The Impact of Impurity Gases on the Hydrogen Embrittlement Behavior of Pipeline Steel in High-Pressure H2 Environments.

The use of hydrogen-blended natural gas presents an efficacious pathway toward the rapid, large-scale implementation of hydrogen energy, with pipeline transportation being the principal method of conveyance. However, pipeline materials are susceptible to hydrogen embrittlement in high-pressure hydrogen environments. Natural gas contains various impurity gases that can either exacerbate or mitigate sensitivity to hydrogen embrittlement. In this study, we analyzed the mechanisms through which multiple impurity gases could affect the hydrogen embrittlement behavior of pipeline steel. We examined the effects of O2 and CO2 on the hydrogen embrittlement behavior of L360 pipeline steel through a series of fatigue crack growth tests conducted in various environments. We analyzed the fracture surfaces and assessed the fracture mechanisms involved. We discovered that CO2 promoted the hydrogen embrittlement of the material, whereas O2 inhibited it. O2 mitigated the enhancing effect of CO2 when both gases were mixed with hydrogen. As the fatigue crack growth rate increased, the influence of impurity gases on the hydrogen embrittlement of the material diminished.

Application of the En Bloc Concept Combined with Anatomic Resection in Laparoscopic Hepatectomy.

Laparoscopic hepatectomy has been reported in many studies, and it is the mainstream method of liver resection. In some particular cases, such as when there are tumors adjacent to the cystic bed, surgeons cannot palpate the surgical margins through the laparoscopic approach, which leads to uncertainty about R0 resection. Conventionally, the gallbladder is resected first, and the hepatic lobes or segments are resected second. However, tumor tissues can be disseminated in the above cases. To address this issue, based on the recognition of the porta hepatis and intrahepatic anatomy, we propose a unique approach to hepatectomy combined with gallbladder resection by en bloc anatomic resection in situ. Firstly, after dissecting the cystic duct, without cutting the gallbladder primarily, the porta hepatis is pre-occluded by the single lumen ureter; secondly, the left hepatic pedicle is made free by the gap of the Laennec membrane and Hilar plate; thirdly, the assistant is asked to drag the fundus of the gallbladder, and the liver parenchyma tissue is resected using a harmonic scalpel along the ischemia line on the liver surface and intraoperative ultrasound. The whole middle hepatic vein (MHV) and its tributaries appear completely; lastly, the left hepatic vein (LHV) is disconnected, and the specimen is taken out from the abdominal cavity. The tumor, gallbladder, and other surrounding tissues are resected en bloc, which meets the tumor-free criterion, and a wide incisal margin and R0 resection are achieved. Therefore, the laparoscopic hepatectomy with the combination of the en bloc concept and anatomic resection is a safe, effective, and radical method with low postoperative recurrence and metastasis.

Idiopathic tenosynovitis of the wrist with multiple rice bodies: A case report and review of literature.

BACKGROUND: Multiple rice bodies in the wrist is a rare disorder that requires surgery, and there are still many uncertainties regarding its diagnosis and treatment. CASE SUMMARY: We described a rare case of chronic idiopathic tenosynovitis with rice bodies of the wrist in a 71-year-old man and reviewed similar topics in the literature. A total of 43 articles and 61 cases were included in the literature review. Our case had a usual presentation: it was similar to those in the literature. The affected population was mainly older adults, with an average age of 59.43 (range, 3 to 90) years. The male-to-female ratio was 1.54:1 (37/24).Most of them showed limited swelling and pain, only 23.0% had carpal tunnel symptoms, and the average disease duration was 18.03 (0.5-60) mo. Wrist flexor tendon sheath involvement was the most common (95.1%, 58/61), and only 3 cases had extensor tendon sheath involvement.The main causes were tuberculosis (34.4%, 21/61), non-tuberculous mycobacteria (24.6%, 15/61), idiopathic tenosynovitis (31.1%, 19/61), and others (9.84%, 6/61). There were 10 patients with recurrences; in 6 of them, were due to non-tuberculous mycobacterial infections. CONCLUSION: We reported a case of wrist idiopathic tenosynovitis with rice body formation, and established a clinical management algorithm for wrist tenosynovitis with rice bodies, which can provide some reference for our clinical diagnosis and treatment. The symptoms of rice-body bursitis of the wrist are insidious, nonspecific, and difficult to identify. The aetiology is mainly idiopathic tenosynovitis and mycobacterial (tuberculosis or non-tuberculous) infections; the latter are difficult to treat and require long-duration systemic combination antibiotic therapies. Therefore, before a diagnosis of idiopathic tenosynovitis is made, we must exclude other causes, especially mycobacterial infections.

