Osteoporotic vertebral compression fracture (OVCF) is a common degenerative disease in the elderly. Biomechanical stimulation plays a key role in regulating bone remodeling and healing. In this study, a solid-liquid two-phase poroelastic finite element model was used to simulate bone remodeling in severely osteoporotic vertebrae under five functional loading modes: standing, flexion, extension, lateral bending, and axial rotation. Changes in tissue differentiation, mean elastic modulus, and interstitial fluid velocity in cortical and cancellous bone were quantitatively analyzed over the 77-day healing period. The results showed that standing and axial rotation significantly increased the elastic modulus of cortical bone and promoted osteogenic maturation, whereas flexion exhibited the weakest osteogenic effect. Cancellous bone regeneration was driven mainly by mesenchymal stem cell diffusion and was less affected by loading patterns. Biophysical stimuli (deviatoric strain and fluid flow) gradually decreased with tissue maturation, and the tissue differentiation follows a typical sequence: fibrous tissue, cartilage, immature bone, mature bone. This study reveals the biomechanical mechanism of bone remodeling under different rehabilitation loads and provides in silico theoretical reference for exploring personalized rehabilitation strategies, and cannot be directly applied as clinical treatment guideline.

Despite advancements in immunotherapy, particularly regarding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 blockades, the clinical outcomes in non-small cell lung cancer (NSCLC) remain variable with limited predictive biomarkers currently available. The present study investigated respiratory microbiota diversity as a potential biomarker to predict the efficacy of PD-1 blockades in patients with advanced NSCLC. A retrospective analysis was conducted on 60 patients treated with PD-1 blockades from May 2019 to May 2023. Clinical data were collected and respiratory microbiota from deep induced sputum specimens were analyzed using 16S rRNA gene sequencing. An index of respiratory microbiota α diversity was applied and exploratory analysis was performed accordingly. The objective response rate (ORR) and disease control rate among the 60 patients receiving PD-1 blockades was 23.3% (95% CI, 13.4-36.0%) and 58.3% (95% CI, 44.9-70.9%), respectively. Analysis of prognostic data of patients with advanced NSCLC receiving PD-1 blockades monotherapy demonstrated a median progression-free survival of 3.4 months (95% CI, 2.54-4.26) and a median overall survival (OS) of 12.3 months (95% CI, 6.29-18.31). Patients were stratified into high and low α diversity groups based on the Shannon diversity index of respiratory microbiota. The ORR was increased in the high diversity group (26.7%) compared with that of the low diversity group (20.0%), although the difference was not statistically significant (P=0.542). Notably, the high diversity group demonstrated a longer median PFS (3.9 vs. 2.8 months; P=0.017) and median OS (16.8 vs. 6.8 months; P=0.016) compared with that of the low diversity group. These findings suggested that PD-1 blockades demonstrate promising therapeutic activity for patients with previously treated advanced NSCLC in clinical practice. Respiratory microbiota α diversity might serve as a potential biomarker to predict the efficacy of PD-1 blockades monotherapy in patients with advanced NSCLC in the future. Therefore, further prospective studies are warranted to validate these findings and to explore the underlying mechanisms by which respiratory microbiota might modulate the immune response to cancer therapy.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease characterized by a poor survival prognosis of only 3-5 years post-diagnosis and limited treatment options. Notably, the incidence of IPF is particularly high among the elderly population. Zanubrutinib is a second-generation Bruton's tyrosine kinase (BTK) inhibitor independently developed by BeOne Medicines Ltd, which is approved by the FDA for a variety of B-cell lymphomas, including mantle-cell lymphoma. In this study, we discuss the potential effects and mechanisms of Zanubrutinib on aging lung fibrosis in vivo and in vitro. In vivo studies demonstrated that Zanubrutinib could effectively alleviate bleomycin-induced pulmonary fibrosis in senescent mice and significantly reduce the expression of fibrosis markers and senescence markers. In vivo studies demonstrated that Zanubrutinib inhibited the fibrotic phenotype as well as the senescent phenotype of mouse fibroblasts and mouse epithelial cells. Zanubrutinib effectively inhibited BTK phosphorylation and Wnt/β-catenin signaling pathway transduction, and reduced β-catenin entry into the nucleus. In conclusion, Zanubrutinib may alleviate the senescence-associated phenotype and mitigate senescence-associated pulmonary fibrosis by inhibiting the Wnt/β-catenin signaling pathway.

