Cadmium aggravates liver injury by activating ferroptosis and neutrophil extracellular traps formation in Nile tilapia (Oreochromis niloticus).

Cadmium (Cd) is a pervasive environmental contaminant and a significant risk factor for liver injury. The present study was undertaken to evaluate the involvement of ferroptosis and neutrophil extracellular traps (NETs) in Cd-induced liver injury in Nile tilapia (Oreochromis niloticus), and to explore its underlying mechanism. Cd-induced liver injury was associated with increased total iron, malondialdehyde (MDA), and Acyl-CoA synthetase long-chain family member 4 (ACSL4), together with reduced levels of glutathione, glutathione peroxidase-4a (Gpx4a), and solute carrier family 7 member 11 (SLC7A11), which are all hallmarks of ferroptosis. Moreover, liver hyperemia, neutrophil infiltration, increased inflammatory factors and myeloperoxidase, as well as elevated serum DNA content in Cd-stimulated Nile tilapia suggested that a considerable number of neutrophils were recruited to the liver. Furtherly, in vitro experiments demonstrated that Cd induced the formation of NETs, and the possible mechanism was related to the generation of reactive oxygen species and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, along with the P38 and extracellular regulated protein kinase (ERK) signaling pathways. We concluded that ferroptosis and NETs are the critical mechanisms contributing to Cd-induced liver injury in Nile tilapia. These findings will contribute to Cd toxicological studies in aquatic animals.

The predictive value of computed tomography value on high-resolution images in differentiating invasive from indolent lung adenocarcinoma.

Background: Invasive adenocarcinoma (IA) has a worse prognosis and different clinical management strategies compared to indolent lung adenocarcinoma including adenocarcinoma in situ (AIS) and minimally IA (MIA). The purpose of this study was to evaluate the predictive value of computed tomography (CT) value in differentiating invasive from indolent lung adenocarcinoma. Methods: The pathological diagnoses and imaging data of confirmed lung adenocarcinomas manifested as lung nodules with homogeneous internal density which were surgically resected between August 2021 and July 2022 were retrospectively analyzed. Differences in CT values between invasive and indolent lung adenocarcinomas were compared in the primary cohort (n=766), and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value. The predictive performance of the cut-off value was evaluated in the validation cohort (n=341). Results: A total of 1,107 lung nodules from 1,014 patients were included in the total cohort. The CT values had a significant difference between invasive and indolent lung adenocarcinomas (P<0.001). Using the primary cohort, we determined the optimal cut-off value of -415 Hounsfield units (HU) of the CT value based on ROC curve, which showed good discrimination between IA and AIS/MIA in both the primary and validation cohorts (sensitivity, 85.98% and 87.42%, specificity, 87.67% and 84.74%, respectively). Conclusions: The CT value of >-415 HU could be an effective predictor of invasive lung adenocarcinoma, thereby providing an appropriate clinical decision guide.

Establishing and validation of the VBV score for assessing Lung ground-glass nodules based on high-resolution computed tomography.

BACKGROUND: The widespread utilization of chest High-resolution Computed Tomography (HRCT) has prompted detection of pulmonary ground-glass nodules (GGNs) in otherwise asymptomatic individuals. We aimed to establish a simple clinical risk score model for assessing GGNs based on HRCT. METHODS: We retrospectively analyzed 574 GGNs in 574 patients undergoing HOOK-WIRE puncture and pulmonary nodule surgery from January 2014 to November 2018. Clinical characteristics and imaging features of the GGNs were assessed. We analyzed the differences between malignant and benign nodules using binary logistic regression analysis and constructed a simple risk score model, the VBV Score, for predicting the malignancy status of GGNs. Then, we validated this model via other 1200 GGNs in 1041 patients collected from three independent clinical centers in 2022. RESULTS: For the exploratory phase of this study, out of the 574 GGNs, 481 were malignant and 93 were benign. Vacuole sign, air bronchogram, and intra-nodular vessel sign were important indicators of malignancy in GGNs. Then, we derived a VBV Score = vacuole sign + air bronchogram + intra-nodular vessel sign, to predict the malignancy of GGNs, with a sensitivity, specificity, and accuracy of 95.6%, 80.6%, and 93.2%, respectively. We also validated it on other 1200 GGNs, with a sensitivity, specificity, and accuracy of 96.0%, 82.6%, and 95.0%, respectively. CONCLUSIONS: Vacuole sign, air bronchogram, and intra-nodular vessel sign were important indicators of malignancy in GGNs. VBV Score showed good sensitivity, specificity, and accuracy for differentiating benign and malignant pulmonary GGNs.