Wood smoke particulate matter (WSPM2.5) induces pyroptosis through both Caspase-1/IL-1ß/IL-18 and ATP/P2Y-dependent mechanisms in human bronchial epithelial cells.

Emerging evidences have linked the air pollution particulate matters, especially the fine particulate matter PM2.5, to the disease development of chronic obstructive pulmonary disease (COPD). Our previous studies reported that biofuel PM2.5 can induce devastated damage of human bronchial epithelial cells, this study aims to further investigate the underlying molecular mechanisms how biofuel PM2.5 induces bronchial epithelial cell death and dysfunction. In this study, biofuel PM2.5 extracted from wood smoke (WSPM2.5) was used according to our previous publication. A 16-HBE cell line was used as the cell model. Results showed that: Firstly, WSPM2.5 induced significant pyroptosis in 16-HBE cells, reflected by the typical changes including elevated release of lactate dehydrogenase release (LDH) and activated activity and expression of Caspase-1/IL-1ß/IL-18 signaling pathway. Then, specific inhibitors for both Caspases (Z-VAD-FMK) and Caspase-1 (VX-765), as well as specific siRNA knockdown of IL-1ß all effectively attenuated the WSPM2.5-induced upregulation of downstream inflammatory cytokines and chemokines (IL-6, IL-8, CXCL-1, CXCL-2, etc), respectively. Notably, WSPM2.5 caused a novel increase of intracellular-to-extracellular ATP secretion, which could also contribute to the WSPM2.5-induced pyroptosis and inflammation by activating the Caspase-1/IL-1ß/IL-18 signaling pathway through possible autocrine and/or paracrine mechanisms. Antagonism of ATP (Apyrase) or specific siRNA knockdown against ATP receptors (P2Y2 and P2Y7) both significantly inhibited the WSPM2.5-induced pyroptosis and inflammation. These results add up to the current knowledge and bring up novel insights that WSPM2.5 could induce significant pyroptosis and inflammation of human bronchial epithelial cells, through both a classic NLRP3/Caspase-1/IL-1ß-dependent and a novel ATP/P2Y-dependent mechanisms.

[A new measurement method of offset in total hip arthroplasty].

Objective: To report a new offset parameter for total hip arthroplasty (THA)-greater trochanter offset (GTO), and analyze the effectiveness and feasibility of this parameter based on clinical data. Methods: The 47 patients who met the selection criteria and admitted between January 2016 and May 2020 were selected as the research object. The global offset (GO) was used as the offset parameter in preoperative design. Firstly, the test-retest reliability and inter-rater reliability of GTO were analyzed based on pelvic X-ray films. The GTO reconstruction was defined as the difference between the operative side and the healthy side within ±5 mm, and 47 patients were divided into the reconstruction group and the non-reconstruction group. General data (age, gender, type and side of fracture, the interval between injury and operation), visual analogue scale (VAS) score, Harris score, gait score, and leg length discrepancy (LLD) were recorded and compared between two groups. Then, the GTO was used as the offset parameter in preoperative design of 21 patients (GTO group) admitted between June 2020 and December 2020. The pre- and post-operative clinical data were compared between GTO group and GO group to explore the feasibility of GTO for THA. Results: Statistical analysis showed that GTO had good test-retest reliability (P<0.001) and inter-rater reliability (P<0.001). There was no significant difference in gender, age, type and side of fracture, the interval between injury and operation, preoperative VAS score, and LLD at 1 year after operation between the GTO reconstruction group and the non-reconstruction group, as well as between the GO and GTO groups (P>0.05). The Harris score and gait score at 1 year after operation, and difference of VAS score between pre- and post- operation in the reconstruction group and GTO group were significantly better than those in the non-reconstruction group and GO group, respectively (P<0.05). There were 23 cases (48.9%) in the GO group and 19 cases (90.5%) in the GTO group with GTO reconstruction, and the difference was significant (χ2=10.606, P=0.001). There were 25 cases (53.2%) in the GO group and 13 cases (61.9%) in the GTO group with GO reconstruction, and the difference was not significant (χ2=0.447, P=0.504). There were 34 cases (72.3%) in the GO group and 19 cases (90.5%) in the GTO group with LLD reconstruction, and the difference was not significant (χ2=2.777, P=0.096). Conclusion: GTO has reliable test-retest reliability and inter-rater reliability. GTO as a parameter of preoperative offset reconstruction plan of THA can obtain good reconstruction of offset and limb length, and obtain a good effectiveness.

