ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

BACKGROUND:Recent research indicates that disc degeneration is closely related to abnormal stress load,and mechanotransduction proteins play a key role in it. OBJECTIVE:To investigate the role and mechanism of mechanotransduction proteins in the mechanotransduction process induced by abnormal mechanical stimulation in disc degeneration,and to summarize the current treatment strategies targeting mechanotransduction to delay intervertebral disc degeneration. METHODS:Using"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanics,signal transduction,protein,biomechanics"as Chinese search terms,and"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanical stimulation,signal transduction,protein,biomechanics"as English search terms,relevant literature in the PubMed and CNKI databases was searched.A total of 88 articles were ultimately included for review. RESULTS AND CONCLUSION:Disc cells can sense external mechanical stimulation through various mechanotransduction proteins and convert it into biological responses within the cells.These transduction proteins mainly include collagen proteins in the extracellular matrix,cell membrane surface receptors(such as integrins and ion channels),and cytoskeleton structural proteins.Their regulation of mechanotransduction processes primarily involves the activation of multiple pathways,such as the PI3K/AKT signaling pathway,nuclear factor-kB signaling pathway,and Ca2+/Calpain2/Caspase3 pathway.Mechanotransduction proteins play a key role in the mechanotransduction of disc cells.Abnormal expression of these proteins or resulting changes in the extracellular matrix environment can disrupt the mechanical balance of disc cells,leading to disc degeneration.In-depth study of the expression and regulatory mechanisms of mechanotransduction proteins in disc cells,and identification of key pathological links and therapeutic targets,is of significant importance for developing treatment strategies for disc degeneration.Current strategies to delay intervertebral disc degeneration by targeting mechanotransduction mainly include regulation of transduction proteins and improvement of the extracellular matrix.However,research in this area is still in its early stages.As research continues,new breakthroughs are expected in the regulation of disc degeneration by mechanotransduction proteins.

BACKGROUND:With advancements in stem cell research,the therapeutic efficacy of adult stem cells such as endothelial progenitor cells and mesenchymal stem cells in atherosclerosis and complications arising from atherosclerosis and vascular stent implantation is gradually being recognized.Due to the limitations of intravenous infusion of adult stem cells,including poor targeting and low treatment efficiency,recent research has focused on surface modification of vascular stents to achieve localized aggregation and functional modulation of endothelial progenitor cells or mesenchymal stem cells. OBJECTIVE:To discuss the therapeutic progress of endothelial progenitor cells and mesenchymal stem cells in vascular stent-related diseases,summarize the research status of the design of vascular stents based on endothelial progenitor cells and mesenchymal stem cells. METHODS:Relevant literature was retrieved on CNKI,WanFang,PubMed,and Web of Science databases since their inception.The Chinese search terms were"endothelial injury,stenting,thrombosis,intimal hyperplasia,atherosclerosis,endothelial repair,endothelial progenitor cell,mesenchymal stem cell,vascular stent."English search terms were"endothelial injury,stenting,thrombosis,intimal hyperplasia,atherosclerosis,endothelial repair,endothelial regeneration,endothelial progenitor cell,mesenchymal stem cell,vascular stent,vascular scaffold."According to inclusion and exclusion criteria,127 articles were finally reviewed. RESULTS AND CONCLUSION:Endothelial progenitor cells and mesenchymal stem cells can treat atherosclerosis and complications of stent implantation through differentiation and paracrine effects,mainly by protecting endothelial cells,regulating the expression of inflammatory cells and cytokines,and modulating smooth muscle cell proliferation and phenotype.Mesenchymal stem cells may have adverse reactions such as thrombosis and vascular calcification in therapeutic applications,and using extracellular vesicles and co-administration with heparin for surface modification is a feasible solution.Currently,there is more research on stents based on endothelial progenitor cells,mainly focusing on recruitment,capture,proliferation,differentiation,and activity.Research on stents based on mesenchymal stem cell capture in the vascular field is relatively scarce,but exosome-loaded stents derived from mesenchymal stem cells have been found to have highly effective therapeutic efficacy.Additionally,some underlying diseases such as diabetes may affect the activity of adult stem cells,leading to the loss of effectiveness in stem cell-based stent designs.Therefore,in future stent designs,consideration should be given to the background diseases.

To analyze the epidemic characteristics and vaccination status of hemorrhagic fever with renal syndrome (HFRS) in Baoji City from 2008 to 2023. The descriptive epidemiological method was used to collect the incidence data of HFRS cases in Baoji City from 2008 to 2003 in the Infectious Disease Reporting Information Management System. The epidemic characteristics of HFRS cases were summarized and analyzed. The data on HFRS vaccination from 2008 to 2023 were consulted through the Baoji Hemorrhagic Fever Vaccination Report, and the relationship between vaccination status and reported incidence was analyzed. The results showed that a total of 2 690 cases of HFRS were reported in Baoji City, with an annual average reported incidence rate of 6.94/100 000, 15 cases died and a case fatality rate of 0.41%. The number of reported HFRS cases showed a fluctuating trend, with a peak in 2011-2013. Since 2016, it entered a low-level stable fluctuation period, and the annual mortality rate dropped to below 1% after 2011. From 2008 to 2023, Fufeng County, Meixian County and Chencang District reported a large number of cases, but Linyou County and other counties in the north showed an upward trend in incidence, with obvious seasonal characteristics. Cases were mainly concentrated from October to January of the following year, accounting for 75.91% of the total number of cases. Farmers were the main reported occupations, accounting for 80.19% of the total number of cases. The ratio of male to female reported cases was 3.30∶1. The age group of 35-59 years old accounted for 51.08% of the cases, and the proportion of the age group of 60 years and above showed an upward trend ( χ2=331.44, P<0.001). From 2008 to 2023, a total of 1 559 619 people were vaccinated, and the vaccination rate of the target population aged 16-60 years reached 72.23%. With the increase in the vaccination rate, the incidence of HFRS continued to decrease. In summary, with the development of HFRS vaccination work, the epidemic characteristics of HFRS in Baoji City have changed, and the peak incidence has been controlled. The proportion of cases in the age group of 60 years and above continues to increase. HFRS vaccination is still an effective way of prevention and control, and vaccination strategies should be continuously optimized according to the characteristics of HFRS.

