Ailanthone synergizes with PARP1 inhibitor in tumour growth inhibition through crosstalk of DNA repair pathways in gastric cancer.

In our previous research, we proved that ailanthone (AIL) inhibits the growth of gastric cancer (GC) cells and causes apoptosis by inhibiting P23. However, we still find some GC organoids are insensitive to AIL. We have done some sequencing analysis and found that the insensitive strains are highly expressed in PARP1. In this study, we investigated whether AIL can enhance the anti-tumour effect of PARPi in GC. CCK8 and spheroid colony formation assay were used to measure anti-tumour effects. SynergyFinder software was used to calculate the synergy score of the drug combination and flow cytometry was used to detect apoptosis. Western blot, IHC, IF tests were used to measure protein expression. Finally, nude mouse xenograft models were used to verify the in vitro mechanisms. High expression of PARP1 was found to be the cause of drug insensitivity. When AIL is paired with a PARP1 inhibitor, olaparib (OLP), drug sensitivity improves. We discovered that this combination functions by blocking off HSP90-BRCA1 interaction and inhibiting the activity of PARP1, thus in turn inhibiting the homologous recombination deficiency and base excision repair pathway to finally achieve synthetic lethality through increased sensitivity. Moreover, P23 can regulate BRCA1 in GC in vitro. This study proves that the inhibitory effect of AIL on BRCA1 allowed even cancer cells with normal BRCA1 function to be sensitive to PARP inhibitors when it is simultaneously administered with OLP. The results greatly expanded the scope of the application of PARPi.

Clinical Characteristics and Risk Factors for Allergic Rhinitis in Children with Epistaxis.

Background: Epistaxis is frequently observed in children with allergic rhinitis. However, few studies have addressed the clinical characteristics and risk factors for allergic rhinitis in children with epistaxis. This study aimed to describe the factors associated with allergic rhinitis in children with epistaxis. Methods: In total, we recruited 80 children (aged 3-14 years) who presented with epistaxis at a tertiary hospital between January 2014 and January 2022. The follow-up duration was at least 3 months, and we performed a multivariate logistic regression analysis to identify the risk factors for allergic rhinitis. Results: Among the 80 children examined, 57 (71.25%) had allergic rhinitis. Epistaxis mainly occurred in autumn in children with allergic rhinitis; in contrast, it mostly occurred in summer in children without it (P = 0.029). Mites are common allergens for allergic rhinitis in children with epistaxis; the univariate analysis revealed significant differences between allergic-rhinitis group and nonallergic-rhinitis group in the number of allergens (P < 0.001) and total IgE (P < 0.001). The difference in severity of nasal symptoms between the two groups was statistically significant and included nasal obstruction (P < 0.001), rhinorrhea (P < 0.001), sneezing (P < 0.001), and nasal itching (P < 0.001). After adjusting for potential confounders, the severity of rhinorrhea symptoms was found to be associated with an increased risk of allergic rhinitis in children with epistaxis (odds ratio: 3.86; 95% confidence interval: 1.61-9.26; P = 0.003). Conclusions: Observing the onset season, number of allergens, total IgE, and nasal symptoms in cases of epistaxis could suggest the presence of associated allergic rhinitis and reduce the number of missed diagnoses; antiallergic drugs could help control epistaxis in these cases.

Hypoactive Visual Cortex, Prefrontal Cortex and Insula during Self-Face Recognition in Adults with First-Episode Major Depressive Disorder.

Self-face recognition is a vital aspect of self-referential processing, which is closely related to affective states. However, neuroimaging research on self-face recognition in adults with major depressive disorder is lacking. This study aims to investigate the alteration of brain activation during self-face recognition in adults with first-episode major depressive disorder (FEMDD) via functional magnetic resonance imaging (fMRI); FEMDD (n = 59) and healthy controls (HC, n = 36) who performed a self-face-recognition task during the fMRI scan. The differences in brain activation signal values between the two groups were analyzed, and Pearson correlation analysis was used to evaluate the relationship between the brain activation of significant group differences and the severity of depressive symptoms and negative self-evaluation; FEMDD showed significantly decreased brain activation in the bilateral occipital cortex, bilateral fusiform gyrus, right inferior frontal gyrus, and right insula during the task compared with HC. No significant correlation was detected between brain activation with significant group differences and the severity of depression and negative self-evaluation in FEMDD or HC. The results suggest the involvement of the malfunctioning visual cortex, prefrontal cortex, and insula in the pathophysiology of self-face recognition in FEMDD, which may provide a novel therapeutic target for adults with FEMDD.