Platelet-lymphocyte ratio is a prognostic marker in small cell lung cancer-A systemic review and meta-analysis.

Aim: The aim of this study was to evaluate the relationship between platelet-lymphocyte ratio (PLR) and prognosis in small cell lung cancer (SCLC) patients. Method: A comprehensive search was carried out to collect related studies. Two independent investigators extracted the data of hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) or progression-free survival (PFS). A random-effect model was applied to analyze the effect of different PLR levels on OS and PFS in SCLC patients. Moreover, subgroup analysis was conducted to seek out the source of heterogeneity. Results: A total of 26 articles containing 5,592 SCLC patients were included for this meta-analysis. SCLC patients with a high PLR level had a shorter OS compared with patients with a low PLR level, in both univariate (HR = 1.56, 95% CI 1.28-1.90, p < 0.0001) and multivariate (HR = 1.31, 95% CI 1.08-1.59, p = 0.007) models. SCLC patients with a high PLR level had a shorter PFS compared with patients with a low PLR level, in the univariate model (HR = 1.71, 95% CI 1.35-2.16, p < 0.0001), but not in the multivariate model (HR = 1.17, 95% CI 0.95-1.45, p = 0.14). Subgroup analysis showed that a high level of PLR shortened OS in some subgroups, including the Asian subgroup, the younger subgroup, the mixed-stage subgroup, the chemotherapy-dominant subgroup, the high-cutoff-point subgroup, and the retrospective subgroup. PLR level did not affect OS in other subgroups. Conclusion: PLR was a good predictor for prognosis of SCLC patients, especially in patients received chemotherapy dominant treatments and predicting OS. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022383069.

IL-17-Mediated Inflammation Promotes Cigarette Smoke-Induced Genomic Instability.

(1) Background: Chronic inflammation has been regarded as a risk factor for the onset and progression of human cancer, but the critical molecular mechanisms underlying this pathological process have yet to be elucidated. (2) Methods: In this study, we investigated whether interleukin (IL)-17-mediated inflammation was involved in cigarette smoke-induced genomic instability. (3) Results: Higher levels of both IL-17 and the DNA damage response (DDR) were found in the lung tissues of smokers than in those of non-smokers. Similarly, elevated levels of IL-17 and the DDR were observed in mice after cigarette smoke exposure, and a positive correlation was observed between IL-17 expression and the DDR. In line with these observations, the DDR in the mouse lung was diminished in IL-17 KO when exposed to cigarette smoke. Besides this, the treatment of human bronchial epithelium cells with IL-17 led to increased levels of the DDR and chromosome breakage. (4) Conclusions: These results suggest that cigarette smoke induces genomic instability at least partially through IL-17-mediated inflammation, implying that IL-17 could play an important role in the development of lung cancer.

Nitric oxide in occurrence, progress and therapy of lung Cancer: a systemic review and meta-analysis.

