SNX3 Promotes Doxorubicin-Induced Cardiomyopathy by Regulating GPX4-Mediated Ferroptosis.

The complete molecular mechanism underlying doxorubicin-induced cardiomyopathy remains incompletely elucidated. In this investigation, we engineered mice with cardiomyocyte-specific sorting nexin 3 knockout (SNX3Cko ) to probe the potential protective effects of SNX3 ablation on doxorubicin-triggered myocardial injury, focusing on GPX4-dependent ferroptosis. Our findings indicate that SNX3 deletion normalized heart contractile/relaxation function and thwarted the escalation of cardiac injury biomarkers following doxorubicin exposure. Additionally, SNX3 deletion in the heart mitigated the inflammatory response and oxidative stress in the presence of doxorubicin. At the molecular level, the detrimental effects of doxorubicin-induced cell death, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction were alleviated by SNX3 deficiency. Molecular analysis revealed the activation of GPX4-mediated ferroptosis by doxorubicin, whereas loss of SNX3 prevented the initiation of GPX4-dependent ferroptosis. Furthermore, treatment with erastin, a ferroptosis inducer, markedly reduced cell viability, exacerbated ER stress, and induced mitochondrial dysfunction in SNX3-depleted cardiomyocytes upon doxorubicin exposure. In summary, our results demonstrate that SNX3 deficiency shielded the heart from doxorubicin-induced myocardial dysfunction by modulating GPX4-associated ferroptosis.

MicroRNA-145 performs as a tumor suppressor in human esophageal squamous cell carcinoma by targeting phospholipase C epsilon 1.

Esophageal squamous cell carcinoma (ESCC) is the leading pathologic type in China. miR-145 has been reported to be downregulated in multiple tumors. This study was aimed to investigate the role of miR-145 in ESCC. miR-145 expression was investigated in 65 ESCC samples as well as four ESCC cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Targetscan 6.2 website (http://www.targetscan.org/) was used to predict the targets of miR-145. Expression of phospholipase C epsilon 1 (PLCE1) messenger RNA and protein was detected by qRT-PCR or Western blot. MTT and wound healing assay were conducted to explore the effects of miR-145 on the proliferation and migration of ESCC cell lines, respectively. miR-145 was significantly decreased in ESCC tissues. An inverse correlation between miR-145 and invasion depth and TNM stage were observed. PLCE1 was a direct target of miR-145, and the expression of PLCE1 was inversely correlated with miR-145 expression in ESCC tissues. In addition, overexpression of miR-145 suppressed cell proliferation and migration in ESCC cells. The enforced expression of PLCE1 partially reversed the suppressive effect of miR-145. These results prove that miR-145 may perform as a tumor suppressor in ESCC by targeting PLCE1.

[Characterization of mutational pattern of patients with core-binding factor acute myeloid leukemia].

OBJECTIVE: To characterize the mutational profile of patients with core-binding factor acute myeloid leukemia (CBF-AML). METHODS: A total of 81 acute myeloid leukemia patients were recruited, which included 36 cases of CBF-AML and 45 cases of cytogenetically normal acute myeloid leukemia (CN-AML) . Mutations of FLT3-ITD, FLT3-TKD, NPM1, c-KIT, NRAS, KRAS, TET2, IDH1/2, RUNX1, DNMT3A, GATA2, ASjXL1, TP53, PTPN11, JAK2V617F, SETBP1 and CEBPA genes were simultaneously detected by DNA-based PCR and Sanger sequencing. RESULTS: Over all, mutations were detected in 68 patients (83.9%), with the most common ones including double CEBPA mutations (n=17), followed by NPM1 (n=15), c-KIT (n=11), NRAS (n=10), TET2 (n=9), FLT3-TKD (n=9), FLT3-ITD (n=8), IDH1 (n=7), RUNX1 (n=7), KRAS (n=7), DNMT3A (n=6), IDH2 (n=4), and GATA2 (n=4) mutations. AML1-ETO and CBFß-MYH11 fusions were present in 21 and 15 patients, respectively. Coexistence of ≥2 mutations was more common in CN-AML comparing with CBF-AML. The mutation rate of NPM1, FLT3-ITD, DNMT3A, IDH1 and CEBPA double mutations were higher in patients with CN-AML. NRAS, c-KIT and KRAS mutations were identified more frequently in patients with CBF-AML (P<0.05). Based on the function, aberration of genes involved in DNA methylation, NPM1 proteins and transcription predominated in CN-AML, while tyrosine kinase receptor signaling and RAS pathways have predominated in CBF-AML. CONCLUSION: The genomic landscape of CBF-AML patients has differed from that of CN-AML patients. Synergy of fusion genes with particular mutations may impact the clinical phenotype and prognosis of patients.

