Establishment of acquired tracheoesophageal fistula using a modified magnetic compression technique in rabbits and its postmodeling evaluation

BACKGROUND Previous studies have validated the efficacy of both magnetic compression and surgical techniques in creating rabbit tracheoesophageal fistula(TEF)models.Magnetic compression achieves a 100%success rate but requires more time,while surgery,though less frequently successful,offers rapid model establishment and technical maturity in larger animal models.AIM To determine the optimal approach for rabbit disease modeling and refine the process.METHODS TEF models were created in 12 rabbits using both the modified magnetic compression technique and surgery.Comparisons of the time to model establishment,success rate,food and water intake,weight changes,activity levels,bronchoscopy findings,white blood cell counts,and biopsies were performed.In response to the failures encountered during modified magnetic compression modeling,we increased the sample size to 15 rabbit models and assessed the repeatability and stability of the models,comparing them with the original magnetic compression technique.RESULTS The modified magnetic compression technique achieved a 66.7%success rate,whereas the success rate of the surgery technique was 33.3%.Surviving surgical rabbits might not meet subsequent experimental requirements due to TEF-related inflammation.In the modified magnetic compression group,one rabbit died,possibly due to magnet corrosion,and another died from tracheal magnet obstruction.Similar events occurred during the second round of modified magnetic compression modeling,with one rabbit possibly succumbing to aggravated lung infection.The operation time of the first round of modified magnetic compression was 3.2±0.6 min,which was significantly reduced to 2.1±0.4 min in the second round,compared to both the first round and that of the original technique.CONCLUSION The modified magnetic compression technique exhibits lower stress responses,a simple procedure,a high success rate,and lower modeling costs,making it a more appropriate choice for constructing TEF models in rabbits.

Relapse of both small cell lung cancer and Lambert-Eaton myasthenic syndrome after a 13-year disease-free survival period

Lambert-Eaton myasthenic syndrome(LEMS) is a paraneoplastic syndrome and only 3%of small cell lung carcinoma(SCLC) patients have LEMS.Moreover,the recurrence of SCLC after a disease-free survival(DFS) of more than 10 years is rare.We report a patient who had a recurrence of both SCLC and LEMS after a 13-year DFS period.A 69-year-old man was diagnosed with LEMS and SCLC(cT0N2M0,stage ⅢA) 13 years ago.Chemoradiotherapy was performed and a complete response was achieved.With anticancer treatment,the LEMS symptoms was alleviated.At the age of 82 years,gait disturbance appeared followed by left supraclavicular lymphadenopathy and further examination revealed the recurrence of SCLC.Careful screening for the recurrence of SCLC might be needed when the patient has recurrent or secondary paraneoplastic neurological syndrome even after a long DFS period.

Histologic Types of Chest Wall Tumors—Nine Years’ Single Center Experience

Background: Chest wall tumors are rare and mostly malignant. More than half of the malignancies are primary and the remainder are metastatic. Many studies have reported that metastatic lesions occur with about the same frequency as primary tumor. We evaluate common histological types of chest wall tumors in a tertiary center for respiratory and thoracic diseases (National Research Institute of Tuberculosis and Lung Disease). Method: We performed a retrospective study of chest wall tumors at National Research Institute of Tuberculosis and Lung Disease (NRITLD) from April 2001 to March 2010. The pathology slides of patients were retrieved from the pathology archive of NRITLD and reviewed by two pathologists. The lesions were classified as primary or metastatic according to the relevant clinical data and imaging findings. Result: A total of 124 chest wall tumors were identified in patients with a mean age of 47.7 years (range 4-90 years). The male/female ratio was 2:1. The most commonly affected side was the right (42.7%). There were 105 malignant tumors (84.7%), out of which 49 (46.2%) were primary and 57 (53.8%) were metastatic in origin. The majority of the metastatic lesions were epithelial tumors (36/57) (63.1%). The metastatic origin was clear in 51 cases, mostly arising from the lungs (35.7%). The most common types of primary chest wall tumors were primitive neuroectodermal tumor (15/49, 30.6%), chondrosarcoma (7/49, 14.3%), and malignant fibrous histiocytoma, undifferentiated pleomorphic sarcoma (5/49, 10.2%). The most common benign tumor was lipoma (5/18, 35.7%). Conclusion: Most common tumors of chest wall in this study were malignant, mostly metastatic epithelial neoplasms.

