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*

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective To investigate the serum tumor necrosis factor like weak inducer of apoptosis(TWE AK),sterol regulatory element-binding protein 1(SREBP-1)levels in patients with prostate cancer(PC)and their relationship with clinical pathological characteristics and progression free survival prognosis.Method A total of 94 PC patients who underwent PC radical surgery in Wuhan Dongxihu District People's Hospital from January 2018 to January 2020 were selected as the PC group.Meanwhile,50 patients with benign prostatic hyperplasia(BPH)during the same period were selected as the BPH group,and 50 healthy individuals who underwent physical examination during the same period were selected as the control group.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of serum TWEAK and SREBP-1.Kaplan-Meier survival analysis was used to analyze the effects of serum TWEAK and SREBP-1 on the progression free survival in prostate cancer patients.Multivariate COX regression analysis was used to analyze factors affecting the prognosis of progression free survival in prostate cancer patients.Results The serum TWEAK(77.14±15.46 ng/L)and SREBP-1(334.14±33.81 ng/L)levels in the PC group were higher than those in the BPH group(38.69±10.58 ng/L,201.69±28.74 ng/L)and control group(36.26±10.27 ng/L,189.51±27.65 ng/L),with significant differences(t=23.752,25.249;34.636,37.821,all P＜0.05).There was a positive correlation between serum TWEAK and SREBP-1 expression in PC patients(r=0.668,P=0.001).The serum TWEAK and SREBP-1 levels in PC patients with Gleason score＞7,TNM stage Ⅲ,and preoperative prostate specific antigen(PSA)level ≥ 20 ng/ml were higher than those with Gleason score≤7,TNM stage Ⅰ～Ⅱ,and preoperative PSA level＜20ng/ml,with significance differences(t=8.465～16.597,all P＜0.05).The 3-year overall progression free survival rates of the TWEAK high expression and low expression groups were 60.42％(29/48)and 86.96％(40/46),respectively.The 3-year overall progression free survival rates of the SREBP-1 high expression and low expression groups were 57.78％(26/45)and 87.76％(43/49),respectively.The 3-year cumulative progression free survival rates of the TWEAK high expression group and the SREBP-1 high expression group were lower than those of the TWEAK low expression group and the SREBP-1 low expression group,and the differences were significant(Log rankx2=8.125,9.547,P=0.004,0.002).TNM stage Ⅲ(OR=1.448,P＜0.001),Gleason score＞7(OR=1.401,P＜0.001),preoperative PSA ≥ 20 ng/ml(OR=1.353,P＜0.001),serum TWEAK(OR=1.338,P＜0.001),and SREBP-1(OR=1.293,P＜0.001)were independent risk factors affecting the progression free survival prognosis of PC patients.Conclusion Serum TWEAK and SREBP-1 in prostate cancer patients were increased,and they were correlated with the clinical pathological characteristics of PC.They could be serum biomarkers for evaluating the prognosis of progression free survival.

Objective To investigate the relationships of preoperative serum V-set and immunoglobulin domain 4 (VSIG4) and long chain non-coding ribonucleic acid (LncRNA) SBF2 antisense RNA1 (SBF2-AS1) with acute kidneyinjury (AKI) after percutaneous nephrolithotomy in patients with renal calculus. Methods A total of 109 patients with renal calculus in the hospital from January 2020 to December 2022 were selected as research objects. Serum VSIG4 level and LncRNA SBF2-AS1 expression were detected in all the patients before operation, and incidence of AKI was recorded after operation. Multiple Logistic regression model was used to analyze the factors affecting AKI after percutaneous nephrolithotomy in patients with renal calculus; the receiver operating characteristic (ROC) curve was used to analyze the values of VSIG4 and LncRNA SBF2-AS1 in predicting AKI after percutaneous nephrolithotomy in patients with renal calculus. Results In this study, 16 cases had AKI after operation. The serum VSIG4 level in the AKI group was significantly lower than that in the non-AKI group, while the LncRNA SBF2-AS1 expression was significantly higher than that in the non-AKI group (P < 0.05). Multivariate Logistic regression analysis showed that preoperative high level of uric acid, preoperative high expression of LncRNA SBF2-AS1, the longer operation time and intraoperative hypotension were the risk factors for AKI after percutaneous nephrolithotomy in patients with renal calculus (P < 0.05), while preoperative high level of VSIG4 was the protective factor (P < 0.05). The values of area under the curve of preoperative serum VSIG4 and LncRNA SBF2-AS1 in predicting AKI after percutaneous nephrolithotomy in patients with renal calculus were 0.854 and 0.705 respectively, and the area under the curve of combined prediction of the two indexes was 0.948, which was significantly higher than that of single index prediction (Z=1.995, 2.958, P < 0.05). Conclusion Decreased preoperative serum VSIG4 level and increased expression of LncRNA SBF2-AS1 in patients with renal calculus are associated with the occurrence of AKI after percutaneous nephrolithotomy, and the combined detection of preoperative VSIG4 and LncRNA SBF2-AS1 can predict the risk of AKI after operation.