A substantial proportion of patients with intrahepatic cholangiocarcinoma (ICC) present with symptoms such as fever or abdominal pain, which are frequently linked to unfavorable prognostic outcomes. A retrospective analysis of the clinical data from 125 patients diagnosed with ICC was conducted. Univariate and multivariate analyses were carried out to assess overall survival (OS) and disease-free survival (DFS). Subsequently, the patients were stratified into 2 groups based on the presence or absence of symptoms. The presence of symptoms is recognized as a risk factor associated with an unfavorable prognosis (OS: 2.026 [1.133–3.624], P = .017); DFS: 1.590 [1.004–2.517], P = .048). Patients presenting symptoms exhibit a higher prevalence of lymph node metastasis ( P = .032), microvascular invasion ( P = .041), and higher CA19-9 levels ( P = .020). Survival curves revealed that OS ( P = .010) and DFS ( P = .017) were significantly poorer among patients with ICC exhibiting COX-2 (+). Moreover, an analysis of the immune microenvironment in patients with COX-2 (+) indicated a higher presence of CD163+ cells ( P = .018) compared to that of patients with COX-2 (−). ICC patients with symptoms are associated with a dismal prognosis and a pronounced expression of COX-2 within the tumor tissues. Our study suggests that preoperative symptoms may serve as a clinical indicator of aggressive tumor biology and immune microenvironment alterations, and that COX-2 expression may represent a potential therapeutic target.

Black raspberry as a functional food is a potential modulator of human metabolic disease. However, the role of black raspberry polyphenols (HSM) in shaping metabolic dysregulation and perturbation in gut microbiota (GM) to promote lipid metabolism and liver regeneration is unclear. In this work, the effects of HSM in mitigating metabolic disturbances and hepatic damage induced by a high-fat diet (HFD) and antibiotics (Abs) in mice were measured. HSM significantly alleviated HFD-induced obesity, insulin resistance, lipid and glucose metabolic dysregulation, as well as hepatic damage by activating the PI3K/AKT pathway and pregnane X receptor (PXR)-farnesoid X receptor (FXR) axis with improved GM, which was evidenced by short-chain fatty acids, 16S, and nontarget metabolism analysis. Excellent results were also evident in mice treated with Abs. Besides, HSM markedly inhibited key digestive enzymes associated with metabolic syndrome and also significantly enhanced antioxidant capacity after metabolized by GM. The discoveries underscored the potential of dietary HSM to manage lipid metabolism and liver regeneration within GM homeostasis.

Pyroptosis, a typical inflammatory cell death mode, has been increasingly demonstrated to have therapeutic value in inflammatory diseases such as sepsis. However, the mechanisms and therapeutic targets of sepsis remain elusive. Here, we reported that REGγ inhibition promoted pyroptosis by regulating members of the gasdermin family in macrophages. Mechanistically, REGγ directly degraded Bim, a factor of the Bcl-2 family that can inhibit the cleavage of GSDMD/E, ultimately preventing the occurrence of pyroptosis. Furthermore, cecal ligation and puncture (CLP)-induced sepsis model mice showed downregulation of REGγ at both the RNA and protein levels. Gasdermin-mediated pyroptosis was augmented in REGγ-knockout mice, and these mice exhibited more severe sepsis-related tissue injury. More importantly, we found that REGγ expression was downregulated in clinical sepsis samples, such as those from patients with Pseudomonas aeruginosa (PA) infection. Finally, PA-infected mice showed decreased REGγ levels in the lung. In summary, our study reveals that the REGγ-Bim-GSDMD/E pathway is a novel regulatory mechanism of pyroptosis in sepsis-related tissue injury.

Objective:To explore the feasibility of sampling Chinese patients by suction curettage for cytological and histological screening of endometrial cancer related to Lynch syndrome. Methods:This retrospective study enrolled patients who underwent endometrial biopsy at our hospital between May 2018 and January 2019. Endometrial sampling (cytological and micro-histological specimens) was conducted by suction curettage. The gold standard for diagnosis was traditional sharp dilation and curettage (D&C). The sensitivity, specificity, and diagnostic accuracy of cytology, micro-histology, and the combination of cytology and micro-histology were calculated. Additionally, receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficiency of three screening methods. Mismatch repair proteins were further detected using immunohistochemistry (IHC) in endometrial cancer. Results:This retrospective finally enrolled 100 patients, which satisfactory samples were obtained from 96 patients for liquid-based cytology and 93 patients for microtissue histology. The concordance rates with D&C, sensitivity, and specificity were 94.8%, 76.9%, and 97.5% for liquid-based cytology, 96.8%, 84.6%, and 98.8% for microtissue histology, and 99.0%, 92.3%, and 100.0% for liquid-based cytology and microtissue histology combined, respectively. The AUC of ROC curves in liquid-based cytology, microtissue histology, and the combined methods for diagnostic ability were 0.873, 0.917, and 0.962, respectively. Absence rates of MLHl, MSH2, MSH6, and PMS2 proteins were 15.3% (2/13), 0% (0/13), 7.7% (1/13), and 15.3% (2/13) in the 13 endometrial cancer samples. Conclusion:Liquid-based cytology and microtissue histology samples from suction curettage combined IHC are useful for endometrial cancer screening.