Surgical treatment in non-small cell lung cancer with pulmonary oligometastasis.

BACKGROUND: Previous studies have demonstrated survival benefits for local treatment in solitary metastatic non-small cell lung cancer (NSCLC).This study aimed to investigate the effect of local surgery for NSCLC with pulmonary oligometastasis. METHODS: This study included 21 patients of NSCLC with pulmonary oligometastasis between January 2003 and December 2013, which were divided into two groups, group A (11 cases) for local surgery and group B (10 cases) for systematic chemotherapy, compared the median survival time (MST) and 5-year survival rate between the two groups, and analyzed the impact of the pathological types, the TNM and pN stage of primary tumor, the site, and the mode and number of oligometastatic nodule on group A. RESULTS: The MST of group A and B were 37 and 11.6 months respectively, 5-year survival rates were 18.2 and 9.1% respectively (p < 0.05). Patients with single nodule, oligo-recurrence, primary tumor of pN0, TNM stage I or II obtained higher survival rate than those with multiple nodules, sync-oligometastases, pN1-2, stage III or IV in group A (p < 0.05). There was no significant survival time difference among pathological types of primary tumor and oligometastatic site (p > 0.05). CONCLUSION: Local surgery significantly prolonged the overall survival time and 5-year survival rate of primary NSCLC with pulmonary oligometastasis.

Esophageal cancer-derived microvesicles induce regulatory B cells.

The role of B cells in the generation of cancer-immune tolerance is unclear. This study aims to investigate the role of cancer-derived microvesicles (Mvcs) in the generation of transforming growth factor (TGF)-ß(+) B cells. In this study, esophageal cancer (Eca) cells were isolated from surgically removed cancer tissue. Mvcs were purified from the culture supernatant and characterized by Western blotting. The immune suppression assay was carried out with a cell culture model and flow cytometry. The results showed that Eca-derived Mvcs were LAMP1 positive and carried MMP9. Exposure to the Mvcs induces naive B cells to differentiate into TGF-ß-producing regulatory B cells; the latter show immune suppressor functions on CD8(+) T-cell proliferation. In conclusion, Eca-derived Mvc can induce TGF-ß(+) B cells; the latter suppress CD8(+) T-cell activities. The MMP9-laden Mvcs may be a new therapeutic target in the treatment of Eca.

Effect of lowering or restricting sympathectomy levels on compensatory sweating.

OBJECTIVE: There is controversy on whether lowering or restricting the level of sympathectomy can reduce compensatory sweating (CS). This study compared the results from sympathectomies performed to treat severe palmar hyperhidrosis using two distinct levels of T2-4 and T3-4. METHODS: One hundred and sixteen patients with primary palmar hyperhidrosis were randomly allocated to undergo either T2-4 sympathectomy treatment (T2-4 group) or T3-4 sympathectomy treatment (T3-4 group). Follow-up data were collected using a telephone questionnaire to assess efficacy, side effects, overall satisfaction, and factors affecting CS and the degree of satisfaction. RESULTS: There were no significant differences with respect to either CS or severe CS between the two treatment groups at 1, 6, or 12 months of follow-up. The total scores of the quality-of-life questionnaires after surgery were remarkably decreased compared with those before surgery in the two groups. However, no significant differences in quality-of-life scores were found between the two groups before surgery, or at 1, 6, or 12 months of follow-up. Age was predictive of severe CS at 6 months of follow-up (P = 0.045). Severe CS was inversely associated with patient satisfaction at 1, 6, and 12 months of follow-up. INTERPRETATION: The issue of whether lowering or restricting the level of sympathectomy reduces CS is controversial and needs more supportive evidence. Age may be a predictive factor for severe CS at 6 and 12 months of follow-up. Severe CS is the only known factor that affects patient satisfaction, and family history may also be associated with patient satisfaction.

