Advances and perspectives of nanozymes in respiratory diseases.

Respiratory diseases, some of the most common human diseases, have become a prominent public health and medical problem. Feasible treatment and prevention strategies are still required to prepare for respiratory emergencies. Nanotechnology has provided new technological conceptions in respiratory disease-related applications and inspired the exploration of various multifunctional nanomaterials. Among them, "nanozymes" with enzyme-like activities and nanomaterials' physicochemical properties may propel the development in this field. Over the past few decades, nanozymes have distinguished themselves in the fields of biosensing, biomedicine, imaging, and environmental protection due to their outstanding enzymatic properties, reactive oxygen species-regulating mechanism, high stability, modifiability, mass production, and others. Herein, this article reviews the research progress of nanozymes in diagnosing, treating, and preventing respiratory diseases, hoping to bring new ideas for promoting nanozymes and their beneficial applications in respiratory diseases.

Correlation between morphological features of the anterior cruciate ligament: A quantitative study using a porcine model.

Introduction: Knowledge of the morphological features of the anterior cruciate ligament (ACL) is critical for accurate reconstruction of it. This study aimed to explore the quantitative correlations among different morphological features of the ACL, thus to provide useful information for improving anatomical reconstruction techniques and designing artificial ligaments. Methods: 19 porcine knees were fixed at full extension using 10% formalin and were dissected to expose the ACL. ACL lengths were measured using a caliper. Mid-substances of the ACL were cut and scanned using X-ray microscopy, and the cross-sectional area (CSA) was measured at the isthmus. Margins of direct and indirect bone insertion sites were distinguished and marked. Measurements were performed on digital photographs to obtain the areas of bone insertions. Statistical analysis using nonlinear regression was used to identify potential correlations among the measurements. Results: The results showed that the CSA at the isthmus was significantly correlated with the total area of the bone insertion sites and the area of tibial insertion. The area of the tibial insertion was significantly correlated with the area of its direct insertion site. In contrast, the area of the femoral insertion was significantly correlated with the area of its indirect insertion site. The area of the indirect tibial insertion showed a weak correlation with the length of ACL, whereas the length of the ACL was not able to predict or be predicted by any other parameters. Conclusions: The CSA at the ACL isthmus is more representative for assessing the size of the ACL. However, ACL length has little correlation with the CSA of the isthmus or bone insertion sites, and thus should be evaluated independently for ACL reconstruction.

Immunoregulatory Effect of Short-Chain Fatty Acids from Gut Microbiota on Obstructive Sleep Apnea-Associated Hypertension.

The intestine is the largest bacterial ecosystem and immune response organ of the human body. The microbiota regulates the metabolic and immune functions of the host through their metabolites. Short-chain fatty acids (SCFAs) are part of the metabolites of the gut microbiota (GM), providing energy to intestinal epithelial cells and regulating the immune system. A decrease in SCFA-producing bacteria, imbalanced effector T-helper cells (Th cells), and increasing corresponding inflammatory cytokine were found in both animal models and clinical patients with obstructive sleep apnea (OSA) and hypertension (HTN). Intervention with probiotics, prebiotics, or postbiotics in animal models simulating OSA-associated HTN restored blood pressure to normal, which allows the hypothesis that GM are involved in the pathophysiology of OSA-induced HTN patients through their metabolites' SCFAs; however, the exact regulatory mechanism is not completely clear. This review describes the potential mechanisms of SCFAs, a major metabolite of the GM, in the pathology of OSA-induced HTN, from the perspective of immune system regulation in the available studies.

Alterations of oral microbiota in patients with obstructive sleep apnea-hypopnea syndrome treated with continuous positive airway pressure: a pilot study.

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for cardiovascular diseases, including hypertension. In our previous study, it was demonstrated that oral microbiota alteration in patients with OSAHS, particularly in the genera Aggregatibacter and Porphyromonas, may influence the development of hypertension. Continuous positive airway pressure (CPAP) is the main therapy for OSAHS and OSAHS-associated hypertension. However, the role of oral microbiota post CPAP treatment remains unknown. METHODS: We conducted 16S rDNA pyrosequencing and bioinformatic analyses to compare the bacterial composition of oral specimens from patients with OSAHS before and after overnight CPAP treatment. RESULTS: This approach enabled a relatively comprehensive description of oral microbiota, with decreases in Gemella and increases in Staphylococcus, f_Lachnospiraceae, Parabacteroides, and f_Ruminococcaceae after CPAP treatment. CONCLUSION: Alteration of oral microbiota may shed new insight on the underlying pathogenesis of OSAHS-associated hypertension.

