Abstract Multiple myeloma (MM) research has predominantly focused on older populations, leaving the burden among adolescents and young adults (AYA; aged 15-39 years) incompletely characterized. This study used Global Burden of Disease Study 2021 data to comprehensively assess global trends in MM burden among AYA from 1990 to 2021. We analyzed age-standardized incidence, mortality, and disability-adjusted life year (DALY) rates across sexes, regions, and sociodemographic index (SDI) levels. Temporal trends were quantified using estimated annual percentage change (EAPC). Decomposition analysis identified drivers of burden changes, whereas inequality was assessed using slope index of inequality (SII) and concentration index. Future projections were generated using the Nordpred model. From 1990 to 2021, global age-standardized incidence rates increased 60% (from 0.05 to 0.08 per 100 000), with incident diagnoses more than doubling from 1013 to 2537. Males experienced 43% higher incidence than females. Middle SDI regions showed the most pronounced prevalence increases (EAPC, 3.50%; 95% confidence interval [CI], 3.31-3.69), whereas high SDI regions exhibited declining mortality (EAPC, −0.15%; 95% CI, −0.25 to −0.06) and DALY rates (EAPC, −0.08%; 95% CI, −0.17 to 0.01). Epidemiological changes drove 47.93% of global DALY increases. Health inequalities worsened for males (SII increased from 2 to 3) but improved for females (SII decreased from 2 to 1). Projections indicate continued burden increases through 2040, particularly among males. MM burden among AYA increased substantially with marked heterogeneity across sexes and SDI regions, necessitating targeted prevention strategies and enhanced care access, particularly in middle SDI regions and male populations.

Multiple myeloma (MM) is an incurable plasma cell malignancy with limited therapeutic options. Although autophagy dysregulation is implicated in MM pathogenesis, its precise regulation, particularly by circular RNAs (circRNAs), is poorly understood. Through clinical RNA sequencing of primary MM patient samples, we identify an autophagy-associated circRNA, circ_0008255, which is markedly upregulated in MM patients and closely correlated with poor disease prognosis. Functional studies reveal that circ_0008255 promotes MM proliferation and tumor growth by enhancing autophagic activity. Mechanistically, it functions as a competitive endogenous RNA for miR-192-5p, leading to elevated expression of the core autophagy protein, autophagy related 2 homolog A (ATG2A). Furthermore, we developed a biomimetic nanoplatform based on layered double hydroxide (LDH) nanosheets coated with myeloma-derived cell membranes for tumor-specific delivery. This system co-delivers siRNA targeting circ_0008255 to suppress autophagosome initiation, while simultaneously leveraging the lysosome-alkalinizing property of LDH to impair autophagosome-lysosome fusion. Together, these actions enforce a synergistic autophagic full-chain blockade, leading to potent antitumor effects in vitro and in vivo. Overall, our study reveals a central regulatory role of circ_0008255 in myeloma autophagy, offering a promising therapeutic paradigm for MM.

ObjectiveThis study aimed to investigate the relationship between autoantibodies, specifically Antinuclear Antibody (ANA) and anti-Sjögren’s-syndrome-related antigen A (SSA), and progression-free survival (PFS) in multiple myeloma (MM) patients.MethodsA retrospective cohort study was conducted on 304 MM patients diagnosed between 2010 and 2020 at Shanghai Changzheng Hospital, with follow-up until October 2023. Patients were stratified based on ANA and SSA positivity. Clinical data were analyzed using Kaplan-Meier survival curves and Cox regression models, adjusting for key prognostic factors. Sensitivity analyses were performed using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to evaluate the robustness of the results.ResultsSSA-positive patients exhibited significantly shorter PFS compared to SSA-negative patients (17 vs. 44 months, HR = 2.93, 95% CI 1.53-5.64, p = 0.001), while ANA positivity was associated with a smaller increase in risk (HR = 1.57, 95% CI 1.04-2.4, p = 0.034). The impact of SSA remained significant after adjusting for various covariates in the Cox regression model and sensitivity analyses. Subgroup analyses revealed consistent effects of SSA positivity across different demographic and clinical factors.ConclusionSSA positivity is associated with a higher risk of disease progression in MM patients, suggesting it may serve as a valuable prognostic marker. The relationship between autoantibodies and MM prognosis warrants further investigation in larger, multicenter studies to elucidate the underlying mechanisms and inform clinical management.

