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.

Objective:To analyze the HIV antibody positivity of new type drug users in drug abuse monitoring sites in Zhejiang Province from 2017 to 2023 and its influencing factors.Methods:From 2017 to 2023, a continuous cross-sectional survey was carried out in HIV monitoring posts among new type drug users in Zhejiang Province,the sample size was 400 people per site of 9 drug abuse surveillance sites in 7 cities. Questionnaires were conducted to investigate their social demographic information, related behavioral information, AIDS awareness, and acceptance of intervention measures, and blood was collected for HIV and syphilis antibody detection, with new type drugs users in the monitoring population as the research object. SPSS 22.0 software was used for statistical analysis.Results:A total of 13 955 new drug users were surveyed, and the number of new drug users was 2 518, 2 292, 2 526, 2 119, 2 161, 1 064 and 1 275 from 2017 to 2023, respectively, the HIV antibody positive rate of new type drugs users was 0.44%, 1.09%, 2.06%, 1.09%, 1.39%, 1.50%, 2.90%, respectively, and the HIV antibody positive standardized rate showed an increasing trend (all P<0.001). The results of multivariate logistic regression analysis showed that marital status: unmarried/divorced/widowed (a OR=3.92, 95% CI: 2.46-6.25), provincial household registration (a OR=3.54, 95% CI: 2.34-5.35), high school education or above (a OR=5.42, 95% CI: 3.68-7.98), sexual activity within the last 1 year after drug use (a OR=1.84, 95% CI: 1.19-2.84), and knowledge that the use of new drugs increases the risk of HIV infection (a OR=2.27, 95% CI: 1.17-4.39) were associated with increased HIV antibody favorable rates among new type drugs users. Conclusions:During 2017-2023, the HIV antibody-positive rate of new type drug users in Zhejiang Province showed an upward trend. It is necessary to strengthen the monitoring and intervention of this population.

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.

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.

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.

Left ventricular assist device (LVAD) serves as a critical therapeutic option for patients with end-stage heart failure, significantly enhancing survival rates and quality of life. However, LVAD implantation exerts complex and profound effects on right ventricular (RV) function, with RV dysfunction emerging as a key factor influencing the prognosis of LVAD patients. This article systematically reviews the relationship between LVAD and RV function, exploring the importance of RV function in LVAD patients, assessment methods, underlying mechanisms of impact, and strategies for prevention and management. Comprehensive evidence suggests that preoperative evaluation of RV function is crucial for predicting the risk of RV dysfunction, while effective prevention and management rely on preoperative optimization, meticulous intraoperative techniques, rigorous postoperative monitoring, and multidisciplinary collaboration. Furthermore, this review discusses the potential and future directions of emerging technologies, such as improved LVAD designs, biventricular assist devices, gene therapy, and personalized medicine, in ameliorating RV dysfunction. In conclusion, RV function is one of the key determinants of successful LVAD therapy. Through comprehensive assessment, prevention, and management of RV function, coupled with the application of novel technologies, the clinical outcomes of LVAD patients can be further improved.

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