Objective:To analyze the relationship between the expression of dynamin 1 (DNM1) gene and clinical pathological parameters and prognosis of colorectal cancer (CRC) patients, and explore the association between DNM1 and autophagy mechanisms.Methods:The tumor genome atlas (TCGA) database was used to analyze the mRNA levels of DNM1 in normal intestinal mucosa and cancer tissues of CRC patients, as well as in early [tumor node metastasis (TNM) stage Ⅰ and Ⅱ] and late (TNM stage Ⅲ and Ⅳ) cancer tissues. The Kaplan-Meier method was used to estimate survival time and analyze prognosis; Immunohistochemical staining was used to detect the expression of DNM1 protein in cancer tissues of 118 CRC patients, and the relationship between its expression characteristics, clinical pathological parameters, and prognosis was analyzed; The signal pathways related to DNM1 and autophagy in cancer tissues of (GSEA) CRC patients were analyzed using gene set enrichment; Confocal microscopy was used to detect and analyze the Pearson correlation coefficient (PCC) of DNM1 [along with five other autophagy related proteins Autophagy-related protein 9B (ATG9B), Unc-51 like autophagy activating kinase 1 (ULK1), Beclin1, sequestosome-1 (P62/SQSTM1), Autophagy related 16 like protein1 (ATG16L1)] and the immunofluorescence double staining of microtubule associated protein 1 light chain 3 (LC3).Resultsl:The expression of DNM1 was increased in CRC tumor tissue, and significantly increased in the late stage of the tumor ( P<005); Kaplan-Meier survival analysis showed that the expression level of DNM1 was negatively correlated with tumor prognosis [ HR=1.71, 95% CI (1.21, 2.40), P<0.01]. The positive intensity of DNM1 was related to the depth of tumor infiltration, lymph node metastasis, cancer nodules, distant metastasis, nerve and vascular invasion, degree of differentiation, histological classification, and special histological classification (all P<0.01). The ordered logistic regression model verified that tumor differentiation and the degree of DNM1 positivity were risk factors for poor prognosis in CRC patients, and a strong positive DNM1 was positively correlated with adenocarcinoma recurrence ( P<0.05). The high expression of DNM1 involved negative regulation of key signaling pathways in negative autophagy, such as rapamycin target protein complex 1 (mTORC1), phosphatidylinositol 3 kinase/protein kinase B/rapamycin target protein (PI3K/AKT/mTOR) ( P<0.05, FDR<0.001). Among the six sets of immunofluorescence double staining, the correlation between the expression patterns of DNM1 and LC3B genes was the highest. Conclusions:High expression of DNM1 is a poor prognostic factor for CRC patients, which may be related to tumor progression through positive regulation of autophagy.

