Preoperative acute lung injury and oxygenation impairment occurred in the patients with acute aortic dissection.

Acute lung injury (ALI) and oxygenation impairment (OI) frequently occur in the patients with acute aortic dissection (AAD), which may necessitate mechanical ventilation and result in adverse outcomes. This paper aims to increase clinicians' awareness of the severe respiratory complications in the patients with AAD, and provide the overview of the epidemiology, adverse outcomes, pathogenesis, predictive markers and therapeutic modalities of the concurrent conditions. Currently, it is considered that inflammatory response plays a great role in the pathogenesis of ALI and OI in the patients with AAD, but the definite pathogenesis remains unclear. Given the great importance of the prediction of the occurrence of the severe respiratory complication at a very early stage, some inflammatory biomarkers have been investigated to predict the occurrence of ALI and OI in several studies. C-reactive protein was found to have a significant predictive effect for the development of ALI and OI. Early use of beta-blockers and the use of bindarit could prevent the occurrence of OI and ALI. Ulinastatin could also improve oxygenation in the patients with type-A AAD. Prevention and management of ALI and OI in AAD remain a great challenge. The definite pathogenesis should be clearly clarified and further studies should be performed to look for potential effective way to predict and manage the severe respiratory conditions.

CX3 CL1 promotes tumour cell by inducing tyrosine phosphorylation of cortactin in lung cancer.

It has been reported that chemokine CX3 CL1 can regulate various tumours by binding to its unique receptor CX3 CR1. However, the effect of CX3 CL1-CX3 CR1 on the lung adenocarcinoma and lung squamous cell carcinoma is still unclear. Here, we showed that CX3 CL1 can further invasion and migration of lung adenocarcinoma A549 and lung squamous cell carcinoma H520. In addition, Western blot and immunofluorescence test indicated CX3 CL1 up-regulated the phosphorylation level of cortactin, which is a marker of cell pseudopodium. Meanwhile, the phosphorylation levels of c-Src and c-Abl, which are closely related to the regulation of cortactin phosphorylation, are elevated. Nevertheless, the src/abl inhibitor bosutinib and mutations of cortactin phosphorylation site could inhibit the promotion effect of CX3 CL1 on invasion and migration of A549 and H520. Moreover, these results of MTT, Hoechst staining and Western blot suggested that CX3 CL1 had no effect on the proliferation and apoptosis of A549 and H520 in vitro. The effects of CX3 CL1 were also verified by the subcutaneous tumour formation in nude mice, which showed that it could promote proliferation and invasion of A549 in vivo. In summary, our results indicated that CX3 CL1 furthered invasion and migration in lung cancer cells partly via activating cortactin, and CX3 CL1 may be a potential molecule in regulating the migration and invasion of lung cancer.

Caveolin-1 Deficiency Induces Atrial Fibrosis and Increases Susceptibility to Atrial Fibrillation by the STAT3 Signaling Pathway.

ABSTRACT: Atrial fibrillation (AF) is a common arrhythmia in the clinic. Ablation failure and recurrence after cardioversion have become medical problems worldwide. An important pathological feature of AF is atrial fibrosis, which increases susceptibility to AF. As an important target of fibrosis signal integration, the signal transducer and activator of transcription 3 (STAT3) signaling pathway plays an important role in fibrosis. Caveolin-1 (CAV1), a cell membrane protein, is involved in a variety of the biological functions of cells. However, the role of CAV1 in atrial fibrosis remains unclear. In this study, Masson's trichrome staining was used to detect the degree of atrial fibrosis, and the expression of CAV1 in the human atrium was evaluated by immunohistochemistry. To further study the role of CAV1, its expression in cultured rat atrial fibroblasts was silenced using siRNAs. Atrial fibroblasts were treated with angiotensin II to observe the effects on CAV1 and the transforming growth factor-ß1 and STAT3 signaling pathways. We also detected the effects of CAV1 scaffolding domain (CSD) peptide on fibrosis through the addition of exogenous CSD peptide. The results showed that CAV1 expression decreased with the aggravation of atrial fibrosis and that this effect increased the incidence of AF. The depletion of CAV1 induced excessive extracellular matrix deposition by activating the STAT3 and transforming growth factor-ß1/SMAD2 signaling pathways, and this effect was exacerbated by stimulation with angiotensin II and improved by CSD peptide. These data suggested that CAV1 not only plays a critical role in fibrosis progression but also provides a target for the treatment of atrial fibrosis and AF.

