Identification of hub genes in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.

Romidepsin exhibits anti-esophageal squamous cell carcinoma activity through the DDIT4-mTORC1 pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4) gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.

Neoadjuvant camrelizumab plus chemotherapy in locally advanced oesophageal squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Neoadjuvant therapy is recommended to improve the prognosis of oesophageal squamous cell carcinoma (ESCC). As a PD-1 inhibitor developed in China, camrelizumab is more accessible and available for Chinese ESCC patients. Camrelizumab plus neoadjuvant chemotherapy has shown promising efficacy with acceptable toxicity for resectable ESCC in the NIC-ESCC2019 trial. However, this was a single-arm trial, so we conducted a retrospective cohort study to compare neoadjuvant camrelizumab plus chemotherapy with neoadjuvant chemotherapy alone in terms of the safety and efficacy in patients with locally advanced ESCC. METHODS: Between January 2017 and December 2021, patients with stage II-IVa ESCC who received neoadjuvant therapy at the First Affiliated Hospital of Chongqing Medical University and underwent radical oesophagectomy were enrolled in our study. These included 19 patients who received neoadjuvant chemotherapy plus camrelizumab (group 1) and 40 patients who only received neoadjuvant chemotherapy (group 2). RESULTS: The baseline characteristics of the patients were comparable between the two groups. The pathological complete response (pCR) rate in group 1 was significantly higher than that in group 2 (26.3% vs. 2.5%, P = 0.018). All patients in group 1 achieved complete resection (R0), compared with 39 (97.5%) patients in group 2. Adverse events occurred in 16 (84%) patients in group 1 versus 35 (87.5%) patients in group 2. No grade ≥ 4 adverse events occurred in either group. No significant difference was found in surgical outcomes or postoperative complications. The 90-day mortality rate was comparable between the two groups (1 patient died in group 1 versus 2 patients in group 2). CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy followed by surgery was associated with a promising pCR rate and a manageable safety profile for patients with locally advanced ESCC.

Impact of delayed veno-venous extracorporeal membrane oxygenation weaning on postoperative rehabilitation of lung transplantation: a single-center comparative study.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a reliable and effective extracorporeal life support during lung transplantation (LTx). However, the clinical benefit of delayed VV-ECMO weaning remains unclear. The current study aims to investigate whether delayed weaning of VV-ECMO is more beneficial to the rehabilitation for lung transplant patients. Patients who underwent LTx with VV-ECMO between January 2017 and January 2019 were included. Enrollment of patients was suitable for weaning off ECMO immediately after surgery. Randomization was performed in the operating room. Postoperative outcomes were compared between the two groups. Besides, univariate and multivariable logistic regressions were performed to estimate risk of postoperative complications. Compared to VV-ECMO weaning immediately after LTx, delayed weaning was associated with shorter hospital length of stay (days, 31 vs. 46; P < 0.05), lower incidence of noninvasive ventilation (4.3% vs. 24.4%; P < 0.05), primary graft dysfunction (PGD) (6.4% vs. 29.3%; P < 0.05), atrial fibrillation (AF) (4.3% vs. 22%, P < 0.05), and respiratory failure (4.3% vs. 19.5%; P < 0.05). Multivariable logistic regressions revealed that VV-ECMO weaning after LTx was independently correlated with increased risk of developing PGD [odds ratio (OR), 5.97, 95% CI 1.16-30.74], AF (OR, 6.87, 95% CI 1.66-28.47) and respiratory failure (OR, 6.02, 95% CI 1.12-32.49) by comparison of delayed VV-ECMO weaning. Patients with delayed VV-ECMO weaning are associated with lower complications and short hospital length of stay, while it relates to longer mechanical ventilation. These findings suggest that delayed VV-ECMO after LTx can facilitate rehabilitation.

Uniportal video-assisted thoracic S9+10 segmentectomy using a single-direction approach is good for pulmonary function.