Purpose Discovery of noninvasive urinary biomarkers for the early diagnosis of esophageal squamous carcinoma (ESCC). Methods We conducted proteomic analyses of 499 human urine samples obtained from healthy individuals (n = 321) and ESCC (n = 83), bladder cancer (n = 17), breast cancer (n = 12), colorectal cancer (n = 16), lung cancer (n = 33) and thyroid cancer (n = 17) patients from multiple medical centers. Those samples were divided into a discovery set (n = 247) and an independent validation set (n = 157). Results Among urinary proteins identified in the comprehensive quantitative proteomics analysis, we selected a panel of three urinary biomarkers (ANXA1, S100A8, TMEM256), and established a logistic regression model in the discovery set that can correctly classify the majority of ESCC cases in the validation sets with the area under the curve (AUC) values of 0.825. This urinary biomarker panel not only discriminates ESCC patients from healthy individuals but also differentiates ESCC from other common tumors. Notably, the panel distinguishes stage I ESCC patients from healthy individuals with AUC values of 0.886. On the analysis of stage-specific biomarkers, another combination panel of protein (ANXA1, S100A8, SOD3, TMEM256) demonstrated a good AUC value of 0.792 for stage I ESCC. Conclusions Urinary biomarker panel represents a promising auxiliary diagnostic tool for ESCC, including early-stage ESCC.

Most antiangiogenic inhibitors targeting endothelium-dependent vessels cannot inhibit tumor growth but promote tumor invasion and metastasis in some patients. Vasculogenic mimicry (VM) employs mechanisms that differ from those used to construct endothelium-dependent vessels. Inhibiting VM may be a novel antiangiogenic strategy against alternative tumor vascularization. In this paper, myricetin was selected from among several flavonoid compounds as an effective PAR1 antagonist. In two different hepatocellular carcinoma (HCC) cell lines high-expressed PAR1, myricetin inhibited cell migration, invasion and VM formation and reversed the expression of epithelial-endothelial transition (EET) markers by inhibiting PAR1 activation. Knockout of PAR1 inhibited HCC cell invasion and metastasis and weakened the inhibitory effect of myricetin on HCC cells. The migration, invasion and tube formation ability of PLC-PRF-5 cells were enhanced after PAR1 overexpression, and the inhibitory effect of myricetin was enhanced. A docking assay revealed that myricetin binds to Leu258 and Thr261 in the PAR1 activity pocket. Mutation of Leu258 and Thr261 inhibited the antitumor effect of myricetin in vitro and in vivo. In summary, myricetin reverses PAR1-mediated EET and inhibits HCC cell invasion, metastasis, VM formation and angiogenesis by targeting PAR1, and Leu258 and Thr261 of PAR1 participate in VM and angiogenesis in HCC tissues.

Acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) was increasingly recognized as one of the most severe acute hyperimmune response of coronavirus disease 2019 (COVID-19). Clofazimine (CFZ) has attracted attention due to its anti-inflammatory property in immune diseases as well as infectious diseases. However, the role and potential molecular mechanism of CFZ in anti-inflammatory responses remain unclear. We analyze the protein expression profiles of CFZ and LPS from Raw264.7 macrophages using quantitative proteomics. Next, the protective effect of CFZ on LPS-induced inflammatory model is assessed, and its underlying mechanism is validated by molecular biology analysis. LC–MS/MS-based shotgun proteomics analysis identified 4746 (LPS) and 4766 (CFZ) proteins with quantitative information. The key proteins and their critical signal transduction pathways including TLR4/NF-κB/HIF-1α signaling was highlighted, which was involved in multiple inflammatory processes. A further analysis of molecular biology revealed that CFZ could significantly inhibit the proliferation of Raw264.7 macrophages, decrease the levels of TNF-α and IL-1β, alleviate lung histological changes and pulmonary edema, improve the survival rate, and down-regulate TLR4/NF-κB/HIF-1α signaling in LPS model. This study can provide significant insight into the proteomics-guided pharmacological mechanism study of CFZ and suggest potential therapeutic strategies for infectious disease.