Disturbances of the Gut Microbiota, Sleep Architecture, and mTOR Signaling Pathway in Patients with Severe Obstructive Sleep Apnea-Associated Hypertension.

Intermittent hypoxia and sleep fragmentation are pathophysiological processes involved in obstructive sleep apnea (OSA) which affect gut microbiota, sleep architecture, and mTOR signaling pathway. However, the involvement of these elements in the pathogenesis mechanism of OSA-associated hypertension remains unclear. Therefore, this study investigated whether the OSA-associated hypertension mechanism is regulated by the gut microbiota and mTOR signaling pathway. Patients were diagnosed by polysomnography; their fecal samples were obtained and analyzed for their microbiome composition by 16S ribosomal RNA pyrosequencing and bioinformatics analysis. Transcript genes on fasting peripheral blood mononuclear cells (PBMCs) were examined using Illumina RNA-sequencing analysis. Totally, we enrolled 60 patients with severe OSA [without hypertension (n = 27) and with hypertension (n = 33)] and 12 controls (neither OSA nor hypertension). Results revealed that severe-OSA patients with hypertension had an altered gut microbiome, decreased short-chain fatty acid-producing bacteria (P < 0.05), and reduced arginine and proline metabolism pathways (P=0.001), compared with controls; also, they had increased stage N1 sleep and reduced stages N2 and N3 sleep accompanied by repeated arousals (P < 0.05). Analysis of PBMCs using the Kyoto Encyclopedia of Genes and Genomes database showed that the mTOR signaling pathway (P=0.006) was the most important differential gene-enriched pathway in severe-OSA patients with hypertension. Our findings extend prior work and suggest a possibility that the regulation of the mTOR signaling pathway is involved in developing OSA-associated hypertension through its interaction with the disturbance of the gut microbiome and sleep architecture.

Comparison of 3D Printing Rapid Prototyping Technology with Traditional Radiographs in Evaluating Acetabular Defects in Revision Hip Arthroplasty: A Prospective and Consecutive Study.

OBJECTIVE: To compare rapid prototyping technology (RP tech) in revision total hip arthroplasty (RTHA) with traditional examination methods and to see how they are different in evaluating acetabular anatomy and designing surgical procedure. METHODS: From February 2014 to March 2018, 43 RTHA patients with complex acetabulum defects were enrolled in this prospective study regardless of age or gender. Incomplete and unclear data were excluded. Three types of radiographic examination were performed on each patient before the revision surgery. Four groups of evaluations were designed: (i) X-ray; (ii) computed tomography (CT-scan); (iii) RP tech; and (iv) CT-aided RP tech. Discrepancies between preoperative radiographic analysis and intra-operative findings were separately compared by a team of surgeons. Premade surgical plans based on each evaluation method were compared with the final surgical procedure. The compliance of anatomic evaluation and surgical plan-design based on 3D RP tech and traditional radiographs were ranked manually by a of team surgeons into: (i) complete accordance; (ii) general accordance; and (iii) undetermined structure/procedure. The difference in ranks between RP tech and traditional radiographic methods were analyzed with a nonparametric Kruskal-Wallis test. P < 0.05 was considered significant. Multiple adjustments were taken for the statistical tests level according to the Bonferroni method. RESULTS: For anatomic analysis, the accordance in four groups of evaluating methods differed from each other (P < 0.05) except for the comparison of RP tech and CT-aided RP tech. RP tech displayed better anatomic evaluating accuracy than traditional methods (X-ray and CT) with the "complete accordance" rates of these groups being 88.37%, 4.65% and 27.91%, respectively. But CT-aided RP tech did not improve accuracy significantly compared with using RP tech individually, although the value seems high in the CT-aided RP group with the "complete accordance" rate of 95.35%. For surgery design, RP tech significantly showed better applicable surgical design compared with X-ray and CT (P < 0.05), and the "complete accordance" rates were 88.37%, 6.98% and 23.26%, but no significant difference was observed between RP tech and CT-aided RP tech, and the "complete accordance" rate of CT-aided RP tech group was 97.67%. RP tech showed remarkable improvement in bone defect assessment and surgical plan design. CONCLUSION: Using RP technology improved both sensibility and accuracy in acetabular defect evaluation with better locating and evaluating efficiency compared with X-ray and CT-scans. It also improved surgical schedule designing in complex acetabular defecting revision surgery. In particularly complex cases, CT aided RP tech may increase the accuracy of RP tech.

