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Abstract Background Patients with obstructive sleep apnoea (OSA), male sex, obesity, older age or hypertension are prone to hypoxemia during flexible bronchoscopy. This study investigated whether using a high-flow nasal cannula (HFNC) could reduce the incidence of oxygen desaturation during bronchoscopy under deep sedation in patients at risk of hypoxemia. Methods A total of 176 patients at risk of hypoxemia who underwent flexible bronchoscopy under deep sedation were randomly assigned to two groups: the HFNC group (humidified oxygen was supplied via a high-flow nasal cannula at a rate of 60 L/min and a concentration of 100%, n = 87) and the facemask group (oxygen was supplied via a tight-fitting facemask at a rate of 6 L/min and a concentration of 100%, n = 89). Results Oxygen desaturation occurred in 4 (4.6%) patients in the HFNC group and 26 (29.2%) patients in the facemask group (P

Objective To investigate the biomechanical effect of different intervertebral reconstructive heights on adjacent segments following C5/C6 anterior cervical discectomy and fusion (ACDF) through finite element analysis. Methods A finite element model of intact C4–C7 segments was developed and validated for the present study. Five additional C4–C7 postoperative models were constructed with 100%, 125%, 150%, 175%, and 200% of the benchmark height of C5/C6 on the basis of the intact model. The changes in intradiscal pressure (IDP) and range of motion (ROM) of adjacent segments before and after reconstruction of C5/C6 were analyzed. Results For the upper adjacent segment (C4/C5), the IDPs under the different loading conditions all increased after reconstruction. The maximum IDPs were 0.387, 0.489, 0.491, and 0.472 MPa under flexion, extension, axial rotation, and lateral bending, respectively, observed at the reconstructive height of 200%. The minimum IDPs were observed at 150% reconstructive height under all loading conditions except extension, and were 57, 86 and 81% of the maximum IDPs under flexion, axial rotation, and lateral bending, respectively. The minimum IDP under extension occurred when the reconstructive height is 125% of the benchmark height. For the lower adjacent segment (C6/C7), the IDPs of postoperative models under all loading conditions also increased compared to the preoperative model. The maximum IDPs after reconstruction under flexion, extension, axial rotation, and lateral bending were 0.402, 0.411, 0.461, and 0.497 MPa, respectively, when the height of the reconstruction was 200% of the benchmark. The minimum IDPs were observed after a reconstruction at 150% of the benchmark, and were 59%, 85%, 82%, and 81% of the maximum IDPs under flexion, extension, axial rotation, and lateral bending loading conditions. Conclusions The reconstructive height is an important factor affecting the IDP and the ROM of adjacent segments after ACDF. To delay the adjacent segment disease, an intervertebral reconstructive height of 150% is an appropriate height in C5/C6 ACDF.

Objective To compare the preventive effects of teriparatide and alendronate on the progression of vertebral body collapse in postmenopausal single‐level Kümmell's disease (KD). Methods From March 2013 to December 2020, the medical records for 53 postmenopausal single‐level KD patients who received conservative treatment with teriparatide (25 patients, teriparatide group) or alendronate (28 patients, alendronate group) were retrospectively reviewed. Midsagittal computed tomography (CT) images were analyzed by ImageJ to assess the intravertebral bone formation (mineralized bone) by calculating the ratio of area of intravertebral mineralized bone (AIMB) to the area of fractured vertebral body (AFVB). The changes in radiological parameters of the fractured vertebral body including kyphosis angle (KA), anterior and posterior border heights (ABH and PBH) and spinal canal diameter (SCD), bone turnover biomarkers (BTMs), and bone mineral density (BMD) were analyzed to evaluate the therapeutic effect. Results At month 12, the ratio of AIMB to AFVB was significantly greater in teriparatide group (54.28% ± 15.30%) than in alendronate group (35.57% ± 17.61%) (P

The three-dimensional (3D) visualization of the functional bundles in the peripheral nerve provides direct and detailed intraneural spatial information. It is useful for selecting suitable surgical methods to repair nerve defects and in optimizing the construction of tissue-engineered nerve grafts. However, there remain major technical hurdles in obtaining, registering and interpreting 2D images, as well as in establishing 3D models. Moreover, the 3D models are plagued by poor accuracy and lack of detail and cannot completely reflect the stereoscopic microstructure inside the nerve. To explore and help resolve these key technical problems of 3D reconstruction, in the present study, we designed a novel method based on re-imaging techniques and computer image layer processing technology. A 20-cm ulnar nerve segment from the upper arm of a fresh adult cadaver was used for acetylcholinesterase (AChE) staining. Then, 2D panoramic images were obtained before and after AChE staining under the stereomicroscope. Using layer processing techniques in Photoshop, a space transformation method was used to fulfill automatic registration. The contours were outlined, and the 3D rendering of functional fascicular groups in the long-segment ulnar nerve was performed with Amira 4.1 software. The re-imaging technique based on layer processing in Photoshop produced an image that was detailed and accurate. The merging of images was accurate, and the whole procedure was simple and fast. The least square support vector machine was accurate, with an error rate of only 8.25%. The 3D reconstruction directly revealed changes in the fusion of different nerve functional fascicular groups. In conclusion. The technique is fast with satisfactory visual reconstruction.

