Although transbronchial lung cryobiopsy (TBLC) is widely used in diagnostic algorithms for various interstitial lung diseases (ILDs), its real-world utility in the therapeutic decision-making strategy for ILD patients remains unclear, in particular, when judging the time to start antifibrotic agents.
Methods
We analyzed medical records of 40 consecutive patients with idiopathic or fibrotic hypersensitivity pneumonitis who underwent TBLC. A TBLC-based usual interstitial pneumonia (UIP) score was used to assess three morphologic descriptors: patchy fibrosis, fibroblastic foci, and honeycombing.
Results
In our 40 patients with ILD, the most frequent radiological feature was indeterminate for UIP (45.0%). Final diagnosis included idiopathic pulmonary fibrosis (22.5%), fibrotic nonspecific interstitial pneumonia (5.0%), fibrotic hypersensitivity pneumonitis (35.0%), and unclassifiable ILD (37.5%). Linear mixed-effects analysis showed that declines in the slopes of %FVC and %DLCO in patients with TBLC-based UIP “Score ≥ 2” were significantly steeper than those of patients with “Score ≤ 1.” During follow-up of patients with Score ≥ 2 (n = 24), more than half of them (n = 17) received an antifibrotic agent, with most patients (n = 13) receiving early administration of the antifibrotic agent within 6 months after the TBLC procedure.
Conclusions
TBLC-based UIP Score ≥ 2 indicated the increased possibility of a progressive fibrosis course that may prove helpful in predicting progressive pulmonary fibrosis/progressive fibrosing ILD even if disease is temporarily stabilized due to anti-inflammatory agents. Patients may benefit from early introduction of antifibrotic agents by treating clinicians.
{"title":"Usefulness of Transbronchial Lung Cryobiopsy When Starting Antifibrotic Treatment and Predicting Progressive Fibrosing Interstitial Lung Disease: Descriptive Research","authors":"Makiko Takatsuka, Hideaki Yamakawa, Tamiko Takemura, Shintaro Sato, Hiroki Ohta, Kenji Kusano, Tomohiro Oba, Rie Kawabe, Keiichi Akasaka, Hiroki Sasaki, Masako Amano, Jun Araya, Hidekazu Matsushima","doi":"10.1111/crj.13809","DOIUrl":"10.1111/crj.13809","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although transbronchial lung cryobiopsy (TBLC) is widely used in diagnostic algorithms for various interstitial lung diseases (ILDs), its real-world utility in the therapeutic decision-making strategy for ILD patients remains unclear, in particular, when judging the time to start antifibrotic agents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed medical records of 40 consecutive patients with idiopathic or fibrotic hypersensitivity pneumonitis who underwent TBLC. A TBLC-based usual interstitial pneumonia (UIP) score was used to assess three morphologic descriptors: patchy fibrosis, fibroblastic foci, and honeycombing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In our 40 patients with ILD, the most frequent radiological feature was indeterminate for UIP (45.0%). Final diagnosis included idiopathic pulmonary fibrosis (22.5%), fibrotic nonspecific interstitial pneumonia (5.0%), fibrotic hypersensitivity pneumonitis (35.0%), and unclassifiable ILD (37.5%). Linear mixed-effects analysis showed that declines in the slopes of %FVC and %DL<sub>CO</sub> in patients with TBLC-based UIP “Score ≥ 2” were significantly steeper than those of patients with “Score ≤ 1.” During follow-up of patients with Score ≥ 2 (<i>n</i> = 24), more than half of them (<i>n</i> = 17) received an antifibrotic agent, with most patients (<i>n</i> = 13) receiving early administration of the antifibrotic agent within 6 months after the TBLC procedure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>TBLC-based UIP Score ≥ 2 indicated the increased possibility of a progressive fibrosis course that may prove helpful in predicting progressive pulmonary fibrosis/progressive fibrosing ILD even if disease is temporarily stabilized due to anti-inflammatory agents. Patients may benefit from early introduction of antifibrotic agents by treating clinicians.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13809","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francisco A. Martínez-Villa, Uriel A. Angulo-Zamudio, Nidia Leon-Sicairos, Ricardo González-Esparza, Jaime Sanchez-Cuen, Jesus J. Martinez-Garcia, Hector Flores-Villaseñor, Julio Medina-Serrano, Adrian Canizalez-Roman
Objective
The objective of this study was to associate the epidemiological and clinical characteristics of patients hospitalized for COVID-19 with the progression to critical illness and death in northwestern Mexico.
Methods
From March to October 2020, we collected the demographic and clinical characteristics of 464 hospitalized patients from northwestern Mexico.
