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*

AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

This study utilized the CCK-8 assay to examine the effects of various concentrations of CoCl2(0,50,100,200,300,400 μmol/L)and different treatment durations(0,6,12,24,48 h)on the viability of adipocytes,in order to determine the most suitable treatment conditions.Western blot analysis was employed to investigate the impact of different concentrations of CoCl2(0,50,100,200,400 μmol/L)on the expression of hypoxia and its downstream key proteins in adipocytes.The results indicated that higher concentrations of CoCl2 led to lower adipocyte viability,with sig-nificant decreases in cell viability observed in the 300,400 μmol/L treatment groups(P＜0.01),while the 200 μmol/L group exhibited the highest cell viability.Compared to the control group,the 200 μmol/L CoCl2 treatment group showed a significant upregulation in the expression of hypoxia and its downstream signaling pathway key molecules:hypoxia-inducible factor 1-alpha(HIF-1α),glucose transporter type 4(GLUT4),vascular endothelial growth factor receptor 1(FLT-1),prolyl hydroxylase 2(PHD2),and vascular endothelial growth factor(VEGF)(P＜0.01).Addi-tionally,the 200 μmol/L CoCl2 treatment group exhibited higher levels of key lipolytic enzymes,including adipose triglyceride lipase(ATGL),perilipin 1(PLIN1),protein kinase A(PKA),and increased phosphorylation levels of hormone-sensitive lipase(HSL)in the 300 and 400 μmol/L groui ps(P＜0.01).CoCl2-mediated hypoxia in the 200 μmol/L treatment group also in-creased the protein expression of phosphatidylinositol 3-kinase(PI3K)and the phosphorylation level of protein kinase B(Akt).These findings suggest that adding 200 μmol/L CoCl2 can enhance the expression of hypoxia-related proteins,lipolytic enzymes,and insulin-related signaling proteins in primary bovine adipocytes.

Objective:To analyze the genes related to platelet activation in essential thrombocythemia (ET)based on transcriptome sequencing technology (RNA-seq ),and to explore the potential targets related to ET thrombosis. Methods:Blood samples from ET patients and healthy individuals were collected for RNA-seq,and differentially expressed lncRNAs,miRNAs,and mRNAs were selected to construct a lncRNA-miRNA-mRNA regulatory network. Differential mRNAs in the regulatory network were enriched and analyzed using Gene Ontology (GO ) and Kyoto Encyclopedia of Genes and Genomes (KEGG).The real-time PCR method was applied to validate differential mRNAs on crucial signaling pathways.Results:A total of 32 lncRNAs (3 up-regulated,29 down-regulated),16 miRNAs (8 up-regulated,8 down-regulated),and 35 mRNAs (27 up-regulated,8 down-regulated)were identified as differentially expressed.Among them,5 lncRNAs,12 miRNAs,and 19 mRNAs constituted the regulatory network.KEGG enrichment analysis showed that the differential mRNAs were related to the platelet activation signaling pathway,and there were 6 differential mRNAs related to platelet activation,namely F2R,ITGA2B,ITGB1,ITGB3,PTGS1,and GP1 BB,which were all up-regulated in their expression.RT-PCR results showed that the expression of five mRNAs including F2R,ITGA2B,ITGB1,ITGB3,and GP1BB were upregulated in ET patients compared with healthy subjects,and consistent with RNA-seq results,while PTGS1 expression was not significantly different.Conclusion:Differential mRNAs in ET patients are related to the platelet activation pathway,and F2R,ITGA2B,ITGB1,ITGB3,and GP1BB mRNAs may serve as novel targets associated with platelet activation in ET.

Objective:To summarize the clinical characteristics of patients with renal angiomyolipoma(RAML)combined with inferior vena cava(IVC)tumor thrombus,and to explore the feasibility of par-tial nephrectomy and thrombectomy in this series of patients.Methods:The clinical data of patients diagnosed with RAML combined with IVC tumor thrombus in the Department of Urology of the Peking University Third Hospital from April 2014 to March 2023 were retrospectively analyzed,and demographic and perioperative data of RAML patients with IVC tumor thrombus were recorded and collected from Elec-tronic Medical Record System,including age,gender,surgical methods,and follow-up time,etc.The clinical characteristics between classic angiomyolipoma(CAML)patients with IVC tumor thrombus and epithelioid angiomyolipoma(EAML)patients with IVC tumor thrombus were compared to determine the clinical characteristics of these patients.Results:A total of 11 patients were included in this study,in-cluding 7 patients with CAML with IVC tumor thrombus and 4 patients with EAML with IVC tumor thrombus.There were 9 females(9/11,81.8％)and 2 males(2/11,18.2％),with an average age of(44.0±17.1)years.9 patients(9/11,81.8％)experienced clinical symptoms,including local symp-toms including abdominal pain,hematuria,abdominal masses,and systemic symptoms including weight loss and fever;2 patients(2/11,18.2％)with RAML and IVC tumor thrombus did not show clinical symptoms,which were discovered by physical examination.Among the 11 patients,10 underwent radical nephrectomy with thrombectomy,of whom,3 underwent open surgery(3/10,30.0％),2 underwent laparoscopic surgery(2/10,20.0％),and 5 underwent robot-assisted laparoscopic surgery(5/10,50.0％).In addition,1 patient underwent open partial nephrectomy and thrombectomy.The patients with EAML combined with I VC tumor thrombus had a higher proportion of systemic clinical symptoms(100％vs.0％,P=0.003),more intraoperative bleeding[400(240,3 050)mL vs.50(50,300)mL,P=0.036],and a higher proportion of tumor necrosis(75％vs.0％,P=0.024)compared to the patients with CAML combined with I VC tumor thrombus.However,there was no statistically significant difference in operation time[(415.8±201.2)min vs.(226.0±87.3)min,P=0.053]between the two groups.Conclusion:Compared with the patients with CAML and IVC tumor thrombus,the patients with EAML and IVC tumor thrombus had a higher rate of systemic symptoms and tumor necrosis.In addi-tion,in the selected patients with CAML with IVC tumor thrombus,partial nephrectomy and tumor thrombectomy could be performed to better preserve renal function.