The association between the incidence risk of pneumonitis and PD-1/PD-L1 inhibitors in advanced NSCLC: A meta-analysis of randomized controlled trials.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) have shown a significant efficacy for patients with non-small cell lung cancer (NSCLC). However, checkpoint inhibitor pneumonitis (CIP) is a rare but severe and life-threatening adverse event. Hence, we performed a systematic review and meta-analysis to evaluate the incidence and risk of CIP in patients with NSCLC. METHODS: Pubmed, Embase, Cochrane Library and ClinicalTrials.gov (http://clinicaltrials.gov/) were searched up to December 15, 2020. Studies regarding all-grade and high-grade pneumonitis were included. The data was analyzed using meta-packages of R 3.6.0. RESULTS: A total of sixteen randomized controlled trials including 9500 patients were identified for further evaluation. The overall incidence of all-grade and high-grade CIP was 4.17% and 2.02%, respectively. Compared with conventional chemotherapy, patients treated with ICIs significantly increased risk of all-grade (RR: 4.11, p < 0.0001) and high-grade (RR: 3.16, p < 0.0001) pneumonitis. Subgroup analysis showed the ICIs combined with chemotherapy was associated with a higher incidence of CIP than monotherapy alone (6.03% vs 3.32%, p = 0.01). And the rate of death owing to CIP was higher than chemotherapy-mediated pneumonitis. CONCLUSION: There were a higher incidence and risk of pneumonitis with the application of ICIs when compared with chemotherapy. Higher mortality rate of pneumonitis was more frequent in ICIs group. Thus, early detection, proper administration and optimal management are needed for physicians prevent potentially CIP deterioration.

Clinical features and risk factors associated with severe COVID-19 patients in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004). CONCLUSIONS: The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.

Transcriptome analysis identifies the differentially expressed genes related to the stemness of limbal stem cells in mice.

Limbal stem cells (LSCs) reside in the basal layer of limbal epithelial cells (LECs). They are crucial for maintenance of corneal epithelium homeostasis and corneal wound healing. Their stemness is determined by their gene expression pattern. Despite of several positive identifiers have been reported, the unique biomarker for LSCs still remain elusive. Differentially expressed genes (DEGs) between stem cells and differentiated cells affect the fate of stem cells via specific signaling pathway. In order to understand the DEGs in the LSCs, RNA-seq was firstly conducted using a mouse model. A total of 1907 up-regulated DEGs and 395 down-regulated DEGs were identified in the limbus (L) compared to central cornea (CC) and conjunctiva (Cj). Reliability of the expression of genes from RNA-seq analysis was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence staining. The expression pattern of putative biomarkers was considered to be age-related. In up-regulated DEGs GO analysis, 570 gene ontology (GO) terms were significantly enriched. Five groups of genes related with biological processes from these significantly enriched GO terms comprised ionic transport, regulation of tissue development, muscle contraction, visual perception, and cell adhesion, which were clustered as a weighted similar network. Whereas, in down-regulated DEGs GO analysis, 61 GO terms were significantly enriched and only one group of ATP biosynthesis and metabolic process were clustered. Furthermore, we identified 55 signaling pathways by the Kyoto Encyclopedia of Genes and Genomes (KEGG) database based on up-regulated genes and 14 KEGG pathways based on down-regulated genes. In this study, we provide a landscape of the expression of putative LSCs biomarkers and stemness-related signaling pathways in a mouse model. Our findings could aid in the identification of LSC niche factors that may be related to the stemness of the LSCs.

Dexamethasone Versus Prednisone or Prednisolone for Acute Pediatric Asthma Exacerbations in the Emergency Department: A Meta-Analysis.