Objective:To explore the relationship between fragmented QRS complex and heart rate variability (HRV) and ventricular arrhythmia in patients with old myocardial infarction.Methods:From August 2018 to October 2019, 200 patients with old myocardial infarction were first treated in the Department of cardiac function examination of the First Affiliated Hospital of Hebei North University. The patients were divided into 99 cases of old myocardial infarction with fragmented QRS wave group and 101 cases of old myocardial infarction without fragmented QRS wave group according to the case bank data and conventional 12 lead ECG diagnosis in our hospital for the first time. Then, the 24-h ambulatory ECG reexamined within 1 year after discharge was retrospectively analyzed. The incidence of ventricular arrhythmia was compared between the two groups by χ 2 test. The difference of heart rate variability between the two groups was compared by rank sum test. Multiple logistic regression was used to analyze the value of different indexes of heart rate variability in the evaluation of fragmented QRS complex in old myocardial infarction. Drawing the receiver operating characteristic (ROC), and the area under the curve (AUC) was used to analyze the diagnostic accuracy of different indexes of heart rate variability in the broken QRS complex of old myocardial infarction. Results:According to the Lown classification of ventricular premature contraction, the number of positive ventricular arrhythmias in patients with Grade Ⅰ of ventricular premature contraction and Grade Ⅲ-Ⅴ of ventricular premature contraction in the old myocardial infarction fragmented QRS group was higher than that in the old myocardial infarction non fragmented QRS group (Grade Ⅰ of ventricular premature contraction: 54.5% (54/99)and 39.6%(40/101); χ 2=4.484, P<0.05;Grade Ⅲ-Ⅴ of ventricular premature contraction: 34.3% (34/99) and 9.9%(10/101); χ 2=17.406, P<0.05)). Ventricular premature contraction Grade 0 old myocardial infarction fragmented QRS group was lower than old myocardial infarction non fragmented QRS group (8.1% (8/99) and 48.5% (49/101); χ 2=37.995, P<0.05). The total number of positive cases of ventricular arrhythmia in the old myocardial infarction group with fragmented QRS wave was higher than that in the old myocardial infarction group without fragmented QRS wave (91.9% (91/99) and 51.5%(52/101); χ 2=57.146, P<0.05)). There was no significant difference in the number of positive ventricular arrhythmias between the old myocardial infarction fragmentation QRS group and the old myocardial infarction non fragmentation QRS group ( P>0.05). The standard deviation of NN intervals (SDNN) and the standard deviation of average NN intervals (SDANN) of HRV time domain indexes in the old myocardial infarction fragmented QRS group were higher than those in the old myocardial infarction non fragmented QRS Group (SDNN:143.00(122.00,166.00) vs. 110.00(95.00,130.50), Z=5.780, P<0.05; SDANN:112.00(100.00,136.00) vs. 96.00(76.00,118.50), Z=4.013, P<0.05). Multiple Logistics regression analysis results of HRV domain shows that HRV time domain SDNN and SDANN have diagnositic value in diagnosis fQRS after OMI(SDNN: OR=0.949, 95% CI:0.922-0.977, P<0.001; SDANN: OR=1.036, 95% CI:1.005-1.068, P=0.022). Area under ROC curve of HRV time domain SDNN and SDANN have particular diagnositic accuracy in diagnosis fQRS after OMI(SDNN: AUC 0.737, 95% CI 0.666-0.807, Sensitivity 0.818, Specificity 0.634; SDANN: AUC 0.664, 95% CI 0.587-0.741, Sensitivity 0.737, Specificity 0.673. 0.5

Objective:To explore the value of quantitative susceptibility mapping (QSM) in evaluating renal injury in patients with early diabetic nephropathy (DN).Methods:From October 2019 to December 2020, 32 patients with early DN were prospectively enrolled in the Third Affiliated Hospital of Soochow University. According to the estimated glomerular filtration rate (eGFR), they were divided into three groups: DN1 (eGFR≥90 ml·min -1·1.73 m -2, 11 cases), DN2 (60-<90 ml·min -1·1.73 m -2, 11 cases) and DN3 (30-<60 ml·min -1·1.73 m -2, 10 cases). At the same time, 32 normal volunteers were recruited as the control group. Both kidneys were scanned by QSM to measure the susceptibility of renal cortex and medulla. Paired samples t-test was used to compare the differences of the susceptibility between left and right kidneys and between cortex and medulla. One-way analysis of variance was performed to compare the differences of corresponding susceptibility values among different groups, and LSD- t was used for the pairwise comparison. Pearson correlation test was performed between the susceptibility value of the medulla and eGFR. The ROC curve was used to analyze the diagnostic efficacy of QSM parameters in the diagnosis of DN and different degrees of severity of DN. Results:The susceptibility values of bilateral renal medulla in normal volunteers and patients with DN were lower than those of renal cortex (all P<0.001). There was no significant difference in the susceptibility value between left and right renal cortex (all P>0.05). There was significant difference in the susceptibility value between left and right medulla (all P<0.05). There was no significant difference in the susceptibility value of bilateral renal cortex among the control group and the DN1－DN3 groups (both P>0.05). The susceptibility values of left renal medulla in control group, DN1, DN2 and DN3 groups were (-4.46±1.16)×10 -2, (-5.96±0.97)×10 -2, (-7.97±1.25)×10 -2, (-9.58±1.45)×10 -2 ppm, of right renal medulla were (-3.70±0.65)×10 -2, (-5.06±1.28)×10 -2, (-7.33±1.46)×10 -2, (-9.09±2.22)×10 -2 ppm, respectively. The overall difference of the susceptibility value of bilateral renal medulla was statistically significant (both P<0.05), and there were significant differences between each two groups (all P<0.05). The linear positive correlation were found between the susceptibility values of renal medulla and the corresponding eGFR (left kidney r=0.732, P<0.001; right kidney r=0.684, P<0.001). The areas under the ROC curve (AUC) of left and right renal medulla susceptibility value in diagnosis of normal and DN were 0.931 and 0.943, of DN1 and DN (2 and 3) were 0.952 and 0.883, of DN (1 and 2) and DN3 were 0.888 and 0.831, respectively. Conclusion:The susceptibility value of QSM quantitative parameter has a certain value in the staging and differential diagnosis of early DN, among which the susceptibility value of renal medulla has higher diagnostic efficiency.