A novel localization technique for peripheral ground glass opacity using geometric parameters measured on CT images.

BACKGROUND: Currently no optimal localization technique has been established for localization of ground glass opacity (GGO). We aimed to introduce a localization technique using geometric localization for peripheral GGO. METHODS: We delineated the location of pulmonary GGO using geometric method which was similar with localization of a point in a spatial coordinate system. The localization technique was based on the anatomical landmarkers (ribs or intercostal spaces, capitulum costae and sternocostal joints). The geometric parameters were measured on preoperative CT images and the targeted GGO could be identified intraoperatively according to the parameters. We retrospectively collected the data of the patients with peripheral GGOs which were localized using this method and were wedge resected between June 2019 and July 2020. The efficacy and feasibility of the localization technique were assessed. RESULTS: There were 93 patients (male 34, median = 55 years) with 108 peripheral GGOs in the study. All the targeted GGOs were successfully wedge resected in the operative field with negative surgical margin at the first attempt. For each GGO, the localization parameters could be measured in 2-4 min (median = 3 min) on CT images before operation, and surgical resection could be completed in 5-10 min (median = 7 min). A total of 106 (98.15%) GGOs achieved sufficient resection margin. No complications and deaths occurred related to the localization and surgical procedure. CONCLUSIONS: The localization technique can achieve satisfactory localization success rate and good safety profile. It can provide an easy-to-use alternative to localize peripheral GGO.

Galectin-3 Induces Atrial Fibrosis by Activating the TGF-ß1/Smad Pathway in Patients with Atrial Fibrillation.

BACKGROUND: Atrial fibrosis plays a critical role in the occurrence and maintenance of atrial fibrillation. The role of TGF-ß1 in mediating atrial fibrosis is well documented. The ß-galactoside-binding lectin galectin-3 (Gal-3) is mainly produced by macrophages in biological events such as inflammation and angiogenesis. Previous studies have shown that Gal-3 is associated with atrial fibrosis, but the relationship between TGF-ß1 and Gal-3 in atrial fibrosis remains unclear. OBJECTIVE: To determine whether Gal-3 induces atrial fibrosis and atrial fibrillation by activating the TGF-ß1/Smad pathway and whether the expression of Gal-3 is mediated by TGF-ß1, which can enable assessing the relationship between Gal-3 and TGF-ß1 in atrial fibrosis. METHODS: In this study, 30 patients' right atrial appendages were collected and divided into 3 groups: congenital heart disease sinus rhythm group (n = 10, as a control group), rheumatic heart disease sinus rhythm group (n = 10), and rheumatic heart disease atrial fibrillation group (n = 10). Rat atrial fibroblasts were cultured in vitro, and recombinant Gal-3 and recombinant TGF-ß1 proteins were added to the cell culture. The expression of Gal-3, TGF-ß1, Smad2, and collagen I was detected by Western blotting and quantitative real-time PCR. Atrial tissues were stained with Masson's trichrome stain to evaluate the extent of atrial fibrosis. The expression of Gal-3 and TGF-ß1 was detected by immunohistochemical staining and immunofluorescence staining. Gal-3 and TGF-ß1 interaction was demonstrated by immunoprecipitation. RESULTS: The expression levels of Gal-3, TGF-ß1, Smad2, and collagen I were elevated in the rheumatic heart disease atrial fibrillation group compared with the congenital heart disease sinus rhythm group and the rheumatic heart disease sinus rhythm group. In cultured atrial fibroblasts, there is a synergistic interaction between Gal-3 and TGF-ß1. Gal-3 stimulated the TGF-ß1/Smad pathway, and overexpression of TGF-ß1 induced Gal-3 expression. CONCLUSIONS: Gal-3 and TGF-ß1 interact with each other and stimulate the downstream TGF-ß1/Smad pathway. This finding suggests that Gal-3 could be an important factor in TGF-ß1-induced fibrosis in atrial fibrillation.

