BackgroundPneumocystis pneumonia (PCP) remains a major cause of morbidity and mortality in immunocompromised individuals. Although baicalin (Ba), a natural bioactive flavonoid, has demonstrated protective and therapeutic effects against PCP, its molecular mechanisms remain undefined. We employed dual RNA sequencing (dual RNA-seq) to characterize host and pathogen transcriptional responses to Ba treatment in an immunosuppressed rat model of PCP.MethodsComparative transcriptomic analyses identified differentially expressed genes in both the host and Pneumocystis, followed by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses. Candidate targets were further investigated using network pharmacology, protein–protein interaction analysis, molecular docking, and molecular dynamics simulations. Key findings were validated by immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative PCR.ResultsBa markedly remodeled host and pathogen transcriptomes. Host transcriptomic analyses showed that Ba attenuated inflammatory and oxidative stress responses by modulating immune-related pathways, including Toll-like receptor, NF-κB, cytokine-cytokine receptor interaction, chemokine signaling, Th17 cell differentiation, and antigen processing and presentation. Experimental validation demonstrated that Ba reduced pulmonary expression of indoleamine 2,3-dioxygenase 1 (IDO1), Toll-like receptor 2 (TLR2), and TLR4 while increasing nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant enzyme heme oxygenase-1 (HO-1). Pathogen transcriptomic analysis identified Pneumocystis Rtt109 (PcRtt109), a fungal histone acetyltransferase, as a potential pathogen-specific target that was significantly downregulated after Ba treatment. Molecular docking and molecular dynamics simulations supported stable interactions between Ba and IDO1, Nrf2, TLR2, TLR4, and PcRtt109, with the strongest predicted binding observed for PcRtt109.ConclusionDual RNA-seq revealed that Ba exerts anti-PCP activity through coordinated modulation of host and pathogen molecular networks. Its therapeutic effects are associated with suppression of inflammatory signaling, enhancement of antioxidant defenses, and inhibition of a fungal virulence-associated target. These findings provide mechanistic insights into host-pathogen interactions during PCP and support Ba as a potential therapeutic candidate for PCP.

To investigate the molecular mechanisms underlying idiopathic pulmonary fibrosis (IPF), we analyzed the GSE173355 and GSE173356 datasets obtained from the NCBI-GEO database. We identified differentially expressed genes (DEGs) and differentially methylated sites. Functional enrichment analysis was conducted for both DEGs and differentially methylated sites. Functional enrichment analysis was performed for both DEGs and differentially methylated sites, alongside an examination of immune-related scores, proportions, and GSVA enrichment scores of immune cells in IPF versus control samples. An integrated gene-methylation association analysis revealed 8 genes with expression levels negatively influenced by methylation. The Rap1 pathway, Focal adhesion, and Axon guidance were significantly enriched among both DEGs and differentially methylated sites. Immune-related scores were notably lower in the IPF group compared to the control group, with marked differences in immune cell proportions and GSVA enrichment scores. Screening of DEGs identified 361 differentially expressed immune-related genes (IRGs). Protein-protein interaction (PPI) network analysis using the STRING database and Cytoscape software unveiled 10 key genes and 3 core subnetworks. RT-qPCR validation in bleomycin-induced IPF mouse model and A549 EMT model confirmed the reliability of most findings. These results provide new insights into IPF pathogenesis and potential therapeutic strategies, necessitating further functional validation.

