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.

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.

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*

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.

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 characteristics and clinicopathology of v-raf murine sarcoma viral oncogene homolog Bl(BRAF)V600E mutations in papillary thyroid carcinoma(PTC)in Air Force flight personnel.Methods Data of cases and test results of BRAF V600E mutation were collected from Air Force aviators pathologically diagnosed with PTC.A univariate analysis of the relationship between BRAF V600E mutations and clinicopathologic features was performed.Results The overall rate of BRAF V600E mutations among 55 PTC flight crew members was 70.91％.The univariate analysis showed that the number of lymph node metastases in the BRAF V600E mutated group was larger than in the BRAF V600E unmutated group,and the proportion of BRAF V600E mutations in flight crews at intermediate risk of recurrence was higher than that in those at low risk of recurrence(P＜0.05).The presence or absence of BRAF V600E mutations did not affect the results of medical evaluation of PTC in flight personnel.Conclusion The rate of PTC BRAF V600E mutations in Air Force flight crews is similar to that of the general Chinese population.BRAF V600E mutations are associated with an increased number of lymph node metastases and risk of recurrence,and follow-up is recommended for flight personnel with PTC,especially those with BRAF V600E mutations.

Animals ; Monkeypox/drug therapy* ; Antiviral Agents/therapeutic use* ; Phosphoric Monoester Hydrolases/therapeutic use* ; Macaca fascicularis

【Objective】 To determine the rare ABO blood subgroups rapidly and ensure the blood transfusion safety of five patients by a series of serological tests and family investigation, as their preliminary serological results of ABO blood grouping was inconsistent. 【Methods】 ABO blood grouping, antibody screening and Coombs′ tests were performed by the routine serological methods, including manual tube and automatic blood group analyzer, which had matched micro-column gel cards from Diagnostic Grifols. Polymerase chain reaction (PCR) was used to amplify the 6 and 7 exons as well as their adjacent intron region of ABO gene. The patients and their relatives′ ABO blood group and subgroup were analyzed and identified through the comparison with serological phenotype database of ABO blood group. The products of PCR were sequenced directly, and the gene mutation was identified through the comparison with the Blood Group Antigen Gene Mutation Database. 【Results】 Whether micro-column gel cards or manual tube test, the forward and reverse tests of serological grouping were not supported by each other on the five patients′ ABO blood grouping. The forward tests of patients No.1~3 showed AwB phenotype and the reverse tests showed B group. No.4 patient was the forward ABw phenotype and the reverse A group, and No.5 patient was the forward normal AB phenotype and the reverse B group, respectively. All of 5 patients′ Rh C/D/E blood grouping showed clearly; the IDT test and antibody screening result of patient No.1 was positive, while the antibody screening result of patient No.4 was negative. 【Conclusion】 The blood group serological characterization of patient No.1~3 met B(A) blood group, and patient No.4~5 met CisAB blood group. These tests can make a preliminary diagnosis of blood group phenotype, which are verified correctly via blood group genotype.

【Objective】 To explore the molecular hereditary and frequency of Jk(a-b-) in blood donors in Yichang. 【Methods】 A total of 49 999 samples from Yichang Red Cross Central Blood Station were screened for Jk(a-b-) by urea hemolysis test(2 mol /L). The phenotypes of JK (a-b -) probands and their families were confirmed by monoclonal anti-Jk^a and anti-Jk^b, and the whole exon of SLC14A1 gene was sequenced. 【Results】 The frequency of Jk(a-b-) in Yichang blood donors was 0.004% (2/49 999), and the exon sequencing of SLC14A1 gene confirmed that both two probands were JK^*02N.01 caused by c. 342-1G>A homozygous mutation.Besides, JK^*01W.01 allele was observed in the pedigree analysis, and weak expression of Jk^a was found in 4 out of 11 family members. 【Conclusion】 The frequency of JK (a-b -) in Yichang blood donors is similar to those in Shanghai 0.004%(2/48 400), and both caused by JK ^* 02N.01 allele with high frequency in Southeast Asia. The epidemiological survey of JK ^* 01w.01 allele frequency should be further performed.