Macrophage-derived PDGF-BB modulates glycolytic enzymes expression and pyroptosis in nucleus pulposus cells via PDGFR-ß/TXNIP pathway.

OBJECTIVE: Intervertebral Disc Degeneration (IVDD) is one of the leading causes of low back pain, significantly impacting both individuals and society. This study aimed to investigate the significance of macrophage infiltration and the role of macrophage-secreted platelet-derived growth factor-BB (PDGF-BB) in IVDD progression. METHODS: To confirm the protective function of macrophage-derived PDGF-BB on nucleus pulposus cells (NPCs), we employed Lysm-Cre transgenic mice to genetically ablate PDGF-B within the myeloid cells. Immunohistochemistry was utilized to detect the expression of glycolytic enzymes and pyroptosis-related proteins during the process of IVDD. Western blot, RT-PCR, ELISA and immunofluorescence were used to detect the protective effect of recombinant PDGF-BB on NPCs. RESULTS: Macrophage-derived PDGF-BB deficiency resulted in the loss of NPCs and the increased ossification of cartilage endplates during lumbar disc degeneration. Also, PDGF-BB deficiency triggered the inhibition of glycolytic enzymes' expression and the activation of pathways related to pyroptosis in the nucleus pulposus. Mechanistically, our results suggest that PDGF-BB predominantly conveys its protective influence on NPCs through the PDGF receptor- beta (PDGFR-ß)/ thioredoxin-interacting protein pathway. CONCLUSIONS: The absence of PDGF-BB originating from macrophages expedites the advancement of IVDD, whereas the application of PDGF-BB treatment holds the potential for retarding intervertebral disc degeneration in the human body.

Upregulation of cIAP1 induced by AZD8330 alleviates osteoarthritis progression by inhibiting the RIP1-associated necrosis signaling pathway.

BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative joint disease [1]. It has come to light that AZD8330 can suppress the generation of proinflammatory factors and deter the inflammatory response [2]. Given that inflammation is a primary causative factor in OA, it is posited that AZD8330 might exhibit superior efficacy in OA management. METHODS: In this study, we investigated the potential of intraperitoneal injection of AZD8330 to retard the progression of osteoarthritis in a murine model with surgically induced medial meniscus destruction (DMM). Concurrently, we employed ATDC5 cartilage cells to dissect the mechanism through which AZD8330 inhibits the TNF-α-induced NF-κB signaling pathway via modulation of RIP1. The findings revealed that AZD8330 mitigated cartilage degradation and the inflammatory response, leading to a substantial reduction in OARSI scores among DMM mice treated with AZD8330. Mechanistically, AZD8330 functioned as a suppressor of the TNF-α-induced NF-κB/p65 signaling pathway by facilitating the phosphorylation activation of cIAP1-mediated RIP1. The combination of data from both in vivo and in vitro experiments supports the conclusion that AZD8330 can attenuate chondrocyte degradation, thereby alleviating OA, by regulating the NF-κB/P65 signaling pathway through modulation of RIP1 activity. Consequently, the utilization of AZD8330 may hold potential in the prophylaxis of osteoarthritis. RESULTS: Our investigation delineates the role of AZD8330 in the regulation of inflammation in the context of OA treatment. Furthermore, we have unveiled that the inhibitory impact of AZD8330 on OA may hinge upon the activation of cIAP1, which in turn downregulates RIP1, thereby restraining the NF-κB/P65 signaling pathway. This study lends credence to the notion that AZD8330 may be a promising contender for osteoarthritis therapy. CONCLUSIONS: Our study provides compelling evidence attesting to the capacity of AZD8330 in managing inflammation within the realm of OA treatment. Likewise, our study has elucidated that the attenuation of OA by AZD8330 relies on the activation of cIAP1 to inhibit RIP1, consequently suppressing the NF-κB signaling pathway. On the strength of our present study, we may have identified a viable drug candidate for OA treatment.

