Zhijun Jie

We report a rare case of a 78-year-old male with lung squamous cell carcinoma (SCC) and concurrent idiopathic pulmonary fibrosis (IPF) who underwent thoracoscopic partial left upper lobectomy and systematic mediastinal lymph node dissection. The tumor remained stable under regular surveillance for 13 months postoperatively. An acute exacerbation of IPF (AE-IPF) then occurred, resulting in severe hypoxemia. Although the patient’s condition temporarily stabilized following antifibrotic therapy and high-flow nasal cannula (HFNC) oxygen therapy, explosive multi-organ metastases appeared within one year of AE-IPF onset, successively involving the liver, abdominal wall, and brain. The unique features of this case are: (1) a clinically “silent” interval of more than one year following curative surgery, after which severe systemic hypoxia accompanying AE-IPF was temporally associated with subsequent explosive tumor dissemination and is hypothesized to be a potential predisposing factor for rapid tumor spread; and (2) rare metastatic patterns for lung SCC, including in abdominal wall subcutaneous metastasis and suspected acral (digital) metastasis whose distinction from a primary trichilemmal carcinoma could not be definitively resolved. This case underscores the importance of early antifibrotic therapy to prevent AE-IPF, maintaining adequate oxygenation, and implementing comprehensive multidisciplinary surveillance for patients with lung cancer comorbid with IPF.

To compare respiratory microbiota across patients with COPD, individuals at high risk for COPD, and healthy controls, and to assess associations with COPD severity. From January 2022 to December 2023, participants were enrolled into four groups: previously diagnosed COPD (PVD-COPD, n=16), newly diagnosed COPD (PLD-COPD, n=16), high-risk individuals (HR, n=20), and healthy controls (HP, n=20). Sputum and saliva samples underwent 16S rRNA gene sequencing. Microbial diversity and taxonomic composition were compared among groups. In patients with COPD, correlations between sputum microbiota features and GOLD grade were analyzed. Seventy-two subjects were included. Alpha diversity (Ace and Chao1) and beta diversity differed significantly among groups (all P1%). Within the COPD cohort, Ace and Chao1 were positively correlated with GOLD grade (r=0.3659, P=0.0394). A Streptococcus-dominant pattern was more frequent in GOLD 1–2, while a Neisseria-dominant pattern was more frequent in GOLD 3–4. Respiratory microbiota composition differs across healthy controls, high-risk individuals, and COPD patients. In COPD, microbiota diversity and dominant genera are associated with disease severity, supporting a link between respiratory microbiota structure and COPD progression.

Hyponatremia is strongly associated with syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present an 82-year-old male with refractory hyponatremia unresponsive to the discontinuation of hydrochlorothiazide and comprehensive treatment (fluid restriction, sodium supplementation, and tolvaptan). Two consecutive urine cultures identified extensively drug-resistant Klebsiella pneumoniae (XDRKP). After tigecycline treatment, serum sodium returned to normal and remained stable during one-year follow-up. This case suggests a close relationship between XDRKP infection and SIADH, highlighting the need to evaluate drug-resistant pathogens in patients with refractory hyponatremia and the importance of antimicrobial therapy in the management of electrolyte disorders secondary to drug-resistant urinary tract infections.

The Birt–Hogg–Dubé (BHD) syndrome is a rare, autosomal dominant disorder caused by germline mutations in the FLCN gene, which encodes a tumor suppressor protein. The syndrome is characterized by cutaneous fibrofolliculomas, pulmonary cysts, spontaneous pneumothoraces, and renal tumors. We report a rare familial case of BHD complicated by primary lung adenocarcinoma in a 69-year-old man. The patient presented with a persistent cough, bilateral pulmonary cysts, and a 4 × 3 cm tumor in the left lung lobe. Genetic testing revealed a novel pathogenic FLCN mutation (c.295_311del p.Asp99Ter) in the patient and several family members, including his son and brother, both of whom exhibited pulmonary cysts and histories of pneumothoraces. The patient was diagnosed with invasive lung adenocarcinoma. Although tumor progression was stabilized with treatment, the clinical course was complicated by severe hyperthyroidism, liver injury, and myelosuppression. This case highlights the complexities of managing lung cancer in BHD patients and suggests a potential role for FLCN mutations in tumorigenesis. Our findings underscore the importance of early diagnosis, genetic testing, and a multidisciplinary approach to the management of BHD in order to improve patient outcomes and prevent complications. In addition, we conducted a literature review of previously reported FLCN mutations in BHD syndrome.