Results
Sixty-four percent (295/464) of the patients became critically ill. Age, occupation, steroid and antibiotic use at previous hospitalization, and underlying diseases (hypertension, obesity, and chronic kidney disease) were associated with critical illness or death (p: < 0.05). No symptoms were associated with critical illness. However, the parameters such as the heart rate, respiratory rate, oxygen saturation, and diastolic pressure and the laboratory parameters such as the glucose, creatinine, white line cells, hemoglobin, D-dimer, and C-reactive protein, among others, were associated with critical illness (p: < 0.05). Finally, advanced age, previous hospital treatment, and the presence of one or more underlying diseases were associated with critical illness and death (p: < 0.02).
Conclusions
Several epidemiological (e.g., age and occupation) and clinical factors (e.g., previous treatment, underlying diseases, and vital signs and laboratory parameters) were associated with critical illness and death in patients hospitalized with COVID-19. These data provide us with possible markers to avoid critical illness or death from COVID-19 in our region.
{"title":"Clinical Characteristics of Hospitalized Patients With COVID-19 and Their Association With the Progression to Critical Illness and Death: A Single-Center Retrospective Study From Northwestern Mexico","authors":"Francisco A. Martínez-Villa, Uriel A. Angulo-Zamudio, Nidia Leon-Sicairos, Ricardo González-Esparza, Jaime Sanchez-Cuen, Jesus J. Martinez-Garcia, Hector Flores-Villaseñor, Julio Medina-Serrano, Adrian Canizalez-Roman","doi":"10.1111/crj.13813","DOIUrl":"10.1111/crj.13813","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to associate the epidemiological and clinical characteristics of patients hospitalized for COVID-19 with the progression to critical illness and death in northwestern Mexico.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From March to October 2020, we collected the demographic and clinical characteristics of 464 hospitalized patients from northwestern Mexico.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixty-four percent (295/464) of the patients became critically ill. Age, occupation, steroid and antibiotic use at previous hospitalization, and underlying diseases (hypertension, obesity, and chronic kidney disease) were associated with critical illness or death (<i>p</i>: < 0.05). No symptoms were associated with critical illness. However, the parameters such as the heart rate, respiratory rate, oxygen saturation, and diastolic pressure and the laboratory parameters such as the glucose, creatinine, white line cells, hemoglobin, D-dimer, and C-reactive protein, among others, were associated with critical illness (<i>p</i>: < 0.05). Finally, advanced age, previous hospital treatment, and the presence of one or more underlying diseases were associated with critical illness and death (<i>p</i>: < 0.02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Several epidemiological (e.g., age and occupation) and clinical factors (e.g., previous treatment, underlying diseases, and vital signs and laboratory parameters) were associated with critical illness and death in patients hospitalized with COVID-19. These data provide us with possible markers to avoid critical illness or death from COVID-19 in our region.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weize Gao, Wenshuai Li, Zhan Wang, Yongxin Li, Mingjun Liu
In previous studies, we developed a novel fusion protein named “melittin-MIL-2” which exhibited more anti-tumor activity. However, it remains unclear whether melittin-MIL-2 possesses antitumor immune effect on lung adenocarcinoma. In this study, the immune effect and mechanism of melittin-MIL-2 inhibiting the growth and invasion of lung adenocarcinoma will be investigated, in order to provide novel perspectives for the immunotherapy of lung cancer. The results indicated that melittin-MIL-2 promoted T cell proliferation, enhanced NK cell cytotoxicity, and boosted IFN-γ secretion in PBMCs. After melittin-MIL-2 stimulation, perforin expression and LAK/NK-like killing activities of human PBMCs and NK cells were significantly enhanced. Melittin-MIL-2 is capable of hampering the development and proliferation of lung adenocarcinoma cell A549. ICAM-1 and Fas expression in A549 cells exposed to melittin-MIL-2 rose significantly. The expression levels of TLR8 and VEGF in A549 cells decreased significantly after melittin-MIL-2 stimulation. In vivo, melittin-MIL-2 substantially impeded the growth of lung adenocarcinoma and formed an immune-stimulating microenvironment locally in tumor tissues. In conclusion, the novel fusion protein melittin-MIL-2 exhibits strong anti-tumor immune effect in lung adenocarcinoma cell A549 via activating the LFA-1/ICAM-1 and Fas/FasL pathways to enhance cytolytic activity, upregulating the secretion of IFN-γ and perforin, and boosting LAK/NK-like killing activities. Immuno-effector cells and their secreted cytokines can form immune stimulation microenvironment locally in lung adenocarcinoma Lewis mice tissue.
