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@#Objective To explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. Methods The clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. Results After preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. Conclusion Pembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.
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@#Objective To investigate the clinical characteristics and risk factors for perioperative lung surgery patients with SARS‐CoV‐2 Omicron variant infection. Methods The clinical data of patients who underwent lung surgery at the Department of Thoracic Surgery, Renmin Hospital of Wuhan University from December 1, 2022 to January 9, 2023 were retrospectively analyzed. The patients were divided into an infection group and a non-infection group according to whether they were infected with SARS-CoV-2. And the clinical data of two groups were collected and compared. Multiple linear regression analysis was used to explore the risk factors affecting the time of hospitalization. Results A total of 70 patients were enrolled in this study, including 36 (51.4%) males and 34 (48.6%) females at a median age of 61.0 (49.0, 66.8) years. There were 28 patients in the infection group and 42 patients in the non-infection group. The proportion of preoperative abnormal coagulation function and the risk of postoperative pulmonary infection in perioperative patients infected with SARS-CoV-2 were higher than those in the non-infection group (P<0.05). Subgroup analysis found that patients with preoperative SARS-CoV-2 infection were more likely to have pulmonary infection after surgery, but did not prolong the time of hospitalization or increase the risk of severe disease rate. The patients with postoperative SARS-CoV-2 infection had worse clinical prognosis, including longer time of hospitalization (P=0.004), higher ICU admission rate (P=0.000), higher lung infection rate (P=0.003) and respiratory failure rate (P=0.000). Multiple linear regression analysis showed that gender and extent of surgery were independent risk factors for prolonged hospitalization time. Conclusion Preoperative infection with SARS-CoV-2 Omicron variant will increase the risk of pulmonary infection, but it will not affect the clinical prognosis. However, postoperative infection with SARS-CoV-2 Omicron variant will still prolong the time of hospitalization, increase the ICU rate, and the risk of pulmonary complications.
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@#Surgery is a classic traditional method for the treatment of early-stage esophageal cancer, and it is also recognized as an effective first-choice method in the medical community. With the development of endoscopic technology, esophagus-preserving comprehensive treatment of esophageal cancer has almost the same or even better effects in some aspects in the treatment of early esophageal cancer than surgery. Many clinical guidelines have also recommended it as the first-choice treatment for early esophageal cancer. The room for surgical treatment of esophageal cancer has been further compressed. This article discusses the comprehensive treatment model of esophageal cancer from the perspective of thoracic surgery, aiming to find a new position of thoracic surgery in the treatment of esophageal cancer.
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Objective:To investigate the role and mechanism of exogenous derivative 4-octyl itaconate (4-OI) in lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods:C57BL/6 male mice were randomly divided into the control group, 4-OI group, LPS group, 4-OI+LPS group and deferiprone (DFP)+LPS group, with 6 mice in each group. LPS-induced ALI model was established by intraperitoneal injection of LPS. For the 4-OI+LPS group, mice were pretreated with 4-OI for 2 h before stimulation with LPS. The mice were sacrificed 12 h later and lung tissues were collected for pathological and molecular biological examination. Hematoxylin-eosin and Masson staining were used to detect the level of lung injury and collagen deposition. The expression levels of inflammatory cytokines and ferroptosis associated genes were detected by real-time quantitative PCR, and ferroptosis associated proteins were detected by Western blotting. The chi-square test was performed before the measurement data were counted. One-way analysis of variance was used to compare differences between multiple groups.Results:Compared with the control group, the histopathological damage was aggravated, and collagen deposition and lung injury score and lung wet-dry ratio were significantly increased in the LPS group (all P<0.05), and 4-OI pre-treatment significantly alleviated LPS-induced ALI. 4-OI treatment also significantly reduced the mRNA level of inflammatory cytokines, including IL-1β [(4.38±0.47) vs. (32.65±4.49)], IL-6 [(3.97±0.64) vs. (12.22±0.91)] and TNF-α [(15.06±2.26) vs. (38.53±2.31)]. At the same time, compared with the control group, the levels of lipid peroxidation metabolite 4-hydroxynonenal and malondialdehyde, iron level of lung tissue were significantly increased in the LPS group, and the mRNA level of ferroptosis marker prostaglandin-endoperoxide synthase 2 was also significantly increased (all P<0.05), but these indicators were significantly lower in the 4-OI+LPS group than in the LPS group. The results of immunofluorescence, Western blotting and PCR showed that the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH1) significantly decreased in the LPS group, while 4-OI treatment significantly increased the Nrf2, GPX4 and FTH1 levels, and showed similar inhibition of ferroptosis with DFP (all P<0.05). Conclusions:4-OI attenuates LPS-induced ALI by increasing Nrf2 and upregulating FTH1 and GPX4, providing a potential drug and its theoretical mechanism for the prevention and treatment of ALI.
