Stenotrophomonas maltophilia is an opportunistic pathogen associated with various nosocomial infections and is known for its intrinsic multidrug resistance. This study aims to provide a comprehensive overview of the epidemiology and resistance patterns of S. maltophilia in China from 2014 to 2021. Data were extracted from the China Antimicrobial Resistance Surveillance System (CARSS) and the Blood Bacterial Resistance Investigation Collaborative System (BRICS), encompassing 1412 medical institutions across 31 provinces in China. We analyzed the prevalence of S. maltophilia in clinical isolates, focusing on specific patient populations and departments, as well as resistance profiles to recommended first-line antibiotics, including sulfamethoxazole-trimethoprim, levofloxacin, and minocycline. A total of 514,768 S. maltophilia strains were analyzed. The overall prevalence of S. maltophilia among all clinical bacterial isolates remained stable at approximately 2.1

Abstract Background Alterations in several tripartite motif-containing (TRIM) family proteins have been implicated in the pathogenesis of lung cancer. TRIM28, a member of the TRIM E3 ligase family, has been associated with tumorigenesis, cell proliferation, and inflammation. However, little is known about TRIM28 expression and its role in the immune microenvironment of non-small cell lung cancer (NSCLC). Methods We assessed the clinical significance of TRIM28 in tissue microarrays and TCGA cohorts. We investigated the function of TRIM28 in syngeneic mouse tumor models, the Kras LSL−G12D/+ ; Tp53 fl/fl (KP) mouse model, and humanized mice. Immune cell composition was analyzed using flow cytometry and immunohistochemistry. Results Our findings revealed a positive correlation between TRIM28 expression and the infiltration of suppressive myeloid-derived suppressor cells (MDSCs) in NSCLC. Moreover, silencing TRIM28 enhanced the efficacy of anti-PD-1 immunotherapy by reshaping the inflamed tumor microenvironment. Mechanistically, we demonstrated that TRIM28 could physically interact with receptor-interacting protein kinase 1 (RIPK1) and promote K63-linked ubiquitination of RIPK1, which is crucial for sustaining activation of the NF-κB pathway. Mutagenesis of the E3 ligase domain corroborated the essential role of E3 ligase activity in TRIM28-mediated NF-κB activation. Further experiments revealed that TRIM28 could upregulate the expression of CXCL1 by activating NF-κB signaling. CXCL1 could bind to CXCR2 on MDSCs and promote their migration to the tumor microenvironment. TRIM28 knockdown increased responsiveness to anti-PD-1 therapy in immunocompetent mice, characterized by increased CD8+T tumor-infiltrating lymphocytes and decreased MDSCs. Conclusion The present study identified TRIM28 as a promoter of chemokine-driven recruitment of MDSCs through RIPK1-mediated NF-κB activation, leading to the suppression of infiltrating activated CD8+T cells and the development of anti-PD-1 resistance. Understanding the regulation of MDSC recruitment and function by TRIM28 provides crucial insights into the association between TRIM28 signaling and the development of an immunosuppressive tumor microenvironment. These insights may inform the development of combination therapies to enhance the effectiveness of immune checkpoint blockade therapy in NSCLC.

目的:探讨细胞分裂周期蛋白42(Cdc42)是否通过内皮-间充质转化(EndMT)参与动脉型肺动脉高压(PAH)小鼠右心纤维化.方法:健康雄性C57BL/6小鼠(5～8周龄)18只,随机分成常氧对照(NC)组、PAH模型[SU5416(血管内皮生长因子受体2抑制剂)+低氧,SuHx]组和SuHx+ML141(Cdc42抑制剂)组,每组6只.所有存活小鼠在4周后用异氟烷麻醉,行心脏超声检查及右心室收缩压(RVSP)监测,之后处死小鼠.用HE和Masson染色观察小鼠右室心肌细胞改变及纤维化程度.使用磁珠分选小鼠心脏内皮细胞并用不同条件处理.通过Western blot检测小鼠心脏组织Cdc42表达水平及内皮细胞Cdc42和EndMT相关蛋白[波形蛋白(vimentin)、α-平滑肌肌动蛋白(α-SMA)、血小板内皮细胞黏附分子1(PECAM-1/CD31)、血管内皮钙黏蛋白(VE-cadherin)和锌指蛋白Snail]表达水平,同时用倒置显微镜观察各组内皮细胞形态.结果:体内实验结果显示,与NC组相比,SuHx组小鼠心脏组织Cdc42表达水平显著升高(P<0.05);预防给予ML141(8 mg/kg)可降低小鼠RVSP,增大三尖瓣环平面收缩期位移(TAPSE),减轻心脏(尤其是血管旁)纤维化(P<0.01).体外实验结果显示,SuHx组和低氧72 h组小鼠心脏内皮细胞Cdc42表达水平显著升高,EndMT增强,EndMT相关蛋白vimentin和α-SMA的表达显著增加,CD31和VE-cadherin的表达显著降低(P<0.05);预防给予ML141(10 µmol/L)后可缓解低氧72 h诱导的EndMT.结论:Cdc42可能通过上调EndMT参与PAH小鼠右心纤维化.