Multiple myeloma (MM) ranks as the second most prevalent blood cancer. In the treatment of MM, resistance to proteasome inhibitors like bortezomib (BTZ) is a significant issue, and the primary regulators and mechanisms are still not completely explored. As a result, this investigation aimed to uncover essential genes and mechanisms contributing to BTZ resistance in MM. Out of 359 differentially expressed genes, DEK oncogene (DEK) was pinpointed as the key drug-resistance gene in MM through bioinformatic analysis and was found to be overexpressed in MM patients. DEK was overexpressed in BTZ-resistant cell lines, enhancing the resistance of MM cells to bortezomib. Also, the depletion of DEK mitigated bortezomib resistance in MM cells by initiating ferroptosis. The findings indicated a novel role of DEK in the resistance of MM to bortezomib, which could inform new treatment strategies for BTZ-resistant MM.

Chemotherapy remains a standard treatment for pancreatic ductal adenocarcinoma (PDAC); however, its effectiveness is limited, and the underlying mechanisms are poorly understood. STING plays diverse and critical roles in cancer, yet the role of PDAC cell-intrinsic STING signaling and its regulation under chemotherapy remain unclear. Here, we report that chemotherapy induces cancer cell-intrinsic STING signaling and that STING deletion in PDAC enhances cell death under chemotherapy while suppressing tumor growth in both immune-deficient and immune-competent mice. Interestingly, chemotherapy selectively inhibits translation of IRE1α, an ER membrane protein and a canonical mediator of ER stress. Loss of IRE1α in PDAC amplifies STING signaling and increases resistance to chemotherapy. Mechanistically, IRE1α interacts with STING via their transmembrane regions, reducing STING stability in PDAC cells. Our study reveals that PDAC cells downregulate IRE1α to reinforce STING-mediated pro-survival response; however, this adaptation also makes them more vulnerable to proteostasis imbalance and ER stress-induced cell death. Notably, we demonstrate that combining ER stress inducers with STING signaling inhibition enhances chemotherapy efficacy both in vitro and in vivo.

Background: Multiple myeloma (MM) is a complex hematological malignancy characterized by the clonal expansion of plasma cells in the bone marrow. Emerging studies have emphasized the importance of lipid metabolism, which is closely associated with the survival, proliferation, and drug resistance of tumor cells. The hypoxic environment in the bone marrow (BM) contributes to metabolic reprogramming in MM cells, including alterations in metabolite levels, changes in metabolic enzyme activity, and metabolic shifts. Cancer cells possess the ability to adapt their metabolism in order to fulfill their continuously increasing energy demands. In this review, we will discuss the alterations in lipid metabolism during the development of MM, and their reciprocal interactions with the tumor microenvironment.

Shigella typically causes gastrointestinal infections, and extra-intestinal manifestations are rare. We report the first known case of pyogenic cervical spondylitis co-infected with Escherichia coli and Shigella flexneri, highlighting the diagnostic challenges and clinical implications. A 53-year-old woman presented with neck pain for one month. MRI revealed C6 and C7 vertebrae abscesses. The patient underwent anterior cervical debridement and bone-graft fusion. Intraoperative pus culture grew Escherichia coli, while metagenomic next-generation sequencing detected both Escherichia coli and Shigella species. Intravenous imipenem 500 mg every 6 h was administered, leading to full wound healing at a 6-month follow-up. This case emphasizes the importance of considering Shigella infection in the differential diagnosis of pyogenic spondylitis and demonstrates the utility of a multi-pronged diagnostic approach.

