BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

Electrical impedance tomography (EIT) is a new non-invasive functional imaging technology, which has the advantages of non-invasion, non-radiation, low cost, fast response, portability and visualization. In recent years, more and more studies have shown that EIT has great potential in the detection of lung diseases and has been applied to early diagnosis and treatment of some diseases. This paper introduced the basic principle of EIT, discussed the research and clinical application of EIT in the detection of acute respiratory distress syndrome, chronic obstructive pulmonary disease, pneumothorax and pulmonary embolism, and focused on the summary and introduction of indicators and functional images of EIT related to the detection of lung diseases. This review will help medical workers understand and use EIT, and promote the further development of EIT in lung diseases as well as other fields.
Humans ; Electric Impedance ; Tomography/methods* ; Lung Diseases/diagnosis* ; Pulmonary Disease, Chronic Obstructive/diagnosis* ; Pulmonary Embolism/diagnosis* ; Respiratory Distress Syndrome/diagnosis*

The aging microenvironment, as a key driver of tumorigenesis and progression, plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype (SASP). SASP consists of a variety of interleukins, chemokines, proteases, and growth factors. It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms, thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment. Furthermore, these secreted factors activate key signaling pathways such as NF-κB, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.

Objective: To investigate the trends in mortality and life loss due to falls among the elderly in Wenzhou City, Zhejiang Province, so as to provide the basis for formulating prevention and control measures for falls among the elderly. Methods: The data on fall-related deaths among the elderly aged 60 and above in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2015 to 2023. The crude mortality was calculated and standardized using the data from the Sixth National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL), average years of life lost (AYLL), and potential years of life lost rate (PYLLR). The trends in mortality and life loss among the elderly were analyzed using the annual percent change (APC) and average annual percent change (AAPC). Results: There were 11 378 deaths due to falls among the elderly in Wenzhou City from 2015 to 2023, with a crude mortality of 82.67/100 000 and a standardized mortality of 65.32/105, which appeared no significant changing trend (AAPC=3.401%、2.995%,both P>0.05). There was a tendency towards a rise from 2019 to 2023 (APC=12.592%、11.507%, both P<0.05). The majority of falls occurred at home, with 6 312 cases accounting for 55.48%. The primary types of fall-related deaths were slips, trips, and falls on the same level, with 8 541 cases representing 75.07%. The crude mortality and standardized mortality of falls in males were 76.63/105 and 60.86/105, which were lower than that in females at 88.72/100 000 and 70.33/100 000 (both P<0.05), and the trends were consistent with the overall population. The crude mortality of falls among the elderly increased with age (P<0.05). From 2015 to 2023, the crude mortality of falls among the elderly aged 60 to <65 years showed an upward trend (AAPC=4.860%, P<0.05), while no significant trend was observed in other age groups (all P>0.05). The PYLL was 5 123 person-years, the AYLL was 0.45 years per person, and the PYLLR was 0.37‰. From 2015 to 2023, PYLL showed an upward trend (AAPC=5.477%, P<0.05). The PYLL, AYLL, and PYLLR for males were 3.08 times, 3.48 times, and 2.67 times those of females, respectively. Conclusions From 2015 to 2023, the mortality of falls among the elderly in Wenzhou City had remained relatively stable. However, PYLL showed an upward trend. Males and older seniors were key groups for falls prevention. It is recommended to enhance health education and promote age-friendly home modifications to prevent falls among the elderly.

OBJECTIVE To retrospectively analyze the prevalence of ventilator-associated pneumonia(VAP)in Gansu Province in 2023 so as to provide scientific bases for formulating and optimizing prevention and control strategies for VAP in the health care institutions of the province.METHODS The data regarding to VAP of 2023 were collected from the regional surveillance platform of Gansu Province Nosocomial Infection Management Quali-ty Control Center.The influencing factors for the VAP were assessed by means of Poisson regression model.RESULTS In 2023,the median incidence of VAP was 3.51 ‰ among the 93 hospitals in Gansu Province.There was significant difference in the incidence of VAP among the different regions,levels and types of hospitals(P＜0.05).The length of hospital stay and ventilator treatment duration of the tertiary hospitals were 3458(1904,6770)days and 1 274(740,2040)days,respectively,higher than those of the secondary hospitals;the incidence of VAP was 4.89(2.82,7.40)‰ in the tertiary hospitals,higher than that in the secondary hospitals(all P＜0.05).The incidence of VAP of the general hospitals was 3.94(2.66,6.92)‰,higher than 2.06(1.03,3.27)‰ of the specialized hospitals(P＜0.001).With the respect to the regional factor,Qingyang City,Baiyin City,Dingxi City and Linxia City were at lower risk of VAP than Lanzhou City after the related factors were controlled through Poisson regression analysis(P＜0.05),while Zhangye City and Jiayuguan City were at higher risk of VAP(P＜0.05).The analysis of seasonal factors showed that the incidence of VAP presented seasonal fluctuation,the inci-dence of VAP was higher in the second and fourth quarters;however,there was no significant difference in the risk of VAP among the quarters.CONCLUSIONS The incidence of VAP is decreased in Gansu Province in 2023 as compared with that in previous years,however,there is certain difference among the different regions.The inci-dence rates of VAP are relatively high in the tertiary hospitals and the general hospitals.It is necessary to strengthen the surveillance in related areas and take active prevention and control measures,so as to reduce the in-cidence of VAP.

lumbar fusion surgery is one of the commonly used surgical interventions and treatments for lumbar degenerative diseases.A small proportion of patients still experience complications such as low back pain after lumbar fusion surgery.Spinal-pelvic parameters are closely related to the occurrence of complications in patients after lumbar fusion surgery.This article reviews the commonly used lumbar fixation and fusion surgical techniques and mainstream sagittal spinal-pelvic parameters.Additionally,it summarizes the research progress and current status regarding the relationship between sagittal spinal-pelvic parameters and various postoperative complications,including low back pain.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Cardiac arrest is a major health event that poses a major threat to human life and health.Post-cardiac arrest brain injury is the main adverse prognostic factor and cause of death in patients who experience cardiac arrest.Currently,the therapeutic methods and effects are limited.In recent years,with the in-depth research on microbiota-gut-brain communication,it has been found that intestinal microbiota and their metabolites may play a role in the regulation of neuroinflammation in post-cardiac arrest brain injury.Short-chain fatty acids are the key substances in microbiota-gut-brain communication,and the mechanism involves immune,endocrine and neuroregulatory pathways.Supplementation of short-chain fatty acid-producing bacteria or short-chain fatty acids can improve intestinal flora disorder and reduce neuroinflammation after cardiopulmonary resuscitation.As a key mediator in microbial-gut-brain communication,short-chain fatty acids have great potential for the treatment of brain injury after cardiac arrest.This review explores the role and regulatory mechanism of microbiota-gut-brain communication in the neuroinflammation of brain injury after cardiopulmonary resuscitation through immune,endocrine and neuro-regulatory pathways,providing a new idea for the treatment of post-cardiac arrest brain injury.