Neo-adjuvant chemotherapy plus immunotherapy in resectable N1/N2 NSCLC.

BACKGROUND: Locally advanced non-small cell lung cancer (NSCLC) with N1/N2 lymph node metastasis is challenging with poor survival. Neo-adjuvant chemo-immunotherapy has gained benefits in a proportion of these patients. However no specific biomarker has been proved to predict the effect before therapy. In addition, the relationship of nodal status and survival after neo-adjuvant chemo-immunotherapy is still not well stated. METHODS: A total of 75 resectable NSCLC patients with N1/N2 stage who received neo-adjuvant chemo-immunotherapy plus surgery were retrospectively studied. The clinical characteristics, surgical information and safety parameters were collected. The correlations of major pathological response (MPR) and pathological complete response (pCR) with clinical data were analyzed. The progression free disease(PFS) and overall survival(OS) were evaluated with pathological response and nodal status. RESULTS: Of the 75 patients, 69 (92%) patients experienced treatment related adverse effects, while grade 3-4 adverse effects occurred in 8 (10%) patients. All the patients received surgical R0 resection with a MPR rate of 60% and a pCR rate of 36%. 67% of N1 patients and 77% of N2 patients had nodal clearance after neo-adjuvant treatment. A significant difference was observed between pathological response with age, histology and multiple lymph node metastasis. The PFS was better in the MPR cohort. The PFS was 90.1% and 83.6% at the nodal clearance group at the time of 12 and 18 months, compared with 70.1% and 63.7% at the nodal residual group. CONCLUSIONS: The neo-adjuvant chemo-immunotherapy for locally advanced NSCLC with nodal positive was safe and feasible. The patients with elder age and squamous-cell carcinoma (SCC) were more likely to have better pathological response, while multiple nodal metastasis was a negative predictor. The clearance of lymph node resulted in significantly longer PFS and OS.

Regulation of mitochondrial structure by the actin cytoskeleton.

Mitochondria are the powerhouse of the cell and play important roles in multiple cellular processes including cell metabolism, proliferation, and programmed cell death. Mitochondria are double-membrane organelles with the inner membrane folding inward to form cristae. Mitochondria networks undergo dynamic fission and fusion. Deregulation of mitochondrial structure has been linked to perturbed mitochondrial membrane potential and disrupted metabolism, as evidenced in tumorigenesis, neurodegenerative diseases, etc. Actin and its motors-myosins have long been known to generate mechanical forces and participate in short-distance cargo transport. Accumulating knowledge from biochemistry and live cell/electron microscope imaging has demonstrated the role of actin filaments in pre-constricting the mitochondria during fission. Recent studies have suggested the involvement of myosins in cristae maintenance and mitochondria quality control. Here, we review current findings and discuss future directions in the emerging fields of cytoskeletal regulation in cristae formation, mitochondrial dynamics, intracellular transport, and mitocytosis, with focus on the actin cytoskeleton and its motor proteins.

Rational design and optimization of acylthioureas as novel potent influenza virus non-nucleoside polymerase inhibitors.

