Scapular dislocation following radical surgical excision of lung sarcomatoid carcinoma: A rare case report.

RATIONALE: Scapular prolapse is a rare complication of thoracotomy. Only a few cases of scapular prolapse after thoracotomy have been reported. Here, we report the case of a 52-year-old male patient who underwent standard posterior thoracotomy for lung sarcomatoid carcinoma invading the left upper chest wall. PATIENT CONCERNS: The surgery was performed to remove some ribs and chest wall muscles; however, no reconstruction or repair of the chest wall defect was performed. The patient experienced a sharp pain and severe limitation of movement of the left shoulder within 1 month of receiving adjuvant therapy. DIAGNOSES: The patient was diagnosed with left intrathoracic scapular prolapse after careful consideration of medical history, physical examination, and chest radiography. INTERVENTIONS: We performed closed manual reduction because the patient refused to undergo surgery. OUTCOMES: The patient's shoulder pain and movement limitation were significantly relieved, but the symptoms relapsed. After repeated closed manual reduction, the patient was instructed not to abduct the shoulder joint above 90°. The patient did not relapse during a 1-year observation period. CONCLUSION: If scapular prolapse occurs, manual or surgical reduction can be selected based on the needs. If a patient refuses to undergo surgery, manual reduction can be an effective treatment method.

Clinical utility of cryptococcal antigen detection in transthoracic needle aspirate by lateral flow assay for diagnosing non-HIV pulmonary cryptococcosis: A multicenter retrospective study.

Lateral flow immunoassay (LFA) detection of cryptococcal capsular polysaccharide antigen (CrAg) is reported to be the most rapid and convenient laboratory method for diagnosing cryptococcosis. Its clinical diagnostic use, however, is not well studied. We retrospectively analyzed the data from 97 patients with suspected pulmonary cryptococcosis (PC) at 2 tertiary care centers. CrAg in both serum and lung aspirate specimens were examined by LFA. We divided the patients who were diagnosed with PC into group I, patients positive for CrAg in both the serum and lung aspirate, and group II, patients positive for CrAg in the lung aspirate but not in the serum. We analyzed the differences in imaging distribution, morphological characteristics, and concomitant signs between the 2 groups. Of all 97 patients, 47 were diagnosed with PC. Lung aspirates were positive for CrAg in 46/47 patients with PC (sensitivity 97.9%, specificity 100%, positive predictive value = 100%, negative predictive value = 98%). There were no false positive results in the noncryptococcosis patients, revealing a diagnostic accuracy of 99%. Serum CrAg tests were positive in 36/47 patients with PC (sensitivity 76.6%, specificity 100%, accuracy 88.7%, positive predictive value = 100%, negative predictive value = 82%). Chest imaging data showed a statistically significant greater number of single lesions in group II than in group I (P < .05). More lesions accompanied by halo signs were showed in group I (P < .01), whereas more accompanied by pleural stretch signs were found in group II (P < .01). The LFA-positive rate of CrAg in lung aspirate samples was higher than that of the serum samples, especially in patients with single pulmonary lesion or in those accompanied by pleural stretch. The direct measurement of CrAg in lung aspirate is a rapid, useful alternative diagnostic method for PC confirmation.

Connexin 43 overexpression induces lung cancer angiogenesis in vitro following phosphorylation at Ser279 in its C-terminus.