Analysis of Etiology, Diagnosis, and Treatment Strategy and Efficacy of Pulsatile Tinnitus Caused by Abnormal Vascular Anatomy.

OBJECTIVE: To investigate the etiology, clinical characteristics, diagnosis, and treatment strategies and efficacy of pulsatile tinnitus (PT) caused by vascular anatomy abnormality. METHODS: The clinical data of 45 patients with PT in our hospital from 2012 to 2019 were collected and retrospectively analyzed. RESULTS: All 45 patients had vascular anatomical abnormalities. The patients were divided into 10 categories according to the different locations of vascular abnormalities: sigmoid sinus diverticulum (SSD), sigmoid sinus wall dehiscence (SSWD), SSWD with high jugular bulb, pure dilated mastoid emissary vein, aberrant internal carotid artery (ICA) in the middle ear, transverse-sigmoid sinus (TSS) transition stenosis, TSS transition stenosis with SSD, persistent occipital sinus stenosis, petrous segment stenosis of ICA, and dural arteriovenous fistula. All patients complained of PT synchronous with heartbeat rhythm. Endovascular interventional therapy and extravascular open surgery were used according to the location of the vascular lesions. Tinnitus disappeared in 41 patients, was significantly relieved in 3 patients, and was unchanged in 1 patient postoperatively. Except for one patient with transient headache postoperatively, no obvious complications occurred. CONCLUSION: PT caused by vascular anatomy abnormalities can be identified by detailed medical history and physical and imaging examination. PT can be relieved or even completely alleviated after appropriate surgical treatments.

Comparison of ZOOMit-DWI sequence and conventional DWI sequence in endometrial cancer. / ZOOMit-DWI序列和常规DWIåºåˆ—åœ¨å­å®«å† è†œç™Œä¸­çš„å¯¹æ¯”.

OBJECTIVES: Magnetic resonance diffusion-weighted imaging (DWI) has important clinical value in diagnosis and curative effect evaluation on endometrial carcinoma. How to improve the detection rate of endometrial small lesions by DWI is the research focus of MRI technology. This study aims to analyze the image quality of small field MRI ZOOMit-DWI sequence and conventional single-shot echo-planar imaging (SS-EPI) DWI sequence in the scanning of endometrial carcinoma, and to explore the clinical value of ZOOMit-DWI sequence. METHODS: A total of 37 patients with endometrial carcinoma diagnosed by operation and pathology in the Second Xiangya Hospital of Central South University from July 2019 to May 2021 were collected. All patients were scanned with MRI ZOOMit-DWI sequence and SS-EPI DWI sequence before operation. Two radiologists subjectively evaluated the anatomical details, artifacts, geometric deformation and focus definition of the 2 groups of DWI images. At the same time, the signal intensity were measured and the signal-to-noise ratio (SNR), contrast to noise ratio (CNR), and apparent diffusion coefficient (ADC) of the 2 DWI sequences were calculated for objective evaluation. The differences of subjective score, objective score and ADC value of the 2 DWI sequences were analyzed. RESULTS: The SNR of the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (301.96±141.85 vs 94.66±41.26), and the CNR of the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (185.05±105.45 vs 57.91±31.54, P<0.05). There was no significant difference in noise standard deviation between the ZOOMit-DWI group and the SS-EPI DWI group (P>0.05). The subjective score of anatomical detail and focus definition in the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (both P<0.05). The subjective score of artifacts and geometric deformation of ZOOMit-DWI group was significantly lower than that of the SS-EPI DWI group (both P<0.05). ADC had no significant difference between the ZOOMit-DWI group and the SS-EPI DWI group (P>0.05). CONCLUSIONS: The image quality of ZOOMit-DWI is significantly higher than that of conventional SS-EPI DWI. In the MRI DWI examination of endometrial carcinoma, ZOOMit-DWI can effectively reduce the geometric deformation and artifacts of the image, which is more conducive to clinical diagnosis and treatment.