Pathogenesis and drug resistance mechanism of Burkholderia pseudomallei

Burkholderia pseudomallei is the pathogen that causes melioidosis.Melioidosis has a long duration of chronic infection,atypical clinical manifestations at acute onset,and is prone to life-threatening complications and poor prognosis.Understanding the pathogenesis and drug resistance mechanism of Burkholderia pseudomallei will effectively help the diagnosis and treatment of the disease and improve the prognosis.This review focuses on the extracellular movement of Burkholderia pseudomallei in host cells,the way of infecting host cells,virulence factors,and drug resistance mechanisms(efflux pumps,changes in target sites,etc.).This study provides a possible direction for the early diagnosis,treatment and control of melioidosis caused by this bacterium.

Impact of random and scattered coincidences from outside of field of view on positron emission tomography/computed tomography imaging with different reconstruction protocols

Image quality in positron emission tomography(PET)is affected by random and scattered coincidences and reconstruction protocols.In this study,we investigated the effects of scattered and random coincidences from outside the field of view(FOV)on PET image quality for different reconstruction protocols.Imaging was performed on the Discovery 690 PET/CT scanner,using experimental configurations including the NEMA phantom(a body phantom,with six spheres of different sizes)with a signal background ratio of 4:1.The NEMA phantom(phantom I)was scanned separately in a one-bed position.To simulate the effect of random and scatter coincidences from outside the FOV,six cylindrical phantoms with various diameters were added to the NEMA phantom(phantom II).The 18 emission datasets with mean intervals of 15 min were acquired(3 min/scan).The emission data were reconstructed using different techniques.The image quality parameters were evaluated by both phantoms.Variations in the signal-to-noise ratio(SNR)in a 28-mm(10-mm)sphere of phantom II were 37.9%(86.5%)for ordered-subset expectation maximization(OSEM-only),36.8%(81.5%)for point spread function(PSF),32.7%(80.7%)for time of flight(TOF),and 31.5%(77.8%)for OSEM+PSF+TOF,respectively,indicating that OSEM+PSF+TOF reconstruction had the lowest noise levels and lowest coefficient of variation(COV)values.Random and scatter coincidences from outside the FOV induced lower SNR,lower contrast,and higher COV values,indicating image deterioration and significantly impacting smaller sphere sizes.Amongst reconstruction protocols,OSEM+PSF+TOF and OSEM+PSF showed higher contrast values for sphere sizes of 22,28,and 37 mm and higher contrast recovery coefficient values for smaller sphere sizes of 10 and 13 mm.

Impact of inhaled corticosteroid use on elderly chronic pulmonary disease patients with community acquired pneumonia

To the Editor:With an aging global population,the incidences of community-acquired pneumonia(CAP)and chronic obstructive pulmonary disease(COPD)have signicantly increased.[1]Previous studies have conrmed that COPD and asthma are independently associated with the prevalence of CAP.The use of inhaled corticosteroid(ICS),the cornerstone of treatment for asthma,COPD with frequent acute exacerbations,and asthma-COPD overlap(ACO)may induce changes in the local lung microbiome and abnormal lung immunity,ultimately,causing a signicantly increased risk of pneumonia.However,in cases of pneumonia,the effect of the use of ICS on CAP mortality remains controversial.While data from one study favored the prior use of ICS,which was associated with a signicantly lower short-term mortality rate,[2]other studies have identied no impact on mortality.To date,data on the impact of the use of ICS on mortality,prehospitalization or during hospitalization,are scarce,particularly in the older population.Therefore,this multicenter,retrospective study explored the association between the use of ICS during hospitalization and short-term mortality in older patients with CAP and those with chronic pulmonary disease(CPD).