PURPOSE:Respiratory support is essential in the clinical management of critically ill patients; however, prolonged exposure to high concentrations of oxygen can result in hyperoxia-induced acute lung injury (HALI). In this study, we developed a model of hyperoxia exposure utilizing C57BL/6 mice and human bronchial epithelial (BEAS-2B) cells. We employed CAV-1 siRNA transfection and CAV-1 expression plasmid techniques to analyze the effects of hyperoxia on the expression of caveolin-1 (CAV-1), the deletion of the phosphatase and tensin homolog (PTEN) gene on chromosome 10, and the apoptotic markers Bax and Bcl-2. Additionally, we explored the mechanisms by which CAV-1 regulates PTEN-mediated apoptosis in the context of HALI. Our findings aim to provide valuable insights for developing effective preventive and therapeutic strategies to combat this condition. METHODS:First, we established a hyperoxia-induced acute lung injury (HALI) model in male C57BL/6 mice. Histopathological examination was conducted using hematoxylin-eosin staining to evaluate the pathological changes and the severity of lung tissue damage. Next, we developed an in vitro HALI model utilizing the BEAS-2B cell line. Subsequently, CAV-1 siRNA and CAV-1 expression plasmids were transfected into BEAS-2B cells. We quantified the expression levels of CAV-1, PTEN, Bax, and Bcl-2 using reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting techniques. Additionally, the impact of altered CAV-1 expression on apoptosis in BEAS-2B cells was assessed through flow cytometry. RESULTS:Exposure to hyperoxia led to pathological alterations in mice's lung tissue, increased the CAV-1, PTEN, and Bax expression levels, and decreased Bcl-2 expression. Initially, there were no notable variances in the expression levels of CAV-1, PTEN, and Bax in the cells. However, as the exposure time to hyperoxia prolonged, there was a significant increase in both mRNA and protein expression levels of CAV-1 and PTEN, while Bcl-2 exhibited a significant decrease. Moreover, CAV-1 knockdown attenuated the expression of PTEN and Bax, and elevated the expression of Bcl-2. However, CAV-1 overexpression showed an opposite result. The expression levels of CAV-1, PTEN, and Bax were positively correlated in mice and cell models, and negatively correlated with those of Bcl-2. Additionally, downregulation of CAV-1 suppressed apoptosis in BEAS-2B cells. CONCLUSION:Our results indicate that CAV-1 plays a pivotal role in regulating the expression of PTEN and the apoptosis-related factors Bax and Bcl-2 in a hyperoxic environment. This regulatory function of CAV-1 on PTEN and its downstream apoptotic pathways suggests a significant correlation between CAV-1 and PTEN-mediated apoptosis. Consequently, CAV-1 is involved in the development of hyperoxic lung injury (HALI) through the PTEN-mediated apoptotic pathway. These findings offer new insights into the molecular mechanisms underlying the pathogenesis of HALI and underscore the potential therapeutic implications of targeting CAV-1 in the management of this condition.

As a ribosomal protein, RPL35A participates in diverse cellular processes, yet its role in lung cancer remains unclear. Here, we demonstrate that RPL35A is upregulated in lung cancer tissues and correlates with poor patient prognosis. Functional studies show that RPL35A overexpression enhances the proliferation, migration, and invasion of lung cancer cells while suppressing apoptosis; conversely, RPL35A knockdown produces opposing effects. In vivo xenograft models confirm that RPL35A depletion significantly inhibits tumor growth. Mechanistically, RPL35A directly interacts with the oncoprotein MYC through its N-terminal domain (amino acids 2-22), facilitating MYC nuclear translocation and recruitment to the SKP2 promoter. This interaction drives SKP2 expression, leading to activation of aerobic glycolysis, as evidenced by increased glucose uptake, lactate production, and extracellular acidification rate. Deletion of the 2 to 22 residue motif (RPL35A-Δ1) abolishes MYC binding and fails to restore SKP2 expression or glycolytic activity in rescue experiments. Furthermore, the oncogenic effects of RPL35A are abrogated by glycolysis inhibition, confirming metabolic reprogramming as a key downstream effector. Collectively, our findings suggest that RPL35A may serve as a valuable prognostic biomarker for lung squamous cell carcinoma (LUSC) patients and a promising therapeutic target.