Evidence suggests that rapidly evolving virus subvariants risk rendering current vaccines and anti-influenza drugs ineffective. Hence, exploring novel scaffolds or new targets of anti-influenza drugs is of great urgency. Herein, we report the discovery of a series of acylthiourea derivatives produced via a scaffold-hopping strategy as potent antiviral agents against influenza A and B subtypes. The most effective compound 10m displayed subnanomolar activity against H1N1 proliferation (EC50 = 0.8 nM) and exhibited inhibitory activity toward other influenza strains, including influenza B virus and H1N1 variant (H1N1, H274Y). Additionally, druggability evaluation revealed that 10m exhibited favorable pharmacokinetic properties and was metabolically stable in liver microsome preparations from three different species as well as in human plasma. In vitro and in vivo toxicity studies confirmed that 10m demonstrated a high safety profile. Furthermore, 10m exhibited satisfactory antiviral activity in a lethal influenza virus mouse model. Moreover, mechanistic studies indicated that these acylthiourea derivatives inhibited influenza virus proliferation by targeting influenza virus RNA-dependent RNA polymerase. Thus, 10m is a potential lead compound for the further exploration of treatment options for influenza.

NRF2 has a splicing regulatory function involving the survival of motor neuron (SMN) in non-small cell lung cancer.

The nuclear factor erythroid 2-like 2 (NFE2L2; NRF2) signaling pathway is frequently deregulated in human cancers. The critical functions of NRF2, other than its transcriptional activation, in cancers remain largely unknown. Here, we uncovered a previously unrecognized role of NRF2 in the regulation of RNA splicing. Global splicing analysis revealed that NRF2 knockdown in non-small cell lung cancer (NSCLC) A549 cells altered 839 alternative splicing (AS) events in 485 genes. Mechanistic studies demonstrated that NRF2 transcriptionally regulated SMN mRNA expression by binding to two antioxidant response elements in the SMN1 promoter. Post-transcriptionally, NRF2 was physically associated with the SMN protein. The Neh2 domain of NRF2, as well as the YG box and the region encoded by exon 7 of SMN, were required for their interaction. NRF2 formed a complex with SMN and Gemin2 in nuclear gems and Cajal bodies. Furthermore, the NRF2-SMN interaction regulated RNA splicing by expressing SMN in NRF2-knockout HeLa cells, reverting some of the altered RNA splicing. Moreover, SMN overexpression was significantly associated with alterations in the NRF2 pathway in patients with lung squamous cell carcinoma from The Cancer Genome Atlas. Taken together, our findings suggest a novel therapeutic strategy for cancers involving an aberrant NRF2 pathway.

Antiviral PROTACs: Opportunity borne with challenge.

Proteolysis targeting chimera (PROTAC) degradation of pathogenic proteins by hijacking of the ubiquitin-proteasome-system has become a promising strategy in drug design. The overwhelming advantages of PROTAC technology have ensured a rapid and wide usage, and multiple PROTACs have entered clinical trials. Several antiviral PROTACs have been developed with promising bioactivities against various pathogenic viruses. However, the number of reported antiviral PROTACs is far less than that of other diseases, e.g., cancers, immune disorders, and neurodegenerative diseases, possibly because of the common deficiencies of PROTAC technology (e.g., limited available ligands and poor membrane permeability) plus the complex mechanism involved and the high tendency of viral mutation during transmission and replication, which may challenge the successful development of effective antiviral PROTACs. This review highlights the important advances in this rapidly growing field and critical limitations encountered in developing antiviral PROTACs by analyzing the current status and representative examples of antiviral PROTACs and other PROTAC-like antiviral agents. We also summarize and analyze the general principles and strategies for antiviral PROTAC design and optimization with the intent of indicating the potential strategic directions for future progress.

Risk factors for postoperative cerebral infarction in patients after lung resection: a single-center case-control study.