目的:探讨支气管镜管腔内活检(EBB)出血与肺癌患者血脂异常的关系.方法:收集2019年2月～2021年2月106例接受EBB诊断为原发性肺癌的患者为研究对象,分为出血组(n=41)和非出血组(n=65).抽取患者入院第2天清晨空腹静脉血,比较两组患者的一般临床资料及生化指标.结果:非出血组患者血清低密度脂蛋白(LDL)和总胆固醇(CHOL)浓度均高于出血组患者(P<0.01).多因素Logistic回归分析显示,CHOL升高(OR=0.161,95％CI:0.073～0.353)可能是EBB出血的保护因素(P<0.05).利用广义可加模型评估显示,随着CHOL水平的增加,EBB期间出血的风险逐渐下降(P<0.01).CHOL可作为EBB出血的预测因子,其截点值为3.45 mmol/L,ROC曲线下面积为0.83(95％CI:0.76～0.91),灵敏度为70.73％,特异度为75.38％.结论:肺癌患者血脂代谢异常与EBB出血密切相关,随着CHOL水平的增加,EBB期间出血的风险逐渐下降,CHOL是出血的保护因素.

Recent studies have indicated that some members of the tripartite motif (TRIM) proteins function as important regulators for non-small cell lung cancer (NSCLC), However, the regulatory mechanism underpinning aberrant expression of TRIM in NSCLC remains unclear. Here we report that TRIM15 plays important roles in NSCLC progression through modulating Keap1-Nrf2 signaling pathway. TRIM15 expression was evaluated by western blot analysis, tissue microarray-based immunohistochemistry analysis. The interactions between TRIM15 and Keap1 were analyzed by co-immunoprecipitation (Co-IP) and immunofluorescence co-localization assay. The correlation between TRIM15 and Keap1 was measured by Co-IP and ubiquitination analysis in vitro. Gain- and lost-of-function experiments were used to detect TRIM15 promotes proliferation and invasion of NSCLC cells both in vitro and vivo. Here, we revealed that TRIM15 was frequently upregulated in NSCLC samples and associated with poor prognosis. Functionally, TRIM15 knockdown resulted in decreased cancer cell proliferation and metastasis, whereas ectopic TRIM15 expression facilitated tumor cancer cell proliferation and metastasis in vitro and in vivo. Moreover, TRIM15 promoted cell proliferation and metastasis depends on its E3 ubiquitin ligase. Mechanistically, TRIM15 directly targeted Keap1 by ubiquitination and degradation, the principal regulator of Nrf2 degradation, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant response and tumor progression. Therefore, our study characterizes the pivotal roles of TRIM15 promotes NSCLC progression via Nrf2 stability mediated by promoting Keap1 ubiquitination and degradation and could be a valuable prognostic biomarker and a potential therapeutic target in NSCLC.