{"title":"The Novel Fusion Protein Melittin-MIL-2 Exhibits Strong Antitumor Immune Effect in Lung Adenocarcinoma Cell A549","authors":"Weize Gao, Wenshuai Li, Zhan Wang, Yongxin Li, Mingjun Liu","doi":"10.1111/crj.13805","DOIUrl":"10.1111/crj.13805","url":null,"abstract":"<p>In previous studies, we developed a novel fusion protein named “melittin-MIL-2” which exhibited more anti-tumor activity. However, it remains unclear whether melittin-MIL-2 possesses antitumor immune effect on lung adenocarcinoma. In this study, the immune effect and mechanism of melittin-MIL-2 inhibiting the growth and invasion of lung adenocarcinoma will be investigated, in order to provide novel perspectives for the immunotherapy of lung cancer. The results indicated that melittin-MIL-2 promoted T cell proliferation, enhanced NK cell cytotoxicity, and boosted IFN-γ secretion in PBMCs. After melittin-MIL-2 stimulation, perforin expression and LAK/NK-like killing activities of human PBMCs and NK cells were significantly enhanced. Melittin-MIL-2 is capable of hampering the development and proliferation of lung adenocarcinoma cell A549. ICAM-1 and Fas expression in A549 cells exposed to melittin-MIL-2 rose significantly. The expression levels of TLR8 and VEGF in A549 cells decreased significantly after melittin-MIL-2 stimulation. In vivo, melittin-MIL-2 substantially impeded the growth of lung adenocarcinoma and formed an immune-stimulating microenvironment locally in tumor tissues. In conclusion, the novel fusion protein melittin-MIL-2 exhibits strong anti-tumor immune effect in lung adenocarcinoma cell A549 via activating the LFA-1/ICAM-1 and Fas/FasL pathways to enhance cytolytic activity, upregulating the secretion of IFN-γ and perforin, and boosting LAK/NK-like killing activities. Immuno-effector cells and their secreted cytokines can form immune stimulation microenvironment locally in lung adenocarcinoma Lewis mice tissue.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Dong, Wentao Zhang, Tingting Wu, Yongxiang Ge, Qi Yang, Jia Xu, Yuna Liu
<div> <section> <h3> Background</h3> <p>Azvudine (FNC) is a novel small molecule antiviral drug for treating COVID-19 that is available only on the Chinese market. Despite being recommended for treating COVID-19 by the Chinese guidelines, its efficacy and safety are still unclear. This study aimed to evaluate the protective effect of FNC on COVID-19 outcomes and its safety.</p> </section> <section> <h3> Methods</h3> <p>We followed the PRISMA 2020 guidelines and searched the PubMed, Embase, Web of Science, Scopus, and China National Knowledge Infrastructure (CNKI) databases to evaluate studies on the effectiveness of FNC in treating COVID-19 in China, focusing on mortality and overall outcomes. Additionally, its impact on the length of hospital stay (LOHS), time to first nucleic acid negative conversion (T-FNANC), and adverse events was evaluated. The inclusion criterion was that the studies were published from July 2021 to April 10, 2024. This study uses the ROBINS-I tool to assess bias risk and employs the GRADE approach to evaluate the certainty of the evidence.</p> </section> <section> <h3> Results</h3> <p>The meta-analysis included 24 retrospective studies involving a total of 11 830 patients. Low-certainty evidence revealed no significant difference in mortality (OR = 0.91, 95% CI: 0.76–1.08) or LOHS (WMD = −0.24, 95% CI: −0.83 to 0.35) between FNC and Paxlovid in COVID-19 patients. Low-certainty evidence shows that the T-FNANC was longer (WMD = 1.95, 95% CI: 0.36–3.53). Compared with the Paxlovid group, low-certainty evidence shows the FNC group exhibited a worse composite outcome (OR = 0.77, 95% CI: 0.63–0.95) and fewer adverse events (OR = 0.63, 95% CI: 0.46–0.85). Compared with supportive treatment, low certainty shows FNC significantly reduced the mortality rate in COVID-19 patients (OR = 0.61, 95% CI: 0.51–0.74) and decreased the composite outcome (OR = 0.67, 95% CI: 0.50–0.91), and very low certainty evidence shows significantly decreased the T-FNANC (WMD = −4.62, 95% CI: −8.08 to −1.15). However, in very low certainty, there was no significant difference in LOHS (WMD = −0.70, 95% CI: −3.32 to 1.91) or adverse events (OR = 1.97, 95% CI: 0.48–8.17).</p> </section> <section> <h3> Conclusions</h3> <p>FNC appears to be a safe and potentially effective treatment for COVID-19 in China, but further research with larger, high-quality studies is necessary to confirm these findings. Due to the certainty of the evidence and the specific context of the studies conducted in China, caution should be exercised when considering whether the results are
