Research Note: Synergistic effect of isopropoxy benzene guanidine and colistin against mcr-1-positive Escherichia coli in vitro and in duck intestine infection models.

Colistin (CST) is considered as "agent of last resort" against gram-negative bacteria as feed additive. Its clinical effectiveness has reduced since the emergence of mcr-1 gene in ducks. Isopropoxy benzene guanidine (IBG), a new guanidine derivative, showed positive effects on improving animal weights and alleviating intestinal pathogens, therefore, the objective of this study was to evaluate the effect of this compound supplement with CST in ducks and explore the possibilities in feed additive. A total of fifteen duck-origin Escherichia coli carrying the mcr-1 gene were included in this study. A checkerboard microdilution assay was used to evaluate the in vitro antibacterial activity of IBG combined with CST against mcr-1-positive E. coli. A 3-by-2 time-kill array of IBG (16, 32, and 64 µg/mL) and CST (1/2 MIC and 1/4 MIC) over 24 hours was utilized to characterize the activity of the agents alone and in combination against E. coli strain 1 in vitro. The intestinal colonization model was used to evaluate the in vivo effect of IBG combined with CST. These results indicated that the combination of IBG plus CST showed a synergistic effect against all clinical isolates (FICI < 0.5). The bacterial burden was reduced by more than 2 log10 CFU/mL when E. coli strain 1 was tested with 1/2 MIC CST plus 64 µg/mL IBG for 24 h. Further experiments in vivo demonstrated that the CST combined with IBG was able to increase duck weights, reduced intestinal pathogenic E. coli and showed a synergistic antibacterial effect. Combination of CST (4 mg/kg b.w.) plus IBG (32 or 64 mg/kg b.w.) achieved 1.84 to 3.29 log10 CFU/g killing after 7 d of therapy, which was significantly different from that in the challenge control group (p<0.05). In summary, our study demonstrated the potential use of IBG as feed additive for veterinary purposes in ducks and provided new insights into overcoming resistance in the future.

Neoadjuvant immunotherapy combined with chemotherapy significantly improved patients' overall survival when compared with neoadjuvant chemotherapy in non-small cell lung cancer: A cohort study.

Background: Programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors displayed considerable advantages in neoadjuvant therapy of non-small cell lung cancer (NSCLC), but the specific application of neoadjuvant immunotherapy has not been well determined, and the long-term prognostic data of neoadjuvant immunochemotherapy combined with surgical resection of NSCLC remains limited. In this study, we intended to assess the efficacy of the neoadjuvant therapy of the PD-1 inhibitor and long-term prognosis in patients with resectable NSCLC. Methods: We retrospectively analyzed NSCLC surgical patients treated with neoadjuvant therapy in our hospital, and divided them into a neoadjuvant chemotherapy group and a neoadjuvant immunotherapy combined with chemotherapy group. The propensity score matching method was used to evaluate the effectiveness of immunotherapy combined with chemotherapy in the treatment of resectable lung cancer, and the long-term prognosis of these two groups was compared. Results: A total of 62 cases were enrolled, including 20 patients (20/62, 32.26%) in the immunotherapy group and 42 patients (42/62, 67.74%) in the chemotherapy group. The clinical baseline data of these two groups were balanced. In the immunotherapy group, all patients had tumor regression in imaging finding (tumor regression ratio: 11.88% - 75.00%). In the chemotherapy group, 30 patients had tumor regression (tumor regression ratio: 2.70% - 58.97%). The R0 removal rates of cancers were comparable between the immunotherapy group and chemotherapy group (19/20, 95.00% vs. 39/42, 92.86%, P=1.000). The two groups were balanced in complete minimally invasive surgery, pneumonectomy, operative duration, blood loss, postoperative complications, and hospital stay. The immunotherapy group had more sleeve resection (36.84% vs. 10.26%, p=0.039) including bronchial sleeve and vascular sleeve, higher pathological complete response (pCR) rate (57.89% vs. 5.13%, P<0.001) and major pathologic response (MPR) rate (78.95% vs. 10.26%, P<0.001). There were no differences in survival curves for: smoker and non-smoker, squamous cell carcinoma and adenocarcinoma, or right lung cancer and left lung cancer. Moreover, patients who achieved MPR (including pCR) had significantly better overall survival (OS) and disease-free survival (DFS). Patients in immunotherapy group had significantly better OS and longer DFS than those in chemotherapy group. Conclusions: In conclusion, neoadjuvant immunotherapy combined with chemotherapy can provide better OS and DFS and improving pCR and MPR rates by shrinking tumors.This study has been registered in the Chinese Clinical Trial Registry, number ChiCTR2200060433. http://www.chictr.org.cn/edit.aspx?pid=170157&htm=4.