Topical Application of Chinese Formula Yeliangen Promotes Wound Healing in Streptozotocin-Induced Diabetic Rats.

Diabetic wound is one of the most severe complications of diabetes mellitus (DM). Despite the associated risks of wound healing impairment in diabetes, treatment strategies remain limited. Yeliangen (YLG) is a Chinese formulation mainly composed of the rhizome of Coptis chinensis, the root of Isatis tinctoria, and the leaf of Isatis indigotica. We investigated the wound healing effects of YLG in type 2 diabetic (T2DM) rats, which were induced by intraperitoneal administration of streptozotocin after a high-fat diet for four weeks. 3 × 3 cm2 full-thickness excisional wounds were created on the dorsal surface of rats and then divided to control (DC), negative (DPJ), positive (DPC), and YLG-treated (DYLG) groups. Rat's wounds were treated twice daily for 21 days. Wound area and wound contraction were detected on days 0, 3, 7, 14, and 21. Histopathological examinations were performed by H&E staining and immunohistochemistry (IHC). The biochemical parameters, mRNAs, and protein expressions were analyzed through enzyme-linked immunoassays (ELISA), qPCR, and western blot, respectively. Compared with other groups, the histological changes of wound tissue in the DYLG group were improved, and the expressions of CD31, eNOS, and PCNA were significantly upregulated. Besides, YLG significantly reduced the inflammatory factors' expressions of TNF-α, NF-κB, MMP-9, and IL-1B on days 7, 14, and 21 postwounding. Moreover, YLG induced angiogenesis and neovascularization by significantly increasing the levels of VEGF, TGF-ß1, EGF, PDGF, and SDF-1α on days 3, 7, and 14. In conclusion, YLG improved wound healing by reducing inflammation and increasing angiogenesis which may provide an alternative and effective approach for diabetic wound therapy.

Problematic smartphone use is associated with differences in static and dynamic brain functional connectivity in young adults.

Introduction: This study aimed to investigate the possible associations between problematic smartphone use and brain functions in terms of both static and dynamic functional connectivity patterns. Materials and methods: Resting-state functional magnetic resonance imaging data were scanned from 53 young healthy adults, all of whom completed the Short Version of the Smartphone Addiction Scale (SAS-SV) to assess their problematic smartphone use severity. Both static and dynamic functional brain network measures were evaluated for each participant. The brain network measures were correlated the SAS-SV scores, and compared between participants with and without a problematic smartphone use after adjusting for sex, age, education, and head motion. Results: Two participants were excluded because of excessive head motion, and 56.9% (29/51) of the final analyzed participants were found to have a problematic smartphone use (SAS-SV scores ≥ 31 for males and ≥ 33 for females, as proposed in prior research). At the global network level, the SAS-SV score was found to be significantly positively correlated with the global efficiency and local efficiency of static brain networks, and negatively correlated with the temporal variability using the dynamic brain network model. Large-scale subnetwork analyses indicated that a higher SAS-SV score was significantly associated with higher strengths of static functional connectivity within the frontoparietal and cinguloopercular subnetworks, as well as a lower temporal variability of dynamic functional connectivity patterns within the attention subnetwork. However, no significant differences were found when directly comparing between the groups of participants with and without a problematic smartphone use. Conclusion: Our results suggested that problematic smartphone use is associated with differences in both the static and dynamic brain network organizations in young adults. These findings may help to identify at-risk population for smartphone addiction and guide targeted interventions for further research. Nevertheless, it might be necessary to confirm our findings in a larger sample, and to investigate if a more applicable SAS-SV cutoff point is required for defining problematic smartphone use in young Chinese adults nowadays.

Papillary thyroid microcarcinoma with contralateral large humerus metastasis and cervical lymph node metastasis: A case report.

