The efficacy of neoantigen-reactive T cells (NRT) therapy in solid tumors, encompassing aspects such as infiltration, recognition, cytotoxicity, and enduring persistence, is notably influenced by the immunological microenvironment. This study endeavors to investigate whether the co-administration of pemetrexed and cisplatin augments the therapeutic efficacy of NRT therapy in lung cancer. Neoantigens were predicted using a comprehensive analysis of mutation data from Lewis lung carcinoma cells and mouse tail tissues. The immunogenicity of NRT cells was assessed through flow cytometry and IFN-γ ELISpot assays. A mouse model of NSCLC was used to investigate the anti-tumor effects of NRT combined with chemotherapy. The combination of NRT cells and chemotherapy significantly inhibited tumor growth in a mouse model, increased CD3+/CD137+ T cells to promote IFN-γ secretion from NRT cells, and up-regulated the levels of inflammatory cytokine proteins including IFN-γ, TNF, IL-6 and IL-10. Immunofluorescence analysis confirmed increased T-cell infiltration in tumor tissues without adverse effects on vital organs. In addition, transcriptome analyses indicated that the tumor microenvironment was altered to favor M1-like macrophages with an increased M1/M2 ratio, creating a pro-inflammatory environment. The integration of NRT with frontline chemotherapy for lung cancer could yield profoundly ideal therapeutic outcomes.

Emerging evidence suggests that tumor-specific neoantigens are ideal targets for cancer immunotherapy. However, how to predict tumor neoantigens based on translatome data remains obscure. Through the extraction of ribosome-nascent chain complexes (RNCs) from LLC cells, followed by RNC-mRNA extraction, RNC-mRNA sequencing, and comprehensive bioinformatic analysis, we successfully identified proteins undergoing translatome and exhibiting mutations in the cells. Subsequently, novel antigens identification was analyzed by the interaction between their high affinity and the Major Histocompatibility Complex (MHC). Neoantigens immunogenicity was analyzed by enzyme-linked immunospot assay (ELISpot). Finally, in vivo experiments in mice were conducted to evaluate the antitumor effects of translatome-derived neoantigen peptides on lung cancer. The results showed that ten neoantigen peptides were identified and synthesized by translatome data from LLC cells; 8 out of the 10 neoantigens had strong immunogenicity. The neoantigen peptide vaccine group exhibited significant tumor growth inhibition effect. In conclusion, neoantigen peptide vaccine derived from the translatome of lung cancer exhibited significant tumor growth inhibition effect.

IntroductionThe homeostasis of the microbiome in lower respiratory tract is crucial in sustaining normal physiological functions of the lung. Different pulmonary diseases display varying degrees of microbiome imbalance; however, the specific variability and clinical significance of their microbiomes remain largely unexplored.MethodsIn this study, we delineated the pathogen spectrum and commensal microorganisms in the lower respiratory tract of various pulmonary diseases using metagenomic sequencing. We analyzed the disparities and commonalities of the microbial features and examined their correlation with disease characteristics.ResultsWe observed distinct pathogen profiles and a diversity in lower airway microbiome in patients diagnosed with cancer, interstitial lung disease, bronchiectasis, common pneumonia, Nontuberculous mycobacteria (NTM) pneumonia, and severe pneumonia.DiscussionThis study illustrates the utility of Metagenomic Next-generation Sequencing (mNGS) in identifying pathogens and analyzing the lower respiratory microbiome, which is important for understanding the microbiological aspect of pulmonary diseases and essential for their early and precise diagnosis.

目的 探讨成年女性气胸患者病因、分类,并了解其中特发性自发性气胸(PSP)患者的体型特点、治疗效果及肺大疱的影像学诊断率.方法 回顾性分析2010年1月至2022年4月收住我科的女性气胸患者的临床资料且进行分类,对其中女性PSP患者,收集其身高、体质量并计算其BMI,根据胸部正侧位片测量胸廓的横径(TT)、矢状径(AP),登记其治疗效果及胸部CT对肺大疱的诊断率.结果 共收集89例女性气胸患者资料,其中,医源性气胸58例(65.2％),继发性自发性气胸20例(22.5％),PSP11例(12.4％);11例女性PSP中,年龄(20.9±3.9)岁;体型多消瘦,BMI值(19.5±3.4)kg/m2;低BMI者6例(54.5％),正常BMI者5例,复发性气胸3例(27.3％);发生左侧气胸者8例(72.7％),右侧气胸3例(27.3％),胸廓AP/TT比值(0.42±0.09);皆无肺部基础疾病,45.5％患者合并直背综合征;胸部高分辨CT发现胸膜下肺大疱者4例,发现率36.4％.结论 住院的女性气胸多为医源性所致,其次为继发性因素,PSP最少(多为低体质量患者,胸廓可呈扁平胸;部分患者肺部高分辨CT可见胸膜下肺大疱).