Lats2 deficiency protects the heart against myocardial infarction by reducing inflammation and inhibiting mitochondrial fission and STING/p65 signaling.

Large tumor suppressor kinase 2 (Lats2) is a member of the Hippo pathway, a critical regulator of organ size. Since Lats2 activity may trigger mitochondrial dysfunction, a key pathogenic factor in acute myocardial infarction (AMI), this study sought to investigate whether Lats2 deletion confers cardioprotection in AMI. AMI was induced in cardiomyocyte-specific Lats2 knockout (Lats2Cko) and control (Lats2flox) mice. Twenty-eight days after AMI surgery, myocardial performance and mitochondrial homeostasis were impaired in Lats2floxmice. In contrast, Lats2Cko mice exhibited markedly preserved cardiac structure and contraction/relaxation activity, decreased fibrosis, reduced circulating cardiac injury biomarker levels, and enhanced cardiomyocyte viability. Consistent with these findings, siRNA-mediated Lats2 silencing sustained mitochondrial respiration and inhibited apoptosis in hypoxia-treated HL-1 cardiomyocytes. Notably, Lats2 deficiency inhibited AMI/hypoxia-related mitochondrial fission and inactivated STING/p65 signaling by preventing hypoxia-induced release of mtDNA into the cytosol. Accordingly, pharmacological reactivation of STING signaling abolished the cardioprotective effects of Lats2 ablation. Those data suggest that AMI-induced Lats2 upregulation is associated with impaired cardiomyocyte viability and function resulting from enhanced mitochondrial fission, mtDNA release, and STING/p65 pathway activation.

Energy metabolism disorder dictates chronic hypoxia damage in heart defect with tetralogy of fallot.

Background: Tetralogy of Fallot (TOF) belongs to cyanotic heart damage, which is the most common in clinic. In the chronic myocardial hypoxia injury related to TOF, the potential molecular mechanism of cardiac energy metabolism remains unclear. Materials and methods: In our study, microarray transcriptome analysis and metabonomics methods were used to explore the energy metabolism pathway during chronic hypoxia injury. The gene expression omnibus (GEO) dataset GSE132176 was obtained for analyzing the metabolic pathways. The clinical samples (right atrial tissues) of atrial septal defect (ASD) and TOF were analyzed by metabonomics. Next, we screened important pathways and important differential metabolites related to energy metabolism to explore the pathogenesis of TOF. Results: Gene set enrichment analysis (GSEA) indicated that fructose 6-phosphate metabolic process, triglyceride metabolic process, and et al. were significantly enriched. Gene set variation analysis (GSVA) results showed that significant difference of ASD group and TOF group existed in terpenoid metabolic process and positive regulation of triglyceride metabolic process. Pathways with significant enrichment (impact > 0.1) in TOF were caffeine metabolism (impact = 0.69), sphingolipid metabolism (impact = 0.46), glycerophospholipid metabolism (impact = 0.26), tryptophan metabolism (impact = 0.24), galactose metabolism (impact = 0.11). Pathways with significant enrichment (impact > 0.1) in ASD are caffeine metabolism (impact = 0.69), riboflavin metabolism (impact = 0.5), alanine, aspartate and glutamate metabolism (impact = 0.35), histidine metabolism (impact = 0.34) and et al. Conclusion: Disturbed energy metabolism occurs in patients with TOF or ASD, and further investigation was needed to further clarify mechanism.

Retraction Notice to: MTTL3 upregulates microRNA-1246 to promote occurrence and progression of NSCLC via targeting paternally expressed gene 3.

[This retracts the article DOI: 10.1016/j.omtn.2021.02.020.].

A gold nanowire-integrated soft wearable system for dynamic continuous non-invasive cardiac monitoring.

