Rationale: Myeloid-derived suppressor cells (MDSCs) play a critical role in inducing T-cell lymphopenia in sepsis, and the highly heterogeneous MDSCs necessitate the identification of key molecules within these cells. Methods: By integrating bulk and single-cell transcriptomic sequences, we identified the critical molecular and MDSC subpopulation in pneumonia-induced sepsis (PIS) models. Through fluorescence-activated cell sorting (FACS) technology, we isolated the primary target subset to evaluate its immunosuppressive potential via T-cell proliferation assays, and investigate the underlying cellular and molecular mechanisms. To assess the immunological consequences of molecular interventions (pharmacologic blockade and shRNA-mediated knockdown), we employed a "two-hit" experimental model to monitor T-cell-aassociated immune responses and hosts' outcomes following secondary infection. Futhermore, we collected and analyzed clinical samples to support of translating the cellular and molecular concept to human context. Results: We confirmed the specific enrichment of arginase-2 (ARG2) in CXCR2Hi MDSCs, which expanded during sepsis and drove immunosuppression via ARG2-mediated arginine depletion. The blockade of ARG2 and arginine supplements improved the proliferation and decreased apoptosis of CD4+ T cells. In PIS models, both ARG2 inhibition and knockdown regained CD4+ T cells in lung and bone marrow sites, thus enhancing host's resistance to secondary infections caused by opportunistic pathogens. Further mechanistic investigations indicated p38-MAPK as a critical regulator of the protein stability of the immunosuppressive molecule ARG2 in CXCR2Hi MDSCs, particularly in response to lipopolysaccharide (LPS) stimulation. In the human context, we revealed that CXCR2Hi MDSC increased in peripheral in septic patients and correlated significantly to lymphopenia and elevated ARG2 levels. Conclusions: Sepsis stimulated p38-MAPK signaling and expanded ARG2-enriched CXCR2Hi MDSCs to mediate septic lymphopenia via arginine depletion. The ARG2 inhibition restored T-cell immunity against secondary infection in septic immunosuppressed hosts. These findings identified CXCR2Hi MDSC-derived ARG2 as a promising target of immune enhancement therapy in sepsis.

IntroductionHepatoid adenocarcinoma of the lung (HAL) is a special type of adenocarcinoma originating from the lung with adenoid- and hepatocyte-like differentiation. HAL is rare in clinical practice. Here, we present the case of a patient with HAL.Case presentationA 59-year-old man was admitted to the hospital 4 days because of lung mas observed. Chest computed tomography (CT) revealed a lobulated mass shadow in the right lower lobe, approximately 3.5 × 3.3 cm in size. CT-guided percutaneous biopsy of the right lower lung was performed. The pathological results indicated a moderately to poorly differentiated adenocarcinoma. The patient underwent thoracoscopic right middle and lower lobectomy and systematic lymph node dissection. The postoperative pathology was primary HAL, with the staging of T2bN2M0 (stage III A). Recurrence-free survival and overall survival were 6 and 19 months, respectively Preoperatively, the level of alpha-fetoprotein was negative; however, after recurrence, it increased to 87.8.ConclusionPulmonary hepatoid adenocarcinoma is a rare subtype of malignant lung tumor, combined silicosis is more rare. Early surgical intervention can benefit patients in the early stages of the disease, whereas chemotherapy remains the main systemic treatment modality for postoperative and advanced stages. With the increasing popularity of genetic testing, it is important to focus on improving genetic examination.

BACKGROUND:Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. OBJECTIVE:The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. METHODS:The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. RESULTS:PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-β signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. CONCLUSION:PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

