Flavokawain C inhibits glucose metabolism and tumor angiogenesis in nasopharyngeal carcinoma by targeting the HSP90B1/STAT3/HK2 signaling axis.

OBJECTIVE: Over the past decade, heat shock protein 90 (HSP90) inhibitors have emerged as promising anticancer drugs in solid and hematological malignancies. Flavokawain C (FKC) is a naturally occurring chalcone that has been found to exert considerable anti-tumor efficacy by targeting multiple molecular pathways. However, the efficacy of FKC has not been studied in nasopharyngeal carcinoma (NPC). Metabolic abnormalities and uncontrolled angiogenesis are two important features of malignant tumors, and the occurrence of these two events may involve the regulation of HSP90B1. Therefore, this study aimed to explore the effects of FKC on NPC proliferation, glycolysis, and angiogenesis by regulating HSP90B1 and the underlying molecular regulatory mechanisms. METHODS: HSP90B1 expression was analyzed in NPC tissues and its relationship with patient's prognosis was further identified. Afterward, the effects of HSP90B1 on proliferation, apoptosis, glycolysis, and angiogenesis in NPC were studied by loss-of-function assays. Next, the interaction of FKC, HSP90B1, and epidermal growth factor receptor (EGFR) was evaluated. Then, in vitro experiments were designed to analyze the effect of FKC treatment on NPC cells. Finally, in vivo experiments were allowed to investigate whether FKC treatment regulates proliferation, glycolysis, and angiogenesis of NPC cells by HSP90B1/EGFR pathway. RESULTS: HSP90B1 was highly expressed in NPC tissues and was identified as a poor prognostic factor in NPC. At the same time, knockdown of HSP90B1 can inhibit the proliferation of NPC cells, trigger apoptosis, and reduce glycolysis and angiogenesis. Mechanistically, FKC affects downstream EGFR phosphorylation by regulating HSP90B1, thereby regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. FKC treatment inhibited the proliferation, glycolysis, and angiogenesis of NPC cells, which was reversed by introducing overexpression of HSP90B1. In addition, FKC can affect NPC tumor growth and metastasis in vivo by regulating the HSP90B1/EGFR pathway. CONCLUSION: Collectively, FKC inhibits glucose metabolism and tumor angiogenesis in NPC by targeting the HSP90B1/EGFR/PI3K/Akt/mTOR signaling axis.

Tragus Perichondrium-Cartilage Island and Temporalis Muscle Fascia for Repairing Tympanic Membrane Perforation Under the Otoendoscope: A Randomized Controlled Trial.

OBJECTIVE: To compare the clinical effects of repairing tympanic membrane perforation (TMP) with the tragus perichondrium-cartilage island and temporalis muscle fascia (TMF) under the otoendoscope. METHODS: The clinical data of 84 patients (total 84 ears) with TMP repaired by otoendoscopy from March 2019 to April 2021 were analyzed. The patients were randomly divided into the control group (n = 42, TMF repair) and the experimental group (n = 42, perichondrium-cartilage island repair). The intraoperative blood loss, operation time, length of hospital stay, success rate of the TMP repair, mean air-conducted sound, and air-bone gap before and after surgery were compared between the two groups. RESULTS: The mean air-bone gap and mean air-conducted hearing threshold in the experimental group were significantly lower after surgery at all frequencies than those of the control group (all P < .05). The reduction of the mean air-conducted hearing threshold in the experimental group was significantly higher than that of the control group (P < .001). The surgery time of the experimental group was significantly shorter than the control group (78.04 ± 2.23 vs. 84.27 ± 1.67 minutes, P < .001). The success rate of the TMP repair was 95.24% (40/42) in the experimental group and 92.86% (39/42) in the control group, indicating that there was no significant difference in the success rate of TMP repair between the two materials (risk ratio = 1.75; 95% confidence interval: .31-12.04; P = .71). CONCLUSION: Repairs with the tragus perichondrium-cartilage island have a short operation time, high healing rate, and more significant postoperative hearing improvement, which makes it a more effective method of TMP repair.

Proteomics analysis of cancer tissues identifies IGF2R as a potential therapeutic target in laryngeal carcinoma.