Discovery of a Potent and Selective ATAD2 Bromodomain Inhibitor with Antiproliferative Activity in Breast Cancer Models.

ATAD2 is an epigenetic bromodomain-containing target which is overexpressed in many cancers and has been suggested as a potential oncology target. While several small molecule inhibitors have been described in the literature, their cellular activity has proved to be underwhelming. In this work, we describe the identification of a novel series of ATAD2 inhibitors by high throughput screening, confirmation of the bromodomain region as the site of action, and the optimization campaign undertaken to improve the potency, selectivity, and permeability of the initial hit. The result is compound 5 (AZ13824374), a highly potent and selective ATAD2 inhibitor which shows cellular target engagement and antiproliferative activity in a range of breast cancer models.

Whole-genome epidemiology and characterisation of mcr-1-encoding Escherichia coli in aquatic bird farms from the Pearl River Delta, China, 2019-2020.

Due to their unique breeding pattern, aquatic bird farms are increasingly considered as hotspots in the development and spread of antimicrobial resistance. However, comprehensive studies addressing the whole-genomic features of colistin-resistant bacteria in aquatic bird farms are scarce. Over a 2-year period, we conducted surveillance to determine the whole-genome epidemiology and characterisation of mcr-1-positive Escherichia coli in aquatic bird farms in southeastern coastal China. A total of 100 mcr-1-producing isolates among 654 E. coli strains were recovered from 781 samples collected in 11 aquatic bird farms and 1 veterinary clinic in the Pearl River Delta area. Higher resistance phenotypes to 17 antibiotics were found in mcr-1-positive isolates compared with other isolates. Subsequently, 20 mcr-1-carrying isolates were sequenced to analyse the whole-genomic features. Molecular typing as well as antimicrobial resistance gene and virulence factor profiles of the isolates showed considerable diversity. Three types of genetic backbones of mcr-1 in the isolates were assembled and were identified in diverse broad-host-range plasmids and bacterial species. Pangenome analyses revealed a large genetic pool composed of the isolates. Furthermore, phylogenetic trees both of the isolates in this study and a global data set were built, indicating the spread of the three mcr-1 backbones and the mcr-1-positive isolates among different habitats, farms and even countries. This study highlights that aquatic bird farms may act as an important reservoir for mcr-1-producing E. coli, from which colistin resistance may be spread to diverse habitats, different geographical locations and even across bacterial species.

[Effect of A High Intensive Preoperative Rehabilitation on the Perioperative 
Complications in Patients with Chronic Obstructive Pulmonary Disease Eligible 
for Lung Cancer Surgery].

BACKGROUND: Chronic obstructive pulmonary disease (COPD) will reduce the cardiopulmonary function and increase perioperative risk. The aim of this study is to investigate the effect of preoperative short-term high intensity lung rehabilitation training on lung function and postoperative complications in patients with COPD who are eligible for lung cancer surgery. METHODS: We analysis of 101 patients with COPD and a diagnosis of lung cancer, with 43 patients in pulmonary rehabilitation group and 58 patients in conventional group. The pulmonary function, postoperative pulmonary complications (PPCs) and length of stay (LOS) will be compared between the two groups, the lung function will be compared before and after the rehabilitation at the same time. RESULTS: There were no significant difference between the two groups in general information, lung function before surgery, postoperative pulmonary infection [8 (18.6%) vs 17 (29.3%)], atelectasis [1 (2.3%) vs 1 (1.7%)], respiratory failure [1 (2.3%) vs 2 (3.4%)] and postoperative LOS [(8.93±3.78) d vs (9.62±3.98) d, P>0.05]. In the rehabilitation group, the FEV1 [(2.06±0.45) L vs (2.15±0.45) L, P<0.001] and PEF [(4.32±0.90) L/s vs (5.15±1.05) L/s, P<0.001) were higher, and PCO2 [(42.42±2.79) mmHg vs (41.58±2.98) mmHg, P=0.009] was lower after rehabilitation, significantly. The increase value of FEV1 in moderate to severe COPD group was higher than that of the mild COPD group after the rehabilitation [(0.16±0.05) L, 8.6% vs (0.06±0.05) L, 2.8%, P<0.001). CONCLUSIONS: The short-term highly-intensity lung rehabilitation can improve lung function in lung cancer patients with COPD, and the improvement of pulmonary function in moderate to severe COPD patients is more obviously.

