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*

Immunotherapy has been widely used in cancer treatment in recent years and functions by stimulating the immune system to kill tumor cells. Radiation therapy (RT) uses radiation to induce DNA damage and kill tumor cells. However, this activates the body's immune system, promoting the release of tumor-related antigens from inactive dendritic cells, which stimulates the recurrence and metastasis of tumors in immune system tissues. The combination of RT and immunotherapy has been increasingly evaluated in recent years, with studies confirming the synergistic effect of the two antitumor therapies. Particularly, the combination of RT by dose adjustment with different immunotherapies has positive implications on antitumor immunity as well as disease prognosis compared with respective monotherapies. This review summarizes the current research status, progress, and prospects of RT combined with immunotherapy in cancer treatment. It additionally discusses the prevalent concerns regarding the dose, time window, and toxicity of this combination therapy.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Combined Modality Therapy ; Radiotherapy/methods*

OBJECTIVE: To study the durability of the anti-demineralization effects of fluoride varnish after being applied to dental root surfaces. METHODS: Coronal and radicular dentin samples were prepared from extracted human teeth. Duraphat^® (DP) was applied to the dentine surfaces to form a protective film. The film-dentin interfaces were observed by scanning electron microscopy (SEM) and the fluoride element was analyzed with energy dispersive spectrometer (EDS). Thus, the differences between applying DP on crowns and roots were compared. Radicular dentin samples were prepared and randomly divi-ded into four groups: (1) Blank: DP was not applied, and demineralized in acetic acid (pH 4.5) for 4 days; (2) Blank+aging: DP was not applied, the samples were put into deionized water for 14 days at room temperature, and then demineralized in acetic acid (pH 4.5) for 4 days; (3) DP: DP was applied and demineralized in acetic acid (pH 4.5) for 4 days; (4) DP+aging: DP was applied, the samples were put into deionized water for 14 days at room temperature, and then demineralized in acetic acid (pH 4.5) for 4 days. Finally, SEM observation and EDS analysis of fluoride content were performed on film-dentin interfaces to evaluate the degree of demineralization, the morphology of DP film, and the penetration of fluorine. RESULTS: The immediate penetration depth of fluoride element from DP was deeper in the coronal dentin than that in radicular dentin. The samples in the blank and blank+aging groups demine-ralized significantly after acid etching. The DP group did not undergo demineralization, and the fluorine element penetrated to (76.00±8.94) μm below the interfaces. The structure of the protective film in the DP+aging group was damaged, but the underneath dentin did not undergo demineralization. The fluorine element still remained at a depth of (5.00±3.53) μm below the interfaces. CONCLUSION DP has an anti-demineralization effect on the root surface, and this effect can still be exerted for a period of time after losing the structure of protective film. It has the ability to prevent root caries and a certain durability.
Humans ; Tooth Root/drug effects* ; Fluorides, Topical/pharmacology* ; Tooth Demineralization/prevention & control* ; Dentin/drug effects* ; Fluorides ; In Vitro Techniques ; Cariostatic Agents/pharmacology*

Objective: To establish a machine learning-based precision blood donor recruitment model at the county level and assess its generalizability and applicability. Methods: A retrospective study was conducted using blood donation and SMS recruitment data from the Taicang Branch of the Suzhou Blood Center between 2019 and 2024. Multiple machine learning algorithms were employed, including extreme gradient boosting, support vector machine, k-nearest neighbor, logistic regression, decision tree, random forest, and multilayer perceptron. These were combined with techniques such as synthetic minority oversampling, undersampling, and cost-sensitive learning (using MFE and MSFE loss functions). Model parameters were optimized through grid search to identify the best-performing model. Results: In a prospective comparative study against conventional methods, the machine learning models increased the recruitment success rate among high-willingness donors by an average of 129.15%, and the recruitment efficiency per SMS improved by 125.02% compared with the traditional method. Under full-scale SMS sending, the recruitment rate per SMS increased by 42.61%, and SMS sending efficiency improved by 31.77%, significantly enhancing recruitment performance. Conclusion: This study represents the first application of a machine learning-based precision donor recruitment model at the county-level in China. The precise recruitment framework not only improves recruitment efficiency and reduces recruitment costs but also demonstrates strong scalability and generalizability. It provides a scientific and feasible intelligent pathway to ensure the safety and sustainability of the blood supply.