Abstract Background Recent studies have demonstrated that synthetic dsRNAs may produce therapeutic effects in a target-independent manner through stimulation of the toll-like receptor-3 (TLR3)/interferon pathway; as a result, angiogenesis and proliferation of tumor cells are inhibited. Thus, this pathway may become a potential target of dsRNA in tumor suppression. In this study, we evaluated the role of synthetic dsRNA as a TLR3 synergist and by combining with sorafenib in anti-hepatocellular carcinoma (HCC) in vitro and in vivo. Methods Four dsRNAs were designed and synthesized. One of them that was capable of activating TLR3 most effectively in human HCC cell line (HepG2.2.15) was selected as a TLR3 synergist (called BM-06). Subsequently, the expression of proteins relating to TLR3 signaling pathway, such as NF-κB, caspase 8 survivin, bcl-2 and PCNA affected by BM-06, sorafenib alone or in combination, was compared. The migration, proliferation and apoptosis of HepG2.2.15 cells were evaluated in presence of BM-06, sorafenib alone or in combination of both. The similar treatments were also applied in an SD rat primary HCC model. Results qRT-PCR data showed that the expression of TLR3 and NF-κB in HepG2.2.15 cells was enhanced. BM-06 was selected as a TLR3 synergist capable of activating the TLR3/interferon pathway most effective among 4 synthetic dsRNAs. The migration and proliferation were significantly inhibited in treated HepG2.2.15 cells with BM-06 or Sorafenib alone as compared with PBS-sham control (P

The aim of this study is to explore the inhibitory effects of RNA interference (RNAi) targeting NET-1 or combined with sorafenib on HCC in vitro and in vivo and the possible underlying mechanisms. The expressions of NET-1 mRNA and protein were detected by RT-QPCR and western blot. The ability of proliferation was determined by CCK-8 assay. Apoptosis was examined by flow cytometry (FCM). Abilities of migration and invasion were measured by scratch-wound assay and transwell assay. MHCC97H cells with stable transfection of NET-1shRNA were injected subcutaneously to prepare nude mice model of HCC and Caspase-3, Caspase-8, and Caspase-9 mRNAs of tumor tissues in different groups were examined. NET-1 mRNA and protein were reduced sharply in MHCC97H cells transfected with NET-1shRNA. The abilities of proliferation and migration were inhibited and apoptosis was promoted in either NET-1shRNA or sorafenib as compared with untreated cells in vitro and in vivo (P

Introduction: Ferroptosis is associated with multiple pathophysiological processes. Inhibition of ferroptosis has received much concern for some diseases. Nonetheless, there is no study comprehensively illustrating functions of ferroptosis-related genes (FRGs) in psoriasis. Methods: In this study, FRGs together with psoriasis-associated data were obtained in Ferroptosis Database (FerrDb) and gene expression omnibus (GEO) database separately. This work identified altogether 199 psoriasis-associated DE-FRGs, and they were tightly associated with immunity and autophagy modulation. Thereafter, the present study utilized SVM-RFE and LASSO algorithms to identify NR5A2, CISD1, GCLC, PRKAA2, TRIB2, ABCC5, ACSF2, TIMM9, DCAF7, PEBP1, and MDM2 from those 199 DE-FRGs to be marker genes. As revealed by later functional annotation, the marker genes possibly had important effects on psoriasis through being involved in diverse psoriasis pathogenesis-related pathways such as cell cycle, toll-like receptor (TLR), chemokine, and nod-like receptor (NLR) pathways. Moreover, altogether 37 drugs that targeted 11 marker genes were acquired. Besides, based on CIBERSORT analysis, alterations of immune microenvironment in psoriasis cases were possibly associated with PRKAA2, PEBP1, CISD1, and ACSF2. Discussion: Taken together, this work established the diagnostic potency and shed more lights on psoriasis-related mechanism. More investigations are warranted to validate its value in diagnosing psoriasis before it is applied in clinic. [ABSTRACT FROM AUTHOR]