Blocking angiogenesis can inhibit tumor growth and metastasis. However, the mechanism underlying regulation of lung cancer angiogenesis remains unclear. The gap junction protein connexin 43 (Cx43) is implicated in angiogenesis. The aim of the present study was to determine the role of Cx43 in angiogenesis in vitro and its signaling pathways. Human pulmonary microvascular endothelial cells were transfected with Cx43-targeting siRNA or Cx43-overexpressing recombinant plasmid vector. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to determine Cx43, zonula occludens-1 (ZO-1), E-cadherin, ß-catenin, von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1) mRNA and protein expression levels, respectively. Tyr265, Ser279, Ser368, and Ser373 phosphorylation levels in the C-terminus of Cx43 and intracellular and membranal Cx43 contents were determined using western blotting. Additionally, immunofluorescence, tube formation, Cell Counting Kit-8, and Transwell migration assays were performed. The results revealed that compared with that in the control samples, Cx43, ZO-1, E-cadherin, ß-catenin, vWF, and PAI-1 mRNA and protein expression were significantly increased in the Cx43 overexpression group and significantly decreased in the Cx43-knockdown group. Moreover, the phosphorylation level of Ser279 as well as cell proliferation and migration rates were markedly increased in the Cx43 overexpression group, and tube formation revealed that the potential of angiogenesis was also increased. Conversely, in the Cx43-knockdown group, the phosphorylation level of Ser279 and cell proliferation and migration rates were reduced, and the potential of angiogenesis was greatly impaired. Under Cx43 overexpression, membranal Cx43 content was significantly increased, whereas under Cx43 knockdown, it was significantly reduced. Therefore, Cx43 overexpression could induce pulmonary angiogenesis in vitro by promoting cell proliferation and migration and activating ZO-1, E-cadherin, ß-catenin, vWF, and PAI-1. This may be achieved by promoting phosphorylation and activation of the intracellular signal site Ser279 at the C-terminus of Cx43.

PM2.5 promotes NSCLC carcinogenesis through translationally and transcriptionally activating DLAT-mediated glycolysis reprograming.

BACKGROUND: Airborne fine particulate matter (PM2.5) has been associated with lung cancer development and progression in never smokers. However, the molecular mechanisms underlying PM2.5-induced lung cancer remain largely unknown. The aim of this study was to explore the mechanisms by which PM2.5 regulated the carcinogenesis of non-small cell lung cancer (NSCLC). METHODS: Paralleled ribosome sequencing (Ribo-seq) and RNA sequencing (RNA-seq) were performed to identify PM2.5-associated genes for further study. Quantitative real time-PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC) were used to determine mRNA and protein expression levels in tissues and cells. The biological roles of PM2.5 and PM2.5-dysregulated gene were assessed by gain- and loss-of-function experiments, biochemical analyses, and Seahorse XF glycolysis stress assays. Human tissue microarray analysis and 18F-FDG PET/CT scans in patients with NSCLC were used to verify the experimental findings. Polysome fractionation experiments, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assay were implemented to explore the molecular mechanisms. RESULTS: We found that PM2.5 induced a translation shift towards glycolysis pathway genes and increased glycolysis metabolism, as evidenced by increased L-lactate and pyruvate concentrations or higher extracellular acidification rate (ECAR) in vitro and in vivo. Particularly, PM2.5 enhanced the expression of glycolytic gene DLAT, which promoted glycolysis but suppressed acetyl-CoA production and enhanced the malignancy of NSCLC cells. Clinically, high expression of DLAT was positively associated with tumor size, poorer prognosis, and SUVmax values of 18F-FDG-PET/CT scans in patients with NSCLC. Mechanistically, PM2.5 activated eIF4E, consequently up-regulating the expression level of DLAT in polysomes. PM2.5 also stimulated transcription factor Sp1, which further augmented transcription activity of DLAT promoter. CONCLUSIONS: This study demonstrated that PM2.5-activated overexpression of DLAT and enhancement in glycolysis metabolism contributed to the tumorigenesis of NSCLC, suggesting that DLAT-associated pathway may be a therapeutic target for NSCLC.

Successful resolution of ectopic Cushing syndrome by minimally invasive thoracoscopic resection of the neuroendocrine tumor of the thymus: a rare case report.

BACKGROUND: Ectopic Cushing syndrome (ECS) is a sporadic condition. Even uncommon is an ECS that derives from a carcinoid tumor of the thymus. These tumors may pose several diagnostic and therapeutic conundrums. This report discusses the differential diagnosis, clinicopathological findings, and effective treatment of a rare case of ECS using a minimally invasive approach. CASE PRESENTATION: A 29-year-old woman with Cushing syndrome presented with facial flushing. Physical examination revealed hypertension (blood pressure: 141/100 mmHg). A mediastinal tumor was discovered to be the cause of the patient's chronic hypokalemia and hypercortisolemia. Cortisol levels increased in the morning, reaching 47.7 ug/dL. The levels of the hormones ACTH, aldosterone, and renin were determined to be 281 pg/mL, 3.0 ng/dL, and 2.1 pg/mL, respectively. The presence of hypertension, hypokalemia, and alkalinity suggested Cushing's syndrome, which was proven to be ACTH-dependent ECS by a dexamethasone suppression test. A chest CT scan revealed inflammation in the posterior basal region of the right lower lobe. The superior anterior mediastinum was characterized by round-shaped isodensity lesions with distinct borders. She underwent thoracoscopic anterior mediastinal tumor excision via the subxiphoid technique (R0 resection); following surgery, her blood pressure returned to normal, and the hypernatremia/hypopotassemia resolved. The tumor was determined to be a thymic carcinoid. Most notably, cortisol levels fell to half of their presurgical levels after one hour of surgery, and other abnormalities corrected substantially postoperatively. CONCLUSION: Thoracoscopic excision of thymic tumors by subxiphoid incision may be a useful treatment option for ECS caused by neuroendocrine tumors of the thymus.