Objective To construct a culture system of endometrial organoids for infertility induced by non-immune or immune factors,and to compare the immune cytokines between them.Methods The samples were collected from infertility patients undergoing hysteroscopy in Department of Reproductive Medicine Center of The First Affiliated Hospital of Naval Medical University(Second Military Medical University).Endometrial tissues were obtained from patients with infertility caused by non-immune factors(n=3)and patients with repeated implantation failure(RIF)(n=5).The tissues were embedded in matrix glue for 3D culture after washing,digestion,re-suspension and plate attachment.The growth of endometrial organoids of the 2 groups was observed under inverted microscope;the expression of estrogen receptor,keratin and E-cadherin,which were specific endometrial markers,was detected by immunofluorescence staining;and the cytokines of the 2 groups were determined by enzyme-linked immunosorbent assay(ELISA)and the differences of cytokines between the 2 groups were observed.Results During the process of in vitro culture of endometrial organoids,the volume of organoids and the number of cells gradually increased.After 7-10 d of culture,the volume of organoids reached a stable state,and the shape gradually became a perfect circle.At the same time,the number of organoids from the infertility patients caused by non-immune factors was more than that from the infertility patients caused by RIF.Immunofluorescence staining showed the expression of endometrial related marker proteins estrogen receptor,keratin and E-cadherin,indicating the successful construction of endometrial organoids.ELISA results showed that the levels of interferon(IFN)-γ,interleukin(IL)-10,tumor necrosis factor(TNF)-α,IL-4 and TNF-α/IL-4 ratio between the 2 groups were significantly different(P＜0.05 or P＜0.01).There were no significant differences in the levels of TGF-β1 or IL-17,the ratios of IL-17/TGF-β1,IFN-γ/IL-10 or TNF-α/IL-10(all P＞0.05).Conclusion Endometrial organoids with proliferative ability from patients with non-immune infertility and RIF have been successfully cultured in vitro,which provides a new model for the basic research of immune infertility.

Objective To detect the expression changes of interleukin-10(IL-10)and transforming growth factor-β1(TGF-β1)during the development of deep vein thrombosis in mice,and to explore the application value of them in thrombus age estimation.Methods The mice in the experimental group were subjected to ligation of inferior vena cava.The mice were sacrificed by excessive anesthesia at 1 d,3 d,5 d,7 d,10 d,14 d and 21 d after ligation,respectively.The inferior vena cava segment with thrombosis was extracted below the ligation point.The mice in the control group were not ligated,and the inferior vena cava segment at the same position as the experimental group was extracted.The ex-pression changes of IL-10 and TGF-β1 were detected by immunohistochemistry(IHC),Western blot-ting and real-time qPCR.Results IHC results revealed that IL-10 was mainly expressed in monocytes in thrombosis and TGF-β1 was mainly expressed in monocytes and fibroblast-like cells in thrombosis.Western blotting and real-time qPCR showed that the relative expression levels of IL-10 and TGF-β1 in each experimental group were higher than those in the control group.The mRNA and protein levels of IL-10 reached the peak at 7 d and 10 d after ligation,respectively.The mRNA expression level at 7 d after ligation was 4.72±0.15 times that of the control group,and the protein expression level at 10 d after ligation was 7.15±0.28 times that of the control group.The mRNA and protein levels of TGF-β1 reached the peak at 10 d and 14 d after ligation,respectively.The mRNA expression level at 10 d after ligation was 2.58±0.14 times that of the control group,and the protein expression level at 14 d after ligation was 4.34±0.19 times that of the control group.Conclusion The expressions of IL-10 and TGF-β1 during the evolution of deep vein thrombosis present time-dependent sequential changes,and the expression levels of IL-10 and TGF-β1 can provide a reference basis for thrombus age estimation.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

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*