Background: Laryngeal cancer (LC) is a prevalent head and neck malignancy; however, the essential pathophysiological mechanism underlying its tumorigenesis and progression remains elusive. Due to the perduring scarcity of effective targeted drugs for laryngeal cancer, insights into the disease's pathophysiological mechanisms would substantially impact the treatment landscape of laryngeal cancer. Methods: To ensure quality consistency, 10 tumor and 9 non-tumor samples underwent proteomic analysis on a single mass spectrometer using a label-free technique. Subsequently, gene expression variations between laryngeal squamous cell carcinoma and normal tissues were analyzed using The Cancer Genome Atlas (TCGA) database. Immunohistochemical expressions of insulin-like growth factor 2 receptor (IGF2R), fibronectin (FN), vimentin, and α-smooth muscle actin (SMA) in LC tissues and normal tissues were determined. Results: In the tumor group, significant variations were detected for 433 upregulated and 61 downregulated proteins. Moreover, the heatmap revealed that the expressions of RNA translation-related proteins and proteins involved in RNA metabolism, such as IGF2R, tenascin C (TNC), periostin (POSTN), proteasome 26S subunit ATPase 4 (PSMC4), serpin family A member 3 (SERPINA3), heat shock protein family B (small) member 6 (HSPB6), osteoglycin (OGN), chaperonin containing TCP1 subunit 6A (CCT6A), and chaperonin containing TCP1 subunit 6B (CCT6B), were prominently elevated in the tumor group. Nonsense-mediated RNA decay (NMD), RNA translation, and protein stability were significantly altered in LC tumors. IGF2R was remarkably upregulated in LC tumors. In the TCGA database, the IGF2R mRNA level was significantly upregulated in LSCC tissues. Additionally, IGF2R mRNA expression was lowest in clinical grade 1 samples, with no significant difference between grades 2 and 3. In LSCC patients, a significant positive correlation between IGF2R expression and the stromal score was detected using the ESTIMATE algorithm to estimate the immune score, stromal score, and tumor purity in the tumor microenvironment. Lastly, immunohistochemical analysis revealed that IGF2R is overexpressed in LC. Conclusion: These results demonstrate the vital role of IGF2R in LC carcinogenesis and progression and may facilitate the identification of new therapeutic targets for the prevention and treatment of LC.

Discovery of an orally active antitumor agent that induces apoptosis and suppresses EMT through heat shock protein 90 inhibition.

Background Nowadays, lung cancer seriously affects human health in the world. Therefore, it is of great significance to develop effective anti-lung cancer drugs. Methods In this work, chalcone derivative HYQ97 was designed via a molecular hybridization strategy. It was synthesized by the cycloaddition in the presence of sodium ascorbate under mild conditions. Lung cancer cell lines were cultured to investigate its antitumor effects in vitro and in vivo. Results HYQ97 inhibited the proliferation of lung cancer cell lines. Specifically, its IC50 value against lung cancer A549 cells was 74.26 nM. It could inhibit heat shock protein 90 (Hsp90) and degrade its client proteins in a dose-dependent manner. Furthermore, HYQ97 suppressed the epithelial mesenchymal transition process and induced apoptosis of A549 cells. Importantly, HYQ97 also had significant inhibitory effects on tumor growth in vivo. Conclusions Chalcone derivative HYQ97 is a promising candidate for lung cancer treatment.

Inflammatory cytokines tumor necrosis factor-α, interleukin-8 and sleep monitoring in patients with obstructive sleep apnea syndrome.

The present study investigated the changes of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and sleep ability in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 684 patients who were admitted to Xuzhou Central Hospital between June 2012 and June 2016 were enrolled to serve as the experimental group and 192 healthy subjects were selected as the control group. Polysomnography was performed on both groups, and serum TNF-α and IL-8 levels were measured by ELISA. Pearson's correlation analysis was used to analyze correlations between factors. Compared with control group, the levels of TNF-α and IL-8, the morning systolic and diastolic pressure in OSAHS group were significantly higher (P<0.01). Furthermore, the mean oxygen saturation (MSaO2) and lowest oxygen saturation (LSaO2) of the OSAHS group were significantly lower compared with those in control group (P<0.01). Results also indicated that TNF-α was positively correlated with apnea-hypopnea index (AHI), morning systolic and diastolic pressure (r=0.621, 0.464, 0.539; P<0.05), and negatively correlated with MSaO2 and LSaO2 (r=-0.526, -0.466; P<0.05). Notably, IL-8 was positively correlated with AHI, morning systolic and diastolic pressure (r=0.337, 0.413 and 0.629; P<0.05), and negatively correlated with MSaO2 and LSaO2 (r=-0.329 and -0.417; P<0.05). Therefore, it was concluded that TNF-α and IL-8 may be involved in the occurrence and development of OSAHS, are closely related to OSAHS and may be important risk factors for cardiovascular disease in patients with OSAHS. The present findings suggest that TNF-α and IL-8 can be used to assess the degree of OSAHS.

The assistance of coblation in arytenoidectomy for vocal cord paralysis.