Congenital tracheoesophageal fistula successfully diagnosed by CT esophagography

Tracheoesophageal 管(TEF ) 或 bronchoesophageal 管可能对损伤先天、煽动性、肿瘤，或第二等。先天的 TEF 或 bronchoesophageal 管通常与食道的闭锁被联系并且乐意地在幼年期被诊断。但是如果它没与食道的闭锁被联系，它可以坚持直到成人生活。一些理论被建议了在诊断解释这延期。我们在场有先天的 TEF 的一个 70 岁的人的一个盒子。TEF 被 multidetector 排 CT esophagography 成功地诊断。

Quantification of the impact of TOF and PSF on PET images using the noise-matching concept: clinical and phantom study

This study was to assess quantitatively the accuracy of ^(18)F-FDG PET/CT images reconstructed by TOF+PSF and TOF only, considering the noise-matching concept to minimize probable bias in evaluating algorithm performance caused by noise. PET images of similar noise level were considered. Measurements were made on an inhouse phantom with hot inserts of Φ10–37 mm, and oncological images of 14 patients were analyzed. The PET images were reconstructed using the OSEM, OSEM+TOF and OSEM+TOF+PSF algorithms. Optimal reconstruction parameters including iteration, subset, and FWHM of post-smoothing filter were chosen for both the phantom and patient data. In terms of quantitative accuracy, the recovery coefficient(RC) was calculated for the phantom PET images. The signal-to-noise ratio(SNR),lesion-to-background ratio(LBR), and SUV_(max)were evaluated from the phantom and clinical data. The smallest hot insert(Ф10 mm) with 2:1 activity concentration ratio could be detected in the PET image reconstructed using the TOF and TOF+PSF algorithms, but not the OSEM algorithm. The relative difference for SNR between the TOF+PSF and OSEM showed significantly higher values for smaller sizes, while SNR change was smaller for Ф22–37 mm inserts both 2:1 and 4:1 activity concentration ratio. In the clinical study, SNR gains were 1.6 ± 0.53 and 2.7 ± 0.74 for the TOF and TOF+PSF, while the relative difference of contrast was 17 ± 1.05 and 41.5 ± 1.85% for the TOF only and TOF+PSF, respectively. The impact of TOF+PSF is more significant than that of TOF reconstruction, in smaller inserts with low activity concentration ratio. In the clinical PET/CT images, the use of the TOF+PSF algorithm resulted in better SNR and contrast for lesions, and the highest SUV_(max)was also seen for images reconstructed with the TOF+PSF algorithm.

Novel mutations in RSPH4A and TTN genes lead to primary ciliary dyskinesia-hereditary myopathy with early respiratory failure overlap syndrome

Primary ciliary dyskinesia(PCD)is an autosomal recessive disease caused by defects in motile cilia and clinically characterized by bronchiectasis,situs inversus,nasosinusitis,recurrent respiratory infections,tympanitis,and/or male infertility.In PCD,impaired function or structure of motile cilia leads to abnormality of mucociliary clearance。

The Association of Hepatitis B Vaccine Supply Policy with Timing of Receipt of the First Dose of Hepatitis B Vaccination

