Real-time, random-access organ screening for carbapenem-resistant organisms (CRO) reduces CRO-associated, donor-derived infection mortality in lung transplant recipients.

PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.

Transforming growth factor-ß1 induces epithelial-to-mesenchymal transition in human lung cancer cells via PI3K/Akt and MEK/Erk1/2 signaling pathways.

Metastasis of tumor cells is associated with epithelial-to-mesenchymal transition (EMT), which is a process whereby epithelial cells lose their polarity and acquire new features of mesenchyme. EMT has been reported to be induced by transforming growth factor-ß1 (TGF-ß1), but its mechanism remains elusive. In this study, we performed a study to investigate whether PI3K/Akt and MAPK/Erk1/2 signaling pathways involved in EMT in the human lung cancer A549 cells. The results showed that after treated with TGF-ß1 for 48 h, A549 cells displayed more fibroblast-like shape, lost epithelial marker E-cadherin and increased mesenchymal markers Vimentin and Fibronectin. Moreover, TGF-ß1-induced EMT after 48 h was accompanied by increased of cell migration and change of Akt and Erk1/2 phosphorylation. In addition, EMT was reversed by PI3K inhibitor LY294002 and MEK1/2 inhibitor U0126, which suggested that A549 cells under stimulation of TGF-ß1 undergo a switch into mesenchymal cells and PI3K/Akt and MAPK/Erk1/2 signaling pathways serve to regulate TGF-ß1-induced EMT of A549 cells.

Transforming growth factor-ß1 promotes lung adenocarcinoma invasion and metastasis by epithelial-to-mesenchymal transition.

Lung cancer is a highly malignant carcinoma, and most deaths of lung cancer are caused by metastasis. The alterations associated with epithelial-to-mesenchymal transition (EMT) may be related to the cancer cell metastasis. Nevertheless, the mechanism of lung cancer metastasis remains unclear. We conducted a study in vitro to investigate whether transforming growth factor-ß1 (TGF-ß1) could induce changes of, such as cell morphology, expression of relative protein markers, and cellular motile and invasive activities. In this research, the changes of cell morphology were first investigated under a phase contrast microscope, then western blotting was employed to detect the expression of E-cadherin, vimentin, and fibronectin, and finally cell motility and invasion were evaluated by cell wound-healing as well as invasion assays. The data indicated that human lung adenocarcinoma cell lines, A-549 and PC-9 cells of epithelial cell characteristics, were induced to undergo EMT by TGF-ß1. Following TGF-ß1 treatment, cells showed dramatic morphological changes assessed by phase contrast microscopy, accompanied by decreased epithelial marker E-cadherin and increased mesenchymal markers vimentin and fibronectin. More importantly, cell motility and invasion were also enhanced in the EMT process. These results indicated that TGF-ß1 may promote lung adenocarcinoma invasion and metastasis via the mechanism of EMT.

[Epithelial-mesenchymal transition (EMT) and its effect on microRNA expression in lung cancer].

OBJECTIVE: To investigate the effect of epithelial-mesenchymal transition (EMT) on the expression of microRNAs (miRNAs) in lung cancer A549 cells. METHODS: Transforming growth factor beta-1 (TGF-beta 1) in different concentrations was used to induce EMT in lung cancer A549 cells. The morphological changes were observed under phase-contrast microscope. The changes of EMT-related proteins were analyzed by Western blot. The changes of miRNAs expression after EMT were detected by microRNA (miRNA) array. Real time quantitative RT-PCR was applied to verify the reliability of miRNA array results. RESULTS: The lung cancer A549 cells became elongated and the cell-cell junction became loose after EMT. The epithelial protein marker E-cadherin was down-regulated and the mesenchymal protein markers vimentin and fibronectin up-regulated. There were 51 miRNAs showing statistically significant changes of expression more than double (P<0.05) after EMT. Among them 18 were up-regulated and 33 down-regulated. Of them, mir-33a was down-regulated by 92.8% and mir-193a-3p by 86.5%. Real time quantitative RT-PCR showed that mir-33a was down-regulated by 73.1% and mir-193a-3p by 56.6%. CONCLUSION: Epithelial-mesenchymal transition has effects on the expression of miRNAs, and miRNAs may regulate the invasion and metastasis of lung cancer cells via EMT.

[Video-assisted thoracic surgery lobectomy versus open lobectomy for mini pathologic N2 non-small cell lung cancer].

OBJECTIVE: To assess early and late outcomes of patients with minimal mediastinal lymph nodes metastasis N2 non-small cell lung cancer disease unexpectedly detected during the operation, who underwent video-assisted thoracic surgery lobectomy for clinical stage I. METHODS: This study retrospectively reviewed and analyzed the medical records of 263 patients underwent surgery between January 2004 and December 2007, who were diagnosed as having early-stage non-small cell lung cancer (clinical stage was cT1-2N0M0, stage I) before the surgery, but were found to have mini mediastinal lymph nodes metastasis disease (clinical stage was pT1-2N2M0, stage IIIa) unexpectedly detected during the operation and after the operation. All patients underwent lobectomy and systematic lymph nodes dissection as radical treatments. Among them, 63 patients underwent video-assisted thoracic surgery (VATS) lobectomy, including 37 male patients (58.7%) with a mean age of (58 ± 11) years old. Two hundred patients underwent open thoracotomy lobectomy, including 132 male patients (66%) with a mean age of (59 ± 11) years old. To compare and analyze clinical features, early and late outcomes of patients in these two groups. RESULTS: A total of 263 patients with an average survival time (34.9 ± 1.2) months (median 31 months), 63 cases in VATS lobectomy group with an average survival time (40.3 ± 2.2) months (median 37 months), 200 cases in open pulmonary lobectomy group with an average survival time (33.1 ± 1.3) months (median 29 months). The 1-, 2-, 3-year over survival rate of all the patients was 92.0%, 57.4%, 29.3%. The 1-, 2-, 3-year survival rate of patients in VATS lobectomy group was 92.1%, 82.5%, 41.3%. The 1, 2, 3 year survival rate of patients in thoracotomy lobectomy group was 92.0%, 49.5%, 25.5%. There was significant difference between the two groups in this factor (χ(2) = 5.58, P = 0.018). CONCLUSIONS: VATS lobectomy is feasibility and safety for unexpected mini N2 disease. Even if lymph node metastasis is unexpectedly detected during video-assisted thoracic surgery lobectomy for clinical stage I disease after rigorous evaluation of preoperative, it is no need to convert to conventional thoracotomy.

[Forensic medicine identification of manual strangulation: an analysis of 21 cases].

OBJECTIVE: To analyze and summarize the rule of manual strangulation, as well as to look for the key points of injury identification, in order to provide information for formulating and revising the identification regulations. METHODS: Twenty-one cases of manual strangulation from 1963 to 2004 in Xiangfan were reviewed and analyzed according to the characters, symptoms and appraisements. RESULTS: The majority of assaulters in manual strangulation was young adult male and often could find the counteracted wounds on them. The throttling mark reaction usually could be found in victims and the cardinal symptoms were contusion in throat and asphyxiation in ocular region. CONCLUSION: The degree of injuries is mainly moderate and slight. There is some inadaptability in the current regulations.