Pneumocystis pneumonia (PCP) is a life-threatening opportunistic infection in immunocompromised individuals. Standard treatment with trimethoprim-sulfamethoxazole is limited by frequent side effects, potential drug resistance, and diminishing efficacy in certain patients, highlighting the need for alternative therapeutic strategies. This study evaluates the therapeutic and prophylactic potential of baicalin (Ba), a flavonoid derived from traditional Chinese medicine, in an immunosuppressed rat model of PCP. The therapeutic experiment involved intragastric administration of Ba at doses of 100, 200, or 400 mg/kg/day for 4 weeks in immunosuppressed rats, in comparison with intragastric administration of TMP-SMZ (50-250 mg/kg/day). Ba treatment demonstrated a dose-dependent reduction in Pneumocystis burden, alongside improved general health and lung histopathological scores, as well as elevated CD4 + T-cell counts, comparable to the effects observed with TMP-SMZ. In the prophylactic experiment, Ba (100 mg/kg/day) was administered intragastrically for 7 weeks, followed by 5 weeks of continued immunosuppression without further Ba treatment. Ba-treated rats exhibited significantly higher CD4 + T-cell counts, lower CD8 + T-cell counts, and attenuated inflammatory cytokine profiles. The effects of Ba treatment are associated with anti-inflammatory and antioxidant activities, regulation of protease/anti-protease balance, and inhibition of pulmonary collagen deposition. These findings support Ba's potential as an alternative treatment regimen for PCP.

Objectives: To investigate the mediating role of the activation degree of arginine-proline metabolism in the association of coal dust and decreased lung function.Methods: Cumulative dust exposure (CDE) represented coal dust exposure, whereas the hydroxyproline-to-arginine concentration ratio (Hyp/Arg) in bronchoalveolar lavage fluid gauged arginine-proline metabolism activation. Pulmonary function indicators, including predicted value of forced vital capacity (FVC%pred), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC%), and the ratio of actual to predicted value of FEV1 (FEV1%pred), diffusing capacity of the lungs for carbon monoxide (DLCO%pred), difference value between alveolar air and arterial partial oxygen pressure (P(A-a) O-2), and 6-minute walking distance test (6MWT), were assessed.Results: Findings revealed a significant association between elevated CDE and increased Hyp/Arg, increased P(A-a) O-2, decreased 6MWT, DLCO%pred, and decreased FVC%pred. However, no statistically significant association was found between CDE and FEV1%pred or FEV1/FVC%. The mediating effect of Hyp/Arg was significant for CDE's impact on P(A-a) O-2 and DLCO%pred but not on 6MWT and FVC%pred.Conclusions: These results highlight the role of Hyp/Arg in mediating the association between CDE and lung function parameters, shedding light on potential therapeutic avenues for mitigating coal dust-induced lung function impairment.

背景:临床前研究表明间充质干细胞可用于尘肺病的治疗,然而由于缺乏体内有效的间充质干细胞示踪技术,相关研究尚停滞于临床前探索,因此间充质干细胞示踪技术的发展是解决此问题的关键.目的:综述尘肺治疗现状、间充质干细胞治疗尘肺以及纳米材料多模态显像示踪技术在间充质干细胞治疗尘肺的研究进展,评价不同类型纳米材料多模态显像示踪技术在间充质干细胞治疗尘肺研究现状中的贡献、效果及前景,分析目前存在的问题及其未来的发展方向.方法:以PubMed为检索数据库,以"pneumoconiosis,pulmonary fibrosis,stem cells,MSCs,trace,nanoparticles,multi-modal imaging,therapy"为关键词进行检索,检索文献时限为2016-2021年,依据纳入和排除标准,最终纳入符合要求的60篇文献进行综述.结果 与结论:①目前的临床前研究显示,金纳米颗粒、磁靶向纳米颗粒及近红外长余辉发光纳米颗粒3种材料设计精巧且新颖,具有良好的生物相容性、稳定性、安全性和多模态成像能力等优点,在间充质干细胞治疗尘肺过程中体内示踪及发挥抗肺纤维化作用疗效评价的临床前应用初显成效,示踪长效性、靶向定位、余辉光学性能顺次分别是上述3种纳米材料的优势.②金纳米颗粒是纳米材料联合多模态显像示踪技术在间充质干细胞治疗尘肺的临床应用中最具应用前景的纳米材料,很大程度上推动了间充质干细胞治疗尘肺领域的进展与临床转化.③纳米材料多模态显像示踪的研究为实现间充质干细胞治疗尘肺的临床应用提供了可靠的新技术,对进一步推进靶向治疗尘肺的临床转化应用与实践具有重要的意义.④在精准医疗引领的新时代,阐明间充质干细胞治疗尘肺机制,解决增强纳米材料标记间充质干细胞的靶向积累、提高间充质干细胞摄取和控制缓释效力、延长药物半衰期以及维持稳定血药浓度等关键问题,以及如何将高度整合的纳米材料多模态成像与具有多重治疗功能且可生物降解和体内清除的诊疗一体化载药体系相结合,尚需未来更为深入及详尽的探索.