An estimated 800,000 - 1.4 million persons in the US have chronic hepatitis B virus (HBV) infection. The risk for chronic infection is greatest among young children;approximately 90% of infants will remain chronically infected with HBV. Approximately 25% of those who become chronically infected during childhood die prematurely from cirrhosis or liver cancer. Hepatitis B vaccination is the most effective measure to prevent HBV infection and its consequences. In 2006, 29 US states had Hepatitis B Vaccine Supply (HBVS) policy which either supplies hepatitis B vaccine at no cost to all providers for all children or provides hepatitis B vaccine to delivery hospitals-only free of charge for all infants;other 21 US states and the District of Columbia did not have. 17,636 infants born in 2006 obtained from 2007-2009 National Immunization Survey (NIS) were analyzed with survival analysis procedures of Kaplan-Meier estimate and Cox proportional hazards model for complex sample survey to evaluate the association between state HBVS policy and the timing of infant age in days to receipt of hepatitis B vaccination. State HBVS policy is associated with infant age in days from birth to receipt of the first dose of hepatitis B vaccine (P < 0.01), and to completion of the 3-dose hepatitis B vaccine series (P < 0.01). Receipt of the first dose of hepatitis B vaccine occurred 31% earlier among infants residing in states with HBVS policy than among infants residing in states without (adjusted hazards ratio 1.31, 95%CI (1.23, 1.39)). Completion of the 3-dose hepatitis B vaccine series were 12% sooner among infants living in states with HBVS policy than among infants living in states without (adjusted hazards ratio 1.12, 95%CI (1.06, 1.18)). State HBVS policy may help overcome barriers to timely delivery of hepatitis B vaccines to infants.

Long noncoding RNA LINC01124 activates hepatocellular carcinoma cell proliferation, migration, and invasion by absorbing microRNA-1247-5p and overexpressing FOXO3

Long intergenic non-protein coding RNA 1124(LINC01124)has been identified as an important regulator of non-small-cell lung cancer.However,the expression and detailed role of LINC01124 in hepatocellular carcinoma(HCC)remain unestablished to date.Therefore,this study aimed to elucidate the role of LINC01124 in the aggressiveness of HCC cells and identify the underlying regulatory mechanism.Quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression of LINC01124 in HCC.Cell Counting Kit-8 assay,Transwell cell migration and invasion assays,and a xenograft tumor model were used to investigate the function of LINC01124 in HCC cells,and bioinformatics analysis,RNA immunoprecipitation,luciferase reporter assay,and rescue experiments were used to elucidate the underlying mechanisms.Herein,LINC01124 overexpression was confirmed in HCC tissues as well as cell lines.Further,the downregulation of LINC01124 decreased HCC cell proliferation,migration,and invasion in vitro,whereas the upregulation of LINC01124 triggered the opposite results.Additionally,LINC01124 ablation impaired tumor growth in vivo.Mechanistic analyses revealed that LINC01124 functions as a competing endogenous RNA to sponge microRNA-1247-5p(miR-1247-5p)in HCC cells.Moreover,forkhead box O3(FOXO3)was identified as a direct target of miR-1247-5p.FOXO3 was positively regulated by LINC01124 in HCC cells through the sequestration of miR-1247-5p.Finally,rescue assays revealed that the inhibition of miR-1247-5p or overexpression of FOXO3 reversed the effects of LINC01124 silencing on the HCC cell malignant phenotype.In summary,LINC01124 plays a tumor-promoting role in HCC by regulating the miR-1247-5p-FOXO3 axis.The LINC01124-miR-1247-5p-FOXO3 pathway may provide a foundation for the identification of alternative therapies for HCC.

Two Molecular Markers of Early Non-Small Cell Lung Carcinoma Based on Gene Expression in Peripheral Blood

Background: Lung cancer is among the most common cancers. Search is ongoing to find biomarkers to improve the diagnosis lung cancer techniques in early stages. In this study we evaluate the sensitivity and specificity of the MUC1 and CEA gene expressions in the peripheral blood of non-small cell lung cancer (NSCLC). Material and Methods: This study was done in Masih Daneshvari Hospital, Tehran, Iran and was case/control study that conducted on 30 NSCLC patients and 30 healthy controls. Peripheral blood was collected and total RNA was extracted then cDNA was synthesized. Sample was separately assessed by real time PCR. Results: The expression of CEA gen was positive in 24 patients indicating 80% sensitivity for this marker. The expression of CEA gen was positive in 9 controls out of 30 each. A statistically significant difference was detected between patients and healthy controls with regard to CEA mRNA expression (P 0.001). The MUC1 gen expressed in 20 out of 30 patients, while it expressed in 3 controls. The difference in MUC1 mRNA expression was statistically significant between NSCLC patients and healthy controls (P 0.001). Conclusion: MUC1 and CEA are molecular biomarkers with relatively favorable sensitivity for primary diagnosis of NSCLC.

