanshinone (CTS), a naturally occurring compound, induces NQO1-dependent necrosis without affecting NQO1 activity. CTS selectively kills NQO1⁺ cancer cells by inducing NQO1-dependent necrosis. Interestingly, CTS directly binds to NQO1 but does not activate its catalytic activity. In addition, CTS enables activation of JNK1/2 and PARP, accumulation of iron and Ca²⁺, and depletion of ATP and NAD⁺. Furthermore, CTS selectively suppressed tumor growth in the NQO1⁺ xenograft models, which was reversed by NQO1 inhibitor and NQO1 shRNA. In conclusion, CTS induces NQO1-dependent necrosis via the JNK1/2/iron/PARP/NAD⁺/Ca²⁺ signaling pathway. This study demonstrates the non-enzymatic function of NQO1 in inducing cell death and provides new avenues for the design and development of NQO1-targeted anticancer drugs.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

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*

As a trends of minimally invasive surgery, robot surgery is widely used in clinical practice, especially in hepatobiliary and pancreatic surgery, because of its better surgical field of view, more flexible robot arm, and more stable for fine operation. This article summarizes the research status and combines the author's own experience to review the current research progress and clinical effect of robotic surgery in pancreatic surgery, liver surgery, biliary surgery and prospect the further development trend of robotic surgery in the future.

With advancements in robotic surgery technology and applications,its prospects in pancreatic surgery are becoming increasingly promising.Recent studies have shown that robotic pancreatic surgery has unique advantages over open and laparoscopic methods in certain aspects.While the international minimally invasive surgery field continues to evolve,the comprehensive clinical application of robotic pancreatic surgery still requires evidence-based medical guidance.Our team has taken the lead in updating and publishing the International Consensus Guidelines for Robotic Pancreatic Surgery(2023 Edition)in the journal Hepatobiliary Surgery and Nutrition,based on the International consensus statement on robotic pancreatic surgery This effort brought together numerous experts in minimally invasive surgery from the United States,Europe,and Oceania.The analysis of 176 studies included after systematic literature evaluation was conducted using the World Health Organization(WHO)Handbook for Guideline Development,GRADE Grid method,Delphi vote,and AGREE-Ⅱ instrument.Detailed discussions were provided on topics such as robotic pancreatoduodenectomy,robotic distal pancreatectomy,and robotic central pancreatectomy.Following expert assessments and a comprehensive evaluation of evidence quality and credibility,19 questions and 14 recommendations were proposed,aiming to provide a basis for the safe and effective promotion of robotic pancreatic surgery in comprehensive or specialty medical centers both in China and elsewhere.The new consensus also emphasizes the importance of randomized controlled trial evidence for several issues,highlighting a direction for further efforts to promote the safe and effective implementation of robotic pancreatic surgery.

Objective To establish a prediction model for heart failure (HF) after percutaneous coronary intervention (PCI) in elderly patients with acute myocardial infarction (AMI). Methods A total of 326 elderly AMI patients in the First Hospital Affiliated to Harbin Medical University from January 2019 to December 2022 were retrospectively enrolled and divided into AMI-HF group (n=89) and non-AMI-HF group (n=237) based on the occurrence of HF at 6 months after surgery. Clinical materials of all the patients were collected through the electronic medical record system. Multivariate Logistic regression analysis was used to screen the risk factors of AMI complicated with HF and to construct a prediction model. The performance of the prediction model was evaluated by the receiver operating characteristic (ROC) curve. Results Univariate analysis showed that compared with the non-AMI-HF group, the AMI-HF group had higher proportions of patients aged over 75 years, diabetics, and higher levels of Gensini score, cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), blood uric acid, and high-sensitivity C-reactive protein (hs-CRP), while the left ventricular ejection fraction (LVEF) and the proportion of grade 3 of Thrombolysis in Myocardial Infarction (TIMI) blood flow were lower in the AMI-HF group, and the differences were statistically significant (P < 0.05). Multivariate Logistic regression analysis revealed that age, Gensini score, NT-proBNP, and hs-CRP were independent risk factors for HF after PCI in elderly AMI patients (P < 0.05), while TIMI grade was a protective factor (P < 0.05). After calculating the C-Index based on the screened risk factors, the ROC curve was used to evaluate the predictive ability of the C-Index for HF, showing an area under the curve (AUC) of 0.878 (95%CI, 0.834 to 0.921), with a sensitivity of 86.52%, a specificity of 75.95%, and an accuracy of 78.83%. Conclusion Age, Gensini score, NT-proBNP and hs-CRP are independent risk factors for HF after PCI in elderly AMI patients, while TIMI grade is a protective factor. The model constructed based on these factors can predict the risk of HF, thereby assisting in the early identification of high-risk HF populations and facilitating individualized interventions.

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62⁺ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62⁺ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

External apical root resorption is among the most common risks of orthodontic treatment, and it cannot be completely avoided and predicted. Risk factors causing orthodontic root resorption can generally be divided into patient- and treatment-related factors. Root resorption that occurs during orthodontic treatment is usually detected by radiographical examination. Mild or moderate root absorption usually does no obvious harm, but close attention is required. When severe root resorption occurs, it is generally recommended to suspend the treatment for 3 months for the cementum to be restored. To unify the risk factors of orthodontic root resorption and its clinical suggestions, we summarized the theoretical knowledge and clinical experience of more than 20 authoritative experts in orthodontics and related fields in China. After discussion and summarization, this consensus was made to provide reference for orthodontic clinical practice.
Humans ; Tooth Movement Techniques/adverse effects* ; Root Resorption/etiology* ; Consensus ; Dental Cementum ; Risk Factors