Thoracoscopic and laparoscopic radical esophagectomy with lateral-prone position.

With 20 years of development, minimally-invasive treatment for esophageal cancer has been widely spread. However, surgeons have not reached consensus about the optimal minimally-invasive operation method, or whether the effect of radical lymph nodes dissection is comparable to the traditional open procedure. Thoracoscopic esophagectomy with lateral-prone position combines the advantages of both lateral position (allowing quick conversion to open procedure) and prone position (good visual area and complete lymphadenectomy). Together with laparoscopic abdominal lymphadenectomy, gastric tube formation and jejunostomy, this approach provides an easier way for minimally-invasive radical esophagectomy. In this article, approaches for thoracoscopic esophagectomy with lateral-prone position and total mediastinal lymphadenectomy, combined with totally laparoscopic gastric mobilization, abdominal lymphadenectomy, gastric tube formation and jejunostomy, will be presented by video instructions. All the procedures were under the rule of radical lymphadenectomy. Cervical lymph nodes dissection and esophago-gastrostomy were the same as those in open procedure, which will not be discussed here.

CYP1A2 rs762551 polymorphism contributes to risk of lung cancer: a meta-analysis.

Previous studies proposed that CYP1A2 rs762551 polymorphism might be associated with risk of lung cancer by influencing the function of CYP1A2. However, previous studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer reported inconsistent findings. We performed a meta-analysis of the published case-control studies to assess the association between CYP1A2 rs762551 polymorphism and risk of lung cancer. PubMed and Embase were searched to identify relevant studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer, and seven studies with a total of 3,320 subjects were finally included into the meta-analysis. The pooled odds ratio (OR) and 95 % confidence interval (95%CI) was calculated to evaluate the association. Meta-analysis of total studies showed that CYP1A2 rs762551 polymorphism contributed to risk of lung cancer under all four genetic models (C versus A: OR = 1.26, 95%CI 1.13 to 1.40, P < 0.001; CC versus AA: OR = 1.61, 95%CI 1.28 to 2.04, P < 0.001; CC versus AA/AC: OR = 1.52, 95%CI 1.11 to 2.09, P = 0.009; CC/AC versus AA: OR = 1.28, 95%CI 1.10 to 1.48, P = 0.001). Subgroup analysis based on ethnicity further suggested that CYP1A2 rs762551 polymorphism was associated with risk of lung cancer in Caucasians. These results from the meta-analysis suggest that CYP1A2 rs762551 polymorphism contributes to risk of lung cancer.

One surgeon's learning curve for video-assisted thoracoscopic esophagectomy for esophageal cancer with the patient in lateral position: how many cases are needed to reach competence?

BACKGROUND: Minimally invasive esophagectomy is a feasible technique shown to be safe and oncologically adequate for the treatment of esophageal cancer. This study aimed to describe one surgeon's learning curve for video-assisted thoracoscopic esophagectomy with the patient in lateral position. METHODS: From May 2010 to June 2012, 89 thoracoscopic esophagectomies for esophageal cancer were performed by one surgeon. The patients were divided into three groups. Group A included the first 30 cases. Group B comprised cases 31 to 60, and group C included the final 29 cases. The demographic characteristics and the intra- and postoperative variables were collected retrospectively and analyzed. RESULTS: One postoperative death occurred. Eight patients required conversion. No significant difference in background or clinicopathologic factors among the three groups was observed. Compared with group A, a significant decrease in intrathoracic operative time (107.7 ± 16.2 min; P = 0.0000), total operative time (326.3 ± 40.7 min; P = 0.0002), and blood loss (290.8 ± 114.3 ml; P = 0.0129) was observed in group B, whereas more retrieved nodes were harvested (20.1 ± 9.5; P = 0.0002). The last 29 patients (group C) involved significantly less intrathoracic operative time (82.8 ± 18.4 min; P = 0.0386), total operative time (294.7 ± 37.4 min; P = 0.0009), and blood loss (234.7 ± 87.8 ml; P = 0.0125) as well as a shorter postoperative hospital stay (12.4 ± 3.7 days; P = 0.0125) compared with group B. A significant decline in the overall morbidity from group A to group C (P = 0.0005) also was observed. CONCLUSIONS: The results of this study suggest that at least 30 cases were needed to reach the plateau of thoracoscopic esophagectomy. After more than 60 cases of thoracoscopic esophagectomies had been managed, lower morbidity could be obtained.

Transcriptome network analysis reveals potential candidate genes for esophageal squamous cell carcinoma.

The esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with a poor prognosis. Understanding molecular changes in ESCC should improve identification of risk factors with different molecular subtypes and provide potential targets for early detection and therapy. Our study aimed to obtain a molecular signature of ESCC through the regulation network based on differentially expressed genes (DEGs). We used the GSE23400 series to identify potential genes related to ESCC. Based on bioinformatics we constructed a regulation network. From the results, we could establish that many transcription factors and pathways closely related with ESCC were linked by our method. STAT1 also arose as a hub node in our transcriptome network, along with some transcription factors like CCNB1, TAP1, RARG and IFITM1 proven to be related with ESCC by previous studies. In conclusion, our regulation network provided information on important genes which might be useful in investigating the complex interacting mechanisms underlying the disease.

Prevention of postoperative chylothorax with thoracic duct ligation during video-assisted thoracoscopic esophagectomy for cancer.

BACKGROUND: Minimally invasive esophagectomy (MIE) is a feasible technique that has been shown to be safe for the treatment of esophageal cancer. Chylothorax remains a challenging and potentially life-threatening postoperative complication of MIE. In this retrospective series, we evaluated the results of preventive intraoperative thoracic duct ligation in patients who underwent video-assisted thoracoscopic esophagectomy for cancer. METHODS: From May 2009 to June 2010, 70 video-assisted thoracoscopic esophagectomies for cancer of the esophagus (group A) were performed without prophylactic thoracic duct ligation. Since June 2010, 65 patients (group B) with esophageal cancer underwent video-assisted thoracoscopic esophagectomy with routine ligation of the thoracic duct during the operation. RESULTS: No intraoperative or postoperative complications directly related to thoracic duct ligation were recorded. Postoperative chylothorax occurred in seven patients in group A and in one patient in group B (P = 0.0375). CONCLUSIONS: The results of this study suggest that thoracic duct ligation during video-assisted thoracoscopic esophagectomy for cancer is an effective and safe method for prevention of postoperative chylothorax.

Retrospective analysis for thirty-nine patients with solitary fibrous tumor of pleura and review of the literature.

BACKGROUND: Solitary fibrous tumor of the pleura (SFTP) is an uncommon neoplasm arising from mesenchymal cells. The aim of this study is to summarize the experience and the outcome of the surgical treatment for 39 cases of SFTP. METHODS: From January 2004 to December 2008, 39 patients underwent surgical resection of SFTP in our department. All patients had clinical follow-up by the same team of surgeons. The mean follow-up was 40.3 months. RESULTS: A local removal of the neoplasm was accomplished by video-assisted thoracic surgery (VATS) in 9 patients (group A) and by thoracotomy in 30 patients (group B) respectively. Comparing with group B, operations in group A took significantly less operative time, blood loss and spent less time in the intensive care unit and hospital. All specimens were positive for CD34 and Bcl-2. One patient developed recurrence, and the remaining 38 patients are alive and disease free at the end of follow-up. CONCLUSIONS: Malignant SFTP still had the potential recurrence. VATS represents the more acceptable choice for the selected patients with SFTP.

[Application of cardiopulmonary bypass during extended resection of locally advanced lung cancer].

BACKGROUND: Locally advanced lung cancer includes IIIA and IIIB lung cancer that tumors are localized within the chest and with no clinic and pathologic distal metastasis. In this study the results of extended resection of a portion of heart or great vessels with cardiopulmonary bypass was summarized in the treatment of locally advanced lung cancer. METHODS: Lobectomy or pneumonectomy combined with extended partial excision of the heart or great vessels were carried out in 10 patients with locally advanced lung cancer. The operations included aortic resection and reconstruction with left heart bypass in 2 cases, extended resection of left atrium with normal cardiopulmonary bypass in 5 cases, and resection and reconstruction of superior vena cava in 3 cases respectively. RESULTS: The patients had no operative complication except for one haemothorax, which was controlled by re-exploration. One patient died of brain metastasis 6 months after operation and another one died of multiple metastasis 26 months after operation. The others were alive. CONCLUSIONS: CPB is a safe and effective anesthetic procedure during extended resection of locally advanced lung cancer although it is controversial for aggravating operative trauma, complex technique and higher cost.

[Sequential variation of pulmonary flow spectrum and its value on the evaluation of risk for pulmonary resection in perioperative patients with lung cancer].

