Objectives:To explore the feasibility of zero-ray radiofrequency catheter ablation for paroxymal atrial fibrillation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.Methods:This is a single-center prospective observational study.A total of 12 patients with paroxysmal atrial fibrillation who underwent radiofrequency catheter ablation in Fuwai Hospital,Chinese Academy of Medical Sciences from June 1,2024 to September 30,2024 were included.All patients underwent successful percutaneous puncture,atrial septal puncture under the guidance of transthoracic echocardiography,and all patients underwent left atrial modeling and discharge ablation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.The disappearance of pulmonary vein potential was confirmed after the ablation operation and as the ablation endpoint and successful ablation marker.The operation results and 1-month and 3-month follow-up results of the patients were observed.Results:There were 12 patients with paroxysmal atrial fibrillation,9 males and 3 females,aged(56.8±11.2)years,with a history of paroxysmal atrial fibrillation(4.2±2.3)years.The mean left atrial diameter was(36.5±2.5)mm,the left ventricular end-diastolic diameter was(47.8±4.1)mm,and the left ventricular ejection fraction was 55%-65%.The mean overall operation time was(102.25±14.51)min,the ultrasound operation time was(29.58±6.23)min,and the catheter operation time was(33.08±4.10)min.All patients completed circumferential pulmonary vein isolation without intraoperative complications.The hospitalization time was 2-6 days.At the 1-month follow-up after ablation,all patients showed sinus rhythm on 24-hour ambulatory electrocardiogram,and 2 patients had occasional atrial premature contractions without recurrence of atrial fibrillation.At the 3-month follow-up,two patients had occasional premature atrial contractions,and no recurrence of atrial fibrillation was recorded on the electrocardiogram of all patients.Conclusions:It is feasible to complete radiofrequency catheter ablation of paroxysmal atrial fibrillation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

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*

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objectives:To understand the awareness of HIV pre-exposure prophylaxis and post-exposure prophylaxis (PrEP/PEP) and related factors among female sex workers (FSWs) in Zhejiang Province to provide a reference for promoting PrEP/PEP.Methods:From April to July 2023, a questionnaire survey was conducted at the surveillance posts of prostitutes in 17 counties (cities and districts) in Zhejiang Province. The sample size of each post was at least 400 FSWs, and the information on social demography, sexual behavior, AIDS knowledge, prevention services, and detection were collected.Results:A total of 6 899 FSWs were surveyed. Most of them were ≥30 years old (57.7%), had secondary school education or below (61.8%), and had worked locally for ≥12 months (52.6%). The prevalence of HIV PrEP and PEP awareness among FSWs was 52.0% (3 589/6 899) and 58.6% (4 045/6 899), respectively. Multivariate logistic regression analysis showed that the negative related factors of awareness of PrEP/PEP among FSWs included age ≥30 years, local working time <6 months, and condom use during commercial sex in the last 1 month. The positive related factors of awareness of PrEP/PEP among FSWs included marital status was married or cohabiting, aware of HIV/AIDS knowledge, working in medium or high-end venues, finding clients primarily online in the past 6 months, receiving HIV prevention services in the past year, and having self-tested for HIV in the past year.Conclusions:The overall awareness of PrEP/PEP was relatively low among FSWs in Zhejiang Province. Efforts should be made to strengthen the publicity and education of PrEP/PEP, especially for those who are older and more mobile and working in low-end venues, combined with HIV prevention services to increase the use of PrEP/PEP.

Objective To investigate the clinical prognosis of untreated residual coronary artery dissection treated with drug coated balloon(DCB).Methods A retrospective analysis was conducted on the clinical and imaging data of patients with primary coronary artery lesions(2.5-4.0 mm)treated with DCB under angiography guidance at Xuzhou Cancer Hospital,Xuzhou New Health Geriatric Hospital,and Peixian Guotai Hospital from September 2017 to April 2023.According to the observation of coronary artery dissection through angiography,the patients were divided into a dissection group and a non dissection group.The main endpoint of this study was the major adverse cardiovascular event(MACE)during a 12-month follow-up.Results A total of 381 patients were enrolled in the three research centers,with 30 cases(30 lesions)in the dissection group and 351 cases(367 lesions)in the non dissection group.There was no significant difference between the two groups in terms of age,gender,hypertension,hyperlipidemia,diabetes,smoking,previous myocardial infarction,previous percutaneous coronary intervention,coronary artery bypass grafting and other baseline clinical characteristics(all P＞0.05).Except for the reference vessel diameter(P=0.049)and DCB pressure(P=0.032),there was no statistically significant difference in the characteristics of coronary angiography lesions between the two groups of patients(both P＞0.05).During a 12-month follow-up,there was no statistically significant difference(P＞0.05)in the incidence of MACE between the dissection group and the non dissection group after DCB treatment for primary coronary artery lesions in situ.Conclusions Untreated residual dissection after DCB treatment of de novo coronary lesions does not lead to an increase in clinical MACE.