BACKGROUND: Uniportal video-assisted thoracic surgery is still a technical challenge, especially anatomical segmentectomy for the lateral basal segment (S9), posterior basal segment (S10), or both (S9+10). Different surgical procedures determine a variable pulmonary functional reduction depending on the extent of the resection. This study aimed to compare the efficiency of uniportal video-assisted thoracic surgery S9+10 segmentectomy with video-assisted thoracic surgery basal segmentectomy in preserving pulmonary function. METHODS: The patients who had undergone single-port video-assisted thoracic surgery S9+10 segmentectomy using a single-direction approach were age, sex, and pulmonary function matched with those undergoing video-assisted thoracic surgery basal segmentectomy. The pulmonary function tests were performed preoperatively, and at 3 and 6 months postoperatively. The operative details, postoperative complications, and pulmonary function were statistically analyzed. RESULTS: After matching, a total of 46 patients undergoing video-assisted thoracic surgery S9+10 segmentectomy and 58 patients undergoing video-assisted thoracic surgery basal segmentectomy were eligible for analysis. There was no significant difference in the average blood loss, the duration of chest tube, intensive care unit stay, or hospital stay between these 2 groups. There were no major postoperative complications and surgical mortality was found in the 2 groups. The uniportal video-assisted thoracic surgery S9+10 segmentectomy group had a greater preserved pulmonary function (concerning the values of the forced vital capacity, forced expiratory volume in 1 second, forced expiratory volume in 1 second %, and diffusion capacity of carbon monoxide %) than video-assisted thoracic surgery basal segmentectomy group at 1 and 3 months postoperatively. CONCLUSION: Uniportal video-assisted thoracic surgery anatomic S9+10 segmentectomy using a single-direction approach was safe and feasible for early stages of nonsmall cell lung cancer, and it offered significantly better functional preservation compared with basal segmentectomy.

Refractory post-thymectomy myasthenia gravis with onset at MGFA stage V: a case report.

BACKGROUND: Post-thymectomy myasthenia gravis (PTMG) is defined as thymoma patients without signs of myasthenia gravis (MG) pre-operation, but develop MG after radical surgical resection. PTMG might be misdiagnosed not only because of its rare incidence, but also the uncertain interval between the removal of thymoma and the new onset MG. Additionally, some surgeons and anesthesiologists pay less attention to those asymptomatic thymoma patients in perioperative management, leading to the neglect of new onset PTMG, and miss the best time to treat it. CASE PRESENTATION: Majority of cases of PTMG with onset at stage I-II on the basis of Myasthenia Gravis Foundation of America (MGFA) classification have been reported, but rarely at stage V, which requiring intubation or non-invasive ventilation to avoid intubation. Herein, we presented a 70-year-old male with PTMG onset at MGFA stage V, meanwhile, he had severe pulmonary infection interfering with the diagnosis of PTMG, and eventually progressed to refractory PTMG, which requiring much more expensive treatments and longer hospital stays. CONCLUSION: In the perioperative management of asymptomatic thymoma patients, careful preoperative evaluation including physical examination, electrophysiological test and acetylcholine receptor antibodies (AChR-Ab) level should be done to identify subclinical MG. Complete resection should be performed during thymectomy, if not, additional postoperative adjuvant therapy is neccessary to avoid recurrence. It's important to identify PTMG at a early stage, especially when being interfered with by postoperative complications, such as lung infection, so that treatments could be initiated as soon as possible to avoid developing to refractory PTMG.

Boyden's triad in the left lung: an interesting phenomenon.

OBJECTIVES: Boyden's triad of the right lung was first proposed in 2021. Here, we report 5 cases of this malformation found in the left lung. METHODS: A total of 5280 patients with pulmonary lesions underwent three-dimensional computed tomography bronchography and angiography between January 2019 and January 2021, prior to surgery; 5 cases of this malformation were identified in the left lung. Bronchovascular patterns were analysed in each patient. RESULTS: The incidence rate of Boyden's triad in the left lung was 0.1%. This malformation was further divided into B3 on B4+5 type and B3 on B4 type. In B3 on B4+5 type, B3 was shifted downwards on the common trunk of B4+5, and A3 arose from the common trunk of A4+5 running alongside B3. In B3 on B4 type, B3 was shifted downwards on B4. A4 and A5 appeared separately. A3 arose from A4, running alongside B3; A5 arose from the common trunk of A8 - 10, and there was also an extraordinary 'posterior vein' (V. post): V1+2c. The incidence of V. post was 0.17%. An additional 'fissure' lies longitudinally between S1+2 and S3+4+5, nearly perpendicular to the oblique fissure, dividing the upper lobe into 'two lobes'. CONCLUSIONS: The B3 downwards-shifting malformation can be found on both lungs, and this is the first description of Boyden's triad in the left lung; it appears to be much rarer than that in the right lung, with some accompanying unique variations.

Impacts of eosinophil percentage on prognosis acute type A aortic dissection patients.

