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Xu-Rui Shen,1,&ast; Ying-Ying Liu,2,&ast; Rui-Qi Qian,1,&ast; Wei-Yun Zhang,2 Jian-An Huang,1 Xiu-Qin Zhang,1 Da-Xiong Zeng2 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Jiangsu, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Suzhou Dushu Lake Hospital, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiu-Qin Zhang, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-18912616972, Email zxq92@sina.com Da-Xiong Zeng, Department of Pulmonary and Critical Care Medicine, Suzhou Dushu Lake Hospital, No. 9 Chongwen Road, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-15895567963, Email zengdaxiong2018@126.comPurpose: Circular RNAs (circRNAs) are newly identified endogenous non-coding RNAs that function as crucial gene modulators in the development of several diseases. By assessing the expression levels of circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD), this study attempted to find new biomarkers for COPD screening.Patients and Methods: We confirmed altered circRNA expression in PBMCs of COPD (n=41) vs controls (n=29). Further analysis focused on the highest and lowest circRNA expression levels. The T-test is used to assess the statistical variances in circRNAs among COPD patients in the smoking and non-smoking cohorts. Additionally, among smokers, the Spearman correlation test assesses the association between circRNAs and clinical indicators.Results: Two circRNAs, hsa_circ_0042590 and hsa_circ_0049875, that were highly upregulated and downregulated in PBMCs from COPD patients were identified and verified. Smokers with COPD had lower hsa_circ_0042590 and higher hsa_circ_0049875, in comparison to non-smokers. There was a significant correlation (r=0.52, P< 0.01) between the number of acute exacerbations (AEs) that smokers with COPD experienced in the previous year and the following year (r=0.67, P< 0.001). Moreover, hsa_circ_0049875 was connected to the quantity of AEs in the year prior (r=0.68, P< 0.0001) as well as the year after (r=0.72, P< 0.0001). AUC: 0.79, 95% CI: 0.1210– 0.3209, P< 0.0001) for hsa_circ_0049875 showed a strong diagnostic value for COPD, according to ROC curve analysis. Hsa_circ_0042590 showed a close second with an AUC of 0.83 and 95% CI: − 0.1972--0.0739 (P < 0.0001).Conclusion: This research identified a strong correlation between smoking and hsa_circ_0049875 and hsa_circ_0042590 in COPD PBMCs. The number of AEs in the preceding and succeeding years was substantially linked with the existence of hsa_circ_0042590 and hsa_circ_0049875 in COPD patients who smoke. Additionally, according to our research, hsa_circ_0049875 and hsa_circ_0042590 may be valuable biomarkers for COPD diagnosis.Keywords: chronic obstructive pulmonary disease, circular RNAs, smoking, acute exacerbation, biomarker

Da-Xiong Zeng Department of Pulmonary and Critical Care Medicine, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Da-Xiong Zeng, Department of Pulmonary and Critical Care Medicine, Suzhou Dushu Lake Hospital, No. 9, Chongwen Road, Suzhou, 215100, People’s Republic of China, Email zengdaxiong@suda.edu.cn

Chang-Guo Wang,1,* Chang Li,2,* Wei Lei,1 Jun-Hong Jiang,1 Jian-An Huang,1 Da-Xiong Zeng1 1Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China *These authors contributed equally to this work Introduction: Chronic hypoxia-induced pulmonary vascular remodeling is a feature of chronic obstructive pulmonary disease (COPD). Our previous reports indicate that neuron-derived orphan receptor 1 (NOR1) promoted pulmonary smooth muscle cell proliferation in vitro. But it remains unclear whether NOR1 participated into hypoxia-induced pulmonary vascular remodeling in COPD patients. Patients and methods: For this study, we collected peripheral lung tissues of 26 male COPD patients with or without hypoxemia. We detected the pulmonary vascular remodeling in all the peripheral lung tissues. Primary human pulmonary arterial smooth muscle cells were also cultured in vitro and stimulated with hypoxia or normoxia. Cell proliferation and protein levels were detected.Results: COPD patients with hypoxemia showed significantly enlarged pulmonary vessels wall thickness and increased protein levels of HIF-1α, smooth muscle actin, cyclin D1, and NOR1 when compared with those in normoxic patients. Moreover, hypoxia induced human pulmonary arterial smooth muscle cell proliferation and NOR1 overexpression in vitro. The plasmid-based NOR1 gene overexpression markedly promoted DNA synthesis and proliferation in hypoxia or normoxic cells. Human NOR1 gene-specific siRNA intensively suppressed DNA synthesis and proliferation. Transfection of NOR1 overexpression plasmid raised cyclin D1 protein levels, which could be significant inhibited by NOR1-specific siRNA or a CDK4/6 inhibitor PD0332991.Conclusion: We concluded that NOR1 upregulation is associated with hypoxia-induced pulmonary vascular remodeling in COPD via promoting human pulmonary arterial smooth muscle cell proliferation. Keywords: pulmonary arterial smooth muscle cells, neuron-derived orphan receptor 1, cyclin D1, hypoxia, pulmonary vascular remodeling

