Outcomes of robot-assisted versus video-assisted mediastinal mass resection during the initial learning curve.

To compare the learning curve of mediastinal mass resection between robot-assisted surgery and thoracoscopic surgery. Retrospective perioperative data were collected from 160 mediastinal mass resection cases. Data included 80 initial consecutive video-assisted thoracoscopic surgery (VATS) resection cases performed from February 2018 to February 2020 and 80 initial consecutive robotic-assisted thoracic surgery (RATS) resection cases performed from March 2020 to March 2023. All cases were operated on by a thoracic surgeon. The clinical characteristics and perioperative outcomes of the two groups were compared. The operation time in both the RATS group and VATS group was analyzed using the cumulative sum (CUSUM) method. Based on this method, the learning curves of both groups were divided into a learning period and mastery period. The VATS group and the RATS group crossed the inflection point in the 27th and 21st case, respectively. Subsequently, we found that the learning period was longer than the mastery period with statistically significant differences in terms of the operating time, and postoperative hospital stay in the VATS group and the RATS group. A certain amount of VATS experience can shorten the learning curve for RATS.

Pulmonary vagus nerve transection for chronic cough after video-assisted lobectomy: a randomized controlled trial.

BACKGROUND: Chronic cough is common after lobectomy. Vagus nerves are part of the cough reflex. Accordingly, transection of the pulmonary branches of vagus nerve may prevent chronic cough. And there are no clear recommendations on the management of the pulmonary branches of vagus in any thoracic surgery guidelines. METHODS: This is a single-center, randomized controlled trial. Adult patients undergoing elective video-assisted thoracoscopic lobectomy and lymphadenectomy were randomized at a 1:1 ratio to undergo a sham procedure (control group) or transection of the pulmonary branches of the vagus nerve that innervate the bronchial stump plus the caudal-most large pulmonary branch of the vagus nerve. The primary outcome was the rate of chronic cough, as assessed at 3 months after surgery in the intent-to-treat population. RESULTS: Between 1 February 2020 and 1 August 2020, 116 patients (59.6±10.1 years of age; 45 men) were randomized (58 in each group). All patients received designated intervention. The rate of chronic cough at 3 months was 19.0% (11/58) in the vagotomy group versus 41.4% (24/58) in the control group (OR=0.332, 95% CI: 0.143-0.767; P =0.009). In the 108 patients with 2-year assessment, the rate of persistent cough was 12.7% (7/55) in the control and 1.9% (1/53) in the vagotomy group ( P =0.032). The two groups did not differ in postoperative complications and key measures of pulmonary function, for example, maximal voluntary ventilation, diffusing capacity of the lungs for carbon monoxide, and forced expiratory volume. CONCLUSION: Transecting the pulmonary branches of vagus nerve that innervate the bronchial stump plus the caudal-most large pulmonary branch decreased the rate of chronic cough without affecting pulmonary function in patients undergoing video-assisted lobectomy and lymphadenectomy.

HOMER3 promotes non-small cell lung cancer growth and metastasis primarily through GABPB1-mediated mitochondrial metabolism.

Cancer metabolism has emerged as a major target for cancer therapy, while the state of mitochondrial drugs has remained largely unexplored, partly due to an inadequate understanding of various mitochondrial functions in tumor contexts. Here, we report that HOMER3 is highly expressed in non-small cell lung cancer (NSCLC) and is closely correlated with poor prognosis. Lung cancer cells with low levels of HOMER3 are found to show significant mitochondrial dysfunction, thereby suppressing their proliferation and metastasis in vivo and in vitro. At the mechanistic level, we demonstrate that HOMER3 and platelet-activating factor acetylhydrolase 1b catalytic subunit 3 cooperate to upregulate the level of GA-binding protein subunit beta-1 (GABPB1), a key transcription factor involved in mitochondrial biogenesis, to control mitochondrial inner membrane genes and mitochondrial function. Concurrently, low levels of HOMER3 and its downstream target GABPB1 led to mitochondrial dysfunction and decreased proliferation and invasive activity of lung cancer cells, which raises the possibility that targeting mitochondrial synthesis is an important and promising therapeutic approach for NSCLC.

Evaluation of pain levels treated by the distal end of the hook-wire positioning needle: A randomized controlled study.