Predictors for the development of preoperative oxygenation impairment in acute aortic dissection in hypertensive patients.

BACKGROUND: Acute aortic dissection (AAD) is an acute life-threatening cardiovascular disease, which is frequently complicated with oxygenation impairment (OI). We aim to investigate predictors of the development of OI in the patients with AAD. METHODS: We retrospectively collected clinical data of AAD in hypertensive patients from July 2012 to March 2020. The patients included in this study were divided into OI (+) group (oxygenation index≤200) and OI (-) group (oxygenation index> 200). Both groups were compared according to demographic and clinical characteristics, and laboratory findings. Characteristics of hypertension in the patients with AAD were described. Predictors for the development of OI were assessed. And cutoff values were determined by receiver operating characteristics (ROC) curve. RESULTS: A total of 208 patients were included in this study and the incidence of OI was 32.2%. In OI (+) group, patients had significantly higher peak body temperature (37.85 ± 0.60 vs 37.64 ± 0.44 °C, P = .005), higher levels of CRP (42.70 ± 28.27 vs 13.90 ± 18.70 mg/L, P = .000) and procalcitonin (1.07 ± 3.92 vs 0.31 ± 0.77µg/L, P = .027), and lower levels of albumin (34.21 ± 5.65 vs 37.73 ± 4.70 g/L, P = .000). Spearman's rank correlation test showed that the minimum oxygenation index was positively correlated with albumin, and was negatively correlated with the peak body temperature, serum CRP, procalcitonin, BNP and troponin. The stepwise multiple linear regression analysis showed that the peak body temperature, serum CRP and albumin were independently associated with development of OI. An optimal cutoff value for CRP for predicting OI was ≥9.20 mg/L, with a sensitivity of 91.0% and a specificity of 61.0%. CONCLUSIONS: The peak body temperature, serum CRP and albumin were independent predictors of OI development in the patients with AAD. The serum CRP on admission≥9.20 mg/L might be a valuable and reliable indicator in predicting the development of OI.

Robot-assisted versus laparoscopic-assisted surgery for colorectal cancer: a meta-analysis.

BACKGROUND AND OBJECTIVES: Robotic surgery is positioned at the cutting edge of minimally invasive management of colorectal cancer. We performed a meta-analysis of data from randomized controlled trials (RCTs) and non-RCTs (NRCTs) that compared the clinicopathological outcomes of robotic-assisted colorectal surgery (RACS) with those of laparoscopic-assisted colorectal surgery (LACS). Inferences on the feasibility and the relative safety and efficacy have been drawn. METHODS: A literature search for relevant studies was performed on MEDLINE, Ovid, Embase, Cochrane Library, and Web of Science databases. Inter-group differences in the standardized mean differences and relative risk were assessed. Operation times, conversion rates to open surgery, estimated blood loss (EBL), early postoperative morbidity, and length of hospital stay (LHS) were compared. Oncologic outcomes assessed were number of lymph nodes harvested and lengths of proximal and distal resection margins. RESULTS: Twenty-four studies (2 RCTs and 22 NRCTs [5 prospective plus 17 retrospective]) with a total of 3318 patients were included. Of these, 1466 (44.18 %) patients underwent RACS and 1852 (55.82 %) underwent LACS. Conversion rates, EBL and LHS were significantly lower, while the operation times and total costs were similar between RACS and LACS. Complication rates and oncological accuracy of resection showed no significant difference. CONCLUSION: Based on this meta-analysis, RACS appears to be a promising surgical approach with its safety and efficacy comparable to that of LACS in patients undergoing colorectal surgery. Further studies are required to evaluate the long-term cost-efficiency as well as the functional and oncologic outcomes of RACS.