Ran Wang,1,* Min Li,2,* Sijing Zhou,1,3 Daxiong Zeng,4 Xuan Xu,5 Rui Xu,1 Gengyun Sun1 1Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Hefei Prevention and Treatment Center for Occupational Diseases, Hefei, People’s Republic of China; 4Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Division of Pulmonary/Critical Care Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA *These authors contributed equally to this work Objective: To evaluate the effect of a single nucleotide polymorphism (rs2910164) in the miR-146a precursor on the expression level of miR-146a, cyclooxygenase-2 (COX2), and production of prostaglandin E2 (PGE2) in lung tissue harvested from smokers with chronic obstructive pulmonary disease, as well as the lung function and disease stages from the same patient population.Methods and results: One-hundred and sixty-eight smokers with diagnosed chronic obstructive pulmonary disease were recruited. The patients were genotyped for rs2910164 polymorphism using Sanger sequencing, and their lung function/disease stages were evaluated following Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Meanwhile, messenger ribonucleic acid and protein expression levels of miR-146a and COX2 as well as PGE2 production were determined in 66 lung tissue samples collected in the patients who received surgical treatment. We confirmed that COX2 is a validated target of miR-146a in human fibroblast cells, and identified the differential expression patterns of miR-146a and COX2 in each rs2910164 genotype group. We observed a significant association between rs2910164 in miR-146a and the levels of either COX2 or PGE2 using real-time polymerase chain reaction and Western blot. Consistently, we were able to demonstrate that the rs2910164 single nucleotide polymorphism has a functional effect on the baseline lung function in the study population.Conclusion: In the present study, the rs2910164 CC and GC genotype was found to be associated with an improved lung function and milder disease stages, at least partially, mediated by its ability to increase in COX2 expression and PGE2 production. Keywords: SNP, miR-146a, COX-2, COPD, lung function

Background and Aims: Early stage administration of Paxlovid has been shown to improve the prognosis of mild to moderate COVID-19 patients with high risk. However, few evidence was validated in severe COVID-19 patients with hypoxemia. It is also unclear whether delayed usage of Paxlovid affected prognosis in COVID-19 patients or not., Methods: In this multiple-centers prospective study, we collected the clinical data in hospitalized severe adult Omicron infection patients with hypoxemia. All patients were divided into two groups according to the time of Paxlovid usage after the symptom onset: early group (Paxlovid administration in 5 days after symptom onset) and delayed group (Paxlovid administration beyond 5 days after symptom onset). The 28-day composite outcomes were evaluated., Results: Totally 198 hospitalized severe omicron-infected subjects with hypoxemia were enrolled. There was no difference between the two groups about the baseline characteristics and laboratory parameters, except for leukocytes (5.29 × 10 9 vs. 7.90 × 10 9 /L, p  = 0.01) and albumin levels (35 vs. 31 g/L, p  = 0.04). The 28-day composite outcomes in early group were slightly lower than that in delayed group but with no difference (12.8% vs. 16.67%, p  = 0.602). The viral clearance ratio at Day 7 after Paxlovid treatment in early group was higher than that in delayed group (79.48% vs. 58.33%, p  = 0.029). The medium hospitalized duration in early group was shorter than that in delayed group (11.31 vs. 15.32 days, p  = 0.005). Logistic analysis showed the independent risk factors of prognosis including underlying diseases ≥ 3 kinds (ORR = 1.72), d-dimer ≥ 2.0 μg/mL (ORR = 1.35), and MODS (ORR = 14.01)., Conclusions: In Omicron-infected subjects with hypoxemia, early usage of Paxlovid received benefits in hospitalized time and viral clearance, but delayed usage did not result in a worse composite prognosis. This result might provide direct evidence of antiviral strategy in severe Omicron infection subjects with hypoxemia., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Competing Interests: The authors have no conflicts of interest to declare.

Competing Interests: The authors have no conflicts of interest to declare.

Objective: To assess and compare the diagnostic efficacy of next-generation ultrathin bronchoscopy (UTB) and conventional bronchoscopy (CB), both combined with radial endobronchial ultrasound (r-EBUS), in the evaluation of peripheral pulmonary lesions (PPL). Methods: A cohort of 39 patients with PPL who underwent multimodal bronchoscopy at Dushu Lake Hospital, Soochow University, from June 1, 2021 to May 31, 2023 was consecutively enrolled. A single bronchoscopist performed multimodal bronchoscopies using CB (external diameter 4.9 mm or 5.9 mm, working channel diameter 2 or 3 mm, CB group) for transbronchial biopsy under r-EBUS guidance (rEBUS-TBLB), followed by UTB (external diameter 3 mm, working channel diameter 1.7 mm, UTB group) for transbronchial biopsy under r-EBUS guidance. Pathological findings and a 6-month clinical follow-up were used as the gold standard to compare the diagnostic yield of biopsy specimens, ultrasound characteristics, and localization rates of the two bronchoscope types. The aim was to evaluate the clinical application value of UTB combined with r-EBUS. Binary variables were analysed using the McNemar test for paired data. Continuous variables or ranked data were analysed using the Wilcoxon signed-rank test for paired data. Results: The diagnostic yields for UTB and CB groups were 66.67% (26/39) and 30.77% (12/39), respectively, with the UTB group significantly surpassing the CB group ( χ 2 =10.56, P =0.001, 1-β=0.968). r-EBUS with CB exhibited no visible lesion in 13 cases, adjacent to the lesion in 19 cases, and within the lesion in 7 cases.Substitution of UTB resulted in r-EBUS images changing from no visible lesion to adjacent to the lesion in 7 cases, from no visible lesion to within the lesion in 3 cases, and from adjacent to the lesion to within the lesion in 12 cases. The positioning of the r-EBUS probe in relation to the lesions improved significantly with UTB usage ( Z =-4.46, P <0.001). Localization rates (number of patients with "within" or "adjacent to" the image/total number of patients) for UTB and CB were 92.30% (36/39) and 66.67% (26/39), respectively ( χ 2 =8.10, P =0.002). UTB improved r-EBUS probe localization rates. The diagnostic yields of UTB were higher than CB for solid lesions, lesions>30 mm in diameter, non-upper lobar location, benign or malignant lesions and lesions with or without a bronchus sign. Conclusion: The UTB group demonstrated a significantly higher diagnostic yield than the CB group, providing superior r-EBUS probe images, and a significant diagnostic advantage for PPL.