Objective To investigate the clinical efficacy of β-blockers in older patients with hypertension combined with vascular dementia.Methods A total of 152 older patients with hypertension combined with vascular dementia who were admitted to Shanxi Provincial Fenyang Hospital between January 2022 and October 2024 were enrolled.The participants were randomly assigned to either the study group or the control group(76 patients each)using the randomized numerical table method.Both groups received conventional treatment,and the study group received metoprolol for 5 weeks in addition to the conventional treatment.Primary outcome indicators,including changes in systolic blood pressure(SBP)and diastolic blood pressure(DBP)before and after treatment,were examined.Additionally,comparison was made to examine the intergroup difference in serological markers,including high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-8,matrix metalloproteinase 9(MMP-9),homocysteine(Hcy),and superoxide dismutase(SOD)levels,and the scores for intelligence,cognitive,and behavioral assessments.Adverse reactions were recorded.Results After treatment,the study group showed reduced SBP from(146.90±7.35)mmHg(1 mmHg=0.133 kPa)to(120.00±6.03)mmHg and reduced DBP from(90.24±5.97)mmHg to(77.23±6.81)mmHg.The reduction in blood pressure in the study group became more significantly when compared with that of the control group,with intergroup difference in SBP reduction being-8.54 mmHg(P<0.001)and intergroup difference in DBP reduction being-10.80 mmHg(P<0.001).Patients in the 2 groups showed statistically significant differences in the levels of hs-CRP,TNF-α,IL-6,IL-8,MMP-9,and Hcy,and in their cognitive and behavioral scores(P<0.05).No statistically significant differences were found in pulse pressure,von Willebrand factor(vWF)levels,or intelligence scores before and after treatment(P>0.05).The main adverse reactions in the study group were central nervous system reactions(22.37%)and withdrawal syndrome(17.11%).Conclusion The β-blocker metoprolol effectively controlled blood pressure,significantly reduced levels of pro-inflammatory factors and specific vascular injury markers,and improved cognitive function and behavioral symptoms in older patients with hypertension combined with vascular dementia,suggesting its therapeutic efficacy for this condition.However,attention should be paid to its associated adverse reactions.

Objective: To construct a Family with sequence similarity 50 member A(FAM50A) gene knockout mouse insulinoma pancreatic β-cell line Beta-TC-6 using CRISPR/Cas9 gene editing technology and to prepare polyclonal antibodies specifically recognizing FAM50A. Methods: Two guide RNAs(sgRNAs) targeting the FAM50A gene were designed,and a recombinant plasmid expressing blue fluorescent protein(BFP) was constructed for gene knockout.The successfully constructed plasmid was transfected into Beta-TC-6 cells,and BFP-positive single cells were isolated for clonal expansion.The expanded monoclonal cell lines were genotyped by Sanger sequencing,and FAM50A protein expression was assessed by Western blot.Purified human recombinant FAM50A protein was used to immunize New Zealand rabbits for the preparation of a polyclonal antibody.The specificity of the prepared antibody was then validated using the successfully established FAM50A knockout cell line. Results: A monoclonal cell line with a successful knockout of the FAM50A gene was identified.Sanger sequencing confirmed base deletions at the target site.Western blot analysis showed a complete absence of FAM50A protein expression in this cell line.The prepared polyclonal antibody successfully recognized endogenous murine FAM50A protein in wild-type Beta-TC-6 cells and in hTERT-RPE1 cells overexpressing human FAM50A-GFP fusion protein,while no signal was detected in the FAM50A knockout cells. Conclusion This study successfully established a FAM50A gene knockout Beta-TC-6 cell model and generated a FAM50A polyclonal antibody,providing powerful tools for future research.

Objective:To explore the histopathological factors affecting the stiffness of papillary thyroid carcinoma (PTC).Methods:Ninety-six patients with PTC confirmed by surgery and pathology in Shanxi Bethune Hospital from January 2019 to December 2020 were selected, including 101 nodules. Two-dimensional ultrasound and shear-wave elastography (SWE) were performed before surgery and the average Young's modulus (Emean) of PTC nodules were measured. Histopathological examinations on the nodules were conducted after surgery to decide the lesion size, number of lesions, calcification type, presence or absence of capsular and extracapsular invasion, degree of fibrosis, microvessel density, and number of tumor cells. The correlations between the lesion size, degree of fibrosis, microvessel density, and number of tumor cells and the Emean were analyzed. The Emeans of nodules with different numbers of lesions, presence or absence of capsular and extracapsular invasion, and different pathological calcification types were compared. The multiple linear regression analysis was used to evaluate the histopathological factors influencing the Emean.Results:The ranges of the lesion sizes, degrees of fibrosis, microvascular density, numbers of tumor cells, and the Emeans of the 101 investigated PTC nodules were (1.29±0.95) cm, (30.64±18.37)%, (101.64±30.7) vessels per high power field, (373.52±149.87) cells per high power field, and (36.47±19.62) kPa, respectively. Correlation analysis showed that the lesion size of PTC and the degree of fibrosis were positively correlated with the Emean ( r=0.660, P＜0.001; r=0.789, P＜0.001), while the microvessel density was negatively correlated with the Emean ( r=-0.198, P=0.047). The Emean of the group with capsular and extracapsular invasion was higher than that of the group without ( P=0.014). There were statistical differences in the Emeans among different types of pathological calcification ( P＜0.001). The multiple linear regression analysis showed that the lesion size ( β=0.325, P＜0.001), degree of fibrosis ( β=0.563, P＜0.001), psammoma bodies ( β=0.177, P=0.001), stromal calcification ( β=0.164, P=0.003), and mixed calcification of both psammoma bodies and stroma ( β=0.163, P=0.003) were independent influencing factors for the Emean. The degree of fibrosis had the greatest impact on the Emean. Conclusions:The Emean of PTC lesions was correlated with the histopathological characteristics of PTC. The lesion size, degree of fibrosis, and calcification had significant impact on the Emean, among which the degree of fibrosis had the greatest impact.