{"title":"Efficacy and Safety of Azvudine in Patients With COVID-19 in China: A Meta-Analysis of Observational Studies","authors":"Tao Dong, Wentao Zhang, Tingting Wu, Yongxiang Ge, Qi Yang, Jia Xu, Yuna Liu","doi":"10.1111/crj.13798","DOIUrl":"10.1111/crj.13798","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Azvudine (FNC) is a novel small molecule antiviral drug for treating COVID-19 that is available only on the Chinese market. Despite being recommended for treating COVID-19 by the Chinese guidelines, its efficacy and safety are still unclear. This study aimed to evaluate the protective effect of FNC on COVID-19 outcomes and its safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We followed the PRISMA 2020 guidelines and searched the PubMed, Embase, Web of Science, Scopus, and China National Knowledge Infrastructure (CNKI) databases to evaluate studies on the effectiveness of FNC in treating COVID-19 in China, focusing on mortality and overall outcomes. Additionally, its impact on the length of hospital stay (LOHS), time to first nucleic acid negative conversion (T-FNANC), and adverse events was evaluated. The inclusion criterion was that the studies were published from July 2021 to April 10, 2024. This study uses the ROBINS-I tool to assess bias risk and employs the GRADE approach to evaluate the certainty of the evidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The meta-analysis included 24 retrospective studies involving a total of 11 830 patients. Low-certainty evidence revealed no significant difference in mortality (OR = 0.91, 95% CI: 0.76–1.08) or LOHS (WMD = −0.24, 95% CI: −0.83 to 0.35) between FNC and Paxlovid in COVID-19 patients. Low-certainty evidence shows that the T-FNANC was longer (WMD = 1.95, 95% CI: 0.36–3.53). Compared with the Paxlovid group, low-certainty evidence shows the FNC group exhibited a worse composite outcome (OR = 0.77, 95% CI: 0.63–0.95) and fewer adverse events (OR = 0.63, 95% CI: 0.46–0.85). Compared with supportive treatment, low certainty shows FNC significantly reduced the mortality rate in COVID-19 patients (OR = 0.61, 95% CI: 0.51–0.74) and decreased the composite outcome (OR = 0.67, 95% CI: 0.50–0.91), and very low certainty evidence shows significantly decreased the T-FNANC (WMD = −4.62, 95% CI: −8.08 to −1.15). However, in very low certainty, there was no significant difference in LOHS (WMD = −0.70, 95% CI: −3.32 to 1.91) or adverse events (OR = 1.97, 95% CI: 0.48–8.17).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FNC appears to be a safe and potentially effective treatment for COVID-19 in China, but further research with larger, high-quality studies is necessary to confirm these findings. Due to the certainty of the evidence and the specific context of the studies conducted in China, caution should be exercised when considering whether the results are ","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13798","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The gradually progressive solitary cystic-solid mass of chest CT scans is highly suggestive of lung cancer. We report a case of a 29-year-old woman with a persistent cystic-solid lesion in the right upper lobe. A chest CT scan showed a 35 mm × 44 mm × 51 mm focal cystic-solid mass in the anterior segment of the right upper lobe. The size of lesion had increased over 3 years, especially for the solid component. The right upper lobe pneumonectomy was performed. Postoperative pathological examination showed placental transmogrification of the lung, which is a rare cause of pulmonary cystic lesion.
胸部 CT 扫描中逐渐进展的单发囊实性肿块高度提示肺癌。我们报告了一例 29 岁女性右上叶持续性囊实性病变的病例。胸部 CT 扫描显示，右上叶前段有一个 35 mm × 44 mm × 51 mm 的局灶性囊实性肿块。三年来，病灶的大小不断增大，尤其是实性部分。患者接受了右上叶肺切除术。术后病理检查显示肺部胎盘变性，这是肺囊性病变的罕见病因。
{"title":"Placental Transmogrification of the Lung Presenting as Cystic-Solid Mass: A Case Report","authors":"Chen Liu, Yunhui Zhang, Dengyuan Li, Danxiong Sun","doi":"10.1111/crj.13807","DOIUrl":"10.1111/crj.13807","url":null,"abstract":"<p>The gradually progressive solitary cystic-solid mass of chest CT scans is highly suggestive of lung cancer. We report a case of a 29-year-old woman with a persistent cystic-solid lesion in the right upper lobe. A chest CT scan showed a 35 mm × 44 mm × 51 mm focal cystic-solid mass in the anterior segment of the right upper lobe. The size of lesion had increased over 3 years, especially for the solid component. The right upper lobe pneumonectomy was performed. Postoperative pathological examination showed placental transmogrification of the lung, which is a rare cause of pulmonary cystic lesion.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13807","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mitochondrial ribosomal protein L35 (MRPL35) has been reported to contribute to the growth of non–small cell lung cancer (NSCLC) cells. However, the functions and mechanisms of MRPL35 on glutamine metabolism in NSCLC remain unclear.