Background: Patients who undergo lung resection are at risk of postoperative cerebral infarction, but the risk factors remain unclear, so the present study was a comprehensive investigation in patients who underwent lung resection for pulmonary nodules. Methods: The clinical characteristics of patients with postoperative cerebral infarction and patients who underwent lung resection on the same day but did not develop cerebral infarction were retrospectively compared. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for cerebral infarction after lung resection. Results: A total of 22 patients with postoperative cerebral infarction and 316 controls were included. Multivariate logistic regression analysis revealed that a history of cerebral infarction [odds ratio (OR), 7.289; P=0.030], activated partial thromboplastin time (APTT) <26.5 s (OR, 3.704; P=0.018), body mass index (BMI) ≥24.0 kg/m2 (OR, 3.656; P=0.015), and surgical method (P=0.005) were independent risk factors for cerebral infarction after lung resection. Compared with patients undergoing lobectomy, the risk for postoperative cerebral infarction was significantly increased in patients undergoing segmentectomy (OR, 24.322; P=0.001), wedge resection (OR, 6.992; P=0.018), or combined surgical approach (OR, 29.921; P=0.028). Conclusions: A history of cerebral infarction, APTT <26.5 s, BMI ≥24.0 kg/m2, and surgical method were independent risk factors for cerebral infarction after lung resection. Strengthening thromboprophylaxis in patients with these risk factors may help to reduce the incidence of postoperative cerebral infarction.

Influence of Huangqin Decoction on the immune function and fecal microbiome of chicks after experimental infection with Escherichia coli O78.

Huangqin Decoction (HQD), a traditional Chinese medicine formula from the Shang Han Lun written by Zhang Zhongjing, has been used in China for nearly two thousand years. According to the traditional Chinese medicine and previous literature, HQD has the effect of clearing heat, removing toxins, relieving diarrhea and pain. Therefore, HQD was used to prevent or cure many diseases, such as inflammation, diarrhea, malaria, and other acute or chronic gastrointestinal diseases. The effect of HQD, one-herb-absent HQD treatments and enrofloxacin (ENR) on the average daily gain (ADG), mortality rates, visceral index and toll-like receptors (TLRs), inflammatory factors and intestinal microflora in E. coli O78-inoculated chicks were investigated. HQD supplementation increased ADG and reduced the mortality rates caused by E. coli challenge, decreased the heart, liver, bursa of Fabricius (BF) and spleen index. HQD supplementation decreased the serum lysozyme (LZM), IL-1ß, TNF-α, IL-10, IL-6 level, down-regulated the mRNA expression of TLR4, -5 and -15 in the spleen by E. coli challenged chicks, and up-regulated the mRNA expression of TLR4, -5 and -15 in BF. At the phylum level, HQD supplementation reversed the increase of Operational Taxonomic Unit (OTUs), decreased the relative abundance of harmful bacteria Proteobacteria, increased the relative abundance of probiotic bacteria Bacteroidetes and Firmicutes. At the genus level, HQD decreased the relative abundance of harmful bacteria Escherichia-Shigella and Pseudomonas. It means that HQD treatment reversed the change of the gut microbiota structure. Compared with HQD, HQD-DZ and HQD-HQ increased the mortality rates. HQD-HQ decreased the ADG and liver index. HQD-GC decreased the spleen index. All herb-absent increased the serum IL-6, but only the HQD-HQ and HQD-SY increased the serum TNF-α. All herb-absent did not activate the TLRs signaling pathways in spleen and BF of chicks. The harmful bacteria Escherichia-Shigella were increased in HQD-HQ and HQD-DZ treatments. HQD-DZ treatment also increased the level of Proteobacteria. The results showed that dietary supplementation with HQD, by down-regulating the mRNA expression of TLR4, -5 and -15 in the spleen, further decreasing the serum LZM and IL-1ß, TNF-α, IL-10, IL-6 level, improves the immune function and reverses the change of fecal microbiome in chicks challenged with E. coli. In herb-absent supplementation, the results showed that SY and DZ play a key role in reducing the levels of inflammatory factors and keeping fecal microbiome balance respectively. More importantly, HQ is indispensable in HQD, not only play a key role in reducing the level of inflammatory factors, but also in keeping the balance of fecal microflora.