Competing Interests: The authors have no conflicts of interest to declare.

BACKGROUND: Obstructive sleep apnoea (OSA) patients have a decreased exercise capacity. Potential cardiovascular capacity in patients with OSA with different severity without known cardiovascular disease has not been described. OBJECTIVE: To evaluate impaired potential exercise cardiovascular capacity during cardiopulmonary exercise testing (CPET) in OSA patients and to compare cardiovascular performance reaction with different severity during graded exercise stages. DESIGN: All participants were accompanied without cardiovascular disease, especially hypertension and arrhythmia. Parameters of different stages were compared between subjects with and without OSA, and among OSA patients with varied severity. RESULTS: Despite having significantly higher peak exercise diastolic blood pressure (DBP) and ventilatory equivalent for CO 2 (EQCO₂), patients with OSA had a lower peak oxygen uptake (VO₂), heart rate (HR), heart rate recovery (HRR) and respiratory reserve (BR) than normal subjects. Furthermore, significant correlations were found between VO₂, DBP, EQCO₂, HRR, BR and the apnoea-hypopnea index. In severe OSA, there was a greater difference in HR and HRR during the anaerobic threshold stages. CONCLUSIONS: OSA patients demonstrate reduced potential cardiovascular capacity, even without documented cardiovascular disease. Patients with severe OSA develop impaired exercise capacity at early stage during exercise. These data point to exaggerated haemodynamic response to graded exercise and delayed post-exercise cardiovascular response recovery in OSA patients. CPET can be a supplement for assessment of OSA severity.

To investigate the role of tracheal wall injury in the development of benign airway stenosis in rabbits. Prospective study. We injured the tracheal walls of 28 New Zealand white rabbits using four different methods. Experimental group: Group A (n = 7, mild injury of tracheal mucosa by ordinary brush under bronchoscopy); Group B (n = 7, severe injury of tracheal mucosa by nylon brush under tracheotomy); Group C (n = 7, tracheal cartilage was injured by vascular clamp after tracheotomy); Group D (n = 7, the tracheal cartilage was injured with vascular forceps and the tracheal mucosa was injured with a nylon brush after tracheotomy). Bronchoscopy was performed on each experimental rabbit at 1, 2, 3 and 4 weeks after operation. High-resolution computed tomography (HRCT) and endobronchial optical coherence tomography (EB-OCT) were performed at 4 weeks, and the rabbits were sacrificed after the examination. Their gross and histological findings were comparatively determined whether the experimental rabbit stenosis was established. No airway stenosis was observed in group A. In group B, 28.57% of experimental rabbits developed tracheal stenosis (granulation tissue proliferation was observed in rabbits No. 2 and No. 6 at 1, 2 and 3 weeks after operation, and the tracheal scar contracture was observed in No.6 rabbit at 4 weeks after operation). Fourteen rabbits in group C and group D had tracheal stenosis caused by granulation tissue proliferation at 1, 2 and 3 weeks after operation. At the fourth week after operation, 71.43% of experimental rabbits had tracheal stenosis due to granulation tissue hyperplasia, 7.14% of experimental rabbits had tracheal stenosis due to scar contracture and granulation hyperplasia, and 21.43% of experimental rabbits had tracheal stenosis due to scar contracture. EB-OCT scan showed that the cartilage layer with low signal reflection band was discontinuous. The injury of cartilage is the key factor of benign airway stenosis. Acute injury of airway mucosa alone is unlikely to cause airway stenosis, but combined with cartilage injury may aggravate airway stenosis. EB-OCT can clearly identify the airway layers of rabbits, which is helpful to evaluate the damage of tracheal cartilage and mucosa. The diagnostic potential of this technique makes EB-OCT a promising approach for the study and monitoring of airway diseases., (© 2023. The Author(s).)

Background: Single-incision laparoscopy surgery (SILS) is a new laparoscopic technique that has emerged in the past decade. Whether it has advantages over conventionl laparoscopy surgery (CLS) is inconclusive. This article aimed to compare the short- and long-term outcomes of single-incision laparoscopic surgery and conventional laparoscopic surgery for colorectal cancer through high-quality literature text mining and meta-analysis., Methods: Relevant articles were searched on the PubMed, Embase, and Cochrane Library databases from January 2012 to November 2021. All data was from randomized controlled trials (RCTs) in order to increase the confidence of the analytical results.The main outcomes were intraoperative and postoperative complications., Results: A total of 10 RCTs were included, involving 1609 patients. The quality of the included studies was generally high. No significant difference was found between SILS and CLS in the postoperative complications, operation time, postoperative hospital stay, number of lymph nodes removed, readmission, reoperation, complication level I- II, complication level IIIa, complication level IIIb, prolonged Ileus, blood loss, infection, anastomotic leakage and operation time. The results showed that SILS group had a higher rate of intraoperative complications, but it had lower incision length and better cosmetic effects., Conclusion: These results indicate that SILS did not have a comprehensive and obvious advantage over the CLS. On the contrary, SILS has higher intraoperative complications, which may be related to the more difficulty of SILS operation, but SILS still has better cosmetic effects, which is in line with the concept of surgical development. Therefore, the SILS needs to be selected in patients with higher cosmetic requirements and performed by more experienced surgeons., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Zeng, Chen, Xu, Tan, Zhang and Xiao.)