Objective: To investigate the feasibility of echocardiography-guided closed-chest repeated intraventricular blood sampling in mice, and to clarify the maximum blood volume that can be collected by this method, and whether the method can be used for long-term repeated blood collection in mice. Methods: Twenty-four male C57BL/6J mice (10-14 weeks old) were divided into the terminal experiment group (n=4, for investigating the maximum blood amount that could be sampled at one time), the repeated 0.5 ml blood collection group (n=10, sampling 0.5 ml whole blood each time, once every two days for consecutive 4 weeks), and the repeated 0.75 ml blood collection group (n=10, sampling 0.75 ml whole blood each time, once every two days for consecutive 4 weeks). High-frequency echocardiography was used to display the largest section of the left ventricle, guiding the insulin syringe needle through the thorax into the left ventricle for blood collection. In the repeated 0.5 ml blood collection group, echocardiography was used to detect the cardiac structure and function before blood collection, three minutes after blood collection, and one week after the last (the 14th) blood collection. Results: We successfully performed echocardiography-guided closed-chest intraventricular blood sampling, with an average operating time (88±19)s per mouse, and a maximum blood volume (1.43±0.11)ml per mouse. In the repeated 0.5 ml blood collection group, heart rate, left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic dimension and left ventricular posterior wall end-diastolic thickness remained uncganged before the first blood collection and after 4 weeks of repeated blood collection (all P>0.05). No death in the repeated 0.5 ml blood collection group. However, in the 0.75 ml blood collection group, two mice died before the end point. Conclusions The echocardiography-guided closed-chest intraventricular blood sampling is a safe, minimally invasive, convenient and efficient method, and can be used repeatedly for long-term blood collection in mice.

Objective: To evaluate heterogeneity and clonal evolution in pediatric ETV6-RUNX1⁺ acute lymphoblastic leukemia (ALL) in China. Methods: Totally 48 children (<14 years) with newly diagnosed ETV6-RUNX1⁺ ALL in Institute of Hematology and Blood Disease Hospital, CAMS and PUMC, from February 2006 to June 2011 were included. The copy number variations were analyzed by quantitative multigene fluorescence in situ hybridization (QM-FISH) in 48 patients. Non-normal distribution of measurement data were shown with Median (range) , count data were shown with percent (%) . Overall survival and event-free survival were estimated by the Kaplan-Meier method and compared with the log-rank test. Results: Forty-eight patients were tested by QM-FISH. Of 48 patients, 70.8% harbored one clone, 18.8% two subclones, and 10.4% three or more subclones. The clone heterogeneity was detected by two different models: the linear succession model and the branching evolution model. ETV6-RUNX1⁺ ALL relapse evolved from an ancestral clone or a new clone. The patients relapsed from a new clone got the worse outcome. Conclusion The clone evolution was detected in pediatric ETV6-RUNX1⁺ ALL in China. QM-FISH might be helpful to evaluate the outcome of relapsed patients. A new clone was associated with a poorer outcome.

AIM:We investigated how AT 1-R stimulated by mechanical stresses induces cardiac fibrosis .METHODS:We produced in vivo cardiac pressure overload model in angiotensinogen knockout ( ATG-/-) mice and in vitro mechanically-stretched cell model in cultured neonatal cardiac cells of ATG-/-mice both lack the participation of Ang II .RESULTS: Pressure overload for 4 weeks in ATG-/-mice induced myocardial hypertrophy accompanied by the significant interstitial fibrosis , however , the TGF-β, a key regulatory factor of fibrosis, was not significantly increased in these ATG-/-mice.Meanwhile, the inhibitor for AT1-R significantly inhibited mechani-cal stress-induced cardiac fibrosis in these ATG-/-models whereas inhibition of TGF-βdid not.CONCLUSION:The results showed that mechanical stress-induced fibrotic responses through AT 1-R required the phosphorylation of Smad 2 but not the involvement of TGF-β.