Identification of a three-gene expression signature and construction of a prognostic nomogram predicting overall survival in lung adenocarcinoma based on TCGA and GEO databases.

Background: Lung adenocarcinoma (LUAD) is the major cause of cancer mortality. Traditional prognostic factors have limited importance after including other parameters. Thus, developing a more credible prognostic model combined with genes and clinical parameters is necessary. Methods: The messenger RNA (mRNA) expression and clinical information from The Cancer Genome Atlas (TCGA)-LUAD datasets and microarray data from three Gene Expression Omnibus (GEO) databases were obtained. We identified differentially-expressed genes (DEGs) between lung tumor and normal tissues through integrated analysis of the three GEO datasets. Univariate and multivariate Cox regression analyses were conducted to select survival-associated DEGs and to establish a prognostic gene signature which was associated with overall survival (OS). The expression of gene proteins was assessed in 180 LUAD tissue microarrays (TMAs) by immunohistochemistry (IHC). We verified its predictive performance with a Kaplan-Meier (KM) curve, receiver operating characteristic (ROC) curve, and Harrell's concordance index (C-index) and validated it in external GEO databases. Multivariate Cox regression analysis was performed to identify the significant prognostic indicators in LUAD. Furthermore, we established a prognostic nomogram based on TCGA-LUAD dataset. Results: A three-gene signature was constructed to predict the OS of LUAD patients. The KM analysis, ROC curve, and C-index present a good predictive ability of the gene signature in TCGA dataset [P<0.0001; C-index 0.6375; 95% confidence interval (CI): 0.5632-0.7118; area under the ROC curve (AUC) 0.674] and the external GEO datasets (P=0.05, 0.004, and 0.04, respectively). Univariate and multivariate Cox regression analyses also verified that LUAD patients with low-risk scores had a decreased risk of death compared to those with a high-risk score in TCGA database [hazard ratio (HR) =0.3898; 95% CI: 0.1938-0.7842; P<0.05]. Finally, we constructed a nomogram integrating the gene signature and clinicopathological parameters (P<0.0001; C-index 0.762; 95% CI: 0.714-0.845; AUC 0.8136). Compared with conventional staging, a nomogram can effectively improve prognosis prediction. Conclusions: The nomogram is closely associated to the OS of LUAD patients. This consequence may be beneficial to individualized treatment and clinical decision-making.

Effects of 24-hour postoperative intravenous fluid on postoperative outcomes after lobectomy: a retrospective observational study.

Background: Postoperative fluid management plays a key role in providing adequate tissue perfusion, stabilizing hemodynamics, and reducing morbidities related to hemodynamics. This study evaluated the dose-response relationship between postoperative 24-hour intravenous fluid volume and postoperative outcomes in patients with non-small cell lung cancer (NSCLC) undergoing video-assisted thoracoscopic surgery (VATS) lobectomy. Methods: A retrospective analysis of adult patients with NSCLC undergoing VATS lobectomy between May 2016 and April 2017 was performed. The primary exposure variable was total intravenous crystalloid infusion in the 24-hour postoperative period. The observation outcomes were postoperative pulmonary complications, acute kidney injury (AKI), in-hospital mortality, readmission within 30 days, prolonged hospital stay, postoperative length of stay, and total hospital care costs. Univariate and multivariate analyses were performed. Results: Of the 563 patients, 136 (24.2%) with pulmonary complications were observed. Binary logistics regression showed that, relative to the group with moderate postoperative 24-hour crystalloid infusion, the risk for postoperative pulmonary complications was significantly increased in the restrictive [odds ratio (OR) 1.815, 95% CI: 1.083-3.043; P=0.024] and liberal (OR 2.692, 95% CI: 1.684-4.305; P<0.001) groups. Conclusions: In patients with NSCLC undergoing VATS lobectomy, both restrictive and liberal 24-hour postoperative crystalloid infusions were related to adverse effects on postoperative outcomes and the optimal volume of 24-hour postoperative intravenous crystalloid infusion was 1,080-<1,410 mL.

