Qing-Dong Cao’s research while affiliated with Sun Yat-Sen University and other places

Background The extracorporeal diaphragmatic pacemaker(EDP),known for its ability to prevent diaphragmatic muscle function decline in chronic and critically ill patients.However,it remains uncertain whether EDP can effectively enhance pulmonary function in patients after surgery. Objective This study aims to determine whether EDP can quickly recover the diaphragm function of lung cancer patients after surgery to improve pulmonary function. Methods This study was designed as a single-blinded randomized controlled trial(RCT).Patients who met the inclusion criteria were randomly divided into two groups.The EDP group received additional EDP stimulation.The primary outcome measures were included diaphragm thickening fraction(DTF),diaphragm thickness at the end of inspiration (DTei),diaphragm excursion(DE),measured on the admission day(T0),the first day after surgery(T1), the day when the thoracic drainage tube was removed(T2).The secondary outcome measures included postoperative complications,chest tube indwelling hours,and visual analog scale(VAS) assessment measured at T1 and T2. Results 78 patients were enrolled,with 39 in the EDP group and 39 in the control group.Both groups demonstrated a significant postoperative decrease in DE and DTei(T1 < T0,EDP group P = 0.000;control group P = 0.000).Following the EDP treatment intervention,the EDP group showed a notable increase in DE and DTei(T2 > T1,P = 0.000;P = 0.000),and the control group also exhibited significant changes in DE and DTei(T2 > T1,P = 0.000;P = 0.005).However,at the T2 time point,there was a statistically significant difference in DE between the EDP group and the control group(P = 0.049).Notably,the EDP group's DTei at the T2 time point recovered to the level of the T0 time point,with no significant difference between the two time points(P = 0.096).Differences in the control group Dtei at the T2 time point compared to the T0 time point(P = 0.000),postoperative complications and chest tube indwelling hours showed no significant differences between the two groups.Statistical significance was found at T2,with the EDP group having a lower VAS value(1.00 ± 0.513 vs1.31 ± 0.521,P = 0.028). Conclusion EDP can significantly improve early diaphragm excursion and reduce pain perception in patients after SPVATS.It is beneficial for accelerating postoperative rehabilitation in lung cancer patients.EDP holds promise for clinical application and merits further clinical promotion. Trial registration The study is registered in the Chinese Clinical Trial (ChiCTR2300072733).

Background Synchronous multiple primary lung cancers associated with small non-dominant nodules are commonly encountered. However, the incidence, follow-up, and treatment of small non-dominant tumors have been but little studied. We explored the prevalence and management of small non-dominant tumors and factors associated with interval growth. Methods This observational, consecutive, retrospective single-center study enrolled patients diagnosed with synchronous multiple primary lung cancers and small non-dominant tumors (≤ 6 mm in diameter) who underwent resection of the dominant tumor. The incidence, follow-up, and management of small non-dominant tumors and predictors of nodule growth were analyzed. Results There were 88 patients (12% of all lung cancer patients) with pathological diagnoses of synchronous multiple primary lung cancers. A total of 131 (18%) patients were clinically diagnosed with at least one small (≤ 6 mm in diameter) multiple primary lung cancer non-dominant tumor. 94 patients with 125 small-nodule non-dominant tumors clinically diagnosed as multiple primary lung cancers were followed-up for at least 6 months. A total of 29 (29/125, 23.2%) evidenced small pulmonary nodules (≤ 6 mm in diameter) that exhibited interval growth on follow-up computed tomography (CT). On multivariate analysis, a part-solid nodule (compared to a pGGN) (OR 1.23; 95% CI 1.08–1.40) or a solid nodule (compared to a pGGN) (OR 3.50; 95% CI 1.94–6.30) predicted small nodule interval growth. Conclusion We found a relatively high incidence of multiple primary lung cancers with small non-dominant tumors exhibiting interval growth on follow-up CT, suggesting that resection of non-dominant tumors at the time of dominant tumor resection, especially when the nodules are part-solid or solid, is the optimal treatment.