Expression of Mammaglobin and Carcinoembryonic Antigen in Peripheral Blood of Patients with Breast Cancer Using Real Time Polymerase Chain Reaction

Background and Objectives: Breast cancer is among the most common causes of cancer related mortality in women worldwide. Early detection and prompt diagnosis of tumor is the first step to prevent cancer-related morbidity and mortality, and a comprehensive understanding of the involved molecular mechanisms can greatly help in this respect. Breast cancer, like many other types of cancer, is caused by a combination of genetic and epigenetic changes such as inactivation of tumor suppressor genes. Materials and Methods: This study was performed on 40 breast cancer patients and 40 healthy controls. Quantitative real time reverse transcription polymerase chain reaction (real time qRT-PCR) was used to assess the expression of carcinoembryonic antigen (CEA) and mammaglobin mRNA in the peripheral blood of patients and healthy controls. The two groups were compared using t-test. Results: The two groups were not significantly different in terms of the mean age. Twenty-nine out of 40 cancer patients were positive for CEA mRNA and its sensitivity was calculated to be 72.5%. Twelve out of 40 healthy controls were positive for CEA mRNA. Twenty-six out of 40 patients were positive for mammaglobin mRNA indicative of 65% sensitivity while only five out of 40 healthy controls were positive for mammaglobin mRNA. Conclusion: Both CEA and mammaglobin mRNA had high sensitivity in cancer patients;thus, they can be used for screening and early detection of breast cancer patients. Further studies with larger sample sizes are required to confirm the current findings.

Human Epididymis Protein-4 Gene Expression as a Biomarker in Patients with Ovarian Cancer in Iran

Introduction: Ovarian cancer is one of the most common malignancies in women and the fifth cause of cancer-related deaths in women worldwide. Contrary to the challenges in developing new clinical markers using the conventional methods, recent advances in genomics and proteomics have led to identification of candidate and promising biomarkers for the diagnosis of ovarian cancer. Human epididymis protein 4 (HE4) is such a marker that has recently been reported to correlate with recurrence or progression of epithelial ovarian cancer. The purpose of this study was to measure the expression level of HE4 gene in women with ovarian cancer. Methodology: We evaluated and compared paraffin-embedded tissue samples of 20 ovarian cancer patients with 10 samples from healthy individuals. RNA was initially extracted from the samples and cDNA was synthetized. Gene expression level was then measured using real-time polymerase chain reaction (PCR). Results: Our results demonstrated that HE4 gene expression level was significantly higher in samples of patients with ovarian cancer compared with samples from healthy individuals. Moreover, higher levels of HE4 gene expression were associated with more advanced disease and larger tumor size. Conclusion: HE4 gene over-expression has the potential to be used as a biomarker for detecting early-stage ovarian cancer in women. Future more comprehensive studies are needed to confirm our findings.

Characteristics of Proinflammatory Cytokines and Chemokines in Airways of Asthmatics： Relationships with Disease Severity and Infiltration of Inflammatory Cells