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Objective:To explore the targeted regulation of the inflammatory pathway and its mechanism after AMPK phosphorylation induced by lipopolysaccharide (LPS) in mice and human monocytes induced by THP-1, so as to provide evidence for the clinical application of Mogrol (MO) in the clinical treatment of acute lung injury.Methods:Twenty-four clean C57BL/6 male mice aged 6-8 weeks were randomly (random number) divided into the control group, MO group, LPS group and LPS+ MO group with 6 mice in each group. Mice in the control group were intraperitoneally injected with normal saline (30 mL/kg), mice in the MO group were intraperitoneally injected with MO (30 mg/kg), mice in the lipopolysaccharide group were intraperitoneally injected with lipopolysaccharide (10 mg/kg), mice in the lipopolysaccharide + MO group were intraperitoneally injected with MO (30 mg/kg), and the other side was injected with lipopolysaccharide (10 mg/kg) 30 min later. After 12 h, the mice were sacrificed for sampling and pathology and molecular biological tests were carried out. Cell experiment: THP-1 cells in good condition were cultured in RPMI 1640 medium containing 10% fetal bovine serum for 24 h, and then induced to differentiate into macrophages with 100 ng/mL PMA. The control group, MO group, LPS group and LPS + MO group were established. After drug stimulation, the cell suspension of each group was collected, and the cells and culture medium supernatants were used for subsequent detectionResults:Compared with the control group, the injury degree of the lipopolysaccharide group was obvious, the alveolar cavity structure was destroyed, the inflammatory cell infiltration was increased, and the alveolar septum was obviously thickened in the tissue sections. After MO intervention, the injury degree of lung tissue injury was greatly improved, and MPO and the lung wet/dry weight ratio were also significantly decreased. The mRNA levels of the inflammatory cytokines IL-1β, IL-6 and TNF- α in lung tissues were also significantly decreased under MO intervention [(2.96±0.10) vs. (5.53±0.14), (8.62±0.17) vs. (12.31±0.09), (3.01±0.09) vs. (4.85±0.36)]. The expression levels of NLRP3, caspase-1 p20, GSDMD-N and ASC in the lung tissues of mice in the lipopolysaccharide group were significantly higher than those in the control group, while the phosphorylation level of AMPK in the lipopolysaccharide + MO group was increased, and the expression of scorched death-related proteins was effectively inhibited [(0.58±0.09) vs. (0.89±0.15), (0.19±0.08) vs. (0.93±0.16), (0.65±0.09) vs. (0.86±0.14), (0.30±0.12) vs. (0.47±0.10), all P<0.05]. At the same time, the secretion of the inflammatory factors IL-1β and IL-18, the main markers of scorch death in the tissue measured by ELISA, could also be alleviated by MO. In the cell experiment, MO also promoted the phosphorylation of AMPK, inhibited the expression of proteins related to NLRP3 inflammatory bodies, and significantly improved cell viability. Conclusions:MO attenuates LPS-induced acute lung injury by inhibiting NLRP3-mediated cell pyrogenesis by promoting the phosphorylation of AMPK.
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BACKGROUND@#Lung cancer has the highest mortality in China. Different treatments are of great significance to the prognosis of patients. By comparing stage Ia non-small cell lung cancer (NSCLC) patients' survival rates for ablation and for sub-lobectomy, we studied the difference in the effects of the two treatments on patient prognosis.@*METHODS@#Using the Surveillance, Epidemiology, and End Results (SEER) database, we screened eligible patients with stage Ia NSCLC from January 2004 to December 2015. Then, 228 patients treated with ablation and 228 patients treated with sub-lobotomy were then selected based on propensity score matching. After stratification, matching, and adjustment the Kaplan-Meier analysis was performed to compare the overall survival rates of patients treated with the two procedures.@*RESULTS@#The Kaplan-Meier survival analysis showed that there is a significant difference between the ablation group and the sub-lobectomy group (P<0.05). In the univarlable analysis, the hazard ratio (HR) of sub-lobotomy group was 0.571 (95%CI: 0.455-0.717) compared with the ablation group. Patients treated with sub-lobectomy had a 0.571 times greater risk of adverse outcomes than those treated with ablation. In the multivariable analysis, the HR for sub-lobectomy group was 0.605 (95%CI: 0.477-0.766) compared with the ablation group. Patients treated with sub-lobectomy had a 0.605 time greater risk of adverse outcomes than those treated with ablation. The results suggested that the overall survival rate of patients with stage Ia NSCLC treated with sub-lobotomy was higher than that of patients treated with ablation.@*CONCLUSIONS@#This study suggests that there is a significant difference in overall survival of stage Ia NSCLC patients treated with ablation and with sub-lobotomy. Patients treated with sub-lobotomy for stage Ia NSCLC had higher overall survival than those treated with ablation.
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The article entitled "Differential expression of exosomal miRNAs in osteoblasts in osteoarthritis" published on Journal of Central South University (Medical Science), in Volume 43, Issue 12, 2018 (DOI: 10.11817/j.issn.1672-7347.2018.12.003) may have an unclear risk of bias due to insufficient understanding for some results. Further experimental studies are needed. We all agree to retract this article, and apologize to the Journal and readers for the possible negative impact.
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To analyze the differentially expressed exosomal miRNAs in subchondral osteoblasts in patients with osteoarthritis (OA) and to investigate the key miRNAs potentially involved in the occurrence and progression of OA. Methods: Subchondral bones were harvested from 6 patients with OA. All subjects were divided into two groups which was based on the severity of joint wear: An OA group, severely worn side of subchondral bone, and a control group, less worn side of subchondral bone. The exosomes were extracted from osteoblast cells and their characteristics were identified. Then exosomal miRNAs were extracted and sequencing analysis was conducted to compare the expression in the two groups. The most differentially expressed ones (log2Ratio≥2) were subject to miRNA target prediction and quantitative reverse transcription PCR (RT-qPCR) to further quantify the difference. Results: Osteoblast extractions were confirmed to be exosomes, which were small double-membranous vesicles with 30-200 nm in diameter and 50-150 nm in peak value of particle size under the scanning microscope. High-throughput sequencing revealed 124 miRNAs whose expression significantly increased in the OA group. The most differentially expressed one with maximum fold change was hsa-miR-4717-5p and its target gene was RGS2. RT-qPCR demonstrated hsa-miR-4717-5p expression in the OA group was relatively higher than that in the control group (2.243 vs 0.480, P<0.01). Conclusion: There is distinct difference in expression profiles of exosomal miRNAs in subchondral osteoblasts between patients with OA and normal subjects. Up-regulated expression of miRANs might participate in OA occurrance and progression.