Multiple primary lung cancer (MPLC) is an increasingly prevalent subtype of lung cancer. According to recent genomic studies, the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence. We performed whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found. Using our own and other relevant public data, evolutionary tree reconstruction revealed that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient were as genetically diverse as those from different patients, while within-tumor genetic heterogeneity was significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample showed a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there was no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggests that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient. To fully exploit the strategic value of precision medicine, targeted therapies should be designed and delivered on a per-lesion basis.

Objectives: This study aims to investigate the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as adjuvant therapy for resected non-small cell lung cancer (NSCLC) patients harboring EGFR mutations compared with adjuvant chemotherapy or placebo, including the latest updated data. Methods: A comprehensively systematic search for relevant randomized controlled trials (RCTs) was performed. Hazard ratios (HRs) and 95% confidence intervals (CI) were used to analyse disease-free survival (DFS) and overall survival (OS). For dichotomous data, risk ratio (RR) of severe adverse events and relapse patterns was calculated as effect measures. Results: Nine RCTs involving 1,835 completely resected patients with NSCLC with EGFR mutations were included in the meta-analysis. The use of EGFR-TKIs resulted in a significant improvement in DFS when compared to non-EGFR-TKIs based treatment (HR:0.45; 95% CI=0.29–0.71, P < 0.0005), but no OS benefit was shown (HR:0.79; 95%CI=0.54–1.16, P =0.23). In subgroup analyses, adjuvant EGFR-TKIs elevated DFS significantly compared to single-agent chemotherapy (HR: 0.50; 95%CI = 0.30–0.82, P = 0.006). Adjuvant EGFR-TKIs following chemotherapy also improved DFS significantly compared with single-agent chemotherapy (HR:0.34; 95%CI=0.16–0.69, P=0.003). No differences were found in DFS between adjuvant EGFR-TKIs versus placebo (HR:0.51; 95% CI=0.18 –1.47, P=0.21). Patients with a median treatment time over 12 months (HR:0.42; 95% CI=0.20–0.86; P =0.02) or diagnosed with stage III non-small cell lung cancer NSCLC (HR:0.42;95% CI = 0.20–0.86; P =0.02) induced better DFS. Elevated DFS from adjuvant EGFR-TKIs was still observed regardless of EGFR Mutation Status. Nevertheless, in subgroup analysis, neither subgroup analysis of therapeutic strategies nor median treatment duration observed any benefit from adjuvant EGFR-TKIs in OS. Moreover, adjuvant EGFR-TKIs decreased the risk of lung recurrence (RR: 0.63 ;95%CI=0.44 –0.89). Rash (RR:15.28; 95% CI = 4.71–49.55), Diarrhea (RR:3.08; 95% CI = 1.26–7.52) and ALT or AST increase (RR:8.85; 95% CI = 4.14–18.90) were several common grades 3 or higher adverse events (AEs) of EGFR-TKIs treatment. Conclusions: EGFR-TKIs treatment exhibited significant improvement in DFS with fewer manageable toxicities for NSCLC patients with EGFR mutations completely resection compared with non-EGFR-TKIs treatment. However, prolonged DFS did not produce any benefits for the OS.

Background Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2 (FGF2) has been reported to be an inflammatory regulator; however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma. Methods First, FGF2 expression was characterised in clinical asthma samples and the house dust mite (HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2 (rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β (IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting. Results Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples (6.70 ± 1.79 vs. 16.32 ± 2.40, P = 0.0184; 11.20 ± 2.11 vs. 21.00 ± 3.00, P = 0.033, respectively) and HDM-induced asthmatic mouse lung lysates (1.00 ± 0.15 vs. 5.14 ± 0.42, P < 0.001). Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model ( R ² = 0.857 and 0.783, P = 0.0008 and 0.0043, respectively). Elevated FGF2 protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration (2.45 ± 0.09 vs. 2.88 ± 0.14, P = 0.0288) and recruited more subepithelial neutrophils after HDM challenge [(110.20 ± 29.43) cells/mm ² vs. (238.10 ± 42.77) cells/mm ² , P = 0.0392] without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels (up to 1.41 ± 0.12- or 1.44 ± 0.14-fold change vs . IL-1β alone groups, P = 0.001 or 0.0344, respectively). The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor (FGFR)/mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. Conclusion Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.