Paroxetine Attenuates Chondrocyte Pyroptosis and Inhibits Osteoclast Formation by Inhibiting NF-κB Pathway Activation to Delay Osteoarthritis Progression.

Background: Osteoarthritis (OA), a common chronic joint disease, is characterized by cartilage degeneration and subchondral bone reconstruction. NF-κB signaling pathway-activated inflammation and NLRP3-induced pyroptosis play essential roles in the development of OA. In this study, we examine whether paroxetine can inhibit pyroptosis and reduce osteoclast formation, thereby delaying the destruction of knee joints. Methods: We employed high-density cultures, along with quantitative polymerase chain reactions and Western blotting techniques, to investigate the effects of paroxetine on extracellular matrix synthesis and degradation. The expression levels of NF-κB and pyroptosis-related signaling pathway proteins were examined by Western blotting and immunofluorescence. Furthermore, the impact of paroxetine on RANKL-induced osteoclast formation was evaluated through TRAP staining and F-actin ring fluorescence detection. To investigate the role of paroxetine in vivo, we constructed a mouse model with destabilization of the medial meniscus (DMM) surgery. Safranin O-Fast Green staining, Hematoxylin-Eosin staining, and immunohistochemistry were conducted to observe the extent of knee joint cartilage deformation. In addition, TRAP staining was used to observe the formation of osteoclasts in the subchondral bone. Results: In the in vitro experiments with ATDC5, paroxetine treatment attenuated IL-1ß-induced activation of the pyroptosis-related pathway and suppressed extracellular matrix catabolism by inhibiting the NF-kB signaling pathway. In addition, paroxetine treatment decreased the expression of RANKL-induced osteoclast marker genes and reduced osteoclast formation. In animal experiments conducted in vivo, mice treated with paroxetine exhibited thicker knee cartilage with a smoother surface compared to the DMM group. Additionally, the formation of osteoclasts in the subchondral bone was reduced in the paroxetine-treated mice. Further analysis revealed that paroxetine treatment played a role in preserving the balance of the extracellular matrix and delaying knee joint degeneration. Conclusion: Paroxetine can inhibit pyroptosis and reduce osteoclast formation via inhibiting the NF-κB signaling pathway, suggesting that it may have therapeutic effects in patients with OA.

Effects of intravenous chemotherapy after TURBT for high-risk nonmuscle invasive bladder cancer: results of a retrospective study.

PURPOSE: This study compared the efficacy and safety of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for high-risk nonmuscle invasive bladder cancer (HRNMIBC) patients after transurethral resection of the bladder tumor (TURBT) surgery. METHODS: A retrospective analysis was performed on 349 HRNMIBC cases admitted to TangDu hospital between January 2014 and June 2019. After TURBT, 262 patients received intravesical chemotherapy alone, whereas 87 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. The recurrence rate and progression rate were assessed by Chi-square test, the prognostic factors for tumor recurrence were predicted by univariable and multivariable Cox hazards analyses, recurrence-free survival (RFS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: In this study, the recurrence rate was 24.7% (19/77) in the intravenous chemotherapy combined group and 41.6% (102/245) in the intravesical chemotherapy group, while the progression rate was 6.5% (5/77) and 14.3% (35/245) in the two groups respectively. The two groups differed significantly in recurrence rate (p = 0.007) while the progression rate did not show a significant difference (p = 0.071). Multivariable analyses revealed that additional intravenous chemotherapy treatment was an independent prognostic factor for tumor recurrence in the cohort (hazard ratio [HR], 0.495, 95% confidence interval [CI], 0.275-0.892, p = 0.019). Kaplan-Meier curves showed significant differences in RFS and PFS between the two groups, with a log-rank P value of p < 0.005 and p = 0.045, respectively. Grade 3/4 toxicity was reported in 2 of 77 patients in the intravenous chemotherapy combined group, including nausea/vomiting 1.3% (1/77) and hypoleukemia 1.3% (1/77). CONCLUSION: Intravenous chemotherapy of gemcitabine and cisplatin combined with intravesical chemotherapy after TURBT can effectively reduce the postoperative recurrence rate, most toxicities were minor and reversible, and it may be considered as a new choice for HRNMIBC patients.