Objective: To explore the pathogenesis and prognostic biomarkers of non-small-cell lung cancer (NSCLC) in female patients via a bioinformatic analysis and functional prediction of potential NSCLC-associated genes in females. Methods: Data for female patients with NSCLC were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified using GEO2R. The DAVID online database was used to perform Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses, and STRING online software was used to perform protein-protein interaction (PPI) analyses. Next, the plug-in (M-CODE) was used to screen the key DEGs; the Oncomine database was analysed for IL6, EGF and MMP9 expression in NSCLC tissues and normal lung tissues and the Kaplan-Meier plotter was used to perform prognostic analyses of key DEGs. Finally, RT-PCR was used to verify the expression of key DEG in NSCLC cells. Results: A total of 500 DEGs were screened, and the functional and pathway enrichment analysis showed that these genes were mainly involved in cell proliferation, cell migration, and vasculature development regulation. The KEGG analysis showed that the pathways were primarily related to ECM-receptor interactions, protein digestion and absorption, and leukocyte transendothelial migration signalling. Three key DEGs were obtained by the PPI network analysis: IL6, EGF and MMP9. The expression of IL6 was low in NSCLC tissues, while that of EGF and MMP9 was high. IL6 and EGF may be biomarkers for predicting the prognosis of female patients with NSCLC. Compared with human bronchial epithelial cell line (16HBE), EGF and MMP-9 were high expressed in NSCLC cells. Conclusion: In female patients, IL6, EGF and MMP9 may be research targets for characterizing the pathogenesis of NSCLC, and IL6 and EGF may be biomarkers for predicting the prognosis of this cancer.

目的 探讨基于ESA(engage—投入、study—学习、activate—活用)的翻转课堂教学模式在呼吸内科实践教学中的应用效果.方法 选取在皖南医学院弋矶山医院呼吸内科实习的临床医学专业实习医生80名,随机分为试验组和对照组,每组40名.在授课内容相同的情况下,试验组实习医生采用基于ESA的翻转课堂教学模式,对照组采用传统教学模式,待实习结束后,比较两组学生的教育处调查评分和出科考核成绩,同时采用问卷调查方式对基于ESA的翻转课堂教学模式的内容进行评价.结果 出科时,基于ESA的翻转课堂教学组学生的教育处调查评分和考核成绩均高于对照组(P<0.05),且试验组医学生对基于ESA的翻转课堂教学模式的评价认可度均超过90％.结论 基于ESA的翻转课堂教学模式应用在呼吸内科实践教学中,不但可以提高临床实习医生的教学满意度和出科考核成绩,而且实习医生对新的教学模式认可度较好.

BACKGROUND:Exosomes are emerging as important mediators of the cross-talk between tumor cells and the microenvironment. The communication between tumor-derived exosomes and macrophages has a critical role in facilitating tumor progression. However, the mechanisms by which exosomes modulate tumor development in lung cancer are not fully understood.METHODS:Short hairpin RNA mediated knockdown or exogenous expression of TRIM59 combined with in vitro and in vivo assays were performed to prove the functional significance of TRIM59. Western blotting, real-time PCR, co-immunoprecipitation, immunofluorescence (IF) staining assays, proximity ligation assay (PLA), ubiquitination assays, lactate secretion and lipid droplets content measurement, and rescue experiments were used to evaluate the mechanism. Lewis lung carcinoma (LLC) cells were injected via subcutaneously or tail vein into C57BL/6 wild-type (WT) and transgenic mice to assess the role of TRIM59 in vivo.RESULTS:We demonstrated that tripartite motif-containing 59 (TRIM59) was expressed in lung cancer cells-derived exosomes, and can be transferred to macrophages through the exosomes. Activated macrophages by TRIM59 promote lung cancer progression in vitro and in vivo. Mechanistic investigations revealed that TRIM59 physically interacts with abhydrolase domain containing 5 (ABHD5) and directly induced the ubiquitination of ABHD5 and led to its proteasome-dependent degradation. ABHD5, an lipolytic co-activator, deficiency induced metabolic reprogramming and enabled NLRP3 inflammasome activation in macrophages. Further studies showed that the exacerbation of NLRP3 inflammasome activation by ABHD5 deficiency, provides a positive feedback loop to promote cancer progression by preferentially secrete the proinflammatory cytokine IL-1β.CONCLUSIONS:Collectively, these data indicate that tumor-derived exosomal TRIM59 converts macrophages to tumor-promoting functions of macrophages via regulating ABHD5 proteasomal degradation, to activate NLRP3 inflammasome signaling pathway to promote lung cancer progression by IL-1β secretion. Our findings also indicate that tumor-derived exosomal TRIM59 has an important role in intercellular communication for fostering an inflammatory microenvironment and promoting lung metastasis.

肺错构瘤的发病率在良性肺肿瘤中最高,约占75％ 或更多. 超过 85％ 的病例中,以肺结节的形式存在,多于体检时发现. 根据疾病的部位,临床分类分为肺内型和支气管型. 其中支气管腔内型错构瘤仅占 1. 4％ ～ 11％ [1] ,最近报道了支气管腔中的肺错构瘤病例如下.