Introduction: Papillary thyroid microcarcinoma (PTMC) that metastasizes to bone, especially metastasizes to contralateral humerus with so large mass, is rarely reported before. Case report: We presented a 50-year-old female patient with a large painful mass in the right humerus for 5 years, presenting with swelling of the right shoulder with limited mobility. Positron emission tomography-computed tomography (PET/CT) showed a large mass in the right humerus, bilateral lung lesions, and enlarged lymph nodes in the right supraclavicular fossa. Right humerus lesion biopsy and immunohistochemical evaluations confirmed that the lesion originated from the thyroid tissue. Then, the thyroid ultrasonography showed a hypo-echoic solid nodule with an irregular taller-than-wide shape in the upper of left thyroid lobe and enlarged lymph nodes with the absence of fatty hilum in the contralateral right IV compartment. The total thyroidectomy and cervical lymph node dissection were undertaken; the histopathology confirmed the diagnosis of PTMC with contralateral cervical lymph node metastasis. Conclusion: We reported a case of PTMC with contralateral large humerus and cervical lymph node metastasis and demonstrated the PET/CT images of the metastatic large humerus and thyroid ultrasonographic appearances of the PTMC and enlarged cervical lymph node.

Changes in brain network properties in major depressive disorder following electroconvulsive therapy: a combined static and dynamic functional magnetic resonance imaging study.

BACKGROUND: Major depressive disorder (MDD) is a common and intractable mood disorder. Electroconvulsive therapy (ECT) is a common means of brain electrical stimulation for the treatment of MDD, but the neurobiological mechanism of its clinical symptom relief effect is still to be explored. This study aims to explore how ECT plays a role in depression remissions by investigating the changes of static and dynamic brain network characteristics in MDD patients before and after ECT. METHODS: Resting-state functional magnetic resonance imaging (fMRI) scans were obtained from nine MDD patients twice before and after a full course of ECT, all of whom responded to ECT as defined by at least a 50% reduction from baseline Hamilton Depression Scale (HAMD) scores. Both static and dynamic characteristics of the functional brain network were compared between the pre- and post-ECT scans for all participants, and the correlations between changes in clinical symptoms and altered network metrics were also investigated. RESULTS: The clustering coefficient and local efficiency in static brain networks were increased significantly, while the global flexibility of dynamic brain networks was decreased significantly after ECT. Several regions of interest (ROIs) that changed significantly at the local level were also identified, which involved regions of the cerebellum, hippocampus as well as frontal and temporal cortices. Although not significant, the decrease of HAMD scores were associated with trends of changed network metrics after ECT. CONCLUSIONS: Our results suggest that ECT may alleviate the depressive symptoms of MDD by decreasing the randomness of the brain network as reflected by changes in both static and dynamic network properties and that the temporal gyrus, frontal gyrus, hippocampus, and cerebellar regions may play key roles in such mechanisms. These findings have important implications for our understandings of ECT and depression. However, this study is limited by a relatively small sample size and the results should be confirmed in larger samples.

Validation of an MRI Technique for the 6-DOF Knee Kinematics Measurement.

Background: For total knee arthroplasty (TKA), the optimal rotational position of the femoral component is felt to be critically important. The current knee joint kinematics measurement technology is unable to identify the exact rotation axis of the knee joint, the main reasons being low measurement accuracy and insufficient three-dimensional data (2D-3D image matching technology). In order to improve the effect of TKA surgery, we proposed a knee joint kinematics measurement method, based on the MRI technology, and verified its measurement accuracy. We then employed this method to identify the personalized optimal rotation axis of the knee joint for TKA patients. Purposes: The purpose of the study was 1) to propose a method for measuring knee joint kinematics and verify its accuracy and 2) to propose a method for determining the optimal rotation axis of knee joint for TKA surgery, based on accurate kinematic measurement results. Materials and Methods: The experiment was divided into two parts: in vitro and in vivo. The purpose of the in vitro experiment was to verify the measurement accuracy of our method. We fixed two aquarium stones (approximately 10 cm * 10 cm * 10 cm in size, close to the size of the distal femur and proximal tibia) firmly on the fixed and moving arms of the goniometer/vernier caliper with glue and immersed the aquarium stones in the water to capture MRI images. The MRI images were then processed with MATLAB software, and the relative motion of the two aquarium stones was measured. The measurement accuracy of our method was verified via the scale reading of the moving arm on the goniometer/vernier caliper. In vivo, 36 healthy elderly participants (22 females, 14 males) were recruited from the local community; our method was then employed to measure the relative motion of the tibia and femur and to observe the rollback and screw home motion of the medial/lateral condyle of the femur, which was identified as specific kinematic features of the knee joint. Results: In vitro, all measurements were accurate to <1 mm and <1°. In vivo, all knee measurements showed rollback motion (the rollback distance of the medial femoral condyle was 18.1 ± 3.7 mm and that of the lateral condyle was 31.1 ± 7.3 mm) and screw home motion. Conclusion: In the application scenario of knee joint kinematics measurement, our method has an accuracy of <1° of rotation angle and <1 mm of translation for all reference points, and it can be employed to identify the most stable axis of the knee joint. Significance: Using our method to accumulate data on the knee rotation axis of more subjects to establish an average rotation axis of a given population may help in knee prosthesis design and reduce the patient dissatisfaction rate. Individually measuring the patient's rotation axis before TKA surgery and adjusting the prosthesis installation in TKA may further reduce the patient dissatisfaction rate, and automatic computer measurement may be realized in the future, but it is still time-consuming for now.