Blood pressure (BP) is a cardiovascular parameter which exhibits significant variability. Whilst continuous BP monitoring would be of significant clinical utility. This is particularly challenging outside the hospital environment. New wearable cuff-based and cuffless BP monitoring technologies provide some capacity, however they have a number of limitations including bulkiness, rigidity and discomfort, poor accuracy and motion artefact. Here, we report on a lightweight, user-friendly, non-invasive wearable cardiac sensing system based on deformation-insensitive conductive gold nanowire foam (G-foam) and pressure-sensitive resistive gold nanowire electronic skin (G-skin). The G-foam could serve as a new soft dry bioelectrode for electrocardiogram (ECG) monitoring; a new soft button-based G-skin design could avoid manual holding for continuous pulse recording. They could be integrated seamlessly with everyday bandage for facile wireless recording of ECG and artery pulses under real-word dynamic environments including walking, running, deep squatting, and jogging. Further machine learning algorithm was developed for estimation of systolic and diastolic BP, showing comparable accuracy to commercial cuff-based sphygmomanometer. The measured dynamic BP changes correlated well with the volunteer's daily activities, indicating the potential applications of our soft wearable systems for real-time diagnostics of cardiovascular functions in complex dynamic real-world setting.

Companion gene mutations and their clinical significance in AML with double or single mutant CEBPA.

INTRODUCTION: We report the co-mutations in AML with CEBPAsm or CEBPAdm and their clinical features in a large cohort (n = 302) of CEBPAmut AML patients. MATERIALS AND METHODS: We retrospectively sequenced 112 genes in 302 patients with CEBPAmut using NGS, and studied the spectrum and clinical impact of co-mutations in CEBPAdm and CEBPAsm. RESULTS: ① The average number of mutations in CEBPAsm and CEBPAdm AML was comparable, but not significant (P = 0.17). ② CEBPAdm patients exhibited more mutations in CSF3R (P = 0.037), GATA2 (P = 0.022), and WT1 (P = 0.046). In contrast, CEBPAsm patients more frequently harbored mutations in NPM1 (P = 0.000), FLT3-ITD (P = 0.025) and NOTCH2 (P = 0.043), as well as mutations in signaling pathways and spliceosomes (P = 0.064, P = 0.027, respectively). ③ Patients with CEBPAsm/TET2mut or CEBPAsm /GATA2mut had higher platelet counts (both P = 0.011), while patients with CEBPAdm /TET2mut had significantly higher hemoglobin levels (P = 0.009). The CR rate of patients with FLT3-ITD mutations was significantly lower in the CEBPAsm group than the CEBPAdm group (P = 0.028). CONCLUSIONS: CEBPAsm and CEBPAdm AML are each associated with their own complex co-mutation cluster. Some co-mutations influence the clinical features and CR rate differently in patients with different CEBPA mutational status.

Comparison of Immunotherapy, Chemotherapy, and Chemoimmunotherapy in Advanced Pulmonary Lymphoepithelioma-Like Carcinoma： A Retrospective Study.

Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare subtype of lung cancer that is associated with the Epstein-Barr virus in Asia. Due to the lack of prospective studies, the best first-line treatment and survival outcomes remain unclear. Herein, This study investigated the efficacy and safety of different treatment regimens for advanced pLELC. This retrospective study included 68 patients with advanced pLELC from two centers in China. Patients were divided into three groups according to different first-line treatments: chemotherapy (n=49, 72.1%), immunotherapy (n=7, 10.3%), and chemoimmunotherapy (n=12,17.6%). The primary endpoint of this study was the 2-year progression-free survival (PFS) of each group. The results show that the median PFS was 6.9 months (range, 2.3-not estimable) in the chemotherapy group, 11.0 months (range, 2-not estimable) in the immunotherapy group, and 11.8 months (range, 6-not estimable) in the chemoimmunotherapy group. There was a significant difference in 2-year PFS between the chemoimmunotherapy group and the chemotherapy group (hazard ratio, 0.38, 95% confidence interval: 0.18-0.78, log-rank P=0.007). The most frequent grade 3-4 adverse event in the chemotherapy and chemoimmunotherapy groups was myelosuppression (10/49 [22.4%] and 4/12 [33.3%], respectively). The most frequent grade 3-4 adverse events in the immunotherapy group were diarrhea (1/7, 14.8%) and hepatotoxicity (1/7, 14.8%). Chemoimmunotherapy had the highest 2-year PFS as a first-line treatment for advanced pLELC compared to chemotherapy and immunotherapy. This study suggests that chemoimmunotherapy may be the best first-line treatment for patients with advanced pLELC.