Methods
The detection of mRNA and protein of MRPL35, ubiquitin-specific protease 39 (USP39), and solute carrier family 7 member 5 (SLC7A5) was conducted using qRT-PCR and western blotting. Cell proliferation, apoptosis, and invasion were evaluated using the MTT assay, EdU assay, flow cytometry, and transwell assay, respectively. Glutamine metabolism was analyzed by detecting glutamine consumption, α-ketoglutarate level, and glutamate production. Cellular ubiquitination analyzed the deubiquitination effect of USP39 on MRPL35. An animal experiment was conducted for in vivo analysis.
Results
MRPL35 was highly expressed in NSCLC tissues and cell lines, and high MRPL35 expression predicted poor outcome in NSCLC patients. In vitro analyses suggested that MRPL35 knockdown suppressed NSCLC cell proliferation, invasion, and glutamine metabolism. Moreover, MRPL35 silencing hindered tumor growth in vivo. Mechanistically, USP39 stabilized MRPL35 expression by deubiquitination and then promoted NSCLC cell proliferation, invasion, and glutamine metabolism. In addition, MRPL35 positively affected SLC7A5 expression in NSCLC cells in vitro and in vivo. Moreover, the anticancer effects of MRPL35 silencing could be rescued by SLC7A5 overexpression in NSCLC cells.
Conclusion
MRPL35 expression was stabilized by USP39-induced deubiquitination in NSCLC cells, and knockdown of MRPL35 suppressed NSCLC cell proliferation, invasion, and glutamine metabolism in vitro and impeded tumor growth in vivo by upregulating SLC7A5, providing a promising therapeutic target for NSCLC.
{"title":"MRPL35 Induces Proliferation, Invasion, and Glutamine Metabolism in NSCLC Cells by Upregulating SLC7A5 Expression","authors":"Wei Hou, Juan Chen, Yaoyuan Wang","doi":"10.1111/crj.13799","DOIUrl":"10.1111/crj.13799","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mitochondrial ribosomal protein L35 (MRPL35) has been reported to contribute to the growth of non–small cell lung cancer (NSCLC) cells. However, the functions and mechanisms of MRPL35 on glutamine metabolism in NSCLC remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The detection of mRNA and protein of MRPL35, ubiquitin-specific protease 39 (USP39), and solute carrier family 7 member 5 (SLC7A5) was conducted using qRT-PCR and western blotting. Cell proliferation, apoptosis, and invasion were evaluated using the MTT assay, EdU assay, flow cytometry, and transwell assay, respectively. Glutamine metabolism was analyzed by detecting glutamine consumption, α-ketoglutarate level, and glutamate production. Cellular ubiquitination analyzed the deubiquitination effect of USP39 on MRPL35. An animal experiment was conducted for in vivo analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MRPL35 was highly expressed in NSCLC tissues and cell lines, and high MRPL35 expression predicted poor outcome in NSCLC patients. In vitro analyses suggested that MRPL35 knockdown suppressed NSCLC cell proliferation, invasion, and glutamine metabolism. Moreover, MRPL35 silencing hindered tumor growth in vivo. Mechanistically, USP39 stabilized MRPL35 expression by deubiquitination and then promoted NSCLC cell proliferation, invasion, and glutamine metabolism. In addition, MRPL35 positively affected SLC7A5 expression in NSCLC cells in vitro and in vivo. Moreover, the anticancer effects of MRPL35 silencing could be rescued by SLC7A5 overexpression in NSCLC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MRPL35 expression was stabilized by USP39-induced deubiquitination in NSCLC cells, and knockdown of MRPL35 suppressed NSCLC cell proliferation, invasion, and glutamine metabolism in vitro and impeded tumor growth in vivo by upregulating SLC7A5, providing a promising therapeutic target for NSCLC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13799","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhiqiang He, Jing Wu, Xiao ming Fu, Xiao ran Li, Hai Xu, Yu-Chen Chen
Renal angiomyolipoma has two histological variants: classical and epithelioid. Epithelioid angiomyolipoma is considered as a potential malignant tumor, often leading to recurrence and metastasis, with rapid progression in most of the cases. The lung is one of the most commonly reported sites of metastasis, and pulmonary metastasis of renal angiomyolipoma is usually diagnostic by computed tomography (CT) scans. Here, we report for the first time renal angiomyolipoma with lung metastasis by combining CT and magnetic resonance imaging (MRI).