BACKGROUND: Eosinophils are pro-inflammatory cells involved in thrombosis and have been proposed as a prognosis marker in acute ischemic stroke and ST-elevation myocardial Infarction. Here, we sought to clarify the prognostic value of eosinophil percentage (EOS%) in patients with acute type A aortic dissection (AAAD). METHODS: We examined 183 consecutive AAAD patients. Based on the optimum cut-off value of EOS% determined by X-tile software, patients were classified into the low EOS% (EOS% ≤ 0.1) and high EOS% groups (EOS% > 0.1). We performed multivariate regression analysis and Kaplan-Meier (KM) survival curves to assess the association between EOS% and mortality. Eosinophil accumulation in aortic dissection intraluminal thrombus was confirmed using hematoxylin-eosin (H&E) staining. An external cohort from Medical Information Mart for Intensive Care IV was performed to validate the results. RESULTS: Relative to surviving patients, those who died during hospitalization had significantly lower EOS% (p = 0.001) but significantly higher WBC (p = 0.002) and neutrophil (p = 0.001) counts. Multivariate regression analysis identified EOS% as an independent predictor of in-hospital and 1-year mortality. KM curves revealed that 1-year cumulative mortality was significantly higher in the low EOS% group, although it was mainly attributed to the higher 30-day mortality. H&E staining revealed massive infiltration of eosinophils in all 20 thrombus specimens. The external validation confirmed that relative to survivors, patients with in-hospital mortality (p = 0.010) had significantly lower EOS%. Moreover, multivariate regression analyses identified that decreased EOS% was independently significantly associated with in-hospital mortality. CONCLUSIONS: Low EOS% is significantly related to increased mortality rates in AAAD patients.

Construction and Integrated Analysis of Competitive Endogenous Long Non-Coding RNA Network in Thoracic Aortic Dissection.

BACKGROUND: Long non-coding RNAs (lncRNAs) can act as a competitive endogenous RNA (ceRNA) to regulate gene expression by sequestering the microRNA (miRNA). However, the lncRNA-miRNA-mRNA ceRNA network in thoracic aortic dissection (TAD) has been rarely documented. METHODS: Three Gene Expression Omnibus (GEO) datasets were used to detect differentially expressed mRNAs, miRNAs, and lncRNAs in TAD. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for the differentially expressed mRNAs. A protein-protein interaction network for differentially expressed mRNAs was also constructed, and hub genes were identified. We established a ceRNA network of TAD based on the differentially expressed miRNAs, mRNAs and lncRNAs, and verified our results using an independent dataset and quantitative real-time PCR (qRT-PCR). RESULTS: In TAD, 267 lncRNAs, 81 miRNAs, and 346 mRNAs were identified as differentially expressed. The established ceRNA network consisted of seven lncRNA nodes, three mRNA nodes, and three miRNA nodes, and the expression of miRNAs in TAD was opposite to that of lncRNAs and mRNAs. Subsequently, an independent GEO dataset and qRT-PCR were used to validate the expression of three mRNAs. In addition, the expression differences in SLC7A5, associated miRNA and lncRNA were verified. According to gene set enrichment analysis of SLC7A5, the most significant KEGG pathway was considerably enriched in spliceosome and pentose phosphate pathway. CONCLUSION: We established a novel ceRNA regulatory network in TAD, which provides valuable information for further research in the molecular mechanisms of TAD.

Survival benefit of perioperative chemotherapy for T1-3N0M0 stage esophageal cancer: a SEER database analysis.

BACKGROUND: The effect of perioperative chemotherapy on patients with lymph node-negative esophageal cancer (EC) is controversial. This study explored which EC patients, staged under the T1-3N0M0, would benefit from perioperative chemotherapy. METHODS: Data on patients with diagnosed primary EC were retrieved from Surveillance, Epidemiology and End Results (SEER) database. Propensity score-matched (PSM) method was performed to balance baseline covariates. Multivariate Cox regression analysis and Kaplan-Meier curve were used to assess potential survival difference between patients undergoing surgery plus perioperative chemotherapy (SA + CT) and those undergoing surgery alone (SA). RESULTS: In a total of 2,711 EC patients (T1-3N0M0), 166 patients underwent SA + CT and 2,545 patients received SA. In the multivariable analysis, T stage was significantly related to prognosis of EC patients before and after matching. Subgroup analysis showed that perioperative chemotherapy was associated with poor cancer-specific survival (CSS) for stage T1 patients. There was no effect of perioperative chemotherapy on overall survival (OS) or CSS for T2 patients, whereas a remarkable improvement in OS and CSS was observed for T3 patients. Survival analysis showed that T3 stage EC patients obtained survival benefit from SA + CT. Prognosis in the SA group was significantly better than in the SA + CT group for T1 patients. However, T2 patients showed no significant increase in survival after undergoing SA + CT compared with SA. CONCLUSIONS: T3 patients benefit more from SA + CT. However, perioperative chemotherapy does not present survival benefit to T1-2 patients, and it is an adverse prognostic factor for T1 patients.