OBJECTIVE: This study evaluates the efficacy and tolerability of dexamethasone (DEX) as an alternative to prednisone/prednisolone (PRED) for the treatment of pediatric asthma exacerbations in emergency department (ED). METHODS: Fixed-effects meta-analyses of selected endpoints were performed by using data taken from relevant studies identified by following a priori eligibility criteria after a comprehensive literature search in several electronic databases. RESULTS: Data from 10 studies (3208 pediatric asthma patients [1616 DEX treated and 1592 PRED treated], 4.77 years [95% confidence interval, 3.80-5.56 years], 63% [57.76%-62.68%] males) were used. Risk of vomiting drug was significantly lower in DEX group than in PRED group (risk ratio, 0.29 [0.18-0.48]; P ˂ 0.00001). Emergency department stay between DEX and PRED treated patients was statistically different (0.16 [0.03-0.40] hours; P = 0.02) but may not be clinically meaningful. The number of ß-agonist therapies received by DEX- and PRED-treated patients was similar. Treatments with both DEX and PRED were associated with improvement in asthma status assessment scores, and there was no significant difference between the groups. There were also no differences between the groups in hospitalization rate, ED revisit rate, and hospital admission rate after relapse. CONCLUSIONS: Dexamethasone is a suitable alternative to PRED for the treatment of pediatric asthma exacerbation in ED.

CT-guided percutaneous implantation of 125I particles in treatment of early lung cancer.

BACKGROUND: To analyze the efficacy of computed tomography (CT)-guided implantation of 125I radioactive particles in treatment of early lung cancer. METHODS: Six patients were analyzed, including 4 squamous cell carcinoma, 1 adenocarcinoma, and 1 small cell lung cancer. TPS software was used to calculate the therapeutic dose amount of particles implanted, and the spacing and distribution of seeds in the target area and adjacent tissues. Under the guidance of CT, 20-55 particles were implanted at each site, with the total number of radioactive particles being 226, the particle spacing being 0.5-1.0 cm, and the implantation being performed in accordance with the principle of uniform implantation. The patients were each followed up with repeated pulmonary CT scans at 1, 3, 6, 12, 18, 24, 30 and 36 months after the procedure. In accordance with the response evaluation criteria in solid tumors (RECIST), the following definitions for responses were used: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD). RESULTS: There were 2 CRs and 4 PRs one month after procedure; six patients were followed up 3 months after procedure, including 2 CRs and 4 PRs; one patient was lost in follow-up, and 5 patients were followed up 6 months after procedure, including 3 CRs and 2 PRs; five patients were followed up 12 months after procedure, including 3 CRs, 1 PR and 1 PD. The single PD patient was again given CT-guided implantation of 125I radioactive particles for the treatment of recurrent lesions. The pulmonary CT was repeated 6 months after procedure, and the response was evaluated as SD. Four patients were followed up 18 months after procedure, including 3 CRs and 1 PR; one patient was lost in follow-up and 3 patients were followed up 24 months after the procedure with the response being evaluated as CR for all of them; one patient was followed up 36 months after procedure, and the response was evaluated as PD. During the follow-up, no serious complications occurred in any of the patients. CONCLUSIONS: The preliminary clinical observation showed that 125I radioactive particle implantation was a safe, reliable and effective therapeutic method for early lung cancer.

Prediction of Rotator Cuff Injury Associated with Acromial Morphology: A Three-Dimensional Measurement Study.

OBJECTIVE: To analyze the relationship between the acromial morphology and the related rotator cuff injury using a three-dimensional (3D) measurement technology. METHODS: For the present study, 226 patients (113 men and 113 women) who underwent shoulder Coarthroscopy from June 2015 to December 2019 at the Department of Orthopedics at our hospital were selected retrospectively. A total of 113 shoulder joints of age-matched healthy people were selected as the control group. A 3D model coordinate system of the shoulder was established based on CT scan images. Patients were grouped according to the condition of the rotator cuff injury during surgery. The patients whose rotator cuff tear site corresponded to the 3D osseous proliferative structure of the acromion were classified into the impingement injury group (II group). The other patients were classified into the non-impingement injury group (NII group). The acromiohumeral interval (AHI), the acromial anterior protrusion (AAP), the acromial inferior protrusion (AIP), the acromioclavicular angle (AC angle), the distance from the most medial edge of the acromial anterolateral protrusion (AALP) to the most lateral point of acromion (MLPA) (a), the distance from the most posteromedial edge of the AALP to the MLPA (b), the anteroposterior diameters of the AALP (c), and the proportion of anteroposterior diameters of AALP to the anteroposterior diameters of acromion, (c/c + d) × 100(%), were measured using the 3D shoulder model. RESULTS: The results of the intraobserver (<5%) and interobserver variability (>87%) analysis found the parameters to have high intraobserver and interobserver concordance. There were no significant differences in age among the control group, the NII group, and the II group (P = 0.8416). There were significant differences in AAP among the three groups (P = 0.0374). The results were the same for men and women, respectively. The AAP in the control group and the NII group did not show a difference, while the AAP in the II group was increased by 26.9% (P = 0.015) and 25% (P = 0.023), respectively, compared with the NII group and the control group. AHI, AIP, and AC angles did not show significant differences among the three groups (P > 0.05). The (a) and (b) of the II group were significantly larger than those of the NII group; P-values were 0.0119 and 0.0003, respectively. The (a) and (b) in patients with rotator cuff injuries were larger than in the normal population (P < 0.05). The above results were the same for men and women. This suggested that the larger width of the AALP might cause the related rotator cuff injury. The (c/c + d) in the II group was significantly larger than those in the control and the NII groups, with P-values of 0.0005 and 0.0021, respectively. The risk of rotator cuff injury due to subacromial impingement was increased when the maximum width of the medial-lateral edge of the AALP exceeded 16.8 mm (17.4 mm in men, 15.1 mm in women), the maximum width of the posterior edge of the AALP exceeded 12.9 mm (13.8 mm in men,12.7 mm in women), or the anteroposterior diameters of the AALP exceeded the anteroposterior diameters of the acromion by 33.5%. CONCLUSION: We could predict the occurrence and development of the related rotator cuff injury in symptomatic patients with specific 3D changes in their acromion and intervene in the acromion of such patients as early as possible to prevent possible rotator cuff injuries in the future.