Background Cholangiocarcinoma represents a malignant neoplasm originating from the hepatobiliary tree, with a subset of tumors developing inside the liver. Intrahepatic cholangiocarcinomas (ICC) commonly exhibit an asymptomatic presentation, rendering both diagnosis and treatment challenging. Cuproptosis, an emerging regulated cell death pathway induced by copper ions, has garnered attention recently. As cancer cells show altered copper metabolism and comparatively higher copper needs, cuproptosis may play a role in the development of ICC. However, studies investigating this possibility are currently lacking. Methods Single-cell and bulk RNA sequence data were analyzed, and correlations were established between the expression of cuproptosis-related molecules and ICC patient survival. Genes with predicting survival were used to create a CUPT score using Cox and LASSO regression and tumor mutation burden (TMB) analysis. The CIBERSORT software was employed to characterize immune cell infiltration within the tumors. Furthermore, immune infiltration prediction, biological function enrichment, and drug sensitivity analyses were conducted to explore the potential implications of the cuproptosis-related signature. The effects of silencing solute carrier family 39 member 4 gene (SLC39A4) expression using siRNA were investigated using assays measuring cell proliferation, colony formation, and cell migration. Key genes of cuproptosis were detected by western blotting. Results The developed CUPT score divided patients into high and low CUPT score groups. Those with a low score had significantly better prognosis and longer survival. In contrast, high CUPT scores were associated with worse clinical outcomes and significantly higher TMB. Comparisons of the two groups also indicated differences in the immune infiltrate present in the tumors. Finally, we were able to identify 95 drugs potentially affecting the cuproptosis pathway. Some of these might be effective in the treatment of ICC. The in vitro experiments revealed that suppressing the expression of SLC39A4 in ICC cell lines resulted in reduced cell proliferation, colony formation, and cell migration. It also led to an increase in cell death and the upregulation of key genes associated with cuproptosis, namely ferredoxin 1 (FDX1) and dihydrolipoyl transacetylase (DLAT). These findings strongly suggest that this cuproptosis-associated molecule may play a pivotal role in the development and metastasis of ICC. Conclusions Changes in the expression of a cuproptosis-related gene signature can predict the clinical prognosis of ICC with considerable accuracy. This supports the notion that cuproptosis influences the diversity and complexity of the immune microenvironment, mutational landscape, and biological behavior of ICC. Understanding this pathway better may hold promise for the development of innovative strategies in the management of this disease.

Extrahepatic cholangiocarcinoma (ECC), a highly malignant type of cancer with increasing incidence, has a poor prognosis due to limited treatment options. Based on genomic analysis of ECC patient samples, here we report that aldo-keto reductase family 1 member C1 (AKR1C1) is highly expressed in human ECC tissues and closely associated with ECC progression and poor prognosis. Intriguingly, we show that inducible AKR1C1 knockdown triggers ECC cells to undergo ferroptosis. Mechanistically, AKR1C1 degrades the protein stability of the cytochrome P450 family member CYP1B1, a newly discovered mediator of ferroptosis, via ubiquitin-proteasomal degradation. Additionally, AKR1C1 decreases CYP1B1 mRNA level through the transcriptional factor aryl-hydrocarbon receptor (AHR). Furthermore, the AKR1C1-CYP1B1 axis modulates ferroptosis in ECC cells via the cAMP-PKA signaling pathway. Finally, in a xenograft mouse model of ECC, AKR1C1 depletion sensitizes cancer cells to ferroptosis and synergizes with ferroptosis inducers to suppress tumor growth. Therefore, the AKR1C1-CYP1B1-cAMP signaling axis is a promising therapeutic target for ECC treatment, especially in combination with ferroptosis inducers.