Background: Hypoxic pulmonary hypertension (HPH) is a common complication of chronic lung disease, which severely affects the survival and prognosis of patients. Several recent reports have shown that DNA damage and repair plays a crucial role in pathogenesis of pulmonary arterial hypertension. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a part of DNA-PK is a molecular sensor for DNA damage that enhances DSB repair. This study aimed to demonstrate the expression and potential mechanism of DNA-PKcs on the pathogenesis of HPH., Methods: Levels of DNA-PKcs and other proteins in explants of human and rats pulmonary artery from lung tissues and pulmonary artery smooth muscle cells (PASMC) were measured by immunohistochemistry and western blot analysis. The mRNA expression levels of DNA-PKcs and NOR1 in PASMCs were quantified with qRT-PCR. Meanwhile, the interaction among proteins were detected by Co-immunoprecipitation (Co-IP) assays. Cell proliferation and apoptosis was assessed by cell counting kit-8 assay(CCK-8), EdU incorporation and flow cytometry. Rat models of HPH were constructed to verify the role of DNA-PKcs in pulmonary vascular remodeling in vivo., Results: DNA-PKcs protein levels were both significantly up-regulated in explants of pulmonary artery from HPH models and lung tissues of patients with hypoxemia. In human PASMCs, hypoxia up-regulated DNA-PKcs in a time-dependent manner. Downregulation of DNA-PKcs by targeted siRNA or small-molecule inhibitor NU7026 both induced cell proliferation inhibition and cell cycle arrest. DNA-PKcs affected proliferation by regulating NOR1 protein synthesis followed by the expression of cyclin D1. Co-immunoprecipitation of NOR1 with DNA-PKcs was severely increased in hypoxia. Meanwhile, hypoxia promoted G 2  + S phase, whereas the down-regulation of DNA-PKcs and NOR1 attenuated the effects of hypoxia. In vivo, inhibition of DNA-PKcs reverses hypoxic pulmonary vascular remodeling and prevented HPH., Conclusions: Our study indicated the potential mechanism of DNA-PKcs in the development of HPH. It might provide insights into new therapeutic targets for pulmonary vascular remodeling and pulmonary hypertension., (© 2022. The Author(s).)

Background: Self-expandable metallic (SEM) airway stents are an important approach to treating malignant central airway obstruction (CAO). Standard over-the-while (OTW) stent needs the guidance of a guide-wire. It should be implanted under flouroscopy or the guidance of bronchoscope visualization. In this study, we evaluated the operation time and safety between OTW stent and a novel through-the-scope (TTS) SEM airway stent., Methods: In this multi-center, randomized, parallel-group superiority study, malignant CAO patients were enrolled randomly assigned (2:1) to the TTS stent implantation group (TTS group) or the standard OTW stent group (OTW group) in six sites across China. The entire process of all surgical procedures was recorded by video. Primary endpoint was the operation time of the airway stent implantation and secondary endpoint was the success rate of the stent implantation as well as its efficacy and safety., Results: From May 15, 2017, to December 30, 2018, 148 patients were enrolled from the six sites. We analyzed 134 patients (including 91 patients from the TTS group and 43 patients from the OTW group) according to the per-protocol set. There were no significant differences in the ages, genders, underlying diseases, and stenosis sites between the two groups. The operation time in the TTS group was significantly shorter than that in the OTW group (104±68 vs. 252±111 seconds, P<0.001). Compared to the OTW group, the efficacy of stent implantation (97.80% vs. 90.70%, P=0.093) and rate of first-time successful stent implantation (78.02% vs. 74.42%, P=0.668) were higher in the TTS group, but did not reach statistically significance. The rates of granulation (28.57% vs. 41.86%, P=0.128) and restenosis (15.38% vs. 30.23%, P=0.064) in the TTS group were slightly lower as compared with the OTW group without achieving statistical significance., Conclusions: The TTS stent implantation procedure time was significantly shorter than that of the OTW airway stent with similar efficacy and complications, which might reduce the risk and flexibility of stent implantation., Trial Registration: Chinese Clinical Trial Registry ChiCTR-IOR-17011431., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-565/coif). HD received Royalties on the Dutau Novatech rigid bronchoscope and is the consultant for Novatech. The other authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

It has been reported that cyclin-dependent kinase like 3 (CDKL3) plays a crucial role in cell proliferation and migration in several cancers. However, the function of CDKL3 in triple-negative breast cancer (TNBC) is still unclear. In the present study, immunohistochemistry (IHC) was conducted to detect the CDKL3 expression. CCK-8, flow cytometry, Transwell assays, and mice xenograft models, were performed to explore the roles of CDKL3 on the proliferation and migration of TNBC in vitro and in vivo. Besides, protein chip analysis was used to screen the potential pathways, which was further confirmed by promoter activity assay, western blotting, and CCK-8 assay. Our findings reveal a high expression of CDKL3 in TNBC tissues, which is closely related to a poor prognosis of patients with TNBC. In TNBC cells, CDKL3 knockdown inhibits cell proliferation and migration, whereas CDKL3 overexpression has exactly the opposite effect. Consistently, CDKL3 knockdown induces cell apoptosis in vitro but suppresses tumor growth in vivo. Furthermore, CDKL3 knockdown increases p53 expression and reduces cell viability, and these effects are significantly weakened by the p53 inhibitor, PFT-α. In conclusion, the current study highlights that CDKL3 promotes TNBC progressions via regulating the p53 signaling pathway, suggesting that CDKL3 is a novel therapeutic target for TNBC treatment.