BACKGROUND: There are many causes for vocal cord paralysis, which can cause difficulty in breathing in serious cases. The common surgical methods for solving vocal cord paralysis include laryngeal splitting or laser surgery, but there are limitations. Plasma radiofrequency ablation is a new treatment with good achievements in clinical applications. OBJECTIVE: To investigate the effect of coblation-assisted arytenoidectomy (CSA) in the treatment of bilateral vocal cord paralysis (BVCP). METHODS: All patients had undergone preoperative electrolaryngoscopic examination of the glottidis rima; electronic laryngoscopy can assess the width of the glottis. The purpose of preoperative electronic laryngoscopic evaluation is to assess the width of the glottis, and arytenoid cartilage movement. Unilateral arytenoid cartilage and a section of the vocal cords were removed in all cases. RESULTS: Of the 14 patients, 13 were successfully extubated after CSA; 1 patient could not be extubated and underwent a second CSA of the contralateral arytenoid cartilage, after which extubation was achieved. All patients were continuously followed up (6 months to 2 years), and all achieved satisfactory results. CONCLUSIONS AND SIGNIFICANCE: CSA can effectively relieve post-CSA dyspnea in patients with BVCP. More patients underwent tracheal cannula extubation after tracheotomy compared with other surgeries.

Treatment of the early-stage glottic cancer using low-temperature radiofrequency coblation.

OBJECTIVE: Radiofrequency (RF) coblation operates at low temperatures (40-70°C) and allows for ablation, hemostasis, and aspiration, in addition to the lesion excision; thermal damage to the surrounding tissues is thus minimized. Herein, we evaluated the benefit of low-temperature RF coblation treatment of the early-stage glottic cancer. The main aim of the study was to evaluate the feasibility, complications, and efficacy of low-temperature RF coblation as a treatment modality for the early-stage glottic cancer. MATERIALS AND METHODS: The data obtained from a 1-year study of six T1 glottic cancer patients treated at our department are presented. Six early-stage glottic cancer (Tla = 5; Tlb = 1) patients (male; mean age 60.1 years) treated using low-temperature RF coblation were enrolled in this study. RESULTS: The outcomes of the surgical technique were analyzed. STATISTICAL ANALYSIS USED: Study outcomes were analyzed (noted and/or photographed). All patients were able to eat on the next day after the surgery. No gastric tube or tracheotomy was required. No postoperative cough, discomfort or difficult breathing was noted. No complications, such as recurrence or cervical lymph node metastasis, occurred over the 6-12 months follow-up. All patients regained satisfactory voice 2 months after the surgery. CONCLUSIONS: Although the current probe design has limitations for the resection of certain tumors, low-temperature RF coblation appears to be a potentially effective method for the endoscopic resection of selected glottic cancers.

Identifying the Functional Flexion-extension Axis of the Knee: An In-Vivo Kinematics Study.

PURPOSE: This study aimed to calculate the flexion-extension axis (FEA) of the knee through in-vivo knee kinematics data, and then compare it with two major anatomical axes of the femoral condyles: the transepicondylar axis (TEA) defined by connecting the medial sulcus and lateral prominence, and the cylinder axis (CA) defined by connecting the centers of posterior condyles. METHODS: The knee kinematics data of 20 healthy subjects were acquired under weight-bearing condition using bi-planar x-ray imaging and 3D-2D registration techniques. By tracking the vertical coordinate change of all points on the surface of femur during knee flexion, the FEA was determined as the line connecting the points with the least vertical shift in the medial and lateral condyles respectively. Angular deviation and distance among the TEA, CA and FEA were measured. RESULTS: The TEA-FEA angular deviation was significantly larger than that of the CA-FEA in 3D and transverse plane (3.45° vs. 1.98°, p < 0.001; 2.72° vs. 1.19°, p = 0.002), but not in the coronal plane (1.61° vs. 0.83°, p = 0.076). The TEA-FEA distance was significantly greater than that of the CA-FEA in the medial side (6.7 mm vs. 1.9 mm, p < 0.001), but not in the lateral side (3.2 mm vs. 2.0 mm, p = 0.16). CONCLUSION: The CA is closer to the FEA compared with the TEA; it can better serve as an anatomical surrogate for the functional knee axis.

Knee alignment in the transverse plane during weight-bearing activity and its implication for the tibial rotational alignment in total knee arthroplasty.