Abstract In recent years, the prevention and treatment of eye diseases in children has become one of the worldwide recognized public health issues. Both genetic and environmental factors can influence the development of offspring visual systems, leading to abnormal vision acuity such as refractive errors, strabismus, and nystagmus. With the aim of elucidating the influencing factors and mechanisms of early life adverse exposures on offspring vision outcomes, the article summarizes the research on exposure in early life and visual acuity in offspring from different perspectives, including tobacco exposure during pregnancy, exposure to microelements, gestational diabetes, gestational hypertension, and drug abuse during pregnancy, so as to provide scientific evidence for the development of more effective strategies to prevent and control eye diseases in children and adolescents.

Objective : To detect the risk factors for bleeding in patients with cirrhosis and esophageal and gastric varices (EGV) and better understand the potentially life-threatening complications． Methods : Retrospectively， and a total of 309 patients with cirrhosis and EGV were enrolled in this study and were divided into the observation group and control based on EGV bleeding or not．Meanwhile，the patients＇epidemiological，clinical，laboratory， and radiological characteristics were collected and analyzed to construct a prediction model．The bootstrap method could be used to validate predictive models and the ROC curves to evaluate its forecasting ability. Results : High- density lipoprotein (HDL) (P＜0. 001，OR = 0. 131，95% CI = 0. 049－0. 350) ，C-reactive protein ( CRP) (P = 0. 010，OR = 2. 657，95% CI = 1. 269－5. 563) ，the width of portal vein (PVW) (P = 0. 050，OR = 1. 156，95% CI = 1. 000 －1. 336) ，the thickness of spleen (P = 0. 035，OR = 1. 492，95% CI = 1. 028 －2. 165) ，Child-Pugh grade B (P = 0. 003 ，OR = 11. 320，95% CI = 2. 232 －57. 407 ) and Child-Pugh grade C ( P = 0. 002 ，OR = 3. 888，95% CI = 1. 659－9. 114) were significantly associated with the occurrence of EGV bleeding．The AUC of the predictive risk model in the modeling group was 0. 802，and the validation group was 0. 836． Conclusion The lower HDL and higher CRP，PVW，the thickness of the spleen，Child-Pugh grade B and C are the risk factors for the occurrence of EGV bleeding.

Objective: To explore the effects of high-altitude hypoxia on thyroid hormone(TH) synthesis by quasi-targeted metabolomics technology. Methods: Twenty SPF male SD rats were randomly divided into Control group and Hypoxia group. An acute hypoxia injury model was established in SD rats by simulating hypoxia stress in a hypobaric oxygen chamber at an altitude of 6 km for 48 hours. The body weight, arterial oxygen partial pressure(PaO2) and blood oxygen saturation(SaO2) were detected. KEGG enrichment analysis was performed after the metabolites in the blood of two groups were detected by quasi-targeted metabolomics technology. The expression levels of sodium iodide symporter(NIS), thyroid peroxidase(TPO) and thyroglobulin(TG) were detected by RT-PCR and Western blot in TH synthesis pathway. The content of serum thyroxine(T4) and the expression levels of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) were detected by ELISA. The expression levels of toll-like receptors-4(TLR-4), interleukin-6(IL-6), nuclear factor-κB/p65(NF-κB/p65) and tumor necrosis factor-α(TNF-α) were detected by RT-PCR, Western blot and ELISA. The expression levels of Pro apoptotic protein Bcl-2 associated X protein(Bax) and inhibitor of apoptosis protein B-cell lymphoma/leukemia-2(Bcl-2) were detected by RT-PCR and Western blot in rats thyroid tissue. Results: Compared with the Control group, the body weight, PaO2and SaO2of rats in the Hypoxia group significantly decreased(P<0.01). The differential metabolites in arterial serum of hypoxia group rats were significantly enriched in the TH synthesis pathway, and the content of the pathway end product T4decreased significantly(P<0.01). In addition, the mRNA and protein expression levels of NIS, TPO, TG in rats thyroid tissue significantly decreased(P<0.05). The ELISA validation results showed that the changes of T4content were completely consistent with the above results. Compared with the Control group, the enzyme activities of SOD and GSH-Px in the serum of rats in the hypoxia group decreased, while the content of MDA increased(P<0.01); the mRNA, protein expression levels and contents of TLR-4, IL-6, NF-κ B/p65, TNF-α significantly increased(P<0.05), while the mRNA and protein expression levels of Bax in thyroid tissue significantly increased, Bcl-2 significantly decreased(P<0.05). Conclusion Hypoxia stress at high altitude leads to apoptosis of thyroid follicular epithelial cells by promoting oxidative stress and inflammatory response, which effects thyroid function and ultimately reduces thyroid hormone synthesis.