Background: A role for autophagy, a conserved cellular response to stress, has recently been demonstrated in human cancers. Aberrant expression of Beclin-1, an important autophagic gene, has been reported in various human cancers. In the present study, we investigated the significance and relationship between Beclin-1 expression and cell proliferation, apoptosis, microvessel density (MVD) and clinical pathological changes or prognosis in human hepatocellular carcinoma (HCC). Methods: A total of 103 primary HCC patients were involved in the study. Expression of Beclin-1, PCNA, NET-1, Bcl-2, Bax, Survivin in cancer cells and CD34 in stromal microvessels were evaluated immunohistochemically in tissue microarrays comprising 103 cases of HCC and 57 matched adjacent nontumor liver tissues. Correlations between clinicopathological characteristics and survival of HCC patients were explored. Results: The positive rate of Beclin-1 was significantly lower in HCC tissues than adjacent tissues (72.8 vs. 89.5%, χ2 = 6.085, P = 0.015). In HCC, Beclin-1 expression was negatively correlated with cirrhosis background (r = -0.216, P = 0.029), Edmondson grade (r = -0.249, P = 0.011), vascular invasion (r = -0.246, P = 0.012), PCNA (r = -0.242, P = 0.014), NET-1 (r = -0.245, P = 0.013), anti-apoptosis protein Bcl-2 (r = -0.245, P = 0.013) and MVD (r = -0.292, P = 0.003), and positively correlated with pro-apoptosis protein Bax (r = 0.242, P = 0.014). Significant differences in the 5-year survival rates were seen among patients with Beclin-1 strong positive (++) (59.1%, 13/22), moderate positive (+) (28.3%, 15/53) and weak negative expression (-) (14.6%, 7/28) (P = 0.043). Significant differences were detected between Beclin-1 (++) and either Beclin-1 (+) (P = 0.036) or Beclin-1 (-) groups (P = 0.008), but no significant difference between Beclin-1 (+) and Beclin-1 (-) groups (P = 0.281) was observed. Survival rates were positively related to high Beclin-1 co-expressed with low PCNA, NET-1, or Bcl-2, lower MVD, and high Bax. Univariate and multivariate Cox regression analysis revealed that Beclin-1 expression was an independent indicator for overall survival in HCC patients (P < 0.05). Conclusions: The pathogenesis and progression of HCC are associated with reduced autophagy. The expression of Beclin-1 and Bax in HCC tissues may provide a synergistic effect towards inhibiting HCC proliferation, infiltration, metastasis and angiogenesis. Beclin-1 expression may be a valuable prognostic marker of HCC. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated that synthetic dsRNAs may produce therapeutic effects in a target-independent manner through stimulation of the toll-like receptor-3 (TLR3)/interferon pathway; as a result, angiogenesis and proliferation of tumor cells are inhibited. Thus, this pathway may become a potential target of dsRNA in tumor suppression. In this study, we evaluated the role of synthetic dsRNA as a TLR3 synergist and by combining with sorafenib in anti-hepatocellular carcinoma (HCC) in vitro and in vivo.Methods: Four dsRNAs were designed and synthesized. One of them that was capable of activating TLR3 most effectively in human HCC cell line (HepG2.2.15) was selected as a TLR3 synergist (called BM-06). Subsequently, the expression of proteins relating to TLR3 signaling pathway, such as NF-κB, caspase 8 survivin, bcl-2 and PCNA affected by BM-06, sorafenib alone or in combination, was compared. The migration, proliferation and apoptosis of HepG2.2.15 cells were evaluated in presence of BM-06, sorafenib alone or in combination of both. The similar treatments were also applied in an SD rat primary HCC model.Results: qRT-PCR data showed that the expression of TLR3 and NF-κB in HepG2.2.15 cells was enhanced. BM-06 was selected as a TLR3 synergist capable of activating the TLR3/interferon pathway most effective among 4 synthetic dsRNAs. The migration and proliferation were significantly inhibited in treated HepG2.2.15 cells with BM-06 or Sorafenib alone as compared with PBS-sham control (P<0.01). However, the role of combination BM-06 with Sorafenib was the most prominent. Tumor cell apoptotic rate was increased by BM-06 or combination when compared to PBS or poly(I:C) (P<0.05). Similarly, in orthotopic HCC SD rats, the effect of the combination was superior to either agent alone on the inhibition of tumor growth and induction of HCC cell apoptosis (P<0.05).Conclusions: dsRNA alone was capable of inhibiting the proliferation of HepG2.2.15 cells and tumor growth of orthotopic HCC SD rats, but the effect of combination of dsRNA with sorafenib was more prominent. These findings implicate the potential role of combined use of a dsRNA, a TLR3 synergist, and sorafenib in inhibition of HCC. [ABSTRACT FROM AUTHOR]