BACKGROUND: To explore the sequential variation of pulmonary flow spectrum and its value on evaluation of risk for pulmonary resection in perioperative patients with lung cancer. METHODS: Forty-nine patients with lung cancer who underwent pneumonectomy (12 cases) and lobectomy (37 cases) were observed for the values of Doppler pulmonary flow spectrum before operation, on the 3-5 days and 8-10 days postoperatively. Moreover the patients were divided into different groups according to the different operative procedures and with or without postoperative cardiac arrhythmia. RESULTS: Doppler pulmonary flow spectrum changed in all cases who underwent pneumonectomy and lobectomy from 3 to 5 days postoperatively. These changs included prolonged preejection period (PEP), shortened acceleration time (ACT), increased PEP/ACT ratio, increased pulmonary artery mean pressure (PAMP), and increased pulmonary vascular resistance (PVR). There were significant differences comparing with those before operation ( P < 0.01). The patients who underwent lobectomy recovered to the same level of pre operation on the 8th to 10th postoperative days. However, the changes of pulmonary flow spectrum continuously existed in the patients who underwent pneumonectomy on the 8th to 10th postoperative days. There were significant differences of pulmonary flow spectrum between patients with postoperative arrhythmia and without postoperative arrhythmia before operation. CONCLUSIONS: Pulmonary hemodynamic obviously changes after pulmonary resection in the patients with lung cancer and the changes last longer in pneumonectomy patients. Patients with postoperative cardiac arrhythmia have marked pulmonary hemodynamic changes before operation. Doppler pulmonary flow spectrum can not only be used to analyse the pulmonary hemodynamic changes for those cases undergoing pulmonary resection after operation, but also to evaluate the risk of pulmonary resection before operation.

[The expression of p63 gene in human non-small cell lung cancer].

BACKGROUND: To investigate the expression of p63 gene and its significance in non-small cell lung cancer (NSCLC) and pulmonary benign disease tissues. METHODS: p63 gene mRNA expression (TAp63 and ΔNp63) was detected in 40 NSCLC and 10 pulmonary benign disease tissues by RT-PCR (reverse transcriptase-PCR) technique, and immunohistochemical method was used to observe p63 protein expression in the above tissues. RESULTS: ΔNp63 mRNA overexpression was observed in 18 squamous cell carcinoma (18/23), 1 bronchioloalveolar carcinoma (1/6) and 2 paracancerous tissues of squamous cell carcinoma (2/23). There was no expression of TAp63 both in NSCLC and benign disease tissues of the lung. Immunochemistry showed that the positive rate and intensity of p63 protein expression were significantly higher in squamous cell carcinoma than those in adenocarcinoma and benign disease tissues of the lung ( P < 0.01). CONCLUSIONS: p63 gene is mainly amplified in squamous cell carcinoma of the lung. It may act as an oncogene in the carcinogenesis and development of squamous cell carcinoma.

[Diagnosis and surgical treatment of middle lobe disease of lung: report of 163 cases].

OBJECTIVE: To discuss the principle of diagnosis and surgical treatment of middle lobe diseases of right lung. METHODS: We analysed the clinical data and prognosis of 163 patients who suffered from middle lobe diseases of right lung and received surgical treatment. RESULTS: There were 97 men and 66 women in the group with the ratio 1.5:1, whose age arranged from 13 to 74 years. The shortest course was one week, and the longest 25 years. The average course was 30.3 months. 78 of 163 patients with tumors were malignant (47.9%) and 85 benign (52.1%). The number of the patients below 50 years old was 91 and 81.3% of them were benign, which was very markedly higher than that of the patients with malignant tumors (P < 0.01). The number of the patients above 50 years old was 72 and 84.7% were malignant, which was very markedly higher than that of the patients with benign tumors (P < 0.01); 8 of 11 patients (72.7%, 8/11) who suffered from tuberculosis combined with bronchoactesis. One of this group died from respiratory failure after operation, packed accumulation of fluid between lobes happened in seven cases (4.3%). The survival rate of 1, 3, 5 years of malignant patients at stages I, II were 88.4%, 62.8%, 51.2%, for that at stages III, IV were 76.5%, 41.2%, 14.7%. All of the four patients who received vage-resection, their malignant tumors recurred in one year after operation. No benign lesion recurred in 10 years. CONCLUSION: (1) It should be noticed that nearly half of middle lobe disease were malignant, especially to those whose ages were above 50 years old. (2) When the diagnosis is hard to be confirmed, open-thoracic exploration should be performed in order not to delay the treatment or enlarge the range of lung resection. (3) Most of middle lobe tuberculosis may be combined with bronchoactesis. (4) Setting drainage tube may be useful to decrease the risk of interlobe accumulation of fluid. (5) Vage resection is not suitable for carcinoma of middle lobe of lung.