[Local injection of gentamycin for female urethral syndrome: a clinical study].

OBJECTIVE: To observe the therapeutic effect of local antibiotic injection into the female prostate on female urethral syndrome (FUS), and search for an effective treatment for this disease. METHODS: This study included 163 FUS patients treated in the out-patient department between July 2009 and December 2010. According to the visiting order, the patients were randomly assigned to Groups A (n = 58), B (n = 55) and C (n = 50). All underwent routine treatment. Inaddition Group A received local injection of 2 ml of 80 000 U gentamycin + 2 ml of lidocaine, and Group B 2 ml of normal saline + 2 ml of lidocaine, both injected into the distal segment of the urethral back wall where the female prostate is located, twice a week for 3 weeks. The therapeutic effects were evaluated according to the changes of the patients' independent symptom scores at 2 and 4 weeks after the treatment. Disappearance of the symptoms was considered as "curative" , > 1/2 reduction in the symptom score as "obviously effective", 1/2 - > 1/4 reduction in the symptom score as "effective", and < 1/4 reduction or increase in the symptom score as "ineffective". RESULTS: At 2 weeks after the treatment, the total effectiveness rate was significantly higher in Group A (77.5%) than in B (67.3%) and C (68.0%) (P < 0.05), but with no statistically significant difference between B and C (P > 0.05). At 4 weeks, the total effectiveness rate of Group A was slightly decreased, but still remarkably higher than that of group B or C (P < 0.05). CONCLUSION: Local injection of gentamycin into the female prostate is effective for the treatment of female urethral syndrome.

MTTL3 upregulates microRNA-1246 to promote occurrence and progression of NSCLC via targeting paternally expressed gene 3.

Non-small cell lung cancer (NSCLC) is one of the major causes of morbidity and mortality worldwide. We aimed to investigate the role of N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3) regulating microRNA-1246 (miR-1246) in the progression of NSCLC by targeting paternally expressed gene 3 (PEG3). METTL3, miR-1246, and PEG3 expression in tissues was assessed, and the predictive role of METTL3 in prognosis of patients with NSCLC was detected. NSCLC cells were relatively treated with altered expression of METTL3, miR-1246, or PEG3 to measure their roles in the proliferation, migration, invasion, apoptosis, and in vivo growth of the NSCLC cells. The RNA m6A level was determined, and the targeting relationship between miR-1246 and PEG3 was confirmed. Our results revealed that METTL3 and miR-1246 were upregulated, whereas PEG3 was downregulated in NSCLC tissues. METTL3 knockdown or PEG3 overexpression in NSCLC cells suppressed malignant behaviors of NSCLC cells. METTL3 affected the m6A modification of miR-1246, thus upregulating miR-1246 and miR-1246-targeted PEG3. The elevation of PEG3 reversed the effects of miR-1246 upregulation on NSCLC cells. This study revealed that m6A methyltransferase METTL3 affects the m6A modification of miR-1246, thus upregulating miR-1246 to promote NSCLC progression by inhibiting PEG3.

Neonatal Heart and Lung Sound Quality Assessment for Robust Heart and Breathing Rate Estimation for Telehealth Applications.

With advances in digital stethoscopes, internet of things, signal processing and machine learning, chest sounds can be easily collected and transmitted to the cloud for remote monitoring and diagnosis. However, low quality of recordings complicates remote monitoring and diagnosis, particularly for neonatal care. This paper proposes a new method to objectively and automatically assess the signal quality to improve the accuracy and reliability of heart rate (HR) and breathing rate (BR) estimation from noisy neonatal chest sounds. A total of 88 10-second long chest sounds were taken from 76 preterm and full-term babies. Six annotators independently assessed the signal quality, number of detectable beats, and breathing periods from these recordings. For quality classification, 187 and 182 features were extracted from heart and lung sounds, respectively. After feature selection, class balancing, and hyperparameter optimization, a dynamic binary classification model was trained. Then HR and BR were automatically estimated from the chest sound and several approaches were compared.The results of subject-wise leave-one-out cross-validation, showed that the model distinguished high and low quality recordings in the test set with 96% specificity, 81% sensitivity and 93% accuracy for heart sounds, and 86% specificity, 69% sensitivity and 82% accuracy for lung sounds. The HR and BR estimated from high quality sounds resulted in significantly less median absolute error (4 bpm and 12 bpm difference, respectively) compared to those from low quality sounds. The methods presented in this work, facilitates automated neonatal chest sound auscultation for future telehealth applications.