Allergic asthma is a chronic airway disease characterized by an allergic response and altered immune tolerance. CD4+ tissue-resident memory T (TRM) cells are crucial in the chronic and relapsing pathogenesis of asthma. Furthermore, promyelocytic leukemia zinc finger (PLZF) is an essential transcription factor involved in asthmatic tolerance and has been implicated in the regulation of CD4+CD44+ memory T cells. However, the role of CD4+ TRM cells in asthmatic tolerance, as well as their potential modulation by PLZF, remain unclear. Therefore, in the current study, we explore the role of CD4+ TRM cells in asthmatic immune tolerance and as well as the regulatory role of PLZF in this process. To elucidate the role of CD4+ TRM cells in immune tolerance, asthma memory mouse models were treated with the immunomodulator FTY720. Subsequently, CD4+ T cells were isolated from the lungs and spleens and transferred to oral tolerance mouse models. To explore the regulation of PLZF in CD4+ TRM cells, asthma and oral tolerance were established in Zbtb16flox/flox CD4Cre and wild-type mice. Flow cytometry, histological analysis, and cytokine measurements were performed to characterize the immune response. The regulatory activity of PLZF on CD4+ TRM cells was analyzed through quantitative proteomics and verified in vitro and vivo. The CD4+ TRM cell proportion positively correlated with the pathological phenotypes and molecular characteristics of asthma. Adoptive transfer of CD4+ TRM cells induced asthmatic phenotypes. This suggested that CD4+ TRM cells contributed to the pathogenesis of asthma. Conditional knockout of PLZF substantially reduced the proportion of CD4+ TRM cells, relieved asthmatic symptoms, and suppressed the interleukin (IL)-15/IL-15Rα signaling pathway. Furthermore, exposure to the IL-15Rα agonist restored asthma-related Th2 inflammation, accompanied by a markedly increased proportion of CD4+ TRM cells. Meanwhile, IL-15 and ovalbumin(OVA)-primed Beas2b supernatant co-stimulation in vitro enhanced the differentiation of pulmonary PLZF-expressing CD4+ T cells into CD4+ TRM cells. This study identified CD4+ TRM cells as key mediators of immune tolerance in asthma. This process is regulated by the transcription factor PLZF in CD4+ T cells through IL-15/IL-15Rα signaling. Thus, targeting PLZF or the IL-15/IL-15Rα pathway may represent a promising therapeutic strategy for treating asthma.

The aim of this retrospective cohort study was to investigate the clinical characteristics and the outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients between different sex. We aimed to collect the first hospitalization patients who were diagnosed as AECOPD between 1 January 2019 to 31 December 2021 from the general ward and intensive care unit in the hole hospital, Shanghai the Fifth People’s Hospital, Fudan University. Demographic data, initial clinical symptoms, on-admission vital signs, comorbidities, laboratory tests and imaging examination, treatment, and follow-up were compared between the two groups. The patients were followed up for 30 days, 90 days, 180 days after the discharge from the hospital, all these differences were not statistically significant in hospital readmissions and mortality (P > 0.05). The multivariate analysis incorporated seven factors according to the results of the univariate regression analysis. The results showed that readmission was independently associated with increased course of disease (P = 0.032), combined with chronic pulmonary heart disease (P = 0.011), and combined with peptic ulcer (P = 0.044). Conversely, there was no correlation between sex and readmission (P = 0.304). The short-term readmission was independently associated with increased course of disease, combined with chronic pulmonary heart disease, and combined with peptic ulcer, but not with sex.

Respiratory syncytial virus (RSV) infection is correlated with the chronic pathogenesis and exacerbation of asthma. However, the mechanism remains unclear. In this study, acute and memory (Mem) asthma models with early RSV infection are established to explore the persistence of the effects of RSV infection on asthma. Intravascular injection of an anti-CD45 antibody is performed to define CD4⁺ TRM cells accurately. RSV infection has a sustained impact on asthma exacerbation for at least six weeks, with high Th2 cytokine secretion in lung tissue instead of IgE response-related B cells. CD45^-CD4⁺ TRM cells are positively correlated with RSV-related asthma exacerbation and severe airway inflammation. Mechanistically, overexpression of the transcription factor PLZF in vitro increases the number of CD4⁺ TRM cells, and conditional knockout of PLZF can decrease the number of CD4⁺ TRM cells to aggravate allergic inflammation and reduce Th2 responses, providing evidence for potential combined strategies that might benefit asthma patients.

Introduction: The aim of the study was to describe psittacosis pneumonia and to assess the predictive value of the C-reactive protein/albumin ratio in psittacosis pneumonia for severity.Methods: Data on psittacosis pneumonia cases diagnosed using metagenomic sequencing were collected from three hospitals in Shanghai, China from Oct. 2019 to Oct. 2022. Serum levels of C-reactive protein and albumin were measured and the C-reactive protein to albumin ratio (CAR) was calculated. Spearman’s correlation analysis, ordered logistic regression analysis, and receiver operating characteristic curve analysis were conducted to examine the correlation and predictive ability of the three indicators on the severity of the disease.Results: A total of 27 patients with psittacosis pneumonia were enrolled, with an average age of 62 years and 70.4% being male. 44.4% of patients had a clear history of contact with poultry or birds. The predominant symptom was fever (100%). Patients treated in the respiratory intensive care unit (RICU) had a higher likelihood of experiencing wheezing (88.9% versus 33.3%, P=0.013) and chest tightness (88.9% vs. 33.3%, P=0.013) than those in the general ward (Non-RICU). The proportion of patients with pleural effusion was significantly higher in the RICU compared to the Non-RICU (88.9% vs. 38.9%, P=0.019). The RICU group had a significantly higher CAR than the Non-RICU group (9.41 vs. 4.05, P=0.017). This result was accompanied by higher intubation and ventilator support (33.3% vs. 0.0%, P=0.029), higher PCT and CRP levels and lower albumin and PaCO2 levels in the RICU than in the Non-RICU. Logistic regression analysis indicated that CAR (OR 1.49; 95% CI 1.07–2.06, P=0.017) was risk factor for prolonged hospitalization (> 14 days).Discussion: Elevated serum CAR levels were found to be associated with a greater risk of severe psittacosis pneumonia. Consequently, it may serve as an uncomplicated and useful diagnostic tool for clinicians to promptly and precisely ascertain the severity of psittacosis pneumonia, ultimately aiding them in devising the most optimal therapeutic plan.