Objective To analyze the trends in the disease burden of tracheal, bronchus, and lung cancer (TBL) in China and in low-, middle-, and high-socio-demographic index (SDI) countries and regions from 1990 to 2021, with the aim of providing evidence for the formulation of targeted prevention and control strategies. Methods Utilizing data from the Global Burden of Disease (GBD) Study 2021, we extracted TBL-related data from 1990 to 2021, stratified by sex, age group, and year. We assessed the disease burden and trends of TBL across different groups, conducted a decomposition analysis to identify the leading contributors to the change in disease burden, and examined the relationship between disability-adjusted life years (DALYs) and SDI. Results In 2021, the overall burden of TBL in China was substantially higher than that in other groups. The fold-increase in the number of prevalent cases, deaths, and DALYs was significantly greater in China. Moreover, the growth rates of the age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) in China were higher than the overall levels in other SDI countries. In all groups, the ASPR of TBL generally followed a pattern of increasing and then decreasing with age; however, for males in China and middle-SDI countries, the ASPR exhibited a decline in the 80-84 age group. Decomposition analysis revealed that the primary drivers of the increasing TBL burden varied among groups: the rise in DALYs in China and middle-SDI countries was mainly driven by population aging, in low-SDI countries by population growth, and in high-SDI countries by epidemiological transition. While global health inequality in TBL showed some improvement, low-SDI countries continued to bear a disproportionately heavy health burden. Conclusion The disease burden of TBL in China has progressively increased from 1990 to 2021, now ranking among the highest globally. Multiple factors, predominantly driven by population aging, are exacerbating this burden. The burden of TBL is influenced by advancing age, sex differences, and SDI levels. China, along with low- and middle-SDI countries, should implement targeted intervention strategies based on epidemiological findings, including expanding investment in public health services and strengthening healthcare systems, to mitigate the growing burden of TBL.

Objective: To explore the clinical safety and efficacy of a single-position robot-assisted radical nephroureterectomy (RRUN) in the treatment of upper tract urothelial carcinoma (UTUC). Methods: A retrospective study was conducted on 136 UTUC patients who underwent RRUN (n=35) and laparoscopic radical nephroureterectomy (LRUN，n=101) in our hospital during Dec.2020 and Aug.2023.The perioperative and safety indicators of the two groups were compared.The intravesical recurrence-free survival (IVRFS)，recurrence-free survival (RFS)，and overall survival (OS) of the two groups were compared using Kaplan-Meier method. Results: There were no significant differences in the baseline data between the two groups (P>0.05).All surgeries were successfully completed without conversion to open surgery.RRUN demonstrated superior perioperative outcomes compared to LRUN in overall postoperative complication rate [37.1%(13/35) vs. 56.4%(57/101)]，postoperative hospital stay [6(5,7) days vs. 7(6,8) days]，and catheter indwelling time [3(2，4) days vs. 4(3，5) days]，with statistically significant differences (P<0.05).Safety indicators of both surgical approaches were similar (P>0.05).Survival analysis showed no significant difference in oncological outcomes between the two groups [IVRFS (1 year：92.1%，2 years：85.2%)，RFS (1 year:82.4%，2 years:74.9%)，OS (1 year:90.6%，2 years:84.2%)] (P>0.05). Conclusion: Compared with retroperitoneal LRUN，single-position RRUN for UTUC demonstrates comparable safety and oncological efficacy，while offering significant advantages in perioperative outcomes such as reducing postoperative complication rate and shortening hospital stay.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

This research investigates the regulatory role of the transcription factor PU.1 in type 1 conventional dendritic cells (cDC1) and its therapeutic potential of modulating the nuclear factor kappaB (NF-κB) cells signaling pathway in non-small cell lung cancer (NSCLC). Utilizing single-cell transcriptome sequencing and comprehensive bioinformatics tools, including the CIBERSORT algorithm, we analyzed the immune cell landscape within NSCLC tissues. Our analysis revealed distinct NSCLC subtypes and delineated the developmental trajectories and functional distinctions of cDC1 cells. Key differentially expressed genes (DEGs) and pivotal functional modules within these cells were identified, highlighting PU.1 as a critical mediator underexpressed in NSCLC samples. Functionally, PU.1 demonstrated the induction of the NF-κB pathway, which led to inhibited tumor proliferation and enhanced activation of cDC1, thereby suggesting its role in tumor immune surveillance. In vivo models confirmed the suppressive effect of PU.1 on NSCLC progression, mediated through its influence on cDC1 functionality via the NF-κB pathway. These findings propose PU.1 as a promising target for NSCLC therapeutic strategies, emphasizing the importance of transcriptional regulators in the tumor microenvironment.

Mitofusin 2 (MFN2) residing on the outer mitochondrial membrane is a pivotal factor participating in mitochondrial fusion and maintaining mitochondrial morphology. Due to its multifaceted cellular functions, MFN2 is implicated in the pathogenesis of diverse maladies, notably type 2 Charcot-Marie-Tooth disease, which has catalyzed a surge in pharmaceutical endeavors directed towards MFN2. This article reviews the function of MFN2 and its role in a variety of diseases, outlines the current status of drug discovery against MFN2, and summarizes potential drug molecules currently in preclinical research, aiming to provide some reference for the research and development of drugs and therapies targeting MFN2.

OBJECTIVE: To reveal the gap between the evidence of systematic reviews (SRs) and clinical concerns by systematically summarizing the evidence on acupuncture and moxibustion for frozen shoulder and investigating the concerns and needs of clinicians in treatment with acupuncture and moxibustion for this disease. METHODS: The articles of SR and Meta-analysis on acupuncture and moxibustion for frozen shoulder were searched from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase and Cochrane Library, starting from the inception of each database up to December 31st, 2022. Two researchers screened the articles and extracted data independently. Using AMSTAR-2, the methodological quality of the included studies was evaluated. Based on systematic reviews and expert discussion, a questionnaire on clinical concerns of acupuncture and moxibustion for frozen shoulder was developed and distributed to clinicians. The discrepancies between the evidence and clinical concerns were compared from 5 dimensions, including population, interventions, control measures, outcome indicators and review time points. RESULTS: The evidence gaps existed between SRs and clinical concerns. In the existing studies, the needs of personalized treatment were not fully considered in terms of different syndromes/patterns of frozen shoulder and stages of illness, the outcome indicators were not employed properly, the time for outcome measurement was vague, the control groups were set up outside of standardization, and the methodological quality was lower. CONCLUSION It is suggested that future studies should improve the quality of methodology, lay more consideration to different patient groups, optimize outcome indicators and standardize the setting of control groups, so as to better meet the needs of patients and achieve the best match between evidence and clinicians' needs.
Humans ; Acupuncture Therapy ; Bursitis/therapy* ; Evidence Gaps ; Moxibustion ; Systematic Reviews as Topic ; Meta-Analysis as Topic

Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/physiology* ; Animals ; Liver Diseases/metabolism* ; Liver/metabolism* ; Reperfusion Injury/metabolism*