Non-small cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer, which constitutes the leading cause of cancer mortality. RAB26, a member of Rab GTPase superfamily, has been suggested to play a role in the tumorigenesis of NSCLC. The present work aimed to explore whether and how RAB26 contributed to the progression of NSCLC. NSCLC cell line A549 was transfection with short hairpin RNA (shRNA) or overexpression (Ov) vector to knockdown RAB26 or overexpress SMAD3, respectively. Then the malignant processes of A549 cells including proliferation, migration, invasion and apoptosis were evaluated by CCK-8, colony formation, wound-healing, transwell and TUNEL assays, respectively. Expression of proteins involved in these processes was measured by western blot. A549 xenograft mice model was established to confirm the effect of RAB26 silence on NSCLC progression in vivo. The relationship between RAB26 and SMAD3 was analyzed by bioinformatics and then verified by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. We found that silence of RAB26 inhibited the proliferation, migration and invasion but promoted apoptosis of A549 cells. In vivo studies revealed that the tumor growth of A549 xenograft was markedly suppressed upon RAB26 silence. Moreover, it was confirmed that SMAD3 bound to the promoter of RAB26 and enhance its expression. Finally, we observed that overexpression of SMAD3 significantly blocked the inhibitory effect of RAB26 silence on NSCLC progression. Collectively, RAB26 may contribute to the progression of NSCLC after being transcriptionally activated by SMAD3.

BACKGROUND:Synaptogyrin-2 (SYNGR2) plays an important role in regulating membrane traffic in non-neuronal cells. However, the role of SYNGR2 in esophageal squamous cell carcinoma (ESCC) remains unclear.METHODS:All original data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated via R 3.5.3. SYNGR2 expression was explored in the TCGA and GEO databases. The correlations between SYNGR2 and cancer immune characteristics were analyzed via the TIMER and TISIDB databases.RESULTS:In general, SYNGR2 was predominantly overexpressed and had reference values in the diagnosis and prognostic estimation of ESCC. Upregulated SYNGR2 was associated with poorer overall survival, disease-specific survival and T stage in ESCC. Mechanistically, we identified hub genes that included a total of 38 SYNGR2-related genes, which were tightly associated with the protein polyubiquitination pathway in ESCC patients. SYNGR2 expression was negatively related to the infiltrating levels of T helper cells. SYNGR2 methylation was positively correlated with the expression of chemokines (CCL2 and CXCL12), chemokine receptors (CCR1 and CCR2), immunoinhibitors (CXCL12 and TNFRSF4) and immunostimulators (CSF1R and PDCD1LG2) in ESCC.CONCLUSION:SYNGR2 may be used as a biomarker for determining prognosis and immune infiltration in ESCC.

Aim: Acute Lung Injury (ALI) is an acute hypoxic respiratory insufficiency caused by various traumatic factors, manifested as progressive hypoxemia and respiratory distress, and lung imaging shows a heterogeneous osmotic outbreak. Isorhamnetin (ISO) is a flavonoid compound isolated and purified from medicinal plants, such as Hippophae rhamnoides L. and Ginkgo, and has multiple pharmacological functions, such as anti-tumor, anti-myocardial hypoxia, and cardiovascular protection. Our previous study has shown that ISO could attenuate lipopolysaccharide (LPS)-induced acute lung injury in mice, but its mechanism is not clear. Methods: In this study, we used LPS-induced mouse and cell models to research the mechanism of ISO alleviating acute lung injury. Results: The results showed that ISO could attenuate the injury of type II alveolar epithelial cells by inhibiting the TLR4/NF-kappa B pathway. Further studies showed that ISO could inhibit the activation of mTOR signal in vivo and in vitro and promote autophagy in alveolar epithelial cells to reduce lung injury caused by LPS. In addition, ISO could inhibit LPS-induced epithelial cell apoptosis. Conclusion: Overall, ISO could suppress injury and apoptosis of epithelial cells and activate autophagy to protect epithelial cells via inhibiting mTOR signal and attenuating LPS-induced acute lung injury in mice.