BACKGROUND: Severe pain can be expected among adult patients undergoing hook-wire CT-guided localization of pulmonary nodules. We compared varying pain degrees between two different treatment techniques. METHODS: Data from 100 patients who underwent hook-wire puncture localization under preoperative CT between May 2022 and October 2022 were prospectively reviewed. Using the random number table method, the patients were assigned to an observation and control group in a 1:1 ratio. In the observation group (n = 50), the external part of the hook-wire positioning needle was cut off; in the control group (n = 50), the external portion of the needle was bent. Static pain scores were measured using the visual analog scale (VAS) at 30 min, 1, and 2 h post localization for patients. RESULTS: No significant differences were present between the two groups in terms of patient age, sex, nodule size, and nodule location. The observation group had lower VAS scores at 30 min (2.57 ± 1.38 vs. 3.51 ± 1.87 p = 0.005), 1 h (2.43 ± 1.14 vs. 3.33 ± 1.76 p = 0.003), and 2 h (2.41 ± 1.12 vs. 3.17 ± 1.74 p = 0.011) after localization. Moreover, the pain level did not gradually worsen in either group. Both groups had a 100% localization success rate. There was no statistically significant difference (p = 0.431) in the localized complication incidences between the two groups. CONCLUSIONS: We found both approaches for handling the hook-wire extending outside the chest to be safe and effective. However, cutting off the hook-wire extending outside the chest is associated with lesser pain. Moreover, pain severity does not worsen with time after localization.

PEDF inhibits LPS-induced acute lung injury in rats and promotes lung epithelial cell survival by upregulating PPAR-γ.

BACKGROUND: The progression of acute lung injury (ALI) involves numerous pathological factors and complex mechanisms, and cause the destruction of epithelial and endothelial barriers. Pigment epithelium-derived factor (PEDF) is an angiogenesis inhibitor and a potential anti-inflammatory factor. The purpose of this study was to investigate the effect of PEDF on lipopolysaccharide (LPS)-induced ALI in rats. METHODS: In vivo, pathological and injury related factors examination were performed on rat lung to investigate the effect of PEDF on ALI. In vitro, the effect of PEDF on inflammatory injury and apoptosis of lung epithelial type II RLE-6TN cell was evaluated, and the expression of inflammatory factors and related pathway proteins and PPAR-γ (in the presence or absence of PPAR-γ inhibitors) were analyzed. RESULTS: In vivo results showed that PEDF inhibited the inflammatory factor expression (TNF-α, IL-6 and IL-1ß) and progression of ALI and reduced lung cell apoptosis in rats. In vitro results showed that PEDF could effectively inhibit LPS-stimulated inflammatory damage and apoptosis of RLE-6TN cells. PEDF inhibited the RLE-6TN cell injury by enhancing the expression of PPAR-γ. CONCLUSIONS: PEDF is an anti-inflammatory factor, which can inhibit apoptosis of lung epithelial cells by upregulating the expression of PPAR-γ and reducing LPS-induced ALI in rats.

The Effect of Examined Lymph Nodes and Lymph Node Ratio on Pathological Nodal Classification in the Lung Adenosquamous Carcinoma After Lobectomy.

Objective: The effects of examined lymph nodes (LNs) and lymph node ratio (LNR) on pN classification and the prognosis are unclear in lung adenosquamous carcinoma (ASC) patients. Thus, this study aimed to investigate the significance of LNs and LNR in the prognosis of ASC and the impact of the abovementioned factors on the pN classification. Methods: Patients diagnosed with pathological stage T1-4N0-2M0 ASC from the Surveillance Epidemiology and End Results database were included in the study. The primary clinical endpoint was cancer-specific survival (CSS). The optimal cutoff values of the LNs and LNR were determined. An LN indicator, including pN0 #LNs ≤9, pN0 #LNs >9, pN+ #LNR ≤0.53, and pN+ #LNR > 0.53, was developed. Concordance index (C-index) was used to compare the prognostic predictive ability between N classification and LN indicator. The univariable and multivariable Cox regression analyses were used in this study. Results: The cohort of 1,416 patients were included in the study. The level of LNs stratified the patients without metastasis of lymph nodes (pN0 #LNs ≤9 vs. pN0 #LNs >9, unadjusted hazard ratio [HR] = 1.255, P = 0.037). Two groups based on the cutoff value of LNR differentiated prognosis of patients with metastasis of lymph nodes (pN+ #LNR >0.53 vs. pN+ #LNR ≤0.53, unadjusted HR = 1.703, P = 0.001). The LN indicator had a much better predictive ability over N classification in this cohort (LN indicator: C-index = 0.615; N classification: C-index = 0.602, P = 0.001). Conclusions: We explored clinicopathological factors affecting prognosis in resected lung ASC patients. Besides, the LN indicator was confirmed to be played an essential role in affecting the survival rate in ASC patients. The high-level LNs or low-level LNR might be corelated to improved survival outcomes.

Inspiratory hyperoxia suppresses lung cancer metastasis through a MYC/SLC1A5-dependent metabolic pathway.