Objective: To explore the clinicopathological characteristics and genomic characteristics of four patients with epidermal growth factor receptor(EGFR)-mutated advanced adenocarcinoma transformed into small-cell lung cancer. Methods: Four cases of EGFR-mutated advanced adenocarcinoma of the lung transformed into small-cell lung cancer were studied by clinical data, pathological morphology, immunohistochemistry and gene detection. Result: EGFR-mutated adenocarcinoma of the lung was heterogeneous in clinical and genomic profiles, of ten characterized by RB1, TP53 and PIK3CA mutations. Its transformation into small-cell lung cancer was a particularly aggressive mechanism of drug resistance, but the machanisms were not clear NSE and other tumor indicators had low diagnostic value for transformation. Conclusions: EGFR-mutated adenocarcinoma of the lung transformed into small-cell lung cancer was one of the reasons for EGFR resistance with avery poor prognosis.

Background: Nearly 20% novel coronavirus disease 2019 (COVID-19) patients have abnormal coagulation function. Padua prediction score (PPS) is a validated tools for venous thromboembolism (VTE) risk assessment. However, its clinical value in COVID-19 patients' evaluation was unclear., Methods: We prospectively evaluated the VTE risk of COVID-19 patients using PPS. Demographic and clinical data were collected. Association of PPS with 28-day mortality was analyzed by multivariate logistic regression and Kaplan-Meier analysis., Results: Two hundred and seventy-four continuous patients were enrolled, with total mortality of 17.2%. Patients in high PPS group, with significantly abnormal coagulation, have a higher levels of interleukin 6 (25.27 vs. 2.55 pg/ml, P < 0.001), prophylactic anticoagulation rate (60.7% vs. 6.5%, P < 0.001) and mortality (40.5% vs. 5.9%, P < 0.001) when compared with that in low PPS group. Critical patients showed higher PPS (6 vs. 2 score, P < 0.001) than that in severe patients. Multivariate logistic regression revealed the independent risk factors of in-hospital mortality included high PPS [odds ratio (OR): 7.35, 95% confidence interval (CI): 3.08-16.01], increased interleukin-6 (OR: 11.79, 95% CI: 5.45-26.20) and elevated d-dimer (OR: 4.65, 95% CI: 1.15-12.15). Kaplan-Meier analysis indicated patients with higher PPS had a significant survival disadvantage. Prophylactic anticoagulation in higher PPS patients shows a mild advantage of mortality but without statistical significance (37.1% vs. 45.7%, P = 0.42)., Conclusion: Higher PPS associated with in-hospital poor prognosis in COVID-19 patients. Prophylactic anticoagulation showed a mild advantage of mortality in COVID-19 patients with higher PPS, but it remain to need further investigation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: The authors have no conflicts of interest to declare.

Objective: Resveratrol has shown benefit for pulmonary hypertension improvement. Our previous reports showed NR4A3/cyclin D1 pathway promoted pulmonary arterial smooth muscle cells (PASMCs) proliferation. This study tried to explore the mechanism underlying this process, focusing on the role of resveratrol in regulation of miRNA and NR4A3., Methods: Rats were injected with monocrotaline (MCT) to establish pulmonary hypertension (PH) models. Resveratrol was used to prevent pulmonary vascular remodeling. Primary rat PASMCs were cultured in vitro and stimulated by platelet-derived growth factor (PDGF) with or without resveratrol. Cells proliferation and expression of miR-638 as well as NR4A3 were evaluated., Results: MCT resulted in significant pulmonary vascular remodeling and down-regulation of miR-638, which could be suppressed by resveratrol. Moreover, PDGF-induced PASMC proliferation and miR-638 down-regulation were both significantly prevented by resveratrol treatment in vitro. MiR-638 mimics markedly inhibited PASMC proliferation and percentage of PCNA-positive cells in vitro. But anti-miR-638 could markedly promote cells proliferation and percentage of PCNA-positive cells. The luciferase reporter assay showed that NR4A3 was a direct target of miR-638. The loss-of-function and gain-of-function experiments indicated that NR4A3 promoted proliferation via cyclin D1 pathway., Conclusion: Our data indicated that resveratrol prevented MCT-induced pulmonary vascular remodeling via miR-638 regulating NR4A3/cyclin D1 pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