BACKGROUND: Nitric oxide (NO) plays an important role in lung cancer. However, the results of previous studies about NO in the occurrence, progress and therapy were not consistent. Therefore, we conducted a meta-analysis to evaluate the relationship between NO and lung cancer. METHOD: We carried out comprehensive search in the databases, and collected related studies. The data of fraction of exhaled nitric oxide (FeNO) or blood NO in different populations (lung cancer patients and control subjects) and different time points (before therapy and after therapy) were extracted by two investigators. A random effect model was applied to analyze the differences of FeNO and blood NO in different populations and different time points. To further compare NO level of each subgroup with different pathological types and different stages, a network meta-analysis (NMA) was performed. RESULTS: Fifty studies including 2551 cases and 1691 controls were adopted in this meta-analysis. The FeNO (SMD 3.01, 95% CI 1.89-4.13, p < 0.00001) and blood NO (SMD 1.34, 95% CI 0.84-1.85, p < 0.00001) level in lung cancer patients was much higher than that in control subjects. NMA model indicated blood NO level in each cancer type except SCLC was higher than that in control patients. There was no significant difference of blood NO level among four kinds of lung cancer patients. Blood NO level in LCC patients (SUCRA = 83.5%) was the highest. Blood NO level in advanced stage but not early stage was higher than that in control subjects. Patients in advanced stage (SUCRA = 95.5%) had the highest blood NO level. No significant difference of FeNO (SMD -0.04, 95% CI -0.46-0.38, p > 0.05) and blood NO level (SMD -0.36, 95% CI -1.08-0.36, p > 0.05) was observed between pretreatment and posttreatment in all patients. However, FeNO level elevated (SMD 0.28, 95% CI 0.04-0.51, p = 0.02) and blood NO level decreased in NSCLC patients (SMD -0.95, 95% CI -1.89-0.00, p = 0.05) after therapy. CONCLUSION: FeNO and blood NO level would contribute to diagnosis of lung cancer and evaluation of therapy effect, especially for NSCLC patients.

Senescence associated long non-coding RNA 1 regulates cigarette smoke-induced senescence of type II alveolar epithelial cells through sirtuin-1 signaling.

OBJECTIVE: The primary aim of our study was to explore the mechanisms through which long non-coding RNA (lncRNA)-mediated sirtuin-1 (SIRT1) signaling regulates type II alveolar epithelial cell (AECII) senescence induced by a cigarette smoke-media suspension (CSM). METHODS: Pharmacological SIRT1 activation was induced using SRT2104 and senescence-associated lncRNA 1 (SAL-RNA1) was overexpressed. The expression of SIRT1, FOXO3a, p53, p21, MMP-9, and TIMP-1 in different groups was detected by qRT-PCR and Western blotting; the activity of SA-ß gal was detected by staining; the binding of SIRT1 to FOXO3a and p53 gene transcription promoters was detected by Chip. RESULTS: We found that CSM increased AECII senescence, while SAL-RNA1 overexpression and SIRT1 activation significantly decreased levels of AECII senescence induced by CSM. Using chromatin immunoprecipitation, we found that SIRT1 bound differentially to transcriptional complexes on the FOXO3a and p53 promoters. CONCLUSION: Our results suggested that lncRNA-SAL1-mediated SIRT1 signaling reduces senescence of AECIIs induced by CSM. These findings suggest a new therapeutic target to limit the irreversible apoptosis of lung epithelial cells in COPD patients.

Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non-small cell lung cancer cells.

Crizotinib, an inhibitor of the hepatocyte growth factor receptor oncogene, has been studied extensively regarding its antitumor and clinically beneficial effects in non-small cell lung cancer (NSCLC). However, crizotinib's effects on cancer cell energy metabolism, which is linked with tumor proliferation and migration, in NSCLC are unclear. Therefore, the present study focused on crizotinib's effect on NSCLC glucose metabolism. Crizotinib's effects on glucose metabolism, proliferation, migration and apoptosis in A549 cells were explored. Several other inhibitors, including 2-DG, rotenone and MG132, were used to define the mechanism of action in further detail. Data showed that crizotinib treatment reduced A549 cell viability, increased glucose consumption and lactate production, while decreased mitochondrial transmembrane potential (Δψm) and ATP production. Crizotinib treatment, combined with rotenone and MG132 treatment, further inhibited ATP production and Δψm and increased reactive oxygen species content. However, crizotinib did not suppress cell proliferation, migration, ATP production, Δψm or mitochondrial-related apoptosis signals further following 2-DG-mediated inhibition of glycolysis. These results indicated that crizotinib induced low mitochondrial function and compensatory high anaerobic metabolism, but failed to maintain sufficient ATP levels. The alternation of metabolic pattern and insufficient ATP supply may serve important roles in the metabolic antitumor mechanism of crizotinib in A549 cells.