Lung cancer is the leading cause of cancer‑related mortality worldwide. Non‑small cell lung cancer (NSCLC) is the most common pathological subtype of lung cancer and is associated with low 5‑year overall survival rates. Therefore, novel and effective chemotherapeutic drugs are urgently required for improving the survival outcomes of patients with lung cancer. Cyclovirobuxine D (CVB‑D) is a natural steroidal alkaloid, used for the treatment of cardiovascular diseases in Traditional Chinese Medicine. Several studies have also demonstrated the antitumor effects of CVB‑D. Therefore, in the present study, the therapeutic effects of CVB‑D in lung cancer and the underlying mechanisms were investigated using the in vivo xenograft model of NSCLC in nude mice and in vitro experiments with the NSCLC cell lines. Bioinformatics analyses of RNA‑sequencing data, and cell‑based functional assays demonstrated that CVB‑D treatment significantly inhibited in vitro and in vivo NSCLC cell proliferation, survival, invasion, migration, angiogenesis, epithelial‑to‑mesenchymal transition and G2/M phase cell cycle. CVB‑D exerted its antitumor effects by inhibiting the KIF11‑CDK1‑CDC25C‑cyclinB1 G2/M phase transition regulatory oncogenic network and the NF‑κB/JNK signaling pathway. CVB‑D treatment significantly reduced the sizes and weights and malignancy of xenograft NSCLC tumors in the nude mice. In conclusion, the present study demonstrated that CVB‑D inhibited the growth and progression of NSCLC cells by inhibiting the KIF11‑CDK1‑CDC25C‑CyclinB1 G2/M phase transition regulatory network and the NF‑κB/JNK signaling pathway. Therefore, CVB‑D is a promising drug for the treatment of NSCLC patients.

Purpose:Pulmonary artery hypertension (PAH) is a common complication of chronic obstructive pulmonary disease and obstructive sleep apnea/hypopnea syndrome worldwide. Pulmonary vascular alterations associated with PAH have multifactorial causes, in which endothelial cells play an important role. Autophagy is closely related to endothelial cell injury and the development of PAH. PIF1 is a multifunctional helicase crucial for cell survival. The present study investigated the effect of PIF1 on autophagy and apoptosis in human pulmonary artery endothelial cells (HPAECs) under chronic hypoxia stress.Methods:Chronic hypoxia Gene expression profiling chip-assays identified the PIF1 gene as differentially expressed, which was verified by RT-qPCR analysis. Electron microscopy, immunofluorescence, and Western blotting were used to analyze autophagy and the expression of LC3 and P62. Apoptosis was analyzed using flow cytometry.Results:Our study found that chronic hypoxia induces autophagy in HPAECs, and apoptosis was exacerbated by inhibiting autophagy. Levels of the DNA helicase PIF1 were increased in HPAECs after chronic hypoxia. PIF1 knockdown inhibited autophagy and promoted the apoptosis of HPAECs under chronic hypoxia stress.Conclusion:Based on these findings, we conclude that PIF1 inhibits the apoptosis of HPAECs by accelerating the autophagy pathway. Therefore, PIF1 plays a crucial role in HPAEC dysfunction in chronic hypoxia-induced PAH and may be a potential target for the treatment of PAH.