Accumulating studies have confirmed that mammary serine protease inhibitor (MASPIN) plays an essential role in non-small cell lung cancer (NSCLC). However, results are still controversial or inconsistent. In the present study, we attempted to identify the clinical significance of MASPIN and its potential molecular roles in NSCLC. The correlation of MASPIN with prognosis and clinicopathological characteristics was assessed by meta-analysis. Additionally, the potential molecular mechanisms of MASPIN in NSCLC was also investigated through several online databases. A total of 2220 NSCLC patients from 12 high quality studies were included and the results indicated that up-regulated MASPIN nucleus and cytoplasm expression was associated with poor overall survival (OS) (hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 1.01-2.04, P<0.05), elevated MASPIN cytoplasm expression was associated with poor OS (HR = 1.45, 95% CI = 1.01-2.07, P<0.05), disease-free survival (DFS) (HR = 1.95, 95% CI = 1.31-2.88, P=0.001), and disease-specific survival (DSS) (HR = 2.17, 95% CI = 1.18-3.99, P=0.013). MASPIN both nucleus and cytoplasm location were associated with clinicopathological characteristics. Bioinformatics analysis validated the above results and suggested that human serpin family B member 5 (SERPINB5) hypomethylated levels were negatively correlated with its mRNA expression. Bioinformatics analysis also revealed the 85 most frequently altered neighboring genes of SERPINB5, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed 20 GO terms and 3 KEGG pathways with statistical significance. MASPIN had a statistically negative correlation with NSCLC prognosis, functioning as an oncoprotein by hypomethylation and influencing specific pathways involving the 85 genes identified herein. MASPIN might be a promising prognostic signature in NSCLC., (© 2020 The Author(s).)

The therapeutic regimen for small cell lung cancer (SCLC) has changed little in the past several decades. Apatinib is a small molecule inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase. Apatinib has demonstrated efficacy against advanced gastric cancer and breast cancer, and recent studies have also reported its successful use in non-SCLC; however, its efficacy in SCLC remains unclear. In this study, we used apatinib as salvage therapy for chemotherapy-refractory SCLC. Five male patients with advanced SCLC were administered oral apatinib (250 mg/day) as 2nd- to 4th-line treatment. One patient showed a partial response to apatinib, one showed stable disease, and three patients showed progressive disease. The progression-free survival durations in the patients with stable disease and partial response were 1.5 and 3 months, respectively. Only three patients showed adverse effects, including mild hypertension, vomiting, and hand-foot syndrome, respectively, all of which were manageable. Apatinib might thus be a salvage option in patients with advanced SCLC after chemotherapy.

Non-small cell lung cancer (NSCLC) is the most commonly diagnosed lung cancer and is associated with poor prognosis. This study aimed to analyze if serum C-reactive protein (CRP), albumin (Alb), and CRP/Alb ratio could provide prognostic information in patients with NSCLC. 387 patients with primary NSCLC were included in this analysis. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95% confidence interval (CI) of death with adjustment for some potential confounders. The multivariate regression analyses revealed the statistically significant associations of decreased survival of patients with NSCLC with elevated CRP, decreased Alb, and elevated CRP/Alb ratio. The HRs of mortality were 1.56 (95% CI: 0.80-3.04) and 2.64 (95% CI: 1.35-5.16) for patients in the second and the highest tertiles of CRP (P-trend = 0.003). For albumin, the HR was 0.50 (95% CI: 0.29-0.85) for the normal group. The CRP/Alb ratio strongly predicted the survival of patients in the highest tertile with a fourfold risk of dying compared with those in the lowest tertile (HR = 4.14, 95% CI: 2.15-7.98). The subgroup analysis according to various patient characteristics confirmed these associations. In conclusion, serum CRP, albumin, and CRP/Alb ratio are predictive of survival for Chinese patients with NSCLC.

Objective: Self-expandable metallic (SEM) airway stents are an important approach to malignant central airway obstruction (CAO). SEM airway stent insertions are usually performed under fluoroscopic guidance over a guide wire placed through a flexible bronchoscope often resulting in a longer procedure time and exposure to radiation. In this pilot study, we designed a novel delivery system of the through-the-scope (TTS) SEM airway stent insertion and observed its feasibility., Methods: From Jan 2015 to Sept 2016, 25 consecutive patients with inoperable malignant CAO were enrolled requiring airway stent implantation. All patients were followed up to death or at least 6 months., Results: 36 TTS stents were inserted into 25 patients using a flexible bronchoscope under general anesthesia or local anesthesia. All stents were successfully deployed directly through the working channel (2.8 mm diameter) of the flexible bronchoscope in 91.7% (33/36) of the subjects. The mMRC score and stenosis grade improved significantly after stent implantation. The common stent-related complications were secretion retention (25%, 9/36), development of granulation tissue (13.9%, 5/36), tumor in-growth (13.9%, 5/36), and hemoptysis (8.3%, 3/36). The 6-month overall survival (OS) was 44% (11/25)., Conclusion: The novel TTS stent release system was an effective and safe approach in malignant central airway obstruction.

Purpose: Platinum-based doublet chemotherapy and radiotherapy are the standard treatment option in advanced squamous cell carcinoma patients. However, few agents could be selected for subsequent post-second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase, apatinib had been proved in advanced gastric cancer. Here, we showed its efficacy and safety in lung squamous cell carcinoma., Methods: In this retrospective study, 13 advanced lung squamous cell carcinoma patients were enrolled. They received doublet chemotherapy or docetaxel as the first-line treatment. After disease progressed, all patients were administrated apatinib monotherapy (250-425 mg/day) for second-line or fourth-line therapy., Results: After apatinib monotherapy, two patients achieved partial response, four patients achieved stable disease, and seven patients achieved progression disease. The medium PFS was 3.1 months. The median OS had not yet been reached. The objective remission rate was 15.4% (2/13). The total disease control rate was 46.2% (6/13). The main advert effects were vomiting and hypertension., Conclusion: Apatinib might be an option as rescue treatment in advanced lung squamous cell carcinoma.