Objective To explore the factors associated with complete resolution of sentinel lymph node metastasis(pCR)after neoadjuvant chemotherapy in breast cancer and to establish a predictive model.Methods The medical records of 136 female patients with breast cancer who received neoadjuvant chemotherapy in the First Hospital of Lanzhou University from January 2022 to February 2024 were retrospectively analyzed.According to the 80/20 rule,the patients were randomly divided into a training set(108 cases)and a validation set(28 cases).Based on the pathological examination results of axillary lymph node dissection(ALND)after neoadjuvant chemotherapy in breast cancer patients,they were classified into the sentinel lymph node pCR group and non-pCR group.Multivariate logistic regression analysis was used to screen the independent risk factors of sentinel lymph nodes failing to reach pCR.Build a nomogram prediction model based on the screened risk factors.By drawing the receiver operating characteristic(ROC)curve calculation curve,the area under ROC curve,sensitivity and specificity are used to evaluate the discrimination of the model.Results Among the 108 breast cancer patients,46 cases achieved pCR in the sentinel lymph nodes,accounting for 42.59％(46 cases/108 cases).In addition,33 cases(30.56％)achieved pCR in the primary tumor lesion.The non-pCR group showed a higher proportion of stage Ⅲ clinical staging,lymph node short-axis reduction of less than 50％before and after treatment,tumor maximum diameter reduction of less than 50％before and after treatment,lymph node type Ⅲ classification,and blood flow grade Ⅲ compared to the pCR group(P＜0.05).Multivariate logistic regression analysis showed that Clinical staging(OR=3.593,95％CI:1.276-10.121),lymph node short-axis reduction of less than 50％before and after treatment(OR=4.272,95％CI:1.517-12.032),tumor maximum diameter reduction of less than 50％before and after treatment(OR=3.710,95％CI:1.317-10.449),lymph node type(OR=3.827,95％CI:1.359-10.779),and blood flow grade(OR=4.764,95％CI:1.691-13.418)were identified as risk factors for not achieving pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients(P＜0.05).The sensitivity of the risk model for predicting non-achievement of pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in the training set of breast cancer patients was 0.826(95％CI:0.705-0.943),with a specificity of 0.826(95％CI:0.712-0.919)and an area under the ROC curve of 0.847(95％CI:0.738-0.952).In the validation set,the sensitivity for predicting non-achievement of pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients was 0.731(95％CI:0.608-0.904),with a specificity of 0.827(95％CI:0.713-0.941)and an area under the ROC curve of 0.834(95％CI:0.729-0.951).Conclusion Clinical staging,changes in lymph node short-axis before and after treatment,changes in tumor maximum diameter before and after treatment,lymph node type,and blood flow grade are associated with pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients.Constructing a predictive model can help evaluate the pCR status of sentinel lymph nodes after neoadjuvant chemotherapy.

Objective To investigate the clinical prognosis of untreated residual coronary artery dissection treated with drug coated balloon(DCB).Methods A retrospective analysis was conducted on the clinical and imaging data of patients with primary coronary artery lesions(2.5-4.0 mm)treated with DCB under angiography guidance at Xuzhou Cancer Hospital,Xuzhou New Health Geriatric Hospital,and Peixian Guotai Hospital from September 2017 to April 2023.According to the observation of coronary artery dissection through angiography,the patients were divided into a dissection group and a non dissection group.The main endpoint of this study was the major adverse cardiovascular event(MACE)during a 12-month follow-up.Results A total of 381 patients were enrolled in the three research centers,with 30 cases(30 lesions)in the dissection group and 351 cases(367 lesions)in the non dissection group.There was no significant difference between the two groups in terms of age,gender,hypertension,hyperlipidemia,diabetes,smoking,previous myocardial infarction,previous percutaneous coronary intervention,coronary artery bypass grafting and other baseline clinical characteristics(all P＞0.05).Except for the reference vessel diameter(P=0.049)and DCB pressure(P=0.032),there was no statistically significant difference in the characteristics of coronary angiography lesions between the two groups of patients(both P＞0.05).During a 12-month follow-up,there was no statistically significant difference(P＞0.05)in the incidence of MACE between the dissection group and the non dissection group after DCB treatment for primary coronary artery lesions in situ.Conclusions Untreated residual dissection after DCB treatment of de novo coronary lesions does not lead to an increase in clinical MACE.