BACKGROUND: The alignment of the knee in the transverse plane is important to the biomechanical functions of the lower limb, and is also associated with the outcomes of the total knee arthroplasty. This study aimed to evaluate the dynamic tibiofemoral alignment in the transverse plane during a weight-bearing activity. METHODS: Knee kinematics of weight-bearing flexion from 0° to 120° was obtained in 16 healthy subjects utilizing biplanar radiography and 3D-2D registration techniques. The anteroposterior axes of the femur at multiple flexion angles in the range of knee motion were used to calculate the anteroposterior axis of motion using the least square method. The latter was compared to six surface-derived anatomical axes in the proximal tibia which were most commonly reported in the literature. The relationship between the anteroposterior axis of motion and the tibial tubercle was also quantified. FINDINGS: The anteroposterior axis of motion did not coincide with any of the six anatomical axes tested. Their orientations varied from 10.3° of external rotation to 9.9° of internal rotation in relation to the former. The anteroposterior axis of motion tended to intersect the tibial tubercle between the medial border and the medial 1/3 point. INTERPRETATION: Instead of any of the tested anatomical axes, the transverse knee alignment during functional movements is associated with the medial 1/3 portion of the tibial tubercle. This region may be helpful for the rotational alignment of the tibial components in total knee arthroplasty.

In vivo motion of femoral condyles during weight-bearing flexion after anterior cruciate ligament rupture using biplane radiography.

The purpose of this study was to investigate in vivo three- dimensional tibiofemoral kinematics and femoral condylar motion in knees with anterior cruciate ligament (ACL) deficiency during a knee bend activity. Ten patients with unilateral ACL rupture were enrolled. Both the injured and contralateral normal knees were imaged using biplane radiography at extension and at 15°, 30°, 60°, 90°, and 120° of flexion. Bilateral knees were next scanned by computed tomography, from which bilateral three-dimensional knee models were created. The in vivo tibiofemoral motion at each flexion position was reproduced through image registration using the knee models and biplane radiographs. A joint coordinate system containing the geometric center axis of the femur was used to measure the tibiofemoral motion. In ACL deficiency, the lateral femoral condyle was located significantly more posteriorly at extension and at 15° (p < 0.05), whereas the medial condylar position was changed only slightly. This constituted greater posterior translation and external rotation of the femur relative to the tibia at extension and at 15° (p < 0.05). Furthermore, ACL deficiency led to a significantly reduced extent of posterior movement of the lateral condyle during flexion from 15° to 60° (p < 0.05). Coupled with an insignificant change in the motion of the medial condyle, the femur moved less posteriorly with reduced extent of external rotation during flexion from 15° to 60° in ACL deficiency (p < 0.05). The medial- lateral and proximal-distal translations of the medial and lateral condyles and the femoral adduction-abduction rotation were insignificantly changed after ACL deficiency. The results demonstrated that ACL deficiency primarily changed the anterior-posterior motion of the lateral condyle, producing not only posterior subluxation at low flexion positions but also reduced extent of posterior movement during flexion from 15° to 60°. Key PointsThree-dimensional tibiofemoral kinematics and femoral condylar motion in ACL-deficient knees during upright weight-bearing flexion were measured using biplane radiography with the geometric center axis.ACL deficiency caused posterior subluxation of the lateral condyle with excess external femoral rotation at early flexion positions.On flexion from 15° to 60°, the lateral condyle moved slightly posteriorly in ACL deficiency leading to reduced extent of external femoral rotation.

[Treatment of early-stage glottic cancer with radiofrequency coblation].

OBJECTIVE: To investigate the impact of radiofrequency coblation for the treatment of Tl glottic cancer. METHOD: Six patients with early-stage glottic cancer (Tla = 5, Tlb = 1) treated with coblation were enrolled in this study. The outcome of the surgery were analyzed. RESULT: No complication happened during the follow-up of 6 to 12 months. All patients achieved satisfactory post-operative voice. CONCLUSION: Although current probe design limits the potential for resection of some tumors, radiofrequency coblation appears to be an attractive evolving technique for the endoscopic resection of selected glottic cancer.

High-intensity focused ultrasound for the treatment of allergic rhinitis using nasal endoscopy.

The present study aimed to observe the therapeutic effect of high-intensity focused ultrasound for the treatment of allergic rhinitis (AR) using nasal endoscopy. A total of 72 patients with perennial AR received treatment using the CZB ultrasonic therapeutic instrument with nasal endoscopy. A scoring method was adopted for evaluation of effectiveness according to the AR therapeutic principles and recommendations described in Allergic Rhinitis and its Impact on Asthma (ARIA) in 2001. The patients were followed up between 2 and 6 months after treatment. The excellence rate was 34.7% (25/72), the effective rate was 62.5% (45/72) and the ineffective rate was 2.8% (2/72). The total effective rate reached 97.2% high (70/72). Endoscopic high-intensity focused ultrasound for the treatment of AR is a non-invasive method and has the advantages of simple manipulation, a short course, high safety and a clear short-term effect.