Correction to: Telmisartan attenuates kidney apoptosis and autophagy-related protein expression levels in an intermittent hypoxia mouse model.

In the article that appeared on Page: 341-348, Vol 23 (15 September 2018) of the Sleep and breathing [1], one error was discovered in Figure 3. The picture of Normoxia and CIH in 100X is the same one. The corrected version of Figure 3 is presented here.

Sodium Tanshinone IIA Sulfonate Attenuates Tumor Oxidative Stress and Promotes Apoptosis in an Intermittent Hypoxia Mouse Model.

OBJECTIVE: Intermittent hypoxia, a significant feature of obstructive sleep apnea, has pro-tumorigenic effects. Here, we investigated the effect of sodium tanshinone IIA sulfonate on oxidative stress and apoptosis in a mouse model of Lewis lung carcinoma with intermittent hypoxia. METHODS: Mice were randomly assigned to normoxia (control), normoxia plus sodium tanshinone IIA sulfonate (control + sodium tanshinone IIA sulfonate), intermittent hypoxia, and intermittent hypoxia + sodium tanshinone IIA sulfonate groups. Intermittent hypoxia administration lasted 5 weeks in the intermittent hypoxia groups. Lewis lung carcinoma cells were injected into the right flank of each mouse after 1 week of intermittent hypoxia exposure. Sodium tanshinone IIA sulfonate was injected intraperitoneally in the control + sodium tanshinone IIA sulfonate and intermittent hypoxia + sodium tanshinone IIA sulfonate groups. Tumor oxidative stress was evaluated by detection of malondialdehyde and superoxide dismutase. The apoptosis of tumor cells was evaluated by the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay as well as by Western blot analysis of B-cell lymphoma 2-associated X protein and cleaved caspase-3 expression. Additionally, the expression of hypoxia-induced factor-1α, nuclear factor erythroid 2-related factor 2, and nuclear factor kappa B was also evaluated by Western blot. RESULTS: Compared with the control group, the intermittent hypoxia treatment significantly increased Lewis lung carcinoma tumor growth and oxidative stress (serum malondialdehyde) but decreased serum levels of SOD and pro-apoptotic markers (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, B-cell lymphoma 2-associated X protein, and cleaved caspase-3). These changes were significantly attenuated by intraperitoneal injection of sodium tanshinone IIA sulfonate. Lower nuclear factor erythroid 2-related factor 2 and higher nuclear factor kappa B levels in the intermittent hypoxia group were clearly reversed by sodium tanshinone IIA sulfonate treatment. In addition, sodium tanshinone IIA sulfonate administration decreased the high expression of hypoxia-induced factor-1α induced by intermittent hypoxia. CONCLUSION: Intermittent hypoxia treatment resulted in high oxidative stress and low apoptosis in Lewis lung carcinoma-implanted mice, which could be attenuated by sodium tanshinone IIA sulfonate administration possibly through a mechanism mediated by the nuclear factor erythroid 2-related factor 2/nuclear factor kappa B signaling pathway.