{"title":"CT and MRI Findings of Renal Angiomyolipoma With Lung Metastasis: A Case Report and Literature Review","authors":"Zhiqiang He, Jing Wu, Xiao ming Fu, Xiao ran Li, Hai Xu, Yu-Chen Chen","doi":"10.1111/crj.13796","DOIUrl":"10.1111/crj.13796","url":null,"abstract":"<p>Renal angiomyolipoma has two histological variants: classical and epithelioid. Epithelioid angiomyolipoma is considered as a potential malignant tumor, often leading to recurrence and metastasis, with rapid progression in most of the cases. The lung is one of the most commonly reported sites of metastasis, and pulmonary metastasis of renal angiomyolipoma is usually diagnostic by computed tomography (CT) scans. Here, we report for the first time renal angiomyolipoma with lung metastasis by combining CT and magnetic resonance imaging (MRI).</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
One hundred eighty pairs of tissues of esophageal squamous cell carcinoma (ESCC) were tested by the transcriptome sequencing in order to explore etiology factors. The chi-square test and correlation analysis demonstrated that the relative expression levels of keratin 17 (KRT17) and collagen type I α1 chain (COL1A1) were significantly higher in EC with diabetes. Expression of KRT17 was correlated with blood glucose (r = 0.204, p = 0.001) and tumor size (r = −0.177, p = 0.038) in patients. COL1A1 correlated with age (r = −0.170, p = 0.029) and blood glucose levels (r = 0.190, p = 0.015). Experimental results of qRT-PCR: KRT17 and COL1A1 genes were highly expressed in ESCC (p < 0.05). When the two genes were used as a combination test, the positive detection rate of EC was 90.6%, and the ROC curve had greater power. The KRT17 and COL1A1 genes had the potential to be biomarkers for the diagnosis of ESCC.
{"title":"Keratin 17 and Collagen type 1 genes: Esophageal cancer molecular marker discovery and evaluation","authors":"Huiwen Pan, Jie Hong, Aizhong Shao, Zhiguo Zhao, Guowen Ding, Zhijie Fang, Keping Chen, Jingfeng Zhu","doi":"10.1111/crj.13793","DOIUrl":"10.1111/crj.13793","url":null,"abstract":"<p>One hundred eighty pairs of tissues of esophageal squamous cell carcinoma (ESCC) were tested by the transcriptome sequencing in order to explore etiology factors. The chi-square test and correlation analysis demonstrated that the relative expression levels of keratin 17 (KRT17) and collagen type I α1 chain (COL1A1) were significantly higher in EC with diabetes. Expression of KRT17 was correlated with blood glucose (<i>r</i> = 0.204, <i>p</i> = 0.001) and tumor size (<i>r</i> = −0.177, <i>p</i> = 0.038) in patients. COL1A1 correlated with age (<i>r</i> = −0.170, <i>p</i> = 0.029) and blood glucose levels (<i>r</i> = 0.190, <i>p</i> = 0.015). Experimental results of qRT-PCR: KRT17 and COL1A1 genes were highly expressed in ESCC (<i>p</i> < 0.05). When the two genes were used as a combination test, the positive detection rate of EC was 90.6%, and the ROC curve had greater power. The KRT17 and COL1A1 genes had the potential to be biomarkers for the diagnosis of ESCC.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Idiopathic pulmonary fibrosis (IPF) is a progressive disease and has a high mortality rates [<span>1</span>]. While the overall prognosis of IPF is poor, the decline in pulmonary function tests and progression to death varies widely [<span>2</span>]. Identification of patients with slow progression or rapid progression would be valuable for subsequent studies, including genetic analyses and investigation of IPF clinical phenotypes. Additionally, it could influence treatment decisions, including the timing of transplantation. We congratulate Doubkova and colleagues for their study aiming to establish the impact of demographic parameters, pulmonary function parameters and high-resolution computed tomography scores [<span>1</span>]. It was revealed that diffusing lung carbon monoxide (DLCO) decline seems to be superior to forced vital capacity (FVC) decline in predicting mortality. After a thorough review of their article, we offer the following comments to enrich the understanding of their study.</p><p>FVC is the most common outcome used in investigating the course of patients with IPF and change in FVC percentage predicted over time is a well-known predictor of mortality [<span>3</span>]. The primary endpoint as FVC decline in INPULSIS [<span>4</span>], ASCEND [<span>5</span>], CAPACITY [<span>6</span>] and TOMORROW [<span>7</span>] studies. However, DLCO decline was found to be an independent predictor of mortality after multivariate analysis instead of FVC decline in this study [<span>1</span>]. Statistically, only more clinically significant parameters should be included in the multivariate analysis among those showing high correlation. In line with this, it should be noted that both FVC and DLCO decline, which are expected to have a high correlation, were included in the multivariate analysis. This may lead to a multicollinearity problem and impact the accuracy of the results. To address this issue, it may be beneficial to create two separate models [Model 1: FVC model (not including DLCO) and Model 2: DLCO model (not including FVC)].