Connexins and angiogenesis: Functional aspects, pathogenesis, and emerging therapies (Review).

Connexins (Cxs) play key roles in cellular communication. By facilitating metabolite exchange or interfering with distinct signaling pathways, Cxs affect cell homeostasis, proliferation, and differentiation. Variations in the activity and expression of Cxs have been linked to numerous clinical conditions including carcinomas, cardiac disorders, and wound healing. Recent discoveries on the association between Cxs and angiogenesis have sparked interest in Cx­mediated angiogenesis due to its essential functions in tissue formation, wound repair, tumor growth, and metastasis. It is now widely recognized that understanding the association between Cxs and angiogenesis may aid in the development of new targeted therapies for angiogenic diseases. The aim of the present review was to provide a comprehensive overview of Cxs and Cx­mediated angiogenesis, with a focus on therapeutic implications.

Localization diagnosis of adrenocorticotrophic hormone-dependent Cushing's syndrome: two case reports and literature review.

BACKGROUND: The common causes of adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome (CS) include Cushing's disease (CD) and ectopic ACTH syndrome (EAS). The differential diagnosis and lesion location of CD and EAS often bring great difficulties to clinical diagnosis and treatment. This article reports the localization diagnosis, treatment, and follow-up results of two patients with ACTH-dependent CS with different causes and reviews the literature. CASE DESCRIPTION: Case 1: a 29-year-old female patient attended the clinic because of irregular menstruation, weight gain, and violaceous striae. The low dose dexamethasone suppression test (LDDST) was not suppressed, and the high dose dexamethasone suppression test (HDDST) suggested the results of serum cortisol and 24-h urine free cortisol were contradictory. Magnetic resonance imaging (MRI) indicated pituitary microadenoma, and bilateral inferior petrosal sinus sampling (BIPSS) indicated ACTH was centrally secreted. CD was diagnosed. The patient underwent transsphenoidal surgery, and the symptoms of CS were improved after the operation. A natural pregnancy occurred more than half a year after the surgery, and a healthy baby boy was delivered 9 months later. Case 2: a 29-year-old female patient complained of facial redness and elevated blood pressure. Examination showed refractory hypokalemia and abnormally elevated serum cortisol and ACTH. Androgens also increased. Neither LDDST nor HDDST was inhibited. Chest-to-pelvis computed tomography (CT) scan revealed a soft tissue mass in the anterior mediastinum, considered as a possible thymoma. EAS and thymoma were diagnosed. An anterior mediastinal mass resection was performed, and pathological results suggested thymic carcinoid weakly positive for ACTH. After the operation, hypertension and hypokalemia were relieved, and cortisol, ACTH and androgens returned to normal levels. CONCLUSIONS: The differentiation between CD and EAS should be comprehensively evaluated in combination with the medical history, function tests, pituitary MRI, and other tests. If the function test results are discordant or pituitary MRI shows the lesion diameter is less than 6 mm, BIPSS should be further performed to confirm the diagnosis. The lesions of EAS are complex and diverse, and it is necessary to pay attention to imaging examinations of the neck-to-pelvis to locate lesion and provide direction for subsequent treatment.

Expression of Connexin43 Stimulates Endothelial Angiogenesis Independently of Gap Junctional Communication In Vitro.