Diagnostic value of microRNA-25 in patients with non-small cell lung cancer in Chinese population: A systematic review and meta-analysis.

OBJECTIVE: Previous studies have shown that microRNA-25 (miR-25) plays a key role in the occurrence and development of non-small cell lung cancer (NSCLC). Many studies have shown that there is a significant increment of miR-25 in circulating blood of patients with NSCLC. The meta-analysis aims to explore diagnostic value of miR-25 in NSCLC in Chinese population. METHODS: PubMed, Web of science, Excerpta Medica Database, China national knowledge infrastructure and China Wanfang database were searched to collect studies upon correlation between miR-25 and diagnosis of the patients with NSCLC until April 2020. Combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under receiver operating characteristic curve were calculated by Stata 15.0 software. Literature assessment was conducted according to quality assessment of diagnostic accuracy studies, and documents with scores above or equal to 11 were included in this meta-analysis. RESULTS: Six studies were included, including 480 cases with NSCLC and 451 healthy controls. The combined sensitivity (0.75, 95% confidence interval [CI]: 0.69∼0.80), specificity (0.81, 95% CI: 0.76∼0.86), positive likelihood ratio (4.04, 95% CI: 3.14∼5.20), negative likelihood ratio (0.31, 95% CI: 0.25∼0.37), diagnostic odds ratio (13.09, 95% CI: 9.37∼18.29) and area under curve (0.85, 95% CI: 0.82∼0.88) indicated that miR-25 had desirable diagnostic accuracy for NSCLC. CONCLUSION: MiR-25 can be applied in diagnosis of NSCLC and has potential of becoming a biomarker for detection of patients with early NSCLC in Chinese population.

CD147 Promoted Epithelial Mesenchymal Transition in Airway Epithelial Cells Induced by Cigarette Smoke via Oxidative Stress Signaling Pathway.

Chronic obstructive pulmonary disease (COPD) is a common airway disease, and epithelial mesenchymal transition (EMT) is participated in the pathogenesis of COPD. However, the role of CD147 in COPD remains largely unknown. In order to clarify the role of CD147 in EMT induced by cigarette smoke, we established animal and cell model of EMT by mean of cigarette smoke exposure and detected the expressions of CD147 and EMT markers via PCR, WB and IF. RNA inference was applied to study the role of CD147 in CSE induced EMT in vitro. NAC and H2O2 were used to study oxidative stress signaling pathway in this model. As a result, cigarette smoke exposure upregulated the expressions of CD147, α-SMA, and Vimentin and downregulated the expression of Ecadherin and ZO1 both in vivo and in vitro, which was accompanied by augmented level of oxidative stress. CD147 knockdown would partly inhibit CSE induced EMT, while preincubation of H2O2 could inverse this effect. In conclusion, CD147 promoted EMT in mice and HBE cells induced by cigarette smoke via oxidative stress signaling pathway.

Meta-analysis of diagnostic and prognostic value of miR-126 in non-small cell lung cancer.