目的 探讨胸腔镜肋骨骨折复位内固定术治疗多发肋骨骨折的安全性和有效性.方法 选择2019年11月至2020年12月厦门大学附属翔安医院收治的多发肋骨骨折患者67例,采用胸腔镜进行肋骨骨折复位并使用记忆合金反向肋骨环抱器进行内固定手术治疗67例多发肋骨骨折(≥3根)患者,回顾性分析切口长度、总手术时间、不同部位每根肋骨平均复位固定手术时间、放置成功率、术后并发症等情况.结果 67例患者均顺利完成手术,手术时间(102.5±31.1)min,无死亡及重大并发症发生.术中每例患者放置胸腔内记忆合金环抱器3～11枚,100％放置成功.手术切口长度(2.8±0.7)cm,出血量(80.7±17.6)ml.单根肋骨的切开复位固定时间,前肋(41.9±7.1)min,侧肋(62.9±14.3)min,后肋(24.7±8.4)min,骨折位于后肋者手术时间较其他部位更短.结论 胸腔镜下使用记忆合金反向肋骨环抱器进行胸腔内肋骨骨折固定安全可靠,内固定环抱器放置成功率高,骨折临床愈合良好,并具有创伤小、同期可治疗肺挫伤、肺大疱、肺结节等胸腔内其他疾病的优势,尤其适合后肋多发骨折的治疗.

目的 介绍胸腔镜下经原切口取出既往因手术治疗肋骨骨折放置的胸腔内记忆合金反向肋骨环抱器(以下简称"腔内接骨板")的方法.方法 回顾性分析2020年7月至2022年1月于胸腔镜下使用原手术切口,在肋骨骨折愈合后取出腔内接骨板的20例患者的临床资料.结果 腔内接骨板均顺利取出,其中接骨板位于右侧10例,左侧8例,双侧2例;单纯使用腔内接骨板8例,腔内接骨板+腔外接骨板12例;肋骨骨折内固定术后在1年内取出腔内接骨板者18例,超过1年取出腔内接骨板者2例.术后所有患者均未出现感染、再骨折、神经损伤、血管损伤及中转开胸.取出术后均获得3个月随访,机体功能均恢复正常.结论 胸腔镜下经原切口取出记忆合金反向肋骨环抱器,未出现感染、神经血管损伤等,无严重并发症,安全可行.

Some studies have suggested heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) to be a promoter in cancer development. Nonetheless, no detailed pan-cancer investigation has been reported. Thus, this study explored the possible oncogenic role of HNRNPA2B1, such as its expression levels, gene alteration, protein–protein interaction network, immune infiltration, and prognostic value in different cancer types using The Cancer Genome Atlas web platform. Many types of cancer exhibit HNRNPA2B1 overexpression, which is notably associated with poor prognosis. We also found that HNRNPA2B1 with different methylation levels causes a varied prognosis in lung adenocarcinoma (LUAD). It is noteworthy that HNRNPA2B1 levels are connected with cancer-associated fibroblasts in cancers, such as adrenocortical carcinoma, LUAD, and stomach adenocarcinoma. In addition, HNRNPA2B1 participates in the spliceosome- and cell cycle-associated pathways. Finally, HNRNPA2B1 is highly valued in the diagnosis of LUAD, lung squamous cell carcinoma, breast invasive carcinoma, esophageal carcinoma, and liver hepatocellular carcinoma. This systematic study highlighted the role of HNRNPA2B1 in pan-cancer progression.

The key N 6 methyladenosine (m 6 A) RNA methylation regulator is associated with multiple tumour progression. However, the m 6 A‐associated regulators that influence non‐small cell lung cancer (NSCLC) development have not been fully clarified. The m 6 A regulator expression pattern of NSCLC patients from The Cancer Genome Atlas (TCGA) dataset was identified. Aberrations of m6A modulators are related to NSCLC development via cBioPortal database. Furthermore, we found that IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO are significantly correlated with advanced stage disease or clinical outcomes in NSCLC by UALCAN and Kaplan–Meier plot. Bioinformatics analysis showed that m 6 A modulators (IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO) are associated with immunomodulator and immune infiltration expression in NSCLC via the Tumor Immune Estimation Resource (TIMER) database. The co‐expression between these m6A‐associated modulators was analysed by protein‐protein interaction networks. Finally, we found that HNRNPA2B1 promotes NSCLC development in vitro by regulating cell proliferation and metastasis functions via Cell Counting Kit 8 (CCK8) and transwell assay. Our study showed that HNRNPA2B1 is a promising target and biomarker for cancer therapy in NSCLC.