</p><p>Regarding baseline characteristics, there were significant differences in the extent of lung involvement, FVC (%) and DLCO (%) found between alive and deceased patients. Deceased patients were more likely to have higher alveolar and interstitial scores, as well as lower DLCO (%) and FVC (%). Since baseline FVC (%) and DLCO (%) were not included in the univariate Cox analysis, we cannot determine the independent effect of decline in FVC (%) and DLCO (%). This is important because patients with more severe baseline conditions are more likely to deteriorate and experience mortality.</p><p>As authors indicated, pulmonary hypertension has not been assessed. However, this may affect the prognostic role of DLCO (%), which is the primary conclusion of this study, because DLCO is expected to be significantly low in patients with pulmonary hypertension. Indeed, given the highly variable clinical course of IPF, the
{"title":"A Commentary on the Role of Pulmonary Function Parameters in Idiopathic Pulmonary Fibrosis Follow-Up","authors":"Guliz Degirmenci, Celal Satici","doi":"10.1111/crj.13797","DOIUrl":"10.1111/crj.13797","url":null,"abstract":"<p>Idiopathic pulmonary fibrosis (IPF) is a progressive disease and has a high mortality rates [<span>1</span>]. While the overall prognosis of IPF is poor, the decline in pulmonary function tests and progression to death varies widely [<span>2</span>]. Identification of patients with slow progression or rapid progression would be valuable for subsequent studies, including genetic analyses and investigation of IPF clinical phenotypes. Additionally, it could influence treatment decisions, including the timing of transplantation. We congratulate Doubkova and colleagues for their study aiming to establish the impact of demographic parameters, pulmonary function parameters and high-resolution computed tomography scores [<span>1</span>]. It was revealed that diffusing lung carbon monoxide (DLCO) decline seems to be superior to forced vital capacity (FVC) decline in predicting mortality. After a thorough review of their article, we offer the following comments to enrich the understanding of their study.</p><p>FVC is the most common outcome used in investigating the course of patients with IPF and change in FVC percentage predicted over time is a well-known predictor of mortality [<span>3</span>]. The primary endpoint as FVC decline in INPULSIS [<span>4</span>], ASCEND [<span>5</span>], CAPACITY [<span>6</span>] and TOMORROW [<span>7</span>] studies. However, DLCO decline was found to be an independent predictor of mortality after multivariate analysis instead of FVC decline in this study [<span>1</span>]. Statistically, only more clinically significant parameters should be included in the multivariate analysis among those showing high correlation. In line with this, it should be noted that both FVC and DLCO decline, which are expected to have a high correlation, were included in the multivariate analysis. This may lead to a multicollinearity problem and impact the accuracy of the results. To address this issue, it may be beneficial to create two separate models [Model 1: FVC model (not including DLCO) and Model 2: DLCO model (not including FVC)].</p><p>Regarding baseline characteristics, there were significant differences in the extent of lung involvement, FVC (%) and DLCO (%) found between alive and deceased patients. Deceased patients were more likely to have higher alveolar and interstitial scores, as well as lower DLCO (%) and FVC (%). Since baseline FVC (%) and DLCO (%) were not included in the univariate Cox analysis, we cannot determine the independent effect of decline in FVC (%) and DLCO (%). This is important because patients with more severe baseline conditions are more likely to deteriorate and experience mortality.</p><p>As authors indicated, pulmonary hypertension has not been assessed. However, this may affect the prognostic role of DLCO (%), which is the primary conclusion of this study, because DLCO is expected to be significantly low in patients with pulmonary hypertension. Indeed, given the highly variable clinical course of IPF, the","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 6","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Background</h3> <p>One of the most crucial and essential methods for the prevention and management of respiratory infections is for healthcare professionals to take precautions for their own safety. Using Protection Motivation Theory (PMT), the current study looked into effective elements influencing the staff at Kazeroon's Valiasr Hospital's preventive actions against respiratory diseases.