Objective: Ginsenoside Rd (GSRd) displays a variety of pharmacological effects. However, the underlying role in acute lung injury (ALI) is not clear. In this study, the protective effect of GSRd on lipopolysaccharide (LPS)-induced ALI is investigated to explore the potential mechanisms. Methods: GSRd-target-ALI-related gene set was constructed. And bioinformatics tools were used to discover the potential mechanism. We observed the survival of subjects for 72 h. In addition, male BALB/c mice were intraperitoneal injected with GSRd (25 and 50 mg/kg) after received one intratracheal instillation of LPS. Inflammatory changes, oxidative stress, and phosphorylation were assessed to study the biological effects. Results: A total of 245 interaction genes were collected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were enriched in immune-inflammatory system. Among them, PI3K-Akt signaling pathway was the highest-ranked pathway of inflammatory response. In vivo study, it was found that GSRd improved survival in endotoxemic mice and inhibited the major characteristic of ALI. And the p-PI3K and p-Akt expression was significantly decreased by GSRd treatment. Conclusion: GSRd could protect mice against LPS-induced ALI effectively by inhibiting the PI3K-Akt signaling pathway.

Idiopathic pulmonary fibrosis is a progressive lung disease with high mortality and limited therapy that is characterized by epithelial cell damage and fibroblast activation. Ellagic acid is a natural polyphenol compound widely found in fruits and nuts that has multiple pharmacological activities. In this study, we explored the potential effects and mechanisms of Ellagic acid on pulmonary fibrosis in vivo and in vitro . In vivo studies showed that Ellagic acid significantly alleviated bleomycin (BLM)-induced pulmonary fibrosis in mice. In vitro experiments indicated that Ellagic acid could suppress Wnt signaling and attenuate Wnt3a-induced myofibroblast activation and the phosphorylation of Erk2 and Akt. Further studies showed that Ellagic acid could induce autophagy formation in myofibroblasts mainly by suppressing mTOR signaling and promoting apoptosis of myofibroblasts. In vivo experiments revealed that Ellagic acid significantly inhibited myofibroblast activation and promoted autophagy formation. Taken together, our results show that Ellagic acid effectively attenuates BLM-induced pulmonary fibrosis in mice by suppressing myofibroblast activation and promoting autophagy and apoptosis of myofibroblasts by inhibiting the Wnt signaling pathway.

The coronavirus disease 2019 (COVID-19) has spread widely around the world and has seriously affected the human health of tens of millions of people. In view of lacking anti-virus drugs target to SARS-CoV-2, there is an urgent need to develop effective new drugs. In this study, we reported our discovery of SARS-CoV-2 Mpro inhibitors. We selected 15 natural compounds, including 7 flavonoids, 3 coumarins, 2 terpenoids, one henolic, one aldehyde and one steroid compound for molecular docking and enzymatic screening. Myricetin were identified to have potent inhibit activity with IC50 3.684 ± 0.076 μM in the enzyme assay. The binding pose of Myricetin with SARS-CoV-2 Mpro was identified using molecular docking method. In the binding pocket of SARS-CoV-2 Mpro, the chromone ring of Myricetin interacts with His41 through π-π stacking, and the 3’-, 4’- and 7-hydroxyl of Myricetin interact with Phe140, Glu166and Asp187 through hydrogen bonds. Significantly, our results showed that Myricetin has potent effect on bleomycin-induced pulmonary inflammation by inhibiting the infiltration of inflammatory cells and the secretion of inflammatory cytokines IL-6, IL-1α, TNF-α and IFN-γ. Overall, Myricetin may be a potential drug for anti-virus and symptomatic treatment of COVID-19.

Background Baicalin is a naturally occurring compound with anticancer, antioxidant, and anti-inflammatory properties. However, the mechanism underlying its anticancer activity on nonsmall cell lung cancer (NSCLC) remains unclear. Methods The effects of baicalin on the progression and metastasis of experimental NSCLC cell lines were studied in vitro and in vivo. Wound-healing and transwell assays were performed to evaluate the potency of baicalin and the motility and migration ability of NCI-H460 cells. Immunofluorescence assay, western blot assay, and immunohistochemistry test were conducted to investigate the inhibiting effect of baicalin on the epithelial-mesenchymal transition (EMT) of NSCLC. Results Baicalin inhibited the proliferation and migration of NCI-H446 human NSCLC cells in a dose-dependent manner, reduced the expression levels of phospho-3-phosphoinositide-dependent protein kinase 1 (p-PDK1) and phosphor-serine/threonine-protein kinase (p-AKT), reversed the levels of EMT markers, and inhibited the migration of NSCLC cells. Conclusions Baicalin impedes EMT by inhibiting the PDK1/AKT pathway in human NSCLC and thus may be an effective alternative treatment for carcinoma and a new candidate antimetastasis drug.