OBJECTIVES Uniportal video-assisted thoracoscopic surgery (UniVATS) is widely used as a minimally invasive thoracic operation. The goal of our study was to analyse the effect of long-term experience with the UniVATS lobectomy on the learning curve. METHODS The learning curves were quantitatively evaluated by the unadjusted cumulative sum, and they were segmented using joinpoint linear regression analysis. The variables were compared between subgroups using trend analysis, and linear regression analysis was applied to correlate clinical characteristics at different stages of the learning curve with the duration of the operation. RESULTS The learning curve for the UniVATS lobectomy can be divided into 3 phases of proficiency at ∼200–300 procedures, with a fourth phase as the number of procedures increases. The 1st–52nd, 52nd–156th, 156th–244th and 244th–538th procedures comprised the preliminary learning stage, preliminary proficiency stage, proficiency stage and advanced proficiency stage, respectively. Surgical outcomes and their variability between stages improved with increasing case numbers, with the most significant addition of an auxiliary operating port and conversions. In multivariable analysis, as stages progressed, influences other than surgical experience increased the operative time, with male and extensive pleural adhesions in the preliminary proficiency stage; male and incomplete pulmonary fissures in the proficiency stage; and male, extensive pleural adhesions and incomplete pulmonary fissures in the advanced proficiency stage. CONCLUSIONS As the number of procedures increases, there may be 4 different proficiency stages in the UniVATS lobectomy learning curve. The surgeon enters the fourth stage at approximately the 244th procedure. Moreover, at stage 4, the perioperative indicators tend to stabilize, and influences other than surgical experience become more significant.

Abstract An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

Objectives: We performed this meta-analysis to compare adjuvant EGFR-TKIs with a placebo or adjuvant chemotherapy among patients with resected non-small cell lung cancer (NSCLC). Materials and methods: A literature search was performed using relevant keywords. All randomized controlled trials (RCTs) that compared the survival benefits of adjuvant EGFR-TKIs with those of placebo or adjuvant chemotherapy for resected NSCLC were eligible for inclusion. Results: The literature search yielded five eligible RCTs including three RCTs that compared adjuvant EGFR-TKIs with a placebo, and two RCTs that compared adjuvant EGFR-TKIs with chemotherapy. For unselected intent-to-treat patients who received adjuvant EGFR-TKIs versus a placebo, the hazard ratio (HR) of disease-free survival (DFS) was 0.88 (95% confidence interval (CI): 0.59-1.32; P = 0.54). For patients with an EGFR mutation, the DFS after adjuvant EGFR-TKIs was superior to that after a placebo, with a HR of 0.59 (95% CI: 0.40-0.88; P = 0.009). For patients with an EGFR mutation, the DFS after EGFR-TKIs was greater than that after chemotherapy, with a HR of 0.42 (95% CI: 0.19-0.93; P = 0.03). For patients with wild-type EGFR, the DFS of adjuvant EGFR-TKIs was similar to the placebo, with a RR of 1.00 (95% CI: 0.62-1.60; P = 0.99). Treatment with EGFR-TKIs resulted in more adverse events compared with the placebo, with a risk ratio (RR) of 2.72, (95% CI: 2.23-3.33; P < 0.00001), but fewer adverse events compared with chemotherapy, with an RR of 0.26 (95% CI: 0.18-0.38; P < 0.00001). Conclusions: For patients with resected NSCLC harboring EGFR mutations, treatment with an adjuvant EGFR-TKI was superior to that of a placebo or chemotherapy in terms of DFS. Treatment with adjuvant EGFR-TKIs were not effective among patients with wild type EGFR NSCLC.