The lack of knowledge about the effect of inspiratory hyperoxia on the lung-specific tumour microenvironment and progression of lung cancer has attracted considerable attention. This study proposes that inspiratory hyperoxia has special significance for the malignant phenotype of lung cancer cells. The effects of different oxygenation parameters on the proliferation, apoptosis, invasion and migration of lung cancer cells were systematically evaluated in vitro and in vivo Our results reveal that inspiratory hyperoxia treatment (60% oxygen, 6 h·day-1) not only has no tumour progression-promoting effects, but also suppresses lung cancer metastasis and promotes long-term survival. In addition, we combined transcriptome, proteome and metabolome analysis and found that hyperoxia treatment induced significant intracellular metabolic changes in lung cancer cells. Overall, we established that MYC/SLC1A5-induced metabolic reprogramming and glutamine addiction is a new mechanism that drives lung cancer metastasis, which can be significantly suppressed by inspiratory hyperoxia treatment. These findings are relevant to the debate on the perils, promises and antitumour effect of inspiratory hyperoxia, especially for patients with lung cancer.

VEGI downregulation is correlated with nodal metastasis and poor prognosis in lung adenocarcinoma.

Although the incidence of lung cancer is increasing worldwide, the molecular mechanisms for its tumorigenesis, progression and prognosis remain unknown. As a member of the tumor necrosis factor superfamily, vascular endothelial growth inhibitor (VEGI) is involved in the development and progression of many malignant diseases. In the present study, the expression of VEGI and CD31 was examined via immunohistochemistry in non-small cell lung cancer (NSCLC) tissues obtained from 150 patients with NSCLC. The inhibitory effect of VEGI on tumor-associated blood vessel formation and growth was investigated by determining the relationship between VEGI protein expression and microvascular density (MVD). Prognostic significance was evaluated using the Kaplan-Meier method. VEGI expression was downregulated or lost in 68.7% (103/150) of patients with NSCLC, an effect that was more prevalent in adenocarcinoma (AC), 76.0% (57/75), than in squamous cell carcinoma, 61.3% (46/75). A significant negative correlation was indentified between VEGI expression and lymphovascular invasion (P=0.039) and lymph node metastasis (P=0.017) in AC tissue. Additionally, MVD was significantly lower in the VEGI-rich group compared with the VEGI-poor group. The downregulation of VEGI expression was also associated with poorer overall survival (P=0.011) in patients with AC. The present study therefore provides evidence that VEGI may be a new and effective prognostic marker of lung AC.

Low levels of AMPK promote epithelial-mesenchymal transition in lung cancer primarily through HDAC4- and HDAC5-mediated metabolic reprogramming.

AMP-activated protein kinase (AMPK) serves as a "supermetabolic regulator" that helps maintain cellular energy homeostasis. However, the role of AMPK in glucose metabolism reprogramming in lung cancer remains unclear. Here, our study shows that low AMPK expression correlates with metastasis and clinicopathologic parameters of non-small-cell lung cancer. Low AMPK significantly enhances the Warburg effect in HBE and A549 cells, which in turn induces the expression of mesenchymal markers and enhances their invasion and migration. At the mechanistic level, low AMPK up-regulates HK2 expression and glycolysis levels through HDAC4 and HDAC5. Collectively, our findings demonstrate that low AMPK-induced metabolism can promote epithelial-mesenchymal transition progression in normal bronchial epithelial cells and lung cancer cells, and increase the risk for tumour metastasis.

Alleviation of sepsis­induced cardiac dysfunction by overexpression of Sestrin2 is associated with inhibition of p­S6K and activation of the p­AMPK pathway.

Sepsis­induced myocardial injury is one of the manifestations of multiple organ dysfunction in sepsis. The aim of the present study was to determine the mechanism of alleviation of lipopolysaccharide (LPS)­induced injury on cardiomyocytes by Sestrin2. A sepsis model using LPS injection was constructed in Sprague­Dawley (SD) rats, and after 6, 12 and 24 h, rat blood was collected and cardiac troponin T (CTnT) levels were determined using ELISA. Heart specimens were excised, tumor necrosis factor­α (TNF­α) and interleukin 6 (IL­6) levels were detected by ELISA, malondialdehyde (MDA) levels were estimated using colorimetric analysis, and phosphorylated (p)­S6K and p­AMP­activated protein kinase (AMPK) levels were determined by western blot analysis. In the septic rats, phenomenon of myocardial fiber rupture, interstitial edema and inflammatory cell infiltration were observed under light microscope. Following LPS injection, CTnT in serum and MDA in myocardial homogenate were increased time­dependently. TNF­α and IL­6 levels were significantly increased, with a peak at 6 h. p­S6K levels were adaptively downregulated, and levels of p­AMPK and Sestrin2 were adaptively upregulated by LPS. In LPS­injured H9c2 cells, Sestrin2 overexpression attenuated the LPS­mediated inhibitory effects on cell viability, suppressed LPS­mediated increase in CTnT, TNF­α, IL­6 and MDA levels, as well as attenuated p­S6K levels and elevated p­AMPK and Sestrin2 levels. Sestrin2 interference showed the opposite effect. Sestrin2 promoted cell viability and inhibited the inflammatory responses of LPS­injured myocardial cells. The phenomena may be associated with inhibition of p­S6K and activation of the p­AMPK pathway.

PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.

Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF's effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size.