Value of C-reactive protein/albumin ratio in predicting the development of preoperative oxygenation impairment in patients with Stanford type-B acute aortic dissection.

Objectives: We aimed to assess the predicting value of C-reactive protein (CRP)/albumin ratio (CAR) in the development of Oxygenation impairment (OI) in the patients with Stanford type-B acute aortic dissection (AAD). Methods: This study included 133 patients (age = 58.8 ± 12.0 years, median age = 61 years, Male/Female = 117/16) diagnosed as Stanford type-B AAD accompanied by hypertension from July 2012 to May 2020. Clinical data were retrospectively extracted from the database. The patients in this study were divided into OI group (oxygenation index ≤ 200) and non-OI group (oxygenation index > 200). Clinical characteristics in both groups were compared, and predicting value of CAR in the development of OI was assessed. Results: Patients in OI group had higher peak body temperature (37.94 ± 0.62 vs. 37.67 ± 0.51 ℃, P =.010), higher levels of serum CRP (41.74 ± 27.71 vs 15.21 ± 19.66 mg/L, P =.000) and plasma B-type natriuretic peptide (292.14 ± 251.11 vs 179.80 ± 241.27 ng/L, P =.016), lower levels of albumin (34.00 ± 5.14 vs 37.72 ± 5.24 g/L, P =.000), and higher CAR (1.27 ± 0.89 vs 0.41 ± 0.53, P =.000). In multivariate regression analysis, CAR (odds ratio: 5.215, 95 % CI: 2.682; 10.137, P =.000) and the peak body temperature (odds ratio: 2.905, 95 % CI: 1.255; 6.724, P =.013) could significantly predict the OI development. The AUC for CAR was 0.831 (95 % CI: 0.756-0.907). An optimal cutoff value for CAR for predicting OI was ≥ 0.70, with a sensitivity of 67.5 % and a specificity of 88.2 %. Conclusions: Compared with CRP or albumin alone, the CAR might be a more accurate marker in predicting OI development in Stanford type-B AAD.

A new colorectal/coloanal anastomotic technique in sphincter-preserving operation for lower rectal carcinoma using transanal pull-through combined with single stapling technique.

PURPOSE: This study aims to introduce a new anastomotic technique-transanal pull-through combined with single stapling technique (PT-SST), and evaluate the value in the sphincter-preserving operation for lower rectal carcinoma. METHODS: Between January 2004 and September 2011, 131 consecutive patients had sphincter-preserving operations using PT-SST and double stapling technique (DST) for low colorectal anastomosis. The data was prospectively collected. RESULTS: There are 45 patients (male 26, median = 55 years) in PT-SST group and 86 (male 46, median = 55 years) in the DST group. Anastomotic leakage took place in three patients in DST group, while no anastomotic leakage happened in PT-SST group. There are recurrences in pelvic cavity for one patient (2.2 %), in anastomotic stoma for no patient, and hepatic metastasis for four patients (8.9 %) in PT-SST group; while there are recurrences in pelvic cavity for three patients (3.5 %), in anastomotic stoma for two patients (2.3 %), and hepatic metastasis for seven patients (8.1 %) in DST group. No significant difference was indicated in the terms of the recurrence and hepatic metastasis between the two groups. Patients were satisfied with functional results. CONCLUSIONS: This new technique can solve some technique problems of DST and has at least comparable outcomes compared with DST. It is a safe and feasible procedure for performing low anastomosis with high rate of sphincter preservation. It can be used especially for patients with small pelvis.

PGRN exacerbates the progression of non-small cell lung cancer via PI3K/AKT/Bcl-2 antiapoptotic signaling.