Systemic immune microenvironment and regulatory network analysis in patients with lung adenocarcinoma.

BACKGROUND: This study applied a complex bioinformatics analysis to explore the hub regulators and immune network to further elucidate the molecular mechanisms of lung adenocarcinoma (LUAD) immune regulation. METHODS: LUAD immunological microenvironment features and microenvironment-related differential expression genes (DEGs) were identified by ESTIMATE algorithm and linear models for microarray analyses (LIMMA), respectively. CIBERSORT and Igraph algorithms were applied to construct the LUAD-related immunocyte infiltration and regulatory network. Kaplan-Meier survival analysis, and univariate and multivariate Cox analysis were used to predict independent risk factors and screen for the hub genes. In addition, hub genes-correlated gene set enrichment analysis (GSEA), tumor mutation burden (TMB), and clinic pathological relation analyses were also performed. RESULTS: Stromal, immune, and microenvironment comprehensive features (ESTIMATE score) were associated with overall survival (OS) in LUAD patients (all, P<0.05). T-cell activation, chemokine activity, and immune effect or dysfunction gene ontology maps were associated with the LUAD immune microenvironment. The immune infiltration cell subtypes mast cells (masT-cells) resting [The Cancer Genome Atlas (TCGA): P=0.01; Gene Expression Omnibus (GEO): P=1.79e-05] and activated T-cells (CD4 memory) (TCGA: P<0.01; GEO: P=8.52e-05) were found to have an important role in the immune cell regulatory network. Finally, ITGAL [univariate hazard ratio (HR) =0.80, 95% confidence interval (CI): 0.69-0.93, P<0.01; multivariate HR =0.59, 95% CI: 0.40-0.86, P=0.01] and KLRB1 (univariate HR =0.78, 95% CI: 0.69-0.89, P<0.01; multivariate HR =0.72, 95% CI: 0.58-0.90, P<0.01) were correlated with the T-cell receptor signaling pathway and anaplastic lymphoma kinase (ALK) fusion (ITGAL: P=0.034; KLRB1: P=0.050), and were considered as candidate biomarkers. A significant relation between KLRB1 expression level and TMB (P=3.6e-05) was identified, while no relation was detected for ITGAL (P=0.11). CONCLUSIONS: The T-cell activation and activated T-cell (CD4 memory) pathways were predominantly involved in LUAD immune microenvironment regulation. The expression levels of ITGAL and KLRB1 were significantly correlated with the T-cell receptor signaling pathway and LUAD TMB, and were independent risk factors for OS.

Survival rates of patients with tumors originating in different segments of the left upper lung in stage I to III non-small cell lung cancer.

BACKGROUND: The aim of this research was to evaluate the effect of spatial location of tumors on the prognosis of patients with left upper lung non-small cell lung cancer (NSCLC), with a focus on the S1+2+3 and lingual segment. METHODS: A total of 486 patients who underwent lobectomy and systematic lymph node dissection were collected retrospectively in this study (354 S1+2+3 and 132 lingual segment patients). Factors impacting survival were assessed via univariate analyses, multivariate analyses, and log-rank tests. RESULTS: Compared with tumor location in S1+2+3, lingual segment tumor location of stage II to III left upper lung NSCLC patients was significantly associated with a better 5-year disease-free survival (DFS) (P=0.041). Multivariate analysis results showed that tumor location in the lingual segment was a good independent prognostic factor of stage II to III left upper lung NSCLC patients [hazard ratio (HR) =0.602, 95% confidence interval (CI): 0.149-0.865, P=0.006). However, in stage I left upper lung NSCLC, tumor location (HR =1.069, 95% CI: 0.571-2.000, P=0.835) was not an independent prognostic factor, and only T2 (HR =2.422, 95% CI: 1.271-4.620, P=0.007) was an independent worse prognosis factor. CONCLUSIONS: Tumor location in the lingual segment of left upper lung stage II to stage III NSCLC is a good independent prognostic factor compared with S1+2+3. Nevertheless, tumor location does not impact the prognosis of patients with stage I NSCLC in the left upper lung.