Rationale: The mechanism of the first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) acquired resistance included T790M mutation, cellular-mesenchymal to epithelial transition factor (MET) or EGFR amplification, PIK3CA mutation, and transformation to small cell lung cancer. MET amplification accounted for only about 5% of the resistance cases., Patients Concerns: Few report detected MET amplification in pleural effusion. Here, we reported 2 lung adenocarcinoma cases with MET amplification in pleural effusion rapidly responded to crizotinib after EGFR-TKIs acquired resistance., Diagnoses: Biopsy via bronchoscopy, next-generation sequencing (NGS) in pleural effusion., Interventions: EGFR-TKIs (Icotinib), MET inhibitor crizotinib., Outcomes: After a progression-free survival of 9 months and 23months, respectively, both cases progressed accompanying with pleural effusion. Results of NGS in pleural effusion showed MET amplification (2-3 times) in both cases. The 2 patients were treated with a MET inhibitor crizotinib and rapidly responded., Conclusion: MET amplification in pleural effusion could predict a perfect response to crizotinib after EGFR-TKIs acquired resistance, even only a low times gene amplification., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Interleukin-17 (IL-17) plays an important role in cancer progression. Previous studies remained controversial regarding the correlation between IL-17 expression and lung cancer (LC) prognosis. To comprehensively and quantitatively summarize the prognostic value of IL-17 expression in LC patients, a systematic review and meta-analysis were performed., Methods: We identified the relevant literatures by searching the PubMed, EMBASE, Cochrane Library, SinoMed, China National Knowledge Infrastructure (CNKI) and Wanfang Data databases, up until April 1, 2017. Overall survival (OS), disease free survival (DFS) and clinicopathological characteristics were collected from relevant studies. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) were calculated to estimate the effective value of IL-17 expression on clinical outcomes., Results: Six studies containing 479 Chinese LC patients were involved in this meta-analysis. The results indicated high IL-17 expression was independently correlated with poorer OS (HR = 1.82, 95% CI 1.44-2.29, P < 0.00001) and shorter DFS (HR = 2.41, 95% CI 1.42-4.08, P = 0.001) in LC patients. Further, when stratified by LC histological type (non-small cell lung cancer and small cell lung cancer), tumor stage (Ⅰ-Ⅲ,Ⅰ-Ⅳ and Ⅳ), detection specimen (serum, intratumoral tissue and pleural effusion), test method (immunological histological chemistry and enzyme linked immunosorbent assay), and HR estimated method (reported and estimated), all of the results were statistically significant. These data indicated that elevated IL-17 expression is correlated with poor clinical outcomes in LC. The meta-analysis did not show heterogeneity or publication bias., Conclusions: The present meta-analysis revealed that high IL-17 expression was an indicator of poor prognosis for Chinese patients with LC. It could potentially help to assess patients' prognosis and estimate treatment efficacy in therapeutic interventions.

Activating KRAS mutations in lung adenocarcinoma are characterized with treatment resistance and poor prognosis. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, apatinib has been proven successful in advanced gastric cancer and breast cancer. In this study, we show the result of apatinib as salvage treatment in lung adenocarcinoma patients with KRAS mutation. Four advanced lung adenocarcinoma patients with KRAS mutation were orally administered apatinib (250 mg/d) after second-line treatment. One patient showed progressive disease, while 3 patients showed stable disease response to apatinib, with a median progression-free survival (PFS) of 3.8 months (1.5-5.5 months). The main toxicities were hoarseness and hemoptysis, which were manageable. Therefore, apatinib might be an optional choice for advanced lung adenocarcinoma patients with KRAS mutation in post second-line treatment., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Chemotherapy is the standard treatment of in advanced lung adenocarcinoma patients without driver mutation. However, few drugs could be selected when diseases progressed after second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested mainly using in advanced gastric cancer. In this study, we showed the results of apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients were administrated apatinib (250-500 mg/d) orally. 3 patients showed partial response and 8 patients showed stable diseases response to apatinib, with a medium progression-free survival (PFS) of 4.4 month (2-10 months). The objective remission rate (ORR) was 18.75%(3/16). The total disease control rate (DCR) was 68.75% (11/16). The main toxicities were hypertension, hand-foot syndrome, proteinuria and thrombocytopenia which were tolerable and manageable. So, apatinib might be an optional choice for post-first-line treatment of EGFR wild-type advanced lung adenocarcinoma patients., Competing Interests: CONFLICTS OF INTEREST The authors declared no conflicts of interest.