Pancreatic ductal adenocarcinoma (PDAC) is a kind of tumor lacking nutrients due to its poor vascularity and desmoplasia. Recent studies have shown that cancer cells might achieve growth advantage through epitranscriptome reprogramming. However, the role of m5C in PDAC was not fully understood. We found that Aly/REF export factor (ALYREF), a reader of m5C modification, was overexpressed in PDAC, and associated with bad prognosis. In addition, the ALYREF expression was negatively related to CD8+ T cells infiltration in clinical samples. ALYREF knockdown decreased tumor growth in vivo partly dependent of immunity. ALYREF silencing decreased SLC7A5 expression and subsequently inactivated mTORC1 pathway, resulting in decreased tumor proliferation. Mechanically, ALYREF specifically recognized m5C sites in JunD mRNA, maintained the stabilization of JunD mRNA and subsequently upregulated transcription of SLC7A5. Since SLC7A5 was a key transporter of large neutral amino acids (LNAAs), overexpression of SLC7A5 on tumor cells depleted amino acid in microenvironment and restricted CD8+ T cells function. Moreover, ALYREF-JunD-SLC7A5 axis was overexpressed and negatively related with survival through TMA assays. In conclusion, this research revealed the relationship between m5C modification, amino acid transportation and immune microenvironment. ALYREF might be a novel target for PDAC metabolic vulnerability and immune surveillance.

Objective:To explore the current status of social support and quality of life among female officers and soldiers stationed on some islands and reefs of Nansha Qundao.Methods:A cross-sectional questionnaire survey was conducted to collect the basic data and demographic characteristics of female officers and soldiers stationed on some islands and reefs of Nansha Qundao，to assess their quality of life and current status of social support. Pearson correlation analysis was employed to examine the correlation between the quality of life and social support，and logistic regression analysis was used to identify the factors affecting the quality of life of female officers and soldiers on some islands and reefs of Nansha Qundao.Results:The total score of social support for female officers and soldiers stationed on some islands and reefs of Nansha Qundao was（19.1 ± 4.8），and the total score of quality of life was（55.6 ± 10.4）. One-way analysis of variance indicated statistically significant differences in subjective support scores among individuals of different ages，objective support scores among individuals of different educational backgrounds，and subjective support scores among individuals of different marital status（ P<0.05 or P<0.01）. There were also statistically significant differences in the scores related to the duration of being stationed on the island/reef，health condition，and sleep time（ P<0.05 or P<0.01）. Female officers and soldiers of different ages demonstrated statistically significant differences in the scores of the physical，psychological，and social relationship domains（ P<0.05 or P<0.01）. There were significant differences in the scores of quality of life in the psychological domain among female officers and soldiers of different marital status and educational backgrounds（ P<0.05）. There were statistically significant differences in the scores across all four domains of quality of life among female officers and soldiers with different durations of being stationed on the island/reef，health condition，and sleep quality（ P<0.05 or P<0.01）. Pearson analysis showed significant positive correlations between the scores of the four domains of quality of life and the scores of three domains of social support for female officers and soldiers stationed on the island/reef（ P<0.05）. Multivariate logistic regression analysis showed that age，educational background，marital status，duration of being stationed on the island/reef，health condition，and sleep quality were the main factors affecting the quality of life of the female officers and soldiers stationed on some islands and reefs of Nansha Qundao（ P<0.05 or P<0.01）. Conclusion:The quality of life of female officers and soldiers stationed on some islands and reefs of Nansha Qundao is significantly positively correlated with their social support. During routine combat readiness training，troop leaders should strengthen social support in order to improve the quality of life of female officers and soldiers in special environments.

针对目前临床检验诊断学学术型研究生的科研培养存在科研水平不足及科研环境欠佳等诸多问题,提出从"人机法料环"5个因素入手,通过发挥自身内驱力、增强导师引导力、提高培养工具性、提高思维科学性、提升环境友好性等对策来提高临床检验诊断学学术型研究生的科研能力和水平.

目的 探讨以临床路径为核心的医学情境模拟教学在实验诊断学教学中的应用.方法 选择2018级临床医学本科5年制大三学生为研究对象,随机分为试验组和对照组,每组50例.试验组采用医学情境模拟教学联合临床路径教学法,对照组采用传统教学法.授课结束后进行理论、实验操作以及案例分析考核,并对试验组进行认同率调查.结果 试验组学生的理论考核、实验操作考核、案例分析考核成绩均高于对照组,差异有统计学意义(P<0.01).调查结果发现,试验组学生对医学情境模拟联合临床路径教学法的认同率较高,认为该方法有助于提高学习兴趣和效率,以及培养临床思维.结论 以临床路径为核心的医学情境模拟教学有助于增强学生学习兴趣,培养临床思维能力,提高教学质量,促进教学相长.