病历摘要患者男,42岁,个体经营户,主因"胸闷1个月,咳嗽、咳痰10d"于2020年7月10日入院.患者1个月前无明显诱因出现胸闷,位于左胸前,伴气促,深呼吸后好转,无胸痛、咯血,无发热,无夜间盗汗.10d前出现咳嗽,咳少许白痰,就诊当地医院.查胸部CT示双肺弥漫性病变,轻度脂肪肝.予"头孢他啶、莫西沙星"抗感染、"氨溴索"化痰等治疗,症状好转.为进一步明确肺部病变性质转诊我院.自发病以来体重无明显变化.既往确诊"2型糖尿病"10d.吸烟20年,每日2包,未戒烟.无酗酒史.家族中无类似及肿瘤疾病者.

OBJECTIVE:To identify the factors influencing the prognosis of patients with acute pulmonary embolism(PE) and to establish a prognostic model.METHODS:The clinical data of 331 patients (141 males and 190 females, aged 9 to 87 years ) with acute PE in Fujian Hospital from January 2007 to September 2013 were analyzed. Univariate analysis and logistic regression analysis were used for selecting the independent prognostic factors for acute PE. Based on logistic regression analysis, a prognostic model for PE was established.RESULTS:Univariate analysis showed that statistically significant (all P<0.05) factors influencing the prognosis of PE were diabetes, tricuspid systolic murmur, body temperature, respiratory rate, heart rate, aspartate aminotransferase, triglycerides, abnormal ECG, mechanical ventilation, circulatory failure during hospitalization, risk stratification of PE, types of treatment, and use of low-molecular-weight heparin and Warfarin. Logistic regression analysis showed that recent (<1 month) operation or fracture, tricuspid systolic murmur, high triglyceride level, circulatory failure during hospitalization and mechanical ventilation were independent factors for poor prognosis of PE, while combined use of low-molecular-weight heparin and Warfarin was a protective factor for the prognosis of PE. The Fisher prognostic model equation was y=0.144+ 1.266x1+ 0.869x2+ 1.794x3-0.517x4+ 3.555x5+ 0.661x6. The accuracy of the Fisher discriminant function was 93.0%.CONCLUSION:Recent (<1 month) operation or fracture, tricuspid systolic murmur, high triglyceride level, shock during hospitalization and mechanical ventilation were signs of poor prognosis for PE, while combined use of low-molecular-weight heparin and Warfarin were beneficial for the prognosis. The discriminant function based on these data can be helpful for predicting the prognosis of patients with PE.

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive interstitial fibrosis, and is associated with a fatal outcome. The critical pathological mechanisms underlying IPF are largely unknown; however, accumulating evidence has indicated similarities between IPF and cancer. Therefore, the present study examined the expression levels of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in Chinese patients with IPF, using an enzyme‑linked immunosorbent assay. To determine the effects of PTEN on the development of pulmonary fibrosis, PTEN was overexpressed in transforming growth factor (TGF)‑β1‑treated human embryonic lung fibroblasts (HFL‑I cells). The serum levels of PTEN were significantly lower in 42 patients with IPF, as compared with in the healthy controls. In addition, PTEN overexpression enhanced apoptosis, and suppressed basal levels of proliferation and migration in fibroblasts. Notably, PTEN was able to specifically inhibit TGF‑β1‑induced proliferation and migration of the cells. Overexpression of PTEN also suppressed phosphorylation of Akt and Smad3, and decreased the expression levels of numerous proteins with critical roles in TGF‑β1‑induced fibrosis, including α‑smooth muscle actin, matrix metalloproteinase (MMP)‑2 and MMP‑9. These results indicated that PTEN may inhibit TGF‑β1‑mediated myofibroblast differentiation of fibroblasts by attenuating signaling via the phosphatidylinositol 3‑kinase/Akt and TGF‑β/Smad3 pathways.

Objective To investigate serum levels of matrix metalloproteinase (MMP) 1,-2 and -9 in patients with idiopathic pulmonary fibrosis (IPF),and to assess their clinical value.Methods 39 clinically confirmed IPF cases and 36 healthy controls were recruited.A sample of 5 ml peripheral blood was collected from each individual and serum levels of MMP-1,-2 and 9 were detected by the enzyme-linked immunosorbent assay.Forced vital capacity (FVC) and diffusing capacity of carbon monoxide (DLCO) were measured in IPF patients.Serum levels of MMP 1,2 and-9 were compared between the groups.The correlations between serum levels of MMPs and lung function indicators were analyzed.Results The median serum levels of MMP 1,MMP-2 and MMP-9 were higher in the IPF group than in the control group [906.30 (613.50-1139.23) μg/L vs.808.38 (596.59 1249.36) μg/L,9.13 (5.95-11.92) μg/L vs.7.72 (5.28 10.35) μg/L,14.56 (8.24-18.96) μg/L vs.11.38 (8.07-17.14) μg/L,Z=-2.397,-3.564,-4.152,respectively,P=0.017,0.000,0.000].In patients with IPF,the serum level of MMP-2 was negatively correlated with DLCO％ (r=-0.53,P=0.011) and the serum level of MMP-9 had a negative correlation with FVC％ (r=-0.49,P=0.020) and DLCO％ (r=0.58,P=0.005).Conclusions Taken together,serum MMP-1,MMP-2 and MMP-9 levels may help in the clinical diagnosis of IPF.MMP 2 and MMP-9 may be important biomarkers to predict the prognosis of IPF.