OBJECTIVE:To investigate the effects of airway epithelial cells on macrophages chemotaxis and inflammatory cytokine expression under hypoxic conditions.
 Methods: Human bronchial epithelial cells (HBE) treated with different concentrations (0, 100, 200, 400, 800 μmol/L) of CoCl2 or transfected with HIF-1α siRNA were co-cultured with THP-1-derived M1 macrophages or M2 macrophages. The chemotactic effects on macrophages were analyzed by Transwell assay. The levels of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were detected by ELISA, and HIF-1α or Cav-1 mRNA expression in HBE or macrophages was detected by RT-qPCR.
 Results: HBE cells promoted macrophages chemotaxis in a time- and concentration-dependent manner. Compared to un-transfected group, the chemotactic ability of HBE transfected with HIF-1α siRNA was significantly weakened (P<0.01). Under the same culture conditions, the chemotaxis of M2 macrophages was greater than that in THP1-derived M1 macrophages. The concentrations of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were increased in a time-and concentration-dependent manner. The concentrations of TNF-α and IFN-γ were increased further after co-culturing for 8 and 12 h; while IL-4, IL-13 and IL-10 concentrations were increased further during 24 h of co-culture. The levels of cytokines in the supernatants of macrophages co-cultured with HBE and transfected with HIF-1α siRNA were significantly lower than those in un-transfected cells (P<0.05 or P<0.01). The reduction of TNF-α or IFN-γ was more obvious. The expression of HIF-1α or Cav-1 mRNA in HBE or macrophages was increased in a concentration-dependent manner after 8 or 12 h co-culture, which was significantly reduced when HBE was transfected with HIF-1α siRNA.
 Conclusion: Airway epithelial cells can enhance macrophages chemotaxis and pro-inflammatory cytokines expressions under hypoxic condition. HIF-1α and Cav-1 may be the important mediators in these processes.

目的:探讨气道上皮细胞对巨噬细胞表型和吞噬活性的影响及缺氧诱导因子1α(HIF-1α)的作用.方法:将不同浓度(0、100、200、400和800μmol/L)氯化钴(CoCl2)处理或转染HIF-1αsiRNA的人支气管上皮(HBE)细胞与12-肉豆蔻酸13-乙酸佛波酯(PMA)诱导人单核细胞系THP-1分化的巨噬细胞共培养,RT-qPCR检测HBE细胞HIF-1α的mRNA表达,流式细胞术检测巨噬细胞表面标志物的表达及对大肠杆菌的吞噬率.结果:CoCl2浓度依赖性增加HBE细胞HIF-1α的mRNA表达,8 h为峰值,同时CoCl2处理的HBE细胞也增加共培养的巨噬细胞CCL3、CD163、CD206和CCL18荧光强度比率,800μmol/L处理的HBE细胞作用最强;共培养8 h和12 h的巨噬细胞CCL3荧光强度比率增加最明显,而共培养24 h的巨噬细胞CD163、CD206和CCL18荧光强度比率上升更明显.转染HIF-1α-Homo-488 siRNA的HBE细胞对巨噬细胞CCL3、CD163、CD206和CCL18的刺激作用明显减弱.与不同浓度CoCl2处理的HBE细胞共培养24 h的巨噬细胞对大肠杆菌的吞噬率最初(60 min以前)均呈不同的上升趋势,其后吞噬率均降低.相对于正常HBE细胞共培养组,400和800μmol/L刺激组在各时点的吞噬率均降低,其中800μmol/L刺激组降低最明显.结论:低氧环境下气道上皮细胞早期增强巨噬细胞向M1优势转化,而长期低氧作用的气道上皮细胞抑制巨噬细胞吞噬作用并向M2优势转化,HIF-1α可能是这些过程的重要介质.