A New Non-Negative Matrix Co-Factorisation Approach for Noisy Neonatal Chest Sound Separation.

Obtaining high quality heart and lung sounds enables clinicians to accurately assess a newborns cardio-respiratory health and provide timely care. However, noisy chest sound recordings are common, hindering timely and accurate assessment. A new Non-negative Matrix Co-Factorisation based approach is proposed to separate noisy chest sound recordings into heart, lung and noise components to address this problem. This method is achieved through training with 20 high quality heart and lung sounds, in parallel with separating the sounds of the noisy recording. The method was tested on 68 10-second noisy recordings containing both heart and lung sounds and compared to the current state of the art Non-negative Matrix Factorisation methods. Results show significant improvements in heart and lung sound quality scores respectively, and improved accuracy of 3.6bpm and 1.2bpm in heart and breathing rate estimation respectively, when compared to existing methods.

Desmoid-type fibromatosis of the chest wall: a case report.

Desmoid-type fibromatosis (DF), also known as deep fibromatosis or desmoid tumor, is an extremely rare neoplasm that develops from fascia and musculoaponeurotic tissue. These tumors are characterized by slow progressive growth, local invasion, and local recurrence after surgical excision, but they lack metastatic potential. DF accounts for 3.5% of all fibrous tumors, with an annual incidence of approximately 2-4/million. Until now, only a small number of cases have been found in the chest wall. Herein, we present a rare case of chest wall DF in a 43-year-old female, which was discovered accidentally due to a thoracic wall mass that extended outward from the sternum. Computed tomography scans revealed a subcutaneous soft tissue mass anterior to the sternum, which was considered to be a mesenchymal tumor or an inflammatory lesion. The patient underwent surgical excision of the mass. The mass was completely removed and all margins were negative. According to the pathological results, the patient was finally diagnosed as DF. Postoperative radiotherapy was suggested subsequently, especially considering the locally aggressive and infiltrative nature of the tumor. However, this was rejected by the patient, and biannual re-examination was recommended instead. Despite the absence of postoperative radiotherapy, there was no evidence of local recurrence 2 years later. We consider regular postoperative follow-up may be able to replace postoperative radiotherapy, and if there exist an opportunity to completely resect the mass, surgical is a worthwhile choice.

Thalidomide inhibits the gene promoter of connective tissue growth factor in human embryonic lung fibroblasts.

BACKGROUND: The etiology and pathogenesis of idiopathic pulmonary fibrosis (IPF) remain unclear, and the early detection and treatment are vital to the prognosis of IPF patients. It's necessary to investigate the effect of thalidomide on the gene promoter activation of connective tissue growth factor (CTGF) induced by transforming growth factor-ß1 (TGF-ß1) in human embryonic lung fibroblast (HELF). METHODS: The gene vector of pGL3-CTGFP containing human CTGF gene promoter was constructed and transfected into HELF cells. We used different TGF-ß1 (0, 2.5, 5, 10 and 20 µg/L respectively) to stimulate HELF to identify the optimal concentration for gene promoter of CTGF. The activity of luciferase was measured to observe the effect of TGF-ß1 and THALIDOMIDE on the activity of CTGF gene promoter. RESULTS: The relative luciferase activity increased significantly with the stimulation of TGF-ß1, and the relative luciferase activity peaked in the 5 µg/L TGF-ß1 group (all P<0.01). The thalidomide inhibited the TGF-ß1-induced activation of CTGF gene promoter in HELF, and the effect peaked in the 25 µg/L group (all P<0.001). CONCLUSIONS: Thalidomide produces a significant inhibitory effect on the gene promoter activation of CTGF induced by TGF-ß1 in HELF, it may be a potentially effective drug for the treatment of pulmonary fibrosis.