目的:分析实验室常见检测指标红细胞分布宽度(RDW)、乳酸脱氢酶(LDH)、中性粒细胞/淋巴细胞比值(NLR)对新型冠状病毒感染(COVID-19)病情危重程度的预测价值.方法:回顾性收集 2022年 12月 12日—2023年 3月 12日于山西医科大学第一医院住院并确诊为 COVID-19病人的临床资料,共入选 197例病人,依据《新型冠状病毒感染诊疗方案》(试行第 10 版)的相关标准,将病人分为非重症组(97例)与重症组(100例).采用多因素Logistic回归分析重症COVID-19的危险因素;绘制受试者工作特征(ROC)曲线,评估 RDW、NLR、LDH以及联合检测对重症 COVID-19的预测效能.结果:重症组年龄、男性及合并脑血管疾病占比高于非重症组(P<0.05),重症组 RDW、中性粒细胞计数(NEU)、NLR、降钙素原(PCT)、超敏肌钙蛋白 I(hs-cTnI)、乳酸脱氢酶(LDH)、肌酸激酶(CK)均高于非重症组(P<0.01),淋巴细胞计数(LYM)则低于非重症组(P<0.01).多因素 Logistic回归分析结果显示,RDW、NLR、LDH升高是重症 COVID-19的独立危险因素(P<0.05),ROC曲线分析结果显示,RDW、NLR、LDH及三者联合评估 COVID-19病情危重程度的曲线下面积(AUC)分别为 0.692,0.721,0.826,0.880,差异均有统计学意义(P<0.01).结论:实验室常见指标RDW、NLR、LDH是预测 COVID-19进展为重症的独立危险因素,三者联合对于预测重症 COVID-19 具有较可靠的诊断价值和临床实用性.

The increasing morbidity and mortality of life-threatening Pneumocystis pneumonia (PCP) in immunocompromised people poses a global concern, prompting the World Health Organization to list it as one of the 19 priority invasive fungal diseases, calling for increased research and public health action. In response to this initiative, we provide this review on the epidemiology of PCP in non-HIV patients with various immunodeficient conditions, including the use of immunosuppressive agents, cancer therapies, solid organ and stem cell transplantation, autoimmune and inflammatory diseases, inherited or primary immunodeficiencies, and COVID-19. Special attention is given to the molecular epidemiology of PCP outbreaks in solid organ transplant recipients; the risk of PCP associated with the increasing use of immunodepleting monoclonal antibodies and a wide range of genetic defects causing primary immunodeficiency; the trend of concurrent infection of PCP in COVID-19; the prevalence of colonization; and the rising evidence supporting de novo infection rather than reactivation of latent infection in the pathogenesis of PCP. Additionally, we provide a concise discussion of the varying effects of different immunodeficient conditions on distinct components of the immune system. The objective of this review is to increase awareness and knowledge of PCP in non-HIV patients, thereby improving the early identification and treatment of patients susceptible to PCP.

Pneumocystis jirovecii is an opportunistic fungus that can cause severe and potentially fatal Pneumocystis pneumonia (PCP) in immunodeficient patients. In this study, we investigated the genetic polymorphisms of P. jirovecii at eight different loci, including six nuclear genes (ITS, 26S rRNA, sod, dhps, dhfr and β-Tub) and two mitochondrial genes (mtLSU-rRNA and cyb) in three PCP cases, including two patients with HIV infection and one without HIV infection in Shanxi Province, P.R. China. The gene targets were amplified by PCR followed by sequencing of plasmid clones. The HIV-negative patient showed a coinfection with two genotypes of P. jirovecii at six of the eight loci sequenced. Of the two HIV-positive patients, one showed a coinfection with two genotypes of P. jirovecii at the same two of the six loci as in the HIV-negative patient, while the other showed a single infection at all eight loci sequenced. None of the three drug target genes (dhfr, dhps and cyb) showed mutations known to be potentially associated with drug resistance. This is the first report of genetic polymorphisms of P. jirovecii in PCP patients in Shanxi Province, China. Our findings expand our understanding of the genetic diversity of P. jirovecii in China.