Mechanical instability generated by Myosin 19 contributes to mitochondria cristae architecture and OXPHOS.

The folded mitochondria inner membrane-cristae is the structural foundation for oxidative phosphorylation (OXPHOS) and energy production. By mechanically simulating mitochondria morphogenesis, we speculate that efficient sculpting of the cristae is organelle non-autonomous. It has long been inferred that folding requires buckling in living systems. However, the tethering force for cristae formation and regulation has not been identified. Combining electron tomography, proteomics strategies, super resolution live cell imaging and mathematical modeling, we reveal that the mitochondria localized actin motor-myosin 19 (Myo19) is critical for maintaining cristae structure, by associating with the SAM-MICOS super complex. We discover that depletion of Myo19 or disruption of its motor activity leads to altered mitochondria membrane potential and decreased OXPHOS. We propose that Myo19 may act as a mechanical tether for effective ridging of the mitochondria cristae, thus sustaining the energy homeostasis essential for various cellular functions.

VATS Versus Open Lobectomy in Pathological T1 SCLC: A Multi-Center Retrospective Analysis.

BACKGROUND: Video-assisted thoracic surgery (VATS) has been widely used in the surgical treatment of thoracic diseases, and it suggested surgical and oncological advantages compared with open surgery. However, reports on the application of VATS in surgery of small cell lung cancer (SCLC) are scarce. This study aimed to explore the advantages and disadvantages of different surgical approaches in the treatment of pathological stage T1(pT1) SCLC in terms of safety, clinical outcomes, and lymph node dissection. PATIENTS AND METHODS: Patients who underwent lobectomy for pT1 SCLC between January 2014 and September 2017 were identified from the National Collaborative Lung Cancer Database (LinkDoc Database). The patients were stratified based on the surgery approach (VATS or open lobectomy). Perioperative outcomes and long-term survival were analyzed using SPSS software. RESULTS: A total of 169 patients with pT1 SCLC met the criteria and were enrolled for this study, including 110 cases of VATS lobectomies and 59 cases of open lobectomies. VATS lobectomy was associated with less blood loss than open surgery (168.1 ± 237.4 vs. 340.0 ± 509.8 mL, P = .002). Open lobectomy harvested more N2 LNs (11.8 ± 8.2 vs. 8.4 ± 5.8, P = .048) and identified more metastasis positive LNs (3.1 ± 6.0 vs. 1.4 ± 3.0, P = .050). Open lobectomy associated with longer overall survival (OS) but has no statistical difference (23.4 ± 13.2 vs. 20.2 ± 10.9, P = .070). CONCLUSION: Open lobectomy had better lymph node dissection results, and comparable postoperative complications, postoperative hospital stay, and OS to VATS lobectomy. Further studies may still be needed to confirm the recommendation of thoracoscopic approach as a routine surgical procedure for operable SCLC, and until then, open surgery should still be considered.

Trends in population mortality rates in the United States from 1969 to 2017.

BACKGROUND: Fundamental transformations in overall population health have occurred in the past five decades and are continuing. Our aim in this study was to characterize the trends in population mortality rates in the United States (U.S.) from 1969 to 2017. METHODS: Data on the 109,836,044 deaths registered in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed by sex, race and ethnicity, and age. Temporal trends in population mortality rates were examined from 1969 to 2017. All data analyses were performed using the SEER*Stat software. RESULTS: The overall mortality rate for males and females in the U.S. per 100,000 population fell by 46.1% and 39.3%, from 1,610.0 and 1,019.3 in 1969 to 867.2 and 619.2 in 2017, respectively. This decline in overall mortality was mainly attributable to a decrease in mortality caused by heart and cerebrovascular diseases. From 1969 to 2017, the overall mortality rate was higher in males than females, and in blacks than whites for both sexes. From 1979 to 2017, the mortality rates of heart diseases, cerebrovascular diseases, and diabetes were all higher in blacks than in whites for both sexes. CONCLUSIONS: The results indicate that the U.S. has dramatically reduced its overall annual mortality rate between 1969 and 2017; however, the disparities among different races are still apparent.