Objective To develop a rehabilitation exercise program for the patients with osteoporotic vertebral compression fractures.Methods An online search was performed across both Chinese and English databases and websites to retrieve literature on rehabilitation exercises and related therapeutic measures for patients with osteoporotic vertebral compression fractures.Two researchers independently screened the retrieved literature,evaluated the quality,and extracted relevant evidence.Semi-structured interviews were conducted among 15 patients at various rehabilitation phases about the requirements of rehabilitation.A preliminary exercise program was developed and verified for the validity and feasibility using Delphi method.Results A rehabilitation exercise program was formulated.The program included five periods of preoperative period,bedridden period after surgery,ambulation period(1 week after surgery),weeks 2-8 after surgery and weeks 9-12 after surgery covering six domains of exercise type,exercise items,exercise duration,exercise frequency,exercise intensity and exercise safety.The response rate and effective rate over the two rounds of expert consultation were both 100.00%,with an authority coefficient of 0.94.The Kendall's W coefficients for secondary indicators in the two rounds of expert consultation were 0.184 and 0.334,respectively(both P<0.001).Conclusion The exercise program developed in this study for the patients with osteoporotic vertebral compression fractures is scientifically reliable and reasonable.The two features of continuity and staged characteristics in rehabilitation process are fully considered,thereby it offers a guidance for clinical healthcare professionals as well as the patients in development of practical and effective rehabilitation exercise plans.

Objective:To evaluate the relevant factors to optimize the learning curve and the impact of the basic skills of endoscopic technology on the learning curve of gasless transaxillary posterior endoscopic thyroidectomy.Methods:A retrospective analysis was performed to evaluate the clinical outcomes of 50 patients who underwent Glandular Ultrasound-Assisted (GUA) thyroid surgery by a surgeon with a background in endoscopic thyroid surgery via the thoracic-areolar approach, and 50 patients operated on by a surgeon without such experience at the Thyroid Surgery Department of Jilin University China-Japan Union Hospital from Apr. to Dec. 2023. The patients were divided into two groups: the Endoscopic Experience Group and the Non-Endoscopic Experience Group. The Cumulative Sum Control Chart (CUSUM) was applied to construct learning curves for both groups, dividing the technical exploration period from the mastery period. The analysis compared the surgical time, postoperative first-day drainage volume, number of central lymph nodes dissected rates, and postoperative complications between the two groups and across the two phases.Results:The analysis of the learning curve revealed that the inflection point of the Endoscopic Experience Group was 15, while of the Non-Endoscopic Experience Group was 18. The learning curve was divided into the technical exploration stage and the proficient mastery stage. The operative time of technical exploration stagde was significantly longer than of proficient mastery stage of both group (183.46±36.13min vs.144.40±26.14min, P<0.001; 186.89±48.91min vs.131.59±22.90min; P<0.001) . The operative time in the proficient mastery stage of the Endoscopic Experience Group was longer than that of the Non-Endoscopic Experience Group (144.40±26.15min vs. 131.59±22.90min, P<0.05) . The postoperative drainage volume in the Endoscopic Experience Group was lower than that in Non-Endoscopic Experience Group in both stages (65.40±32.48mL vs.93.22±30.67mL, 57.40±15.35mL vs.78.50±28.30mL, P<0.05) , and the postoperative drainage volume in the proficient mastery stage of the Non-Endoscopic Experience Group was significantly lower than in the technical exploration stage (93.22±30.67mL vs.78.50±28.30mL, P<0.05) .No significant differences in central lymph node dissection numbers or postoperative complications were observed between the groups at both stages. Conclusions:There is a specific learning curve in the early stage of gasless transaxillary posterior endoscopic thyroidectomy. After crossing the learning curve, the operation time is obviously shortened with the improvement of the operator's surgical technique.Having a basic understanding of endoscopic technology in the early stage can reduce the occurrence of postoperative drainage, but has a minimal impact on the learning curve.

Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO₂), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO₂ plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

Kidney fibrosis is the final common pathway of virtually all chronic kidney disease (CKD). However, despite great progress in recent years, no targeted antifibrotic therapies have been approved. Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of CKD. Senescent renal tubular cells, fibroblasts, endothelial cells, and podocytes have been detected in the kidneys of patients with CKD and animal models. Nonetheless, although accumulated evidence supports the essential role of cellular senescence in CKD, the mechanisms that promote cell senescence and how senescent cells contribute to CKD remain largely unknown. In this review, we summarize the features of the cellular senescence of the kidney and discuss the possible functions of senescent cells in the pathogenesis of kidney fibrosis. We also address whether pharmacological approaches targeting senescent cells can be used to retard the the progression of kidney fibrosis.
Humans ; Cellular Senescence/physiology* ; Fibrosis ; Renal Insufficiency, Chronic/pathology* ; Kidney/pathology* ; Animals