目的 对2株临床分离的烟曲霉菌株进行病原学检测和分子鉴定,并对不同检测方法进行比较分析.方法 收集2例侵袭性肺曲霉菌病(IPA)患者痰液标本,采用直接压片、亚甲蓝染色和改良GMS染色,以及分离、培养等病原学检测,应用rodA、anxc4、β-tub、ITS、cyp51A和cyp51B基因进行PCR、环介导等温扩增(LAMP)、分子克隆和Sanger测序.结果 痰涂片镜检可见典型的烟曲霉鹿角样菌丝、分生孢子头和分生孢子;真菌显色培养基上菌落颜色由白色转为蓝绿色;rodA、anxc4、β-tub、ITS、cyp51A和cyp51B与Genbank数据库中烟曲霉相应序列的同源性均在99.7％以上;LAMP扩增产物肉眼可见白色沉淀,琼脂糖凝胶电泳呈典型梯度条带,HNB可视化检测结果呈淡蓝色,real-time LAMP呈"S"型扩增曲线.结论 临床疑似烟曲霉感染时,可通过LAMP进行快速分子鉴定,辅助临床提升诊断效率,为临床治疗提供依据.

耶氏肺孢子菌是一种可感染人的机会致病性真菌,可致严重的肺孢子菌肺炎,尤其见于免疫功能低下者.肺孢子菌最初被认为是一种原虫,命名为卡氏肺孢子虫.20世纪80年代末,运用分子生物学技术对其基因序列进行检测分析,证实肺孢子虫是一种非典型真菌.由于缺乏有效的体外培养体系,很难清楚地了解肺孢子菌的病原生物学特性和流行病学特征.随着分子生物学技术的广泛应用,耶氏肺孢子菌分子分型的方法近年来得到了全面发展和研究,然而其基因分型方案缺乏国际标准化和全球共识,致使耶氏肺孢子菌临床分离株的流行病学及种群结构、传染源追溯、传播特性以及肺孢子菌肺炎的发病机制和防治等研究受到阻碍.为纪念耶氏肺孢子菌更名20周年,本文就其基因分型的研究进展进行综述.

Background Pneumocystis jirovecii ( P. jirovecii ) is an opportunistic fungus and is a well-known cause of potentially fatal Pneumocystis jirovecii pneumonia (PJP). However, the epidemiology and biology of P. jirovecii is limited because of the lack of a continuous and reliable culture system in vitro. This study was performed with the objectives of investigating the genetic polymorphisms of P. jirovecii from 3 cases in Shanxi Province PR China with the utilizations of molecular biological technique. Methods Analysis of genetic polymorphisms in P. jirovecii including the internal transcribed spacer regions of rRNA operon (ITS), superoxide dismutase (SOD), dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR), cytochrome b (CYB) and the mitochondrial large-subunit rRNA (mt LSU rRNA) genes were performed by Nested-PCR amplification, TA clone, sequencing and genotyping. We assessed its correlation with clinical characteristics of patients with P. jirovecii pneumonia (PJP). Results Of three patients with PJP included in the present study, the genetic diversities and polymorphic combinations of SOD 1, DHFR 312C, DHPS WT, mt3 genotypes separately occurred in the two HIV-positive patients, while coinfections with two genotypes of P. jirovecii in the same patient without HIV were detected for different genetic loci including ITS, SOD, CYB and mt LSU rRNA in this study. The pulmonary concurrent infection with other pathogens was detected in this HIV-negative patient. Conclusions The present study is the first analyzed and assessed the genetic polymorphisms of 3 cases P. jirovecii in Shanxi province PR China suggesting that genetic diversities and concurrent infection with other pathogens were possibly associated with the clinical characteristics and outcomes in PJP patients especially those without HIV. Trial registration Not applicable.

目的 比较耶氏肺孢子菌(P.jirovecii)不同病原学染色形态特征,分析其在肺孢子菌肺炎(PJP)诊断中的价值.方法 收集1例PJ P患者的支气管肺泡灌洗液,制成涂片,运用不同病原学染色方法分别对其进行染色,分析、评价不同染色方法在PJ P诊断中的效果.结果 革兰染色和抗酸染色可见透明空泡样结构;真菌荧光染色可见发出蓝色荧光的P.jirovecii包囊;HE染色P.jirovecii包囊囊壁不着色,呈透明晕圈状,囊内可见4～8个囊内小体;Wright-Giemsa染色和改良Giemsa染色可见圆形或卵圆形P.jirovecii包囊,囊壁不着色但折光性强,呈新月形,囊内可见4～8个囊内小体;改良GMS染色P.j irovecii包囊囊壁为深褐色或黑色,呈特征性括弧样结构,囊内小体不着色,中间有1条黑色褶皱或中心点状深染.结论 HE染色、Wright-Giemsa染色、改良Giemsa染色、改良GMS染色均可用于确诊PJP,但HE染色、Wright-Giemsa染色、改良Giemsa染色对检验人员要求较高,而改良GMS染色的染色效果好,是临床确诊PJP的推荐病原学染色方法.