Background: Zc3h12d is a negative regulator which plays a crucial role in immune modulation. However, the role of zc3h12d in lung adenocarcinoma (LUAD) remains unclear. We aim to explore the prognostic of zc3h12d and investigate the relationship between zc3h12d expression and immune infiltration in LUAD. Methods: TIMER site was used to analyze the expression of zc3h12d in LUAD. The zc3h12d protein levels in patient tissue samples were detected by immunohistochemistry staining assays. Meanwhile, based on UALCAN database and samples' data from our cohort, we explored the relationship of clinicopathological features and zc3h12d expression to determine the clinical effect of zc3h12d in LUAD. Several databases including GEPIA, Kaplan-Meier plotter and our samples' data were used to explore the prognostic value of zc3h12d in LUAD. Cox regression analysis was established to further evaluate the prognostic value of zc3h12d in LUAD. In addition, zc3h12d promoter methylation was analyzed by UALCAN database. Genetic alteration analysis was observed in the cBioPortal web. GO and KEGG analyses were conducted to elucidate the underlying mechanisms. Finally, the correlation between zc3h12d and tumor-infiltrating immune cells in LUAD was investigated by TIMER database. The B cells level was investigated by flow cytometry analysis of peripheral blood from our LUAD cohort. Results: Zc3h12d expression was significantly higher in LUAD, compared with adjacent normal tissues. The clinical data from the UALCAN database demonstrated that zc3h12d expression was closely related with cancer stage and nodal metastasis. However, patient sample detection revealed that zc3h12d expression was closely related to pathological N (p = 0.0431) and grade (p = 0.004). Moreover, low zc3h12d expression was associated with poorer overall survival in LUAD. We analyzed the methylation level of zc3h12d in LUAD and found that the methylation levels of zc3h12d promoter in LUAD were significantly reduced. In addition, zc3h12d genetic alterations, including deep deletion, could be found in LUAD. GO and KEGG pathway analysis results indicated that zc3h12d has a certain value in immune infiltration. We investigated the expression of zc3h12d in tumor-immune interactions. It was found that zc3h12d might be associated with the immune infiltration and markers of infiltrating immune cells of LUAD. The results of patient sample detection confirmed that B cells level was significantly lower in the patients with low zc3h12d expression than those in the patients with high zc3h12d expression. Conclusion: zc3h12d might be considered as a potential biomarker for determining prognosis and immune-related therapeutic target in LUAD.

Abstract Purpose The objective of our study was to investigate the epidemiologic characteristics and prognostic factors in patients with pulmonary acinar cell carcinoma (PACC). Methods PACC patients diagnosed between 1975 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The trend in PACC incidence was assessed using joinpoint regression software. Overall survival (OS) and disease‐specific survival (DSS) were evaluated using the Kaplan–Meier method and log‐rank test. Univariate and multivariate Cox regression analysis was performed to identify the independent prognostic factors for OS and DSS. Nomograms to predict survival possibilities were constructed based on the identified independent prognostic factors. Results A total of 2918 patients were identified with PACC. The mean age was 65.2 ± 8.95 years with a female to male of 1.6:1. The incidence of PACC steadily increased by an annual percentage change (APC) of 3.2% (95% CI 2.1–4.4, p < 0.05). Multivariate Cox regression analysis revealed that age, gender, race, stage, grade, tumor size, number of positive lymph nodes, surgery, and chemotherapy were independent prognostic factors for survival. Nomograms specifically for PACC were constructed to predict 1‐ and 5‐year OS and DSS possibility, respectively. The concordance index (C‐index) and calibration plots showed the established nomograms had robust and accurate performance. Conclusion PACC was rare but the incidence has been steadily increasing over the past four decades. Survival has improved in recent years. Surgery or chemotherapy could provide better OS and DSS. The established nomograms specifically for PACC were robust and accurate in predicting 1‐ and 5‐year OS and DSS.

Wei Li* Xiaoqing Li * Xiaoping Li Mingjiang Li Pan Yang Xuhui Wang Lei Li Bo Yang 1Department of Thoracic Surgery, Tianjin First Central Hospital, Tianjin 300192, People’s Republic of China; 2Phase I Clinical Trial Department, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Centre for Cancer, Tianjin 300052, People’s Republic of China