Survival differences between chemotherapy and chemoradiotherapy in metastatic esophageal cancer: a propensity score-matched study based on the SEER database.

BACKGROUND: The aim of this study was to explore the impact of chemotherapy (CT) and chemoradiotherapy (CRT) on prognosis in metastatic esophageal cancer (mEC) patients. METHODS: Information of patients with mEC from 2010 to 2016 was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic and clinical data between CT and CRT groups were compared. Propensity score matching (PSM) analysis was used to reduce the influence of potential confounding factors. Multivariate Cox regression analysis was used to evaluate prognostic factors. Moreover, interaction tests and survival analyses were performed to determine whether pathological type conferred any survival benefits in subgroups. RESULTS: A total of 3,352 mEC patients were recruited including 1,697 CT patients and 1,655 CRT patients. In multivariable Cox regression, marital status, gender and pathological type were identified as independent prognostic factors for mEC. There was no statistical significance between the CT group and CRT group in overall survival (OS) and cancer-specific survival (CSS) in the matched and unmatched cohort. In subgroup analyses, patients with esophageal adenocarcinoma (EAC) undergoing CT had favorable prognosis. However, in the subgroup of esophageal squamous cell carcinoma (ESCC), patients in the CT group had worse outcomes compared with patients in the CRT group. CONCLUSIONS: Patients with EAC and ESCC could respectively benefit from CT and CRT. Besides, we recommend individualizing the treatment strategy for mEC based on the pathological type.

Effects of corticosteroids on new-onset atrial fibrillation after cardiac surgery: A meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative atrial fibrillation (POAF) occurs commonly after cardiac surgery. Studies suggest that corticosteroid can reduce the incident of POAF. However, the results remain controversial. This meta-analysis aimed to evaluate the efficacy and safety corticosteroid on the prevention of POAF following cardiac surgery. METHODS: Randomized controlled trials were identified through a systematic literature search. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Primary outcome was the incidence of POAF as well as length of hospital stay and intensive care unit stay, wound and other infection, mortality, duration of ventilation, myocardial infarction, gastrointestinal complications, high blood sugar, stroke, and postoperative bleeding. RESULTS: Fourteen studies with 13,803 patients were finally involved in the present study. Overall, corticosteroid significantly decreased the risk of POAF (relative risk [RR], 0.7; 95% confidence interval [CI], 0.55-0.89; P = .003). There were no significant differences in the incidence of length of intensive care unit stay (RR, -2.32; 95% CI, -5.44 to 0.80; P = .14) and hospital stay (RR, -0.43; 95% CI, -0.84 to -0.02; P = .04), infections (RR, 1.01; 95% CI, 0.83-1.23; P = .9), mortality (RR, 0.87; 95% CI, 0.71-1.06; P = .16), duration of ventilation (RR, -0.29; 95% CI, -0.65 to 0.07; P = .12), gastrointestinal complications (RR, 1.26; 95% CI, 0.91-1.76; P = .16), high blood sugar (RR, 1.98; 95% CI, 0.91-4.31; P = .09), stroke (RR, 0.9; 95% CI, 0.69-1.18; P = .45), postoperative bleeding (RR -44.54; 95% CI, -115.28 to 26.20; P = .22) and myocardial infarction (RR, 1.71; 95% CI, 0.96-1.43; P = .12). CONCLUSION: Our review suggests that the efficacy of corticosteroid might be beneficial to POAF development in patients undergoing cardiac surgery. The strength of this association remains uncertain because of statistical and clinical heterogeneity among the included studies.

Vein or artery-first resection in right middle lobe segmentectomy: which preserves more lung?

We report the thoracoscopic RS5 segmentectomy with VVBA (V, vein; V, ventilation; B, bronchus; A, artery) method and confirmed that the segmental plane visualized by vein-first resection is slightly narrower than the traditional artery-first resection.

Melatonin Alleviates Cardiac Dysfunction Via Increasing Sirt1-Mediated Beclin-1 Deacetylation and Autophagy During Sepsis.