Pneumocystis jirovecii (P. jirovecii), an opportunistic fungal pathogen, is the primary cause of Pneumocystis pneumonia (PCP), which affects immunocompromised individuals and leads to high morbidity and mortality. P. jirovecii colonization is associated with development of chronic obstructive pulmonary disease (COPD) in patients with HIV infection, and also non-sufferers, and in primate models of HIV infection. However, the mechanisms underlying P. jirovecii infection in the pathogenesis of COPD have yet to be fully elucidated. To investigate the pathogenicity of P. jirovecii infection and its role in COPD development, the present study established a PCP rat model induced by dexamethasone sodium phosphate injection. Expression of COPD-related biomarkers, including matrix metalloproteinases (MMPs) MMP-2, MMP-8, MMP-9, and MMP-12, and heat shock protein-27 (HSP-27), were quantified in the rat PCP model using reverse transcription-quantitative polymerase chain reaction, ELISA, western blot analysis, immunohistochemistry and gelatin zymography. Body weight, COPD symptoms, and pulmonary histopathology were assessed. Inflammatory cell counts in splenic tissues were measured using flow cytometry. It was identified that MMP and HSP-27 expression increased in the PCP rats, which was in agreement with previous literature. Therefore, it was hypothesized that P. jirovecii infection may have an important role in COPD development.

The novel coronavirus pneumonia caused by 2019-nCoV has led to a global pandemic. As the pandemic is spreading, researches on the characteristics, pathogenic mechanism and transmission route of 2019-nCoV are helpful in controlling the epidemic situation as soon as possible. Recent advances in genomics, epidemiology and laboratory diagnosis of 2019-nCoV are reviewed in this paper.

Background Pneumocystis jirovecii ( P. jirovecii ) is an opportunistic fungal pathogen and the role of its colonization in pulmonary diseases has become a popular focus in recent years. The aim of this study is to develop an improved loop-mediated isothermal amplification (LAMP) assay for detection of Pneumocystis jirovecii ( P. jirovecii ) DNA and use it to examine the prevalence and association of P. jirovecii colonization among non-HIV patients with various pulmonary diseases. Methods We modified the previously reported LAMP assay for P. jirovecii by adding real-time detection. This method was used to detect P. jirovecii colonization in pulmonary samples collected from 403 non-HIV patients with various pulmonary diseases enrolled from 5 hospitals in China. We determined the prevalence of P. jirovecii colonization in 7 types of pulmonary diseases and assessed the association of P. jirovecii colonization with clinical characteristics of these diseases. Results The new LAMP assay showed no cross-reactivity with other common pulmonary microbes and was 1,000 times more sensitive than that of conventional PCR. Using the new LAMP assay, we detected P. jirovecii colonization in 281 (69.7%) of the 403 patients enrolled. P. jirovecii colonization was more common in interstitial lung diseases than in chronic obstructive pulmonary disease (COPD) (84.6% vs 64.5%, P < 0.05). Patients with acute exacerbation of COPD had a higher prevalence of P. jirovecii colonization compared to patients with stabilized COPD (67.4% vs 43.3%, P < 0.05). P. jirovecii colonization was associated with decreased pulmonary function, increased levels of 1,3-β-D-glucan and C-reactive protein, and decreased levels of CD4+ T-cell counts (P < 0.05 for each). Approximately 70% of P. jirovecii colonized patients had confections with other fungi or bacteria. Conclusions We developed an improved LAMP assay for detecting P. jirovecii . Our multi-center study of 403 patients supports that P. jirovecii colonization is a risk factor for the development of pulmonary diseases and highlights the need to further study the pathogenesis and transmission of P. jirovecii colonization in pulmonary diseases.