Regulating COX10-AS1 / miR-142-5p / PAICS axis inhibits the proliferation of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the main causes of death in the world. To improve the diagnostic level and find new biological targets，GSE datasets were selected from GEO databaseto analyze the differential expression genes and construct ceRNA network. Cell apoptosis detection showed that both the early and late apoptosis rates were increased after inhibition of COX10-AS1. Glycolysis cell-based assay also found that the content of L-lactate decreased significantly after using miR-142-5p mimics but increased after using si-COX10-AS1. Dual-luciferase reporter analysis showed that the luciferase activity of PAICS-WT reporter vector was inhibited by miR-142-5p mimics, but there was no significant change in PAICS-MUT reporter vector after transfection of miR-142-5p mimics. And overexpression of miR-142-5p reduced the level of PAICS, but inhibition of miR-142-5p expression increased the expression of PAICS. After using COX10-AS1, the expression of PAICS inhibited by miR-142-5p was restored. Through bioinformatics analysis, we constructed the COX10-AS1/miR-142-5p/PAICS axis, which is a ceRNA regulatory network. We confirmed that COX10-AS1 down-expression can restore the inhibitory effect of miR-142-5p on PAICS, promote the apoptosis of NSCLC cells, and inhibit the proliferation of NSCLC cells. This process may be mediated by the activation of glycolysis pathway. The glycolysis-related gene PAICS may be a new and significant target for the regulation of the development of NSCLC.

Identification of key pathways and core genes involved in atherosclerotic plaque progression.

BACKGROUND: Atherosclerosis leads to the occurrence of cardiovascular diseases. However, the molecular mechanisms that contribute to atherosclerotic plaque rupture are incompletely characterized. We aimed to identify the genes related to atherosclerotic plaque progression that could serve as novel biomarkers and interventional targets for plaque progression. METHODS: The datasets of GSE28829 in early vs. advanced atherosclerotic plaques and those of GSE41571 in stable vs. ruptured plaques from Gene Expression Omnibus (GEO) were analyzed by using bioinformatics methods. In addition, we used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the expression level of core genes in a mouse atherosclerosis model. RESULTS: There were 29 common differentially expressed genes (DEGs) between the GSE28829 and GSE41571 datasets, and the DEGs were mainly enriched in the chemokine signaling pathway and the Staphylococcus aureus infection pathway (P<0.05). We identified 6 core genes (FPR3, CCL18, MS4A4A, CXCR4, CXCL2, and C1QB) in the protein-protein interaction (PPI) network, 3 of which (CXCR4, CXCL2, and CCL18) were markedly enriched in the chemokine signaling pathway. qRT-PCR analysis showed that the messenger RNA levels of two core genes (CXCR4 and CXCL2) increased significantly during plaque progression in the mouse atherosclerosis model. CONCLUSIONS: In summary, bioinformatics techniques proved useful for the screening and identification of novel biomarkers of disease. A total of 29 DEGs and 6 core genes were linked to atherosclerotic plaque progression, in particular the CXCR4 and CXCL2 genes.

Perioperative comparison of video-assisted thoracic surgery and open lobectomy for pT1-stage non-small cell lung cancer patients in China: a multi-center propensity score-matched analysis.