目的 探讨外周血细胞形态学教学视频在住院医师规范化培训检验科轮转教学中的应用.方法 选取 2018 年—2021 年海军军医大学第二附属医院检验科轮转的住院医师为研究对象.完全随机将住院医师分为观察组(n=18)和对照组(n=18).观察组接受外周血细胞形态学教学视频教学,视频课程采用动画演示、3D模型展示和视频剪辑标注等方式.对照组采用传统教学方式,包括幻灯片展示和面授课程.课程结束后,进行细胞形态学理论和细胞鉴别读片考核评估.通过调查问卷对指导医师和住院医师进行双向评估,并评价住院医师对教学视频的满意度.采用SPSS 26.0 进行统计描述.结果 观察组住院医师细胞形态学的理论成绩总分与对照组相比无统计学意义.观察组的细胞鉴别读片总分明显高于对照组(P<0.001).在住院医师评价方面,观察组在操作指导、责任心和工作态度方面得分明显高于对照组(P<0.001).在教师评价方面,观察组在师德师风、操作指导、责任心和工作态度方面得分明显低于对照组(P<0.001),读片能力和临床诊断能力均优于对照组(P<0.001),观察组的教学压力也明显小于对照组(P<0.001).超过 90.0%的住院医师对教学视频的总体质量表示满意,观察组住院医师一致认为视频教学可以提高学习兴趣和细胞形态鉴别能力.结论 外周血细胞形态学教学视频有助于住院医师掌握鉴别外周血细胞形态的能力,提高住院医师的学习兴趣和积极性.因此,在检验科轮转教学中广泛应用外周血细胞形态学教学视频值得深入探索和应用.

Background: Multiple myeloma (MM) is a hematological malignancy in which plasma cells proliferate abnormally. 5-methylcytosine (m(5)C) methylation modification is the primary epigenetic modification and is involved in regulating the occurrence, development, invasion, and metastasis of various tumors; however, its immunological functions have not been systematically described in MM. Thus, this study aimed to clarify the significance of m(5)C modifications and how the immune microenvironment is linked to m(5)C methylation in MM. Method: A total of 483 samples (60 healthy samples, 423 MM samples) from the Gene Expression Omnibus dataset were acquired to assess the expression of m(5)C regulators. A nomogram model was established to predict the occurrence of MM. We investigated the impact of m(5)C modification on immune microenvironment characteristics, such as the infiltration of immunocytes and immune response reactions. We then systematically evaluated three different m(5)C expression patterns to assess immune characteristics and metabolic functional pathways and established m(5)C-related differentially expressed genes (DEGs). In addition, biological process analysis was performed and an m(5)C score was constructed to identify potentially significant immunological functions in MM. Result: Differential expressions of m(5)C regulators were identified between healthy and MM samples. The nomogram revealed that m(5)C regulators could predict higher disease occurrence of MM. We identified three distinct m(5)C clusters with unique immunological and metabolic characteristics. Among the three different m(5)C clusters, cluster C had more immune characteristics and more metabolism-related pathways than clusters A and B. We analyzed 256 m(5)C-related DEGs and classified the samples into three different m(5)C gene clusters. Based on the m(5)C and m(5)C gene clusters, we calculated m(5)C scores and classified each patient into high- and low-m(5)C score groups. Conclusion: Our study demonstrated that m(5)C modification is involved in and contributes to the diversity and complexity of the immune microenvironment, which offers promise for the development of accurate therapeutic strategies.