</p> </section> <section> <h3> Methods</h3> <p>One hundred ninety-two male and 108 female employees of the Valiasr Hospital in Kazeroon, Iran, participated in this cross-sectional study, in May 2022. Census data were used as the sample technique. A questionnaire based on the PMT and a questionnaire collecting demographic data served as the data collection method. The study's content validity was confirmed by 10 health education experts, and its reliability was assessed using internal consistency techniques, resulting in a Cronbach's alpha coefficient of 0.87.The statistical program SPSS 24 was used to examine the data using the independent <i>t</i> test, logistic regression, and Pearson correlation.</p> </section> <section> <h3> Results</h3> <p>The average age was 34.11 ± 8.91 for men and 32.77 ± 6.09 for women. The majority of participants were married (73.3%), had university education (76.7%), and earned a monthly income between 10 and 15 million Tomans (75%). Notably, 97.7% of participants had received the COVID-19 vaccine, and 77.7% had undergone training related to respiratory infections. The most common preventive practices included avoiding touching the eyes, noses, or mouths, wearing appropriate protective gear, and maintaining a safe distance of 1–2 m from others. Analysis of PMT constructs showed that participants had a generally positive perception toward preventive behaviors. Perceived vulnerability (<i>P</i> = 0.02), perceived cost (<i>P</i> = 0.03), and motivation (<i>P</i> = 0.001) were the three analyzed components that had the greatest impact on respiratory infection preventative behavior. Logistic regression revealed that perceived susceptibility, cost, and motivation significantly predicted the prevention of respiratory infections, with a predictive power of 45%. These findings highlight the importance of understanding the factors influencing preventive behaviors among hospital staff, from respiratory infections like COVID-19.</p> </section> <section> <h3> Conclusion</h3> <p>According to the findings, the personnel at Kazeroon's Valiasr Hospital wore gloves, goggles, and other appropriate personal protective equipment. The
{"title":"Preventive behaviors of respiratory infections in staff of hospital in Kazeroon, Fars, Iran: An application of protection motivation theory","authors":"Tayebeh Rakhshani, Zohreh Shafiei, Samira Taravatmanesh, Seyyed Mansour Kashfi, Pooyan Afzali Harsini, Amirhossein Kamyab, Ali Khani Jeihooni","doi":"10.1111/crj.13791","DOIUrl":"10.1111/crj.13791","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>One of the most crucial and essential methods for the prevention and management of respiratory infections is for healthcare professionals to take precautions for their own safety. Using Protection Motivation Theory (PMT), the current study looked into effective elements influencing the staff at Kazeroon's Valiasr Hospital's preventive actions against respiratory diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>One hundred ninety-two male and 108 female employees of the Valiasr Hospital in Kazeroon, Iran, participated in this cross-sectional study, in May 2022. Census data were used as the sample technique. A questionnaire based on the PMT and a questionnaire collecting demographic data served as the data collection method. The study's content validity was confirmed by 10 health education experts, and its reliability was assessed using internal consistency techniques, resulting in a Cronbach's alpha coefficient of 0.87.The statistical program SPSS 24 was used to examine the data using the independent <i>t</i> test, logistic regression, and Pearson correlation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The average age was 34.11 ± 8.91 for men and 32.77 ± 6.09 for women. The majority of participants were married (73.3%), had university education (76.7%), and earned a monthly income between 10 and 15 million Tomans (75%). Notably, 97.7% of participants had received the COVID-19 vaccine, and 77.7% had undergone training related to respiratory infections. The most common preventive practices included avoiding touching the eyes, noses, or mouths, wearing appropriate protective gear, and maintaining a safe distance of 1–2 m from others. Analysis of PMT constructs showed that participants had a generally positive perception toward preventive behaviors. Perceived vulnerability (<i>P</i> = 0.02), perceived cost (<i>P</i> = 0.03), and motivation (<i>P</i> = 0.001) were the three analyzed components that had the greatest impact on respiratory infection preventative behavior. Logistic regression revealed that perceived susceptibility, cost, and motivation significantly predicted the prevention of respiratory infections, with a predictive power of 45%. These findings highlight the importance of understanding the factors influencing preventive behaviors among hospital staff, from respiratory infections like COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>According to the findings, the personnel at Kazeroon's Valiasr Hospital wore gloves, goggles, and other appropriate personal protective equipment. The ","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 6","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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