Progranulin (PGRN) is a growth factor that is involved in the progression of multiple tumors. However, the effects and molecular mechanisms by which PGRN induces lung cancer remain unclear. The expression level of PGRN was analyzed by conducting immunohistochemistry of the histological sections of lung tissues from non-small-cell lung carcinoma (NSCLC) patients. The proliferation, apoptosis, migration, and invasion of NSCLC cells were assessed by the MTT assay, Western blot, degree of wound healing, and Transwell assays. A nude mouse xenograft model was used to validate the role of PGRN in vivo. The expression level of PGRN was higher in male patients with lung adenocarcinoma than in those with lung squamous cell carcinoma; by contrast, no difference was observed in female patients. The overexpression of PGRN promoted the proliferation and anti-apoptosis of H520 (derived from lung squamous cell carcinoma) cells, whereas knockdown of PGRN inhibited the proliferation and anti-apoptosis of A549 (derived from lung adenocarcinoma) cells. Copanlisib (targeting PI3K) inhibited the increase in the expression of cell anti-apoptosis marker Bcl-2 induced by rhPGRN protein; the PI3K agonist 740 Y-P partially reversed the decrease in Bcl-2 expression induced by PGRN deficiency in both A549 and H520 cells. PGRN increased the expression of Ki-67, PCNA, and Bcl-2 in vivo. PGRN inhibited cell apoptosis depending on the PI3K/Akt/Bcl-2 signaling axis; PGRN positivity correlated with lung adenocarcinoma. PGRN is a potential biomarker for the treatment and diagnosis of NSCLC, especially in lung adenocarcinoma.

MG53/CAV1 regulates transforming growth factor-ß1 signaling-induced atrial fibrosis in atrial fibrillation.

Atrial fibrosis plays a significant role in the development of atrial fibrillation (AF). Previously, we showed that mitsugumin 53 (MG53) regulates TGF-ß1 signaling pathway-induced atrial fibrosis. Recent studies have shown that caveolin-1 (CAV1) is an important anti-fibrosis signaling mediator that inhibits the TGF-ß1 signaling pathway. Here, we further study the mechanism underlying the related action of MG53 and CAV1. We demonstrate that CAV1 expression was decreased while MG53 expression was increased in atrial tissue from AF patients. In cultured atrial fibroblasts, MG53 depletion by siRNA caused CAV1 upregulation and TGF-ß1/SMAD2 signaling pathway downregulation, while MG53 overexpression via adenovirus had the opposite effect. CAV1 inactivated the TGF-ß1/SMAD2 signaling pathway. In addition, using an Ang II-induced fibrosis model, we show that MG53 regulates TGF-ß1 signaling via CAV1. Therefore, CAV1 is critical for the MG53 regulation of TGF-ß1 signaling pathway-induced atrial fibrosis in AF. These findings reveal the related underlying mechanism of action of MG53 and CAV1 and provide a potential therapeutic target for fibrosis and AF.

Ciprofloxacin promotes polarization of CD86+CD206­ macrophages to suppress liver cancer.

Gut microbiota can promote tumor development by producing toxic metabolites and inhibiting the function of immune cells. Previous studies have demonstrated that gut microbiota can reach the liver through the circulation and promote the occurrence of liver cancer. Ciprofloxacin, an effective broad­spectrum antimicrobial agent, can promote cell apoptosis and regulate the function of immune cells. As an important part of the tumor microenvironment, macrophages play an important role in tumor regulation. The present study demonstrated that the treatment of macrophages with ciprofloxacin was able to promote the production of interleukin­1ß, tumor necrosis factor­α and the polarization of CD86+CD206­ macrophages, while inhibiting the polarization of CD86­CD206+ macrophages. This transformation may help macrophages promote tumor cell apoptosis, inhibit tumor cell proliferation, reduce metastasis and downregulate the phosphoinositide 3­kinase/AKT signaling pathway in liver cancer cell lines. In vivo experiments demonstrated that macrophages treated with ciprofloxacin inhibited the growth of subcutaneous implanted tumors in nude mice. In conclusion, the findings of the present study indicated that ciprofloxacin may inhibit liver cancer by upregulating the expression of CD86+CD206­ macrophages. This study further revealed the biological mechanism underlying the potential value of ciprofloxacin in antitumor therapy and provided new targets for the treatment of liver cancer.