Background：Increased proinflammatory cytokines and chemokines might contribute to infiltration of inflammatory cells and remodeling in airways of asthma.Although these molecules may be associated with asthma,there is lack of systemic evidence showing which and how important these events are in the disease.We aimed to analyze the concentrations of these molecules in the airways and relationships with disease severity and with airway infiltration of inflammatory cells in a large cohort of asthmatics （n =70,including 37 mild and 33 moderate/severe asthmatics） compared with controls （n =30）.Methods：Meso scale discovery system and commercial ELISA kits were used to measure the concentrations ofproinflammatory cytokines interleukin （IL）-1 β;tumor necrosis factor-alpha （TNF-α）;IL-6;and IL-17 and CC and CXC chemokines CCL2,CCL4,CCL 11,CCL 13,CCL17,CCL22,and CCL26 and CXCL8,CXCL9,CXCL10,and CXCL1 1 in bronchoalveolar lavage fluid of asthmatics and controls.Results：The concentrations ofIL-1,TNF-α,IL-6,CXCL8 and CXCL 10,and CCL4,CCL 11,CCL 17,and CCL22 were significantly elevated in asthmatics compared with controls （P 〈 0.05）.The concentrations of TNF-α and CXCL8,but not others,were negatively correlated with severity of disease （lung function forced expiratory volume in 1 s） （TNF-α vs.total：r =-0.359,P =0.002 vs.moderate/severe：r =-0.541,P =0.001;CXCL8 vs.total：r =-0.327,P =0.006 vs.moderate/severe：r =-0.625,P =0.0001,respectively）.In addition,concentrations of these two molecules were also correlated with the absolute numbers of infiltrating eosinophils and neutrophils in asthmatic airways.Conclusions：Increased concentrations of TNF-α and CXCL8 are associated with pathogenesis of asthma.Targeting these molecules might provide an alternative therapeutic for this disease.

Applying comprehensive histologic assessment and genetic testing to synchronous multifocal lung adenocarcinomas and further survival analysis

To the Editor:The differentiation of multiple primary lung adenocarcinomas (MPLAs) from metastases is important to allow for proper clinical management and prognostic prediction.The current revised diagnostic criteria for MPLAs proposed by the American College of Chest Physicians (ACCP) have been commonly applied since 2003.[1] However, it remains technically challenging to determine whether 2 or more lung adenocarcinomas from the same patient are homologous.Various approaches and algorithms including gene mutation analysis addressing this problem have been described.[2,3] Here, we present a cohort of 45 patients with synchronous multifocal lung adenocarcinomas.

Targeted genome engineering in human induced pluripotent stem cells by penetrating TALENs

Background:Zinc-finger nucleases(ZFNs)and transcription activator-like effector nucleases(TALENs)have been successfully used to knock out endogenous genes in stem cell research.However,the deficiencies of current gene-based delivery systems may hamper the clinical application of these nucleases.A new delivery method that can improve the utility of these nucleases is needed.Results:In this study,we utilized a cell-penetrating peptide-based system for ZFN and TALEN delivery.Functional TAT-ZFN and TAT-TALEN proteins were generated by fusing the cell-penetrating TAT peptide to ZFN and TALEN,respectively.However,TAT-ZFN was difficult to purify in quantities sufficient for analysis in cell culture.Purified TAT-TALEN was able to penetrate cells and disrupt the gene encoding endogenous human chemokine(C-C motif)receptor 5(CCR5,a co-receptor for HIV-1 entry into cells).Hypothermic treatment greatly enhanced the TAT-TALENmediated gene disruption efficiency.A 5%modification rate was observed in human induced pluripotent stem cells(hiPSCs)treated with TAT-TALEN as measured by the Surveyor assay.Conclusions:TAT-TALEN protein-mediated gene disruption was applicable in hiPSCs and represents a promising technique for gene knockout in stem cells.This new technique may advance the clinical application of TALEN technology.

Expert consensus on COVID-19 vaccination in children

Coronavirus disease 2019(COVID-19)is a public health disaster that has not been encountered for a hundred years.On January 12,2020,the World Health Organization(WHO)confirmed and named the coronavirus which caused unexplained pneumonia as 2019 novel coronavirus(2019-nCoV).Since then,the disease caused by this virus had been named as coronavirus disease 2019(COVID-19).On February 11,2020,the International Committee on Taxonomy of Viruses announced that the English name of the novel coronavirus was severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[1].At present,SARS-CoV-2 infection is still rampant worldwide.As of September 10,2021,there were about 222 million confirmed cases of COVID-19 and more than 4.5 million deaths worldwide[2].According to the American Centers for Disease Control and Prevention,by July 29,2021,4.19 million pediatric COVID-19 cases had been reported in the United States。