Connexins (Cx) form gap junctions (GJ) and allow for intercellular communication. However, these proteins also modulate gene expression, growth, and cell migration. The downregulation of Cx43 impairs endothelial cell migration and angiogenetic potential. Conversely, endothelial Cx43 expression is upregulated in an in vivo angiogenesis model relying on hemodynamic forces. We studied the effects of Cx43 expression on tube formation and proliferation in HUVECs and examined its dependency on GJ communication. Expectedly, intercellular communication assessed by dye transfer was linked to Cx43 expression levels in HUVECs and was sensitive to a GJ blockade by the Cx43 mimetic peptide Gap27. The proliferation of HUVECs was not affected by Cx43 overexpression using Cx43 cDNA transfection, siRNA-mediated knockdown of Cx43, or the inhibition of GJ compared to the controls (transfection of an empty vector, scrambled siRNA, and the solvent). In contrast, endothelial tube and sprout formation in HUVECs was minimized after Cx43 knockdown and significantly enhanced after Cx43 overexpression. This was not affected by a GJ blockade (Gap27). We conclude that Cx43 expression positively modulates the angiogenic potential of endothelial cells independent of GJ communication. Since proliferation remained unaffected, we suggest that Cx43 protein may modulate endothelial cell migration, thereby supporting angiogenesis. The modulation of Cx43 expression may represent an exploitable principle for angiogenesis induction in clinical therapy.

Primary pulmonary extranodal natural killer/T-cell lymphoma (ENKTL), nasal type: Two case reports and literature review.

INTRODUCTION: Extranodal natural killer/T-cell lymphoma (ENKTL) - nasal type is an aggressive form of malignant non-Hodgkin lymphoma with a very poor prognosis. Especially primary pulmonary ENKTL is a relatively rare form of non-Hodgkin lymphoma. Until now, the prevalence of primary pulmonary ENKTL is unknown. Since 2001, only 18 cases of primary pulmonary ENKTL have been published, in addition to the 2 cases reported here. PATIENT CONCERNS: We describe 2 cases of primary pulmonary ENKTL. Both patients were male non-smokers, aged 61 and 49 years. Their main clinical symptoms included cold-like symptoms and intermittent fever (39.3°C and 38.8°C) for some days (40 days and 3 weeks). Both patients had no relevant personal or family medical history. DIAGNOSIS: The patients were initially misdiagnosed with community-acquired pneumonia. Primary pulmonary ENKTL was confirmed by immunohistochemical staining of computed tomography-guided transthoracic needle biopsy specimens. Both cases were positive for CD56, CD3, and in situ hybridization for Epstein-Barr virus-encoded small RNA, but negative for CD20. INTERVENTIONS: Initially, both patients were treated inadequately with intravenous moxifloxacin administration (unknown dosage and 400 mg q.d) in their local hospitals. Once diagnosed with primary pulmonary ENKTL in our hospital, they received 3 cycles of chemotherapy with combined regimens of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE), and in the second patient, bone marrow transplantation was performed following the third chemotherapy cycle. OUTCOMES: Clinical follow-up after the chemotherapy showed that the condition of the first patient progressively deteriorated. He died 2 months following the initial diagnosis. However, the presence of the hemophagocytic lymphohistocytosis gradually improved in the second patient during chemotherapy. Ultimately, the second patient died of acute transplant rejection 6 months after the initial diagnosis. CONCLUSION: The diagnosis of ENKTL should be considered when patients present with fever and expansile consolidation of the lung not responding to antibiotics. The diagnosis depends on histopathology and immunophenotyping. Percutaneous transthoracic needle biopsy is a safe and effective biopsy method. Chemotherapy may improve the prognosis, but this should be confirmed by prospective multicenter studies.

SP1 induced long non-coding RNA LINC00958 overexpression facilitate cell proliferation, migration and invasion in lung adenocarcinoma via mediating miR-625-5p/CPSF7 axis.