Cardiac dysfunction is a major cause leading to multiple organ failure in sepsis. Beclin-1-dependent autophagy has been evidenced to exert protective effects on hearts in sepsis. However, the mechanisms on how Beclin-1 and autophagy are regulated remains enigmatic. To explore the detailed mechanisms controlling Beclin-1-dependent autophagy in septic heart and whether melatonin could protect against sepsis via regulating cardiac autophagy, adult Sprague-Dawley (SD) rats were subjected to cecal ligation and puncture (CLP) to induce sepsis. Rats were intraperitoneally administrated with 30 mg/kg melatonin within 5-min post-CLP surgery. Our data showed that sepsis induced Becline-1 acetylation and inhibited autophagy in hearts, resulting in impaired cardiac function. However, melatonin treatment facilitated Beclin-1 deacetylation and increased autophagy in septic hearts, thus improved cardiac function. Moreover, melatonin increased the expression and activity of Sirtuin 1 (Sirt1), and inhibition of Sirt1 abolished the protective effects of melatonin on Beclin-1 deacetylation and cardiac function. In conclusion, increased Beclin-1 acetylation was involved in impaired autophagy in septic hearts, while melatonin contributed to Beclin-1 deacetylation via Sirt1, leading to improved autophagy and cardiac function in sepsis. Our study sheds light on the important role of Beclin-1 acetylation in regulating autophagy in sepsis and suggests that melatonin is a potential candidate drug for the treatment of sepsis.

The VVBA method for thoracoscopic right middle lobe segmentectomy.

The right middle lobe segments (RS4 and RS5) are very small and the technique for segmentectomy is rarely reported. Here, we report 3 cases of thoracoscopic RS4 segmentectomy with VVBA (V, vein; V, ventilation; B, bronchus; A, artery) method. The VVBA method for thoracoscopic segmentectomy is a simple, safe, and effective procedure for RS4 segmentectomy with clear procedural steps. It overcomes the difficulty in manipulation of incomplete lung fissures and simplifies the surgical procedures.

MicroRNA-92a -mediated endothelial to mesenchymal transition controls vein graft neointimal lesion formation.

PURPOSE: Long-term failure of vein grafts due to neointimal hyperplasia remains an important problem in coronary artery bypass graft surgery. Endothelial to mesenchymal transition (EndMT) contributes to vein graft vascular remodeling. However, there is little study on microRNA-mediated EndMT contributions to neointimal formation in vein graft. We hypothesized that microRNA-92a (miR-92a) might play an important role in determining EndMT contributions to neointimal formation. METHODS: miR-92a and EndMT-related proteins detected by qRT-PCR and Western blot in vitro and in vivo. Adeno-associated virus 6 (AAV6) delivery gene therapy was used to inhibit neointimal formation in vivo. The intimal hyperplasia of vein grafts was measured by HE staining, the expression of EndMT-related protein in vein grafts was measured by immunofluorescence. Immunohistochemistry and luciferase assay were used to detect potential targets of miR-92a. RESULTS: The expression of miR-92a was found to be upregulated in neointimal hyperplasic lesions after vein grafting. Using cultured human umbilical vein endothelial cells (HUVECs), we show that TGF-ß1 treatment of HUVECs significantly increased miR-92a expression and induced EndMT, characterized by suppression of endothelial-specific markers (CD31 and VE-cadherin) and an increase in mesenchymal-specific markers (a-SMA and vimentin), while inhibition of miR-92a expression blunted EndMT in cultured HUVECs. Furthermore, AAV6 mediated miR-92a suppression gene therapy effectively resulted in decreased EndMT and less neointimal formation in vein grafts in vivo. We further identified that integrin alpha 5 (ITGA5) is a potential target gene involved in the development of neointima formation in these vein grafts. CONCLUSION: This data suggests that neointimal formation does not solely rely on vascular smooth muscle cell phenotypic switching but is also related to EndMT, and miR-92a-mediated EndMT is an important mechanism underlying neointimal formation in vein grafts.

Analysis of the variation pattern in left upper division veins and establishment of simplified vein models for anatomical segmentectomy.

BACKGROUND: Three-dimensional computed tomography bronchography and angiography (3D-CTBA) is a powerful tool to analyze pulmonary anatomy. We used 3D-CTBA to analyze variations of the pulmonary veins of the left upper division (LUD) and created a simplified LUD vein model. METHODS: Between January 2019 and October 2019, 124 patients with left-sided pulmonary lesions were admitted and underwent 3D-CTBA prior to surgery. We reviewed the anatomical variations of the LUD veins in these patients using 3D-CTBA images and classified them according to their position in relation to the bronchus. To facilitate this process, the same nomenclature as that used to describe the veins of the right upper lobe (RUL) is used for the LUD. RESULTS: The pattern of LUD veins could be classified into three forms: an anterior + central form, an anterior form and a central form. For the central form, V 1+2 a, V 1+2 b, V 1+2 c and V 1+2 d drained into V. cent. For the anterior form, V 1+2 d drained into V. ant. The anterior + central form could be further classified into three subtypes (V abc, V ab and V a). CONCLUSIONS: This is the first report to categorize the pattern of veins in the LUD. This may facilitate the creation of simplified models for use in pre-operative planning for segmentectomy.