MiR-323-3p Targeting Transmembrane Protein with EGF-Like and 2 Follistatin Domain (TMEFF2) Inhibits Human Lung Cancer A549 Cell Apoptosis by Regulation of AKT and ERK Signaling Pathways.

BACKGROUND Non-small-cell lung cancer (NSCLC) is predominant and has low 5-year relative survival rate. Therefore, the mechanisms of NSCLC tumorigenesis must be comprehensively elucidated. MicroRNA-323-3p (miR-323-3p) has been widely explored and found to exert functions in tumorigenesis of several cancer types. However, the expression pattern and biological function of miR-323-3p and the molecular mechanism underlying NSCLC development and progression remain unclear. MATERIAL AND METHODS Quantitative reverse-transcription polymerase chain reaction was used to detect the expression of miR-323-3p and TMEFF2 in NSCLC cell lines (A549, NCI-H3255, and H1299) and normal cell line (BEAS-2B). Methylthiazolyl tetrazolium, colony formation, and flow cytometry assays were performed to evaluate the effects of miR-323-3p and TMEFF2 on cell proliferation. Transwell assay was conducted to determine the effects of TMEFF2 on cell migration and invasion. Dual-luciferase reporter assay was used to verify whether TMEFF2 is a target of miR-323-3p. Western blot analysis was performed to analyze protein expression. RESULTS The expression of miR-323-3p increased in the 3 NSCLC cell lines (A549, NCI-H3255, and H1299). miR-323-3p regulated cellular progression by directly suppressing TMEFF2 expression and indirectly prohibited the activation of AKT and ERK pathways in NSCLC. CONCLUSIONS Overall, miR-323-3p was considered a lung cancer oncogene and could be a valuable target for NSCLC therapy.

Does mobile-bearing have better flexion and axial rotation than fixed-bearing in total knee arthroplasty? A randomised controlled study based on gait.

OBJECTIVE: To analyse the 6 degrees of freedom of the knee and gait data of patients with medial knee osteoarthritis before and after fixed-bearing (FB) and mobile-bearing (MB) total knee arthroplasty (TKA) â€‹and examine the influence of TKA on gait characteristics and the difference between FB and MB prosthesis. We also sought to explore the prosthesis options available for TKA in these patients. METHODS: Thirty patients who underwent TKA at the Department of Orthopedics at our hospital from June to October 2017 were included. All patients had a lower limb mechanical axis (hip-knee-ankle angle) of less than 180° which were regarded as genu varum knees and had medial knee osteoarthritis. Patients were randomised divided into the FB group â€‹and the MB group according to the knee prosthesis implanted. An infrared navigation three-dimensional portable knee motion analysis system (Opti-Knee®, Shanghai Innomotion, Inc.) was used to acquire data on the 6 degrees of freedom of both knees when walking on flat ground before and after surgery (angle of tibia relative to femur parameters: flexion-extension, internal rotation-external rotation, abduction-adduction; displacement parameters: anterior-posterior, proximal-distal, medial-lateral). Postoperative follow-up efficacy was assessed using the Oxford Knee Score system. RESULTS: There were significant differences in the maximum values of the internal/external rotation and flexion/extension angle between patients post-TKA and the healthy population, p values were 0.007 and <0.001,respectively. The postoperative maximum values of genu varum and internal rotation in both FB [(-9.49 â€‹± â€‹5.99°), (-5.77 â€‹± â€‹3.42°), respectively] and MB [(-9.64 â€‹± â€‹4.83°), (-7.54 â€‹± â€‹4.51°), respectively] groups were lower than the preoperative ones [FB (-15.13 â€‹± â€‹6.78°), (-8.28 â€‹± â€‹4.83°); MB (-13.28 â€‹± â€‹3.98°), (-9.46 â€‹± â€‹4.99°), respectively] (p â€‹≤ â€‹0.001), while the postoperative maximum values of flexion angle and anterior displacement in both FB [(46.11 â€‹± â€‹4.14°), (0.71 â€‹± â€‹0.35 â€‹cm), respectively] and MB [(49.33 â€‹± â€‹3.98°), (0.75 â€‹± â€‹0.89 â€‹cm), respectively] groups were larger than the preoperative ones [FB (43.15 â€‹± â€‹3.77°), (0.26 â€‹± â€‹0.74 â€‹cm); MB (44.62 â€‹± â€‹5.92°), (0.33 â€‹± â€‹0.79°), respectively] (p â€‹≤ â€‹0.001). The postoperative range of flexion/extension angle in both FB (40.13 â€‹± â€‹4.14°) and MB (45.82 â€‹± â€‹3.76°) groups was significantly larger than the preoperative one [FB (36.17 â€‹± â€‹6.07°), MB (37.09 â€‹± â€‹3.93°), respectively] (p â€‹≤ â€‹0.001). There were also significant increases in range of anterior-posterior displacement in the FB group (0.85 â€‹± â€‹0.32 â€‹cm) postoperatively compared with the preoperative one (0.71 â€‹± â€‹0.92 â€‹cm) (p â€‹= â€‹0.016) â€‹and significant increases in range of medial-lateral displacement (0.64 â€‹± â€‹0.73 â€‹cm) in the MB group postoperatively compared with the preoperative one (0.52 â€‹± â€‹0.91 â€‹cm) (p â€‹= â€‹0.025). The mean flexion/extension angle of the MB group was significantly greater than the FB group after surgery in both the stance phase and the swing phase (p â€‹< â€‹0.001). There were significant differences in postoperative knee axial rotation during the gait cycle between the MB and FB groups (p â€‹= â€‹0.028) â€‹and that postoperative internal rotation of the tibia relative to the femur increased in the MB group. The Oxford Knee Score at the last follow-up visit about 7.5 months after surgery was 15.6 â€‹± â€‹1.3 and 15.1 â€‹± â€‹1.1 points for FB and MB groups, respectively. This difference was not significant (p â€‹= â€‹0.428). CONCLUSIONS: TKA can make the parameters of knee gait characteristics closer to the normal population. Medial knee osteoarthritis patients who received a MB prosthesis in TKA had better joint flexion function and axial rotation than the FB one. However, there is insufficient evidence to suggest that the MB prosthesis is a better option for patients with medial knee osteoarthritis. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: To date, no consensus for prosthesis selection in TKA has been established. This study found significant differences in joint flexion/extension angle and internal/external rotation during gait post-TKA surgery in medial knee osteoarthritis patients who received different prostheses. This will provide some references for prosthesis selection for a large number of genu varum patients in clinical practice.