BACKGROUND: Compared with open surgery, video-assisted thoracic surgery (VATS) has innovated the concept of the minimally invasive approach for non-small cell lung cancer (NSCLC) patients in past decades. This present study aimed to compare the perioperative and lymph node dissection outcomes between VATS lobectomy and open lobectomy for pathological stage T1 (pT1) NSCLC patients from both surgical and oncologic perspectives. METHODS: This was a retrospective multicenter study. Patients who underwent surgical resection for pT1 NSCLC between January 2014 and September 2017 were retrospectively reviewed from 10 thoracic surgery centers in China. Perioperative and lymph node dissection outcomes of pT1 NSCLC patients who accepted VATS or open lobectomies were compared by propensity score matching (PSM) analysis. RESULTS: Of the 11,360 patients who underwent surgery for pT1 NSCLC, 7,726 were enrolled based on the selection criteria, including 1,222 cases of open lobectomies and 6,504 cases of VATS lobectomies. PSM resulted in 1,184 cases of open lobectomies and 1,184 cases of VATS lobectomies being well matched by common prognostic variables, including age, sex, and surgical side. VATS lobectomy led to better perioperative outcomes, including less blood loss (133.5±200.1 vs. 233.3±318.4, P<0.001), lower blood transfusion rate (2.4% vs. 6.4%, P<0.001), shorter postoperative hospital stay (8.6±5.7 vs. 10.1±5.1, P<0.001), less chest drainage volume (1,109.5±854.0 vs. 1,324.1±948.8, P<0.001), and less postoperative complications (4.9% vs. 8.2%, P<0.001). However, open lobectomy had better lymph node dissection outcomes than VATS, with increased lymph node dissection numbers (16.1±9.4 vs. 13.7±7.7, P<0.001) and more positive lymph nodes being dissected (1.5±3.9 vs. 1.1±2.5, P=0.002). Compared with VATS, open lobectomy harvested more lymph node stations (5.5±1.9 vs. 5.2±1.8, P=0.001), including more pathological N2 (pN2) lymph node stations (3.4±1.4 vs. 3.1±1.3, P<0.001). CONCLUSIONS: VATS lobectomy was associated with better perioperative outcomes, such as less blood loss, lower blood transfusion rate, shorter postoperative hospital stay, less chest drainage volume and less postoperative complications. Open lobectomy has improved lymph node dissection outcomes, as more lymph nodes and positive lymph nodes were dissected for pT1 NSCLC patients during surgery.

Effects of preoperative pulmonary function on short-term outcomes and overall survival after video-assisted thoracic surgery lobectomy.

BACKGROUND: Preoperative pulmonary function tests are a necessary preoperative assessment tool for non-small cell lung cancer (NSCLC) patients awaiting surgery. We studied the effects of preoperative pulmonary function on short-term outcomes and overall survival (OS). METHODS: A retrospective cohort study was undertaken with adult NSCLC patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy between May 2016 and April 2017. The primary exposure variables were the percentage of predicted peak expiratory flow (PEF%), the percentage of predicted forced vital capacity (FVC%), and the percentage of predicted forced expiratory volume in 1 s. The observation outcomes were postoperative pulmonary complications (PPCs), acute kidney injury (AKI), in-hospital mortality, readmission within 30 days, and OS. Univariate and multivariate analyses were performed. RESULTS: Of the 548 patients, postoperative pneumonia was observed in 206 (37.6%). The results of the binary logistics regression analysis showed that relative to the moderate PEF% group, the risk of postoperative pneumonia was significantly increased in the marginal PEF% [odds ratio (OR) 2.076; 95% confidence interval (CI): 1.211-3.558; P=0.008] and excellent PEF% (OR 1.962; 95% CI: 1.129-3.411; P=0.017) groups. Relative to the good FVC% group, the risk of postoperative pneumonia was significantly increased in the marginal FVC% (OR 2.125; 95% CI: 1.226-3.683; P=0.007) and moderate FVC% (OR 2.230; 95% CI: 1.298-3.832; P=0.004) groups. The OS analysis did not reveal any correlations among the pulmonary function parameters and OS in this cohort. CONCLUSIONS: Preoperative PEF% and FVC% are associated with postoperative pneumonia in NSCLC patients undergoing VATS lobectomy. Preoperative PEF% is as important as FVC% in pulmonary function assessment before lung surgery.