BACKGROUND: Increasing evidences have underlined the importance of long non-coding RNAs (lncRNAs) in human malignancies. LINC00958 has been found involved in some cancers. However, the underlying mechanical performance of LINC00958 in lung adenocarcinoma (LAD) has not been explored yet. METHODS: The expression of relevant mRNA and protein were measured by qRT-PCR and western blot assays. EdU, colony formation, TUNEL and transwell assays were performed to investigate the function of LINC00958 on LAD progression. Luciferase reporter, RNA pull down and RIP assays were conducted to investigate the molecular mechanism of relevant RNAs. RESULTS: LINC00958 was found notably overexpressed in LAD, which was associated with the stimulation of its promoter activity induced by SP1. LINC00958 depletion dramatically inhibited LAD cell proliferation, migration and invasion capacities by acting as a miR-625-5p sponge. MiR-625-5p curbed LAD progression via targeting CPSF7 and down-regulating its expression. Mechanically, LINC00958 was identified as a competing endogenous RNA (ceRNA) and positively regulated the expression of CPSF7 via sponging miR-625-5p. CONCLUSIONS: LINC00958 might drive LAD progression via mediating miR-625-5p/CPSF7 axis, indicating the potential of targeting LINC00958 for the treatment of LAD.

Surgical Treatment of Tracheal Lipoma after Multiple Bronchoscopy Interventions and Placements of a Tracheal Stent.

Background The majority of adult primary tracheal tumors are malignant; however, as one type of benign tumors, lipoma is extremely uncommon. Case Description We report a case where lipoma was first misdiagnosed as bronchial asthma, followed by sudden aggravation of dyspnea after trauma, and computed tomography (CT) examination of the neck and chest confirmed a tracheal tumor. Through multiple bronchoscopy interventions and placements of a tracheal stent, little therapeutic benefit was discovered, and resection of the tracheal tumor combined with tracheal end-to-end anastomosis was performed to ultimately achieve a cure. Conclusion Primary tracheal tumors should be highly suspected in patients with recurrent and gradually worsening dyspnea; timely cervical, thoracic CT and bronchoscopy can provide an accurate diagnosis. Surgical radical resection is the only way to cure all benign tracheal tumors such as lipoma.

Surgical treatment of the severe thoracic gastrocutaneous fistula by pedicled muscle flap filling and thoracoplasty after oesophagectomy for oesophageal squamous cell carcinoma: A case report.

BACKGROUND: Thoracic anastomotic fistula (TAF) is a severe postoperative complication of oesophagectomy, and its occurrence coupled with a thoracic gastrocutaneous fistula (TGCF) and tracheostenosis is very unusual and may lead to a fatal consequence. CASE PRESENTATION: We describe a case of an old female diagnosed with mid-oesophageal carcinoma, who presented with a TAF after oesophagectomy, which was healed by an effective treatment, while a severe TGCF and tracheostenosis appeared one month postoperation. The complications were detected by gastroscopy, barium oesophagogram and thoracic computed tomography (CT). Through surgical treatments, including pedicled muscle flap filling and thoracoplasty, and a correlated corrective procedure, the patient completely recovered and was discharged six months after the admission. CONCLUSION: Treatment by pedicled muscle flap filling and thoracoplasty after oesophagectomy for oesophageal squamous cell carcinoma can be a curative alternative for the severe thoracic gastrocutaneous fistula.

TGF-ß1 induces human aortic vascular smooth muscle cell phenotype switch through PI3K/AKT/ID2 signaling.

The vascular smooth muscle cell (VSMC) phenotypic switch is considered to be the key pathophysiological change in various cardiovascular diseases, such as aortic dissection, atherosclerosis, and hypertension. The results in this study showed that TGF-ß1 promotes the proliferation, migration and morphological changes of VSMC.TGF-ß1 promoted the expressions of PI3K, P-PI3K, AKT, P-AKT, ID2, and OPN protein and suppressed the expressions of α-SMA and SM22α protein; the opposite results were observed for TGF-ß1 inhibitor group, AKT inhibitor group and Combined inhibitors group. After the stimulation of TGF-ß1 signaling, the mRNA levels of PI3K, AKT, ID2, and OPN were the highest, while the mRNA levels of α-SMA and SM22α were the lowest; the opposite results were found in the same groups above. These results suggested the PI3K/AKT/ID2 signaling pathway is involved in TGF-ß1-mediated human aortic VSMC phenotypic switching, that is from a contractile to synthetic phenotype, and Combined inhibitors was more effective in inhibiting the phenotypic switch than a single inhibitor. The Combined inhibitors experiments may provide new avenues for the prevention and treatment of thoracic aortic dissection (TAD) that are based on the pathological effects of phenotypic switching.