Dynamic spatiotemporal expression pattern of limbal stem cell putative biomarkers during mouse development.

Limbal stem cells (LSCs), a subpopulation of limbal epithelial basal cells, are crucial to the homeostasis and wound healing of corneal epithelium. The identification and isolation of LSCs remains a challenge due to lack of specific LSCs biomarkers. In this study, Haematoxylin-eosin (HE), 4', 6-diamidino-2-phenylindole (DAPI), and immunohistochemistry (IHC) stains were performed on the pre- and post-natal limbus tissues of mice which has the advantage of more controllable in term of sampling age relative to human origin. By morphological analysis, we supported that there is an absence of the Palisades of Vogt (POV) in the mouse. The development of prenatal and neonatal cornea was dominated by its stroma, whereas after eyelids opened at P14, the corneal epithelial cells (CECs) quickly go stratification in response to the liquid-air interface. Based on IHC staining, we found that the expression of LSCs putative biomarkers in limbal epithelial basal cells appeared in chronological order as follows: Vim = p63 > CK14 > CK15 (where = represents same time; > represents earlier), and in corneal epithelial basal cells were weakened in chronological order as follows: Vim > p63 > CK15 > CK14, which might also represent the stemness degree. Furthermore, the dynamic spatial expression of the examined LSCs putative biomarkers during mouse development also implied a temporal restriction. The expression of Vim in epithelial cells of mouse ocular surface occurred during E12-E19 only. The expression of CK15 was completely undetectable in CECs after P14, whereas the others putative molecular markers of LSCs, such as p63 and CK14, still remained weak expression, suggesting that CK15 was suitable to serve as the mouse LSCs biomarkers after P14. In this study, our data demonstrated the dynamic spatiotemporal expression pattern of LSCs putative biomarkers in mouse was age-related and revealed the time spectrum of the expression of LSCs in mouse, which adds in our knowledge by understanding the dynamic expression pattern of biomarkers of stem cells relate to maintenance of their stemness.