In recent years, many studies on the relationship between the expression of microRNA-126 (miR-126) and the diagnostic and prognostic value of non-small cell lung cancer (NSCLC) have been made, but the results were still controversial. The aim is to explore the expression of miR-126 and the diagnosis and prognosis value of NSCLC, and to provide relevant evidence for clinical diagnosis and treatment. Literature related to miR-126 and NSCLC were searched in PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang from the inception to February 2020. Stata 15.0 was used for meta-analysis. The diagnostic value data were used to calculate the pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the prognostic value data were used to calculate the pooled risk ratio (hazard ratio, HR) of overall survival (OS) and its 95% confidence interval (95% CI). Thirteen studies were included, among which five were related to diagnosis containing 439 patients and 463 healthy controls, and eight related to prognosis containing 1102 patients. The results of miR-126 expression and diagnostic value of NSCLC showed that the pooled sensitivity was 0.83 (95% CI: 0.59-0.94), specificity = 0.83 (95% CI: 0.71-0.90), PLR = 4.78 (95% CI: 2.97-7.69), NLR = 0.20 (95% CI: 0.08-0.54), DOR = 23.48 (95% CI: 7.87-70.10), and the area under the summ ary receiver operating characteristic curve (SROC) was 0.89 (95% CI: 0.86-0.91). The results of prognostic value indicated that the expression of miR-126 was related to the OS of NSCLC (HR = 0.79, 95% CI: 0.63-0.98). In conclusion, the expression of miR-126 has medium diagnostic value, and it is related to the prognosis of patients with NSCLC, with poor prognosis of miR-126 low expression.

Serine Deficiency Exacerbates Inflammation and Oxidative Stress via Microbiota-Gut-Brain Axis in D-Galactose-Induced Aging Mice.

Inflammation and oxidative stress play key roles in the process of aging and age-related diseases. Since serine availability plays important roles in the support of antioxidant and anti-inflammatory defense system, we explored whether serine deficiency affects inflammatory and oxidative status in D-galactose-induced aging mice. Male mice were randomly assigned into four groups: mice fed a basal diet, mice fed a serine- and glycine-deficient (SGD) diet, mice injected with D-galactose and fed a basal diet, and mice injected with D-galactose and fed an SGD diet. The results showed that D-galactose resulted in oxidative and inflammatory responses, while serine deficiency alone showed no such effects. However, serine deficiency significantly exacerbated oxidative stress and inflammation in D-galactose-treated mice. The composition of fecal microbiota was affected by D-galactose injection, which was characterized by decreased microbiota diversity and downregulated ratio of Firmicutes/Bacteroidetes, as well as decreased proportion of Clostridium XIVa. Furthermore, serine deficiency exacerbated these changes. Additionally, serine deficiency in combination with D-galactose injection significantly decreased fecal butyric acid content and gene expression of short-chain fatty acid transporters (Slc16a3 and Slc16a7) and receptor (Gpr109a) in the brain. Finally, serine deficiency exacerbated the decrease of expression of phosphorylated AMPK and the increase of expression of phosphorylated NFκB p65, which were caused by D-galactose injection. In conclusion, our results suggested that serine deficiency exacerbated inflammation and oxidative stress in D-galactose-induced aging mice. The involved mechanisms might be partially attributed to the changes in the microbiota-gut-brain axis affected by serine deficiency.

Effects of genistein on lipopolysaccharide-induced injury of mouse alveolar epithelial cells and its mechanism.

Alveolar and bronchial epithelial cells have critical functions in acute respiratory distress syndrome progress. Genistein could protect the lungs from acute lung injury, however, whether genistein protects the alveolar epithelial cells from LPS-induced injury was less studied. Spectrophotometric method 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and enzyme-linked immunosorbent assay (ELISA) were performed to detect cell viability and levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6. Flow cytometry and western blot assay were performed to detect cells apoptosis and protein levels. In LPS-induced model of mouse lung epithelial (MLE)-12 cells, PBEF (proinflammatory cytokine) expression, and cell apoptosis were increased and cell viability was decreased, whereas NF-κB was activated and expression levels of TNF-α, IL-1ß, and IL-6 were increased. However, genistein partly reversed the effect of LPS, and it plays a protective role in lung injury by reducing expression of PBEF, inhibiting the activation of NF-κB and alleviating inflammatory response of cells.

Identification of a novel homozygous mutation in the MYO15A gene in a Kazakh family with non-syndromic hearing loss.