Objective: This study aimed to evaluate fluorine-18 fludeoxyglucose positron emission tomography-CT ((18)F-FDG PET-CT) for the diagnosis, targeted biopsy and therapy of relapsing polychondritis (RP)., Methods: The literature pertaining to the use of (18)F-FDG PET-CT in patients with RP was retrieved from the Cochrane Library, PubMed, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI) and Wanfang databases until July 2015. Clinical characteristics, auxiliary examination results, chest CT findings, tracheoscopy and biopsy findings, high metabolic activity lesions, maximum standardized uptake values, (18)F-FDG PET-CT-guided biopsy site, pathologic results of biopsy samples and alteration in high (18)F-FDG-uptake lesions after treatment were retrospectively analysed., Results: 18 publications with 26 cases were enrolled. The five most common symptoms of patients with RP diagnosed with (18)F-FDG PET-CT were cough, fever, chest tightness, sore throat and arthralgia. Of the 26 patients, 23 patients had multiple and symmetric cartilage lesions with high metabolic activity, revealed by (18)F-FDG PET-CT. The disease mainly affected organs such as the bronchus, trachea, throat, costicartilage and auricle. The maximum standardized uptake values ranged from 1.93 to 13.03 (mean, 4.94). (18)F-FDG PET-CT revealed that patients with RP with tracheal and bronchial involvement had a close correlation with cough (χ(2) = 6.80, p = 0.006). (18)F-FDG PET-CT showed a significantly higher positive biopsy rate compared with bronchoscopy (χ(2) = 12.91, p < 0.001) for targeted lesions with high metabolic activity. Post-treatment re-examinations with (18)F-FDG PET-CT showed obvious subsidence or complete disappearance of high (18)F-FDG-uptake lesions in 13 cases, showing highly consistent symptom improvements., Conclusion: (18)F-FDG PET-CT is likely to become a valuable imaging tool in the diagnosis and treatment of RP., Advances in Knowledge: The presence of symmetrically distributed high FDG-uptake lesions may be a criterion for the diagnosis of RP. (18)F-FDG PET-CT is useful for targeting biopsy sites, which remarkably increase the positive biopsy rate. Therefore, (18)F-FDG PET-CT may be of great value in the diagnosis and treatment of RP.

Aims: As a transcription factor of the nuclear receptor superfamily, neuron-derived orphan receptor 1 (NOR1) is induced rapidly in response to various extracellular stimuli. But, it is still unclear its role in pulmonary artery smooth muscle cells proliferation., Materials and Methods: Human PASMCs were cultured in vitro and stimulated by serum. The special antisense oligodeoxynucleotides (AS-ODNs) were used to knockdown human NOR1 gene expression. Real-time PCR and Western-blot were used to evaluate the gene expression and protein levels., Results: Fetal bovine serum (FBS) induced human PASMCs proliferation in a dose dependent manner. Furthermore, FBS promoted NOR1 gene expression in a dose dependent manner and a time dependent manner. 10% FBS induced a maximal NOR1 mRNA levels at 2 h. FBS also induced a significant higher NOR1 protein levels as compared with control. The NOR1 over-expressed plasmid significantly promoted DNA synthesis and cells proliferation. Moreover, the special AS-ODNs against human NOR1 not only prevented NOR1 expression but also inhibited DNA synthesis and cells proliferation significantly. The NOR1 over-expression plasmid could up-regulate cyclin D1 expression markedly, but the AS-ODNs inhibited cyclin D1 expression significantly., Conclusion: So, we concluded that NOR1 could promote human PASMCs proliferation. Cyclin D1 might be involved in this process.

Cigarette smoking contributes to the development of pulmonary hypertension (PH) complicated with chronic obstructive pulmonary disease (COPD), and the pulmonary vascular remodeling, the structural basis of PH, could be attributed to abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs).In this study, morphometrical analysis showed that the pulmonary vessel wall thickness in smoker group and COPD group was significantly greater than in nonsmokers. In addition, we determined the expression patterns of connective tissue growth factor (CTGF) and cyclin D1 in PASMCs harvested from smokers with normal lung function or mild to moderate COPD, finding that the expression levels of CTGF and cyclin D1 were significantly increased in smoker group and COPD group. In vitro experiment showed that the expression of CTGF, cyclin D1 and E2F were significantly increased in human PASMCs (HPASMCs) treated with 2% cigarette smoke extract (CSE), and two CTGF siRNAs with different mRNA hits successfully attenuated the upregulated cyclin D1 and E2F, and significantly restored the CSE-induced proliferation of HPASMCs by causing cell cycle arrest in G0. These findings suggest that CTGF may contribute to the pathogenesis of abnormal proliferation of HPASMCs by promoting the expression of its downstream effectors in smokers with or without COPD.

Objective: To explore the value of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) combined with transbronchial needle aspiration (TBNA) in diagnosing atypical relapsing polychondritis (RP)., Methods: Data from two patients with atypical RP, which had been diagnosed in our hospital using FDG PET-CT combined with TBNA, were retrospectively analyzed. A review of the relevant literature was also performed., Results: Consistent with the previously reported 20 cases of RP that had been diagnosed using FDG PET-CT, the two patients in the present study showed the involvement of multiple organs, including the nose, throat, trachea, bronchi, costicartilage and joint cartilages, and increased FDG uptake was found in these areas. The mean value of SUVmax was 5.14. PET-CT revealed that 86.4% of the patients with RP had airway involvement. TBNA technique was used for biopsy of the hypermetabolic lesions, and pathologic examinations confirmed the diagnosis of RP. The time to diagnosis in these two patients and the 20 cases reported previously was about 6.9 months, significantly shorter than the average diagnosis time (20 months)., Conclusions: FDG PET-CT has several advantages for diagnosing RP, especially atypical RP. TBNA is a minimally invasive and safe technique for obtaining airway cartilage. Combining PET-CT with TBNA may play an important role in shortening the time to diagnosis in patients with RP involvement of airway.