Isolated ventricular apical hypoplasia: A report of four cases and literature review.

Isolated ventricular apical hypoplasia (IVAH) is a rare congenital cardiac anomaly, with clinical manifestations depending on the age of the patient, ranging from no symptoms in children to congestive heart failure or even malignant tachycardia in adults. Herein, we describe the clinical and anatomical findings in four cases with hypoplasia of the right or left ventricular apex, and we discuss the possible mechanisms and differential diagnosis of this malformation. Echocardiography is a rapidly accessible, low cost, noninvasive technique for the detection and evaluation of IVAH.

Age-Related Decrease in Default-Mode Network Functional Connectivity Is Accelerated in Patients With Major Depressive Disorder.

Major depressive disorder (MDD) is a common psychiatric disorder which is associated with an accelerated biological aging. However, little is known whether such process would be reflected by a more rapid aging of the brain function. In this study, we tested the hypothesis that MDD would be characterized by accelerated aging of the brain's default-mode network (DMN) functions. Resting-state functional magnetic resonance imaging data of 971 MDD patients and 902 healthy controls (HCs) was analyzed, which was drawn from a publicly accessible, multicenter dataset in China. Strength of functional connectivity (FC) and temporal variability of dynamic functional connectivity (dFC) within the DMN were calculated. Age-related effects on FC/dFC were estimated by linear regression models with age, diagnosis, and diagnosis-by-age interaction as variables of interest, controlling for sex, education, site, and head motion effects. The regression models revealed (1) a significant main effect of age in the predictions of both FC strength and dFC variability; and (2) a significant main effect of diagnosis and a significant diagnosis-by-age interaction in the prediction of FC strength, which was driven by stronger negative correlation between age and FC strength in MDD patients. Our results suggest that (1) both healthy participants and MDD patients experience decrease in DMN FC strength and increase in DMN dFC variability along age; and (2) age-related decrease in DMN FC strength may occur at a faster rate in MDD patients than in HCs. However, further longitudinal studies are still needed to understand the causation between MDD and accelerated aging of brain.

RETRACTED: Long non-coding RNA LINC00052 regulates miR-608/EGFR axis to promote progression of head and neck squamous cell carcinoma.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the corresponding author and the Editor-in-chief The corresponding author claims that the authors confused multiple pictures in different groups, resulting in overlapping figures among different groups. Fig. 7B has partial overlap with Fig. 7D of a paper authored by a different research group (Y. Gao, et al., LINC00311 promotes cancer stem-like properties by targeting miR-330-5p/TLR4 pathway in human papillary thyroid cancer, Cancer Med. 9 (2019) 1515-1528, https://doi.org/10.1002/cam4.2815). The author claimed that they had sent the pathological sections to a shared platform and that the platform mistakenly sent back pathological results from other institutions which were then used in the manuscript. The Editor-in-Chief has lost the trust in the data and the conclusion, and decided to retract the paper.

MicroRNA-4497 functions as a tumor suppressor in laryngeal squamous cell carcinoma via negatively modulation the GBX2.