Circular RNAs (circRNAs) are RNA molecules with a stable closed-loop structure that are found in a variety of organisms. CircRNAs are highly stable and conserved, and they play important roles in transcriptional regulation and splicing. Multiple Myeloma (MM) is a malignant proliferative disease for which there are currently no effective and comprehensive treatments. Numerous circRNAs may contribute to the development and progression of MM by acting as oncogenes or regulators. Due to the unique function of circRNAs, they have a high potential for regulating the biological functions (including proliferation and apoptosis) of MM cells, and their expression levels and molecular mechanism are closely related to their diagnostic value, therapeutic sensitivity, and clinical prognosis of MM patients. In this review, we aim to provide a detailed overview of the structure and function of circRNAs and demonstrate the potential therapeutic value and potential mechanism of circRNAs in MM via experiments and clinical trials.

BACKGROUND:N6-methyladenosine (m6A) is the addition of a methyl group on the N6 position of adenosine and is the most prevalent and abundant epigenetic modification in eukaryote mRNA. m6A marks are added to mRNA by the m6A methyltransferase complex ("writers"), removed by m6A demethylases ("erasers"), and recognized by m6A-binding proteins ("readers"). Recent evidence has shown that the m6A modification plays a crucial role in the pathogenic mechanism and malignant progression of pancreatic cancer, with roles in cell survival, proliferation, migration, invasion, tumor metastasis, and drug resistance. METHODS:Literature was searched in Pubmed and Web of Science for the following keywords: "N6-methyladenosine", "pancreatic cancer", "epigenetic modification", "immunotherapy". RESULTS:Among classical m6A regulators, while METTL3, METTL14, WTAP, FTO, YTHDF2, IGF2BP1-3, hnRNPC, and NKAP are upregulated in pancreatic cancer, METTL16 and ALKBH5 are downregulated in pancreatic cancer. m6A modification has been investigated in pancreatic cancer therapy. CONCLUSION:Dysregulated m6A and its related factors in pancreatic cancer cells and patients indicate their potential values as novel biomarkers in pancreatic cancer diagnosis and targeted therapy.

检验医学科住院医师规范化培训(简称住培)在我国已开展数年,招收的住院医师由医学检验专业学生逐渐调整为临床医学专业为主要生源,临床医学生在临床思维、结合疾病解读检验报告相对具有优势,但在检验专业理论知识、检验项目实践等方面还存在不足,如何培养具有临床思维同时检验技术扎实的检验医师是目前需要解决的问题之一.海军军医大学第二附属医院检验医学科专业基地一直以来十分注重检验人才的培养,该文结合《医学实验室质量和能力认可准则》中的检验前中后全流程质量管理理念,围绕当下临床医学专业医学生参加检验医学科住培中所存在的问题进行探索,思考相应的解决方案,以期更好地提高检验医学科住院医师的培训效果.

检验医师规范化培训是医学生毕业后教育的重要组成部分,是培养合格检验医师人才的重要途径,在临床医学检验教育承前启后中具有重要地位.该文对现阶段检验医师在规范化培训中的发展现状与未来前景进行了剖析和思考.

Recently, homologous pleckstrin-homology (PH)-domain leucine-rich-repeat protein phosphatases (PHLPP2) has been reported as a tumor suppressor in colon cancer. This study aimed to unravel the possible involvement of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) regulating PHLPP2 in colon cancer. Expressions of candidate lncRNAs and miRNAs were verified by the RT-qPCR and Western blot analyses in colon cancer. The roles of candidate genes in colon cancer were investigated in HT-29 cells in vitro and in mouse tumor xenograft model in vivo. PHLPP2, a target of miR-141 and miR-424, was downregulated in colon cancer. PHLPP2 upregulation and miR-141 and miR-424 downregulation suppressed the colon cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition, and promote cell apoptosis, which also resulted in suppression of tumor metastasis and formation. Furthermore, LINC00402, LINC00461, and SFTA1P were identified as the targets of miR-141 and miR-424 and acted as competitive endogenous RNAs (ceRNAs) of PHLPP2. The upregulation of LINC00402, LINC00461, and SFTA1P was verified to enhance the suppressive effects of PHLPP2 in the pathogenesis of colon cancer. Conjointly, our results demonstrated the suppressive effects of PHLPP2 in colon cancer and proved that LINC00402, LINC00461, and SFTA1P acted as ceRNAs of PHLPP2 by competitive binding to miR-141 and miR-424.