Lung cancer ( LC ) is a devastating malignancy with no effective treatments, due to its complex genomic profile. Using bioinformatics analysis and immunohistochemical of lung carcinoma tissues, we show that TRIM 59 as a critical oncoprotein relating to LC proliferation and metastasis. In this study, high TRIM 59 expression was significantly correlated with lymph node metastasis, distant metastasis, and tumour stage. Furthermore, up‐regulation of TRIM 59 expression correlated with poorer outcomes in LC patients. Mechanistically, TRIM 59 play a key role in promoting LC growth and metastasis through regulation of extracellular‐signal regulated protein kinase (ERK) signalling pathway and epithelial‐to‐mesenchymal transition ( EMT )‐markers, as validated by loss‐of‐function studies. In‐depth bioinformatics analysis showed that there is preliminary evidence of co‐expression of TRIM 59 and cyclin dependent kinase 6 ( CDK 6) in LC . Notably, CDK 6 expression significantly decreased when TRIM 59 was knocked down in the LC cells. In contrast, exogenous up‐regulation of TRIM 59 expression also induced significant increases in the expression of CDK 6. Moreover, the expression of CDK 6 was also inhibited by the ERK signalling inhibitor, U0126. The results of both loss‐ and gain‐of‐function studies showed that TRIM 59 could regulate the expression of CDK 6. Collectively, these data provide evidence that TRIM 59 is involved in lung carcinoma growth and progression possibly through the induction of CDK 6 expression and EMT process by activation of ERK pathway.

Objective:To retrospectively analyze the clinical effects and differences in survival in 70 patients with advanced squamous carcinoma or adeno-carcinoma received chemotherapy with docetaxel plus platinum( DP regimen) in order to supply evidence for tailored treatment of the non-small cell lung cancer.Methods:Thirty-five patients with advanced pulmonary adenocarcinoma and another 35 with advanced pulmonary squamous carcinoma,pathologi-cally confirmed in Yijishan Hospital of Wannan Medical College from March of 2013 to December of 2015,underwent intravenous docetaxel( administered on day 1) plus platinum(given from day 1 to day 3) in dose of 75 mg/m2 for 4 therapy circles(21 days as one circle).Then the two groups were evaluated regarding the clinical effects and adverse response.Results:The objective response rate(ORR) was 20.0%and 28.6%,and disease control rate(DCR) was 74.3%and 71.4%,respectively for cases of advanced pulmonary adenocarcinoma and squamous carcinoma .Median survival as well as 1-and 2-year surviv-al was 16.6 months and 18.2 months,25.7%and 17.1%,and 2.9%and 5.7%for adenocarcinoma and squamous carcinoma cases,respectively.The toxic effects were generally associated with bone marrow arrest and digestive tract reaction ,and liver damage and skin rash occurred in a few of cases in the two groups of patients.Conclusion:Docetaxel plus platinum may lead to similar effects on the lung adenocarcinoma or squamous carcinoma as well as to pro-longed survival time.The side effects can be tolerated by such patients during chemotherapy.

Synchronous multiple primary lung cancer is an uncommon and difficult to distinguish from metastatic disease. The present study reported an extremely rare case of a 66-year-old male with non-small lung cell cancer in the left lobe and synchronous small cell lung cancer in the right lobe. The diagnosis of multiple primary lung cancer not only depends on biopsy pathology, but also requires molecular biology results. This is of great significance for the management and prognosis of multiple primary lung cancer. The management of patients with non-small cell lung cancer-small cell lung cancer produces certain unique challenges, which may require individualized treatment modality that may not strictly comply with standard practices in the setting of a single tumor.

AIM: To explore the anticancer function of Shp2 in lung adenocarcinoma A549 cells and the related molecular mechanisms.METHODS: The viability and proliferation of A549 cells treated with Shp2 specific inhibi-tor Phps-1 or cisplatin (DDP) were measured by CCK-8 assay and EdU assay.Annexin V-FITC/PI double staining was ap-plied to detect apoptotic rate of A549 cells with different interventions.The protein levels of caspase-3-17p, Bcl-2, Bax, p-STAT3 /STAT3 and p-ERK/ERK were determined by Western blot.RESULTS: Compared with control group, Phps-1 at the concentration of 20 μmol/L significantly increased the viability of A549 cells after 24 h of treatment ( P <0.05). Meanwhile, the proliferation rate of A549 cells in Phps-1 20 μmol/L group was significant increased compared with control group (P <0.05).The apoptotic rate of A549 cells in DDP treatment group decreased from 13.01% ±2.62% to 3.67%±0.93% after adding Phps-1 (P <0.05).Phps-1 down-regulated the protein levels of caspase-3-17p, Bax and p-ERK, but up-regulated p-STAT3.CONCLUSION: Shp2 is a tumor suppressor in A549 cells, which may be associated with the activation of STAT3 signal pathway.