OBJECTIVE: MicroRNAs (miRNAs) are aberrantly expressed in various tumors and play a critical role in the progression and development of tumors. However, there is little information about the role of miR-4497 in laryngeal squamous cell carcinoma (LSCC). The aim of this study is to investigate the role of miR-4497 in LSCC. METHODS: MiR-4497 expression in tumor tissues and adjacent normal tissues was measured by RT-PCR. The effects of miR-4497 on cell viability and apoptosis were evaluated by the MTT assay, Flow cytometry and caspase-3 activity assay. Western blot analysis was used to measure the expression of various proteins. Bioinformatic analysis and luciferase reporter assay were applied to investigate the relationship between miR-4497 and GBX2. RESULTS: We found that miR-4497 expression was downregulated in LSCC tumor tissues and cell lines compared to the normal counterparts. Overexpression of miR-4497 inhibits the proliferation and induces apoptosis of LSCC cells accompanied by the down-regulation of anti-apoptotic Bcl-2 proteins. Mechanisms investigation revealed that GBX2 is a direct target of miR-4497. miR-4497 expression was inversely correlated with GBX2 expression in LSCC tissues. Moreover, overexpression of miR-4497 leads to the activation of ERK, JNK but not p38. Inhibition of ERK by specific inhibitor SCH772984 could interfere the apoptosis induced by overexpression of miR-4497. CONCLUSION: Therefore, our results indicate that miR-4497 may play a suppressive role in LSCC by targeting GBX2, which offer new insights into the tumorigenesis of LSCC.

Triple-Modal Imaging-Guided Chemo-Photothermal Synergistic Therapy for Breast Cancer with Magnetically Targeted Phase-Shifted Nanoparticles.

Current nanodrug-based cancer therapy is susceptible to the problems of rapid clearance from circulation and limited therapeutic efficacy. Herein, we report a magnetically targeted and photothermal-triggered drug release nanotheranostics system based on superparamagnetic iron oxide (Fe3O4), IR780, doxorubicin (DOX), and perfluoropentane (PFP) entrapped poly-lactide- co-glycolide (PLGA) nanoparticles (IR780/Fe3O4@PLGA/PFP/DOX NPs) for triple-modal imaging-guided synergistic therapy of breast cancer. In this work, IR780 and Fe3O4 convert light into heat, which triggers DOX release from IR780/Fe3O4@PLGA/PFP/DOX NPs and a phase-shift thermoelastic expansion of PFP; this procedure further accelerates the DOX release and tissue extrusion deformation. Fe3O4 NPs also serve as the target moiety by an external magnet directed to the tumor. Specifically, the IR780/Fe3O4@PLGA/PFP/DOX NPs can be used for triple-modal imaging, including near infrared fluorescence, magnetic resonance, and ultrasound. Furthermore, the antitumor therapy studies reveal the extraordinary performance of IR780/Fe3O4@PLGA/PFP/DOX NPs in magnetically targeted synergistic chemo-photothermal therapy of cancer. Therefore, the multifunctional IR780/Fe3O4@PLGA/PFP/DOX NPs guided by the magnetic field show a great potential for cancer theranostics.

Phase-shifted paclitaxel-loaded multifunctional contrast agent for US/MR imaging and synergistic hyperthermal/chemotherapy of metastasis in lymph nodes.

The existing approaches used to detect a tumor-induced sentinel lymph node and treat metastasis have limitations. In this study, by encapsulating perfluoropentane (PFP), magnetic iron oxide nanoparticles (Fe3O4) and the chemotherapy drug paclitaxel (PTX), we fabricated novel polymer nanoparticles (NPNs) that can effectively absorb heat after irradiation by near-infrared irradiation (NIR), thereby synergistically enhancing tumor therapy via a phase-shift thermoelastic expansion effect. These NPNs can be used for dual-modal ultrasound (US) and magnetic resonance (MR) imaging and to treat metastasis in lymph nodes under NIR irradiation-triggered drug delivery. The enhancement of US/MR imaging proved effective in vitro and in vivo, and NIR irradiation proved valid, promoting PTX release at the target site. A lower proliferation index and density and a higher tumor cell apoptotic index in the histopathology results confirmed the effectiveness of NPN chemotherapy for lymph nodes.