BACKGROUND: Millions of people around the world are plagued by hearing loss. More than 50% of congenital or pre-lingual deafness is associated with genetic factors and has highly genetic heterogeneity. To date, although hundreds of genes have been found to be implicated in non-syndromic deafness, there are still lots of genes or loci that we need to verify. METHODS: In this study, we performed target sequencing and Sanger sequencing in a Kazakh consanguineous family with autosomal recessive non-syndromic hearing loss. Following that, functional and structural studies predicted the pathogenic effect of novel mutations by use of the online tools. RESULTS: We identified a novel homozygous mutation p.R3191C in MYO15A gene causing deafness in this family. The mutation p.R3191C co-segregated with the disease phenotype in this family and was not present in any public databases. Automatic tools predict that the novel mutation makes a great impact on the function and structure of MYO15A protein. CONCLUSIONS: This is a novel mutation of MYO15A causing deafness and also the first report of MYO15A mutations causing deafness in the Kazakh families. This finding expanded the spectrum of MYO15A mutations, making it more precise for future genetic diagnosis in patients with deafness.

Primary endobronchial liposarcoma successfully resected via bronchoscopy: A rare case report with genetic analysis.

Liposarcoma is the most common type of soft-tissue sarcoma, and predominantly originates from the extremities and retroperitoneal cavity. However, primary endobronchial liposarcoma is extremely rare. The present study reports on the case of a 54-year-old man, a smoker, diagnosed with primary endobronchial atypical lipomatous tumor/well-differentiated liposarcoma (ALT-WDLS), which was successfully resected via bronchoscopy. Chest computed tomography (CT) revealed a neoplasm in the left main bronchus measuring 12.8×7.8 mm. Bronchoscopy demonstrated multiple roundish, pedunculated, polypoid masses in the left main bronchus. Bioptic specimens were obtained from the roundish masses, and pathological examination revealed an adipose tissue-derived tumor. The masses were completely resected during the second bronchoscopy under general anesthesia. Histopathological examination of the radical resection specimen revealed that it was an ALT-WDLS. The patient showed good quality of life at the 6-month postoperative follow-up without evidence of recurrence. Immunohistochemistry was completed with the human homologue of murine double-minute type 2 (MDM2) (+), cyclin-dependent kinase 4 (CDK4) (+), p16 (+), S-100 (+), Ki-67 (+), cluster of differentiation 34 (CD34) (+) and retinoblastoma protein (+), confirming ALT-WDLS. However, the fluorescence in situ hybridization assay revealed no amplification of MDM2 and CDK4 in the ALT-WDLS. To the best of our knowledge, the present case report is the first to describe the clinicopathologic features and genetic analysis of endobronchial liposarcoma. Although rare, this case is a reminder that clinicians should consider the possibility of this rare endobronchial tumor in patients with nonspecific symptoms including chronic cough, chest pain and recurrent pneumonia. As in this case, endoscopic treatment provided an excellent clinical outcome in patients with primary endobronchial ALT-WDLS.

MTOR Suppresses Cigarette Smoke-Induced Epithelial Cell Death and Airway Inflammation in Chronic Obstructive Pulmonary Disease.

Airway epithelial cell death and inflammation are pathological features of chronic obstructive pulmonary disease (COPD). Mechanistic target of rapamycin (MTOR) is involved in inflammation and multiple cellular processes, e.g., autophagy and apoptosis, but little is known about its function in COPD pathogenesis. In this article, we illustrate how MTOR regulates cigarette smoke (CS)-induced cell death, airway inflammation, and emphysema. Expression of MTOR was significantly decreased and its suppressive signaling protein, tuberous sclerosis 2 (TSC2), was increased in the airway epithelium of human COPD and in mouse lungs with chronic CS exposure. In human bronchial epithelial cells, CS extract (CSE) activated TSC2, inhibited MTOR, and induced autophagy. The TSC2-MTOR axis orchestrated CSE-induced autophagy, apoptosis, and necroptosis in human bronchial epithelial cells; all of which cooperatively regulated CSE-induced inflammatory cytokines IL-6 and IL-8 through the NF-κB pathway. Mice with a specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly augmented airway inflammation and airspace enlargement in response to CS exposure, accompanied with enhanced levels of autophagy, apoptosis, and necroptosis in the lungs. Taken together, these data demonstrate that MTOR suppresses CS-induced inflammation and emphysema-likely through modulation of autophagy, apoptosis, and necroptosis-and thus suggest that activation of MTOR may represent a novel therapeutic strategy for COPD.