Differential expression of microRNAs in xenografted Lewis lung carcinomas subjected to intermittent hypoxia: a next-generation sequence analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased cancer mortality, but the underlying mechanism remains poorly understood. MicroRNAs (miRNAs) are confirmed to be involved in tumorigenesis and tumor progression. However, whether miRNAs have any differential expressions in OSA population needs to be elucidated. The aim of this experimental study was to determine the alterations of various miRNAs in xenograft mice exposed to chronic intermittent hypoxia (IH) which is considered a hallmark of OSA. METHODS: Sequencing was applied to screen the miRNAs of tumor tissues in xenograft mice exposed to IH and normoxia (control, CTL), respectively. Most differentially expressed miRNAs were verified by the quantitative real-time polymerase chain reaction (qRT-PCR). Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway were performed to reveal the functional enrichment of the target genes regulated by the miRNAs. RESULTS: A total of 485 miRNAs (259 novel miRNAs and 226 known miRNAs) were differentially expressed between the IH and CTL groups. 154 miRNAs were upregulated and 331 miRNAs were downregulated among them. The top 5 differentially expressed known (miR-767, miR-466f-5p, miR-5122, miR-124-3p and miR-590-3p) and novel (miR-140, miR-130, miR-301, miR-177 and miR-90) miRNAs were validated by qRT-PCR. MiR-767, miR-124-3p, miR-590-3p and all novel miRNAs were upregulated while miR-466f-5p and miR-5122 were downregulated in IH-induced xenograft mice. In addition, GO and KEGG pathway analysis demonstrated that the predicted target genes, which were regulated by differentially expressed miRNAs were markedly enriched in related biological processes and pathways, including biological processes, cell metabolic and biosynthetic processes and molecular functions. CONCLUSIONS: Several altered miRNAs were detected in xenograft mice exposed to IH. The differentially expressed miRNAs in IH indicates that these miRNAs might involve in the molecular mechanism of tumorigenesis and tumor progression in OSA. Further studies are required to determinate the exact intermediation of certain miRNAs between IH and tumor progression.

A review of the association between oral bacterial flora and obstructive sleep apnea-hypopnea syndrome comorbid with cardiovascular disease.

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS), a common sleep disorder, has been shown to be an independent risk factor for cardiovascular disease (CVD). Recent studies have focused on the important roles of microorganisms in human health; for example, microorganisms are reportedly associated with obesity, metabolic disorders, and CVD. The number of oral bacteria in patients with OSAHS is considerably higher than that in healthy individuals, and infection with oral bacterial pathogens is associated with the development of CVD. However, whether changes in the oral microbiota mediate the development of OSAHS and CVD remains unknown. METHODS: Therefore, we attempted to review the association between changes in oral microbiota in patients with OSAHS and the development of CVD. RESULTS: Oral microbiota possibly acts via multiple pathways including direct invasion, platelet aggregation, immune response, inflammatory response, and oxidative stress response, leading to the development of CVD in patients with OSAHS. In particular, the strains Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia have demonstrated profound effects. OSAHS leads to changes in the oral bacterial flora and thus may facilitate the occurrence and development of CVD. CONCLUSION: We propose that the underlying mechanism of CVDs resulting from oral microbiota in patients with OSAHS should be elucidated in further studies.

ß-Elemene suppresses the proliferation of human airway granulation fibroblasts via attenuation of TGF-ß/Smad signaling pathway.

BACKGROUND: Benign airway stenosis is easily to recur as a result of hyperplastic airway granulation tissues. Our previous study proved that a Chinese drug, ß-elemene, could inhibit the proliferation of fibroblasts cultured from these tissues, which could decrease the recurrence rate of this disease. METHODS: To find out the mechanism for this effect, we first cultured normal human airway fibroblasts and human airway granulation fibroblasts with different concentrations of ß-elemene for the same time or the same dose of ß-elemene for different times to explore the dose/time-effect relationship between the drug and these cells. Then we used gene microarray to screen out the most important pathway by which the drug influenced human airway granulation fibroblasts. At last, we assessed the condition of this pathway in human airway granulation fibroblasts and verified the effect of this drug on this pathway. RESULTS: ß-Elemene inhibited the proliferation of human airway granulation fibroblasts in a dose but no time-dependent manner and did not affect normal human airway fibroblasts. Affecting the expression of transforming growth factor ß (TGF-ß)/Smad pathway may be the key mechanism for this effect. This pathway was activated in human airway granulation fibroblasts and ß-elemene inhibited it in a dose-dependent manner. This effect was similar to the pathway inhibitor, SB431542, and exogenous TGF-ß could attenuate this effect. CONCLUSION: These results indicated that suppressing TGF-ß/Smad pathway was possibly the key mechanism by which ß-elemene inhibits the proliferation of human airway granulation fibroblasts. This pathway may be a promising target to treat benign airway stenosis.