CIP2A, an oncoprotein, is associated with cell proliferation, invasion and migration in laryngeal carcinoma cells.

Laryngeal carcinoma is one of the most common malignant tumors in otorhinolaryngology. Moreover, experimental investigation showed that cancerous inhibitor of protein phosphatase 2A (CIP2A) expressed highly in various cancers. Therefore, we investigated whether CIP2A can regulate the proliferation, invasion and migration by RNA interference in Hep-2 cells and AMC-NH-8 cells and further affect the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Overexpression of CIP2A was evaluated in tumor tissue and laryngeal cancer cell lines (Hep-2 and AMC-NH-8 cells) by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assay. In a follow-up experiment, we confirmed that CIP2A siRNA effectively suppressed the cell proliferation at 48 and 72 h, and arrested cell cycle at G0/G1 in Hep-2 cells and AMC-NH-8 cells. The invasion and migration of cell in siRNA CIP2A group were markedly inhibited. Moreover, the experimental results showed that the expression levels of invasion- and migration-related genes, including E-cadherin, metastasis-associated gene 1 (MTA1) and matrix metalloproteinases-2/9 (MMP-2/9), were regulated by CIP2A siRNA. Phosphorylation levels of PI3K and AKT proteins were reduced by CIP2A siRNA. Importantly, it suggested signaling through PI3K/Akt as a critical mechanism by which CIP2A siRNA may suppress cell proliferation, invasion and migration in laryngeal carcinoma cells.

The clinical analysis of bilateral successive sudden sensorineural hearing loss.

The objective of this study is to investigate the clinical characteristics of successive bilateral sudden sensorineural hearing loss (SSNHL) with an interval of more than 1 year to aid the evaluation and management of successive bilateral SSNHL (BSSNHL). 14 successive BSSNHL patients and 118 unilateral SSNHL patients with severe and profound hearing loss were reviewed retrospectively. Information about successive BSSNHL was collected included demographics, the intervals between the attacks of bilateral ears, the past medical history, inducing factors, accompanying symptoms, pure-tone tests, blood tests, b-ultrasound examinations of vertebral artery and carotid artery, and medical interventions. And the comparison of improvement rate was made between successive BSSNHL and unilateral SSNHL. SPSS 15.0 was used to analyze the data. In successive BSSNHL, there were six males and eight females; the average aged was 49.86 ± 15.45 years (20-73 years). The interval of the two attacks was 11.43 ± 12.07 years (1-50 years) on average. The onset of treatment was 18.86 ± 12.71 days. Tinnitus was seen in 100 % of the patients, followed by vertigo in 42.85 %, and ear fullness in 21.43 %. 3 of 14 patients described obvious inducing factor: tiredness. Five patients (35.71 %) had hypertension histories, three (21.43 %) had diabetes histories, two (14.29 %) had surgery histories, one (7.14 %) was with depression history, one (7.14 %) was with coronary heart disease history. 30 % (3/10) patients were with atherosclerotic plaque in carotid artery. 4 (28.57 %) patients were with high blood sugar. 8 patients (57.14 %) were with high blood lipids. Thyroid function tests were positive in 27.27 % (3/11) patients. No abnormality was found in antinuclear antibodies titer. The percentage of profound and severe hearing loss were 71.43 and 78.57 % in the recently affected ear and contralateral ear separately. The PTAs of the recently affected ear were 77.14 ± 27.12 dB before treatment and 68.84 ± 22.32 dB after treatment, the improvement rate was 28.57 %. No improvement was found in the contralateral ears. In unilateral SSNHL, the average age was 42.47 ± 14.18 years. The onset of treatment was 18.08 ± 15.84 days. The improvement rate was 57.63 %, which was much higher than that of successive BSSNHL. There was no difference in age and time of onset of treatment between successive BSSNHL and unilateral SSNHL (p > 0.05). Successive BSSNHL is rare, the hearing impairment is severe, and the outcome of treatment is poorer. It may have a completely different profile compared with the simultaneous BSSNHL and unilateral SSNHL.