目的：探讨 ICU罹患重症肺炎患者的危险因素及其预后。方法对我院 ICU 197例肺炎患者的临床资料进行回顾性分析。采用病例对照研究，将其中符合重症肺炎诊断标准的92例设为重症组，余105例非重症肺炎为非重症组，对相关资料作单因素及多因素 Logistic回归分析。结果年龄>75岁、合并呼吸衰竭、PT延长、需机械通气为 ICU 罹患重症肺炎患者的主要危险因素。凝血异常、有否合并慢性肺病、神经系统疾病、有否机械通气、感染性休克是影响重症肺炎的独立预后因素。结论 ICU重症肺炎患者影响预后的因素众多，基础病多、并发感染性休克、需要机械通气往往提示预后不良。

ObjectiveTo improve the awareness of primary pulmonary cryptococcosis(PC). Method One case of primary pulmonary cryptococcosis was analysed and relevant literatures were reviewed.Result A 29-year-old male patient was admitted to the hospital on July, 2014 because of cough and expectoration for a month and dyspnea for 22 days.The lung CT showed multiple subpleural patchy or mass shadows within the both lungs. The bronchial lung biopsy has confirmed the dianogsis.Fluconnazole was given intravenously for 2 weeks but failed. A percutaneous lung biopsy and a pathological examination were performed to comfirm the diagnosis of PC again.The patient was reevaluated and considered as severe condition. Amphotericin B plus 5-fluorine cytosine were used for 1 month and followed by fluconazole as the antifungal therapy.The patient’s condition was alleviated and the lung lesion was significantly absorbed.Conclusion Primary pulmonary cryptococcosis lacking in specificities of clinical and imaging findings is easily misdiagnosed and mistreated.Prompt lung biopsy and pathology with special stains can confirm the diagnosis. Less invasive percutaneous lung biopsy is recommended. As severe condition was less commonly seen in PC patients, clinicians should strive to obtain tissue cultures and perform a sensitivity test.Antifungal therapy should refer to the cryptococcus neoformans meningitis treatment.

Objective To investigate the influence of Six1 on cell proliferation and migration in A549 cell line and its mechanism.Methods Six1 specific Si-RNA was transfected into human lung carcinoma cell line A549.We detected the efficien-cy of transfection by Western blot.The effects of si-Six1 on A549 cell growth was by means of MTT and cell count assay;The effects of Six1 on A549 cell migration was by means of cell scratch test and transwell assay;The protein expression of PI3K Sig-nal pathway was detected by western blot.Results In A549 cell line,the expression of Six1 was knocked-down by specific si-RNA,and down-regulation of Six1 decreased the expression of p-AKT,which led to decrease of the ability of proliferation and migration of A549.Conclusion Six1 inhibits the proliferation and migration of A549 cells through PI3K pathway.

Objective To study elderly patients with severe pneumonia risk factors and prognostic factors.MethodsBy a case-control study,collection 101 case from Fujian Provincial Hospital ICU in June 2007 ~ December 2008 of elderly(≥65 years) pneumonia patients,62 cases are elder severe pneumonia,set it to case group,and the remained 39 cases of elder non-severe pneumonia as the control group.Univariate analysis(chi-square test and rank sum test) and multivariate Logistic regression were used for statistics analysis.ResultsThe average age of patients is [mean age(79.32±6.71) years],the total number of hospitalization days is [mean(53.53±60.12) days],the number of hospitalization days in ICU is[mean(33.08±48.77) days],fatality rate is 32.25%.The main pathogen is gram negative bacilli(62.69%),acinetobacter baumannii occupied 25.37%.Multivariable logistic regression analysis showed that: Fine ⅣⅤ,respiratory failure,PT13.0S and TBIL17.0 μmol/L are the independent risk factors of occurred elderly severe pneumonia.Haemoglobin 90 g/L,mechanical ventilation and FineⅤ are independent predictive factor.ConclusionFine ⅣⅤ,respiratory failure,PT13.0S and TBIL17.0 μmol/L are the independent risk factors of occurred the elder severe pneumonia.Haemoglobin90 g/L,mechanical ventilation and FineⅤare independent predictive factor.Fine′s risk classification has great value in elderly patient′s condition assessment and prediction of prognosis.