PD0325901, an ERK inhibitor, attenuates RANKL-induced osteoclast formation and mitigates cartilage inflammation by inhibiting the NF-κB and MAPK pathways.

Osteoarthritis (OA), a degenerative disease affecting the joint, is characterized by degradation of the joint edge, cartilage injury, and subchondral bone hyperplasia. Treatment of early subchondral bone loss in OA can inhibit subsequent articular degeneration and improve the prognosis of OA. PD0325901, a specific inhibitor of ERK, is widely used in oncology and has potential as a therapeutic agent for osteoarthritis In this study, we investigated the biological function of PD0325901 in bone marrow monocytes/macrophages (BMMs)treated with RANKL and found that it inhibited osteoclast differentiation in vitro in a time- and dose-dependent manner. PD0325901 restrained the expression of osteoclast marker genes, such as c-Fos and NFATc1 induced by RANKL. We tested the biological effects of PD035901 on ATDC5 cells stimulated by IL-1ß and found that it had protective effects on ATDC5 cells. In animal studies, we used a destabilization of the medial meniscus (DMM) model and injected 5 mg/kg or 10 mg/kg of PD0325901 compound into each experimental group of mice. We found that PD0325901 significantly reduced osteochondral pathological changes in post-OA subchondral bone destruction.Finally, we found that PD0325901 down-regulated the pyroptosis level in chondrocytes to rescue cartilage degeneration. Therefore, PD0325901 is expected to be a new generation alternative therapy for OA.

Associations Between Physical Activity, Tinnitus, and Tinnitus Severity.

OBJECTIVES: To examine the associations between physical activity and tinnitus development and physical activity and tinnitus severity in a large representative sample of US adults. DESIGN: Data were obtained from 3826 eligible participants (20 to 69 years) in the National Health and Nutrition Examination Survey between 2015 and 2016. Physical activity was assessed using a Global Physical Activity Questionnaire. We used multivariable logistic regression to test the associations of physical activity (without physical activity, with physical activity) and amount of physical activity (min/week, in quartiles) with tinnitus symptoms. Adults with depressive symptoms were excluded, and the models were controlled for relevant sociodemographic, lifestyle, and health-related covariates. A restricted cubic spline was used to explore the dose-response relationship between the amount of physical activity and tinnitus. RESULTS: Overall, 12.8% of the population who engaged in physical activity reported tinnitus, compared with 18.5% of the population who did not ( p = 0.005). Subgroup analysis based on the amount of physical activity showed that participants who performed physical activity (150 to 300, 310 to 540, and 550 to 4800 min/week) had lower risks of tinnitus than those with no physical activity (odds ratio = 0.72, 0.56, and 0.62, respectively), after adjusting for covariates. However, no correlation was observed between physical activity and tinnitus severity in the present study. The dose-response analysis showed a nonlinear relationship (P for nonlinearity = 0.04) between the amount of physical activity and the risk of tinnitus. CONCLUSIONS: Physical activity may be associated with a reduced risk of tinnitus. Further research using a longitudinal design is required to confirm these findings and clarify the direction of causation.

Predicting prognosis and immunotherapeutic response of clear cell renal cell carcinoma.

Immune checkpoint inhibitors have emerged as a novel therapeutic strategy for many different tumors, including clear cell renal cell carcinoma (ccRCC). However, these drugs are only effective in some ccRCC patients, and can produce a wide range of immune-related adverse reactions. Previous studies have found that ccRCC is different from other tumors, and common biomarkers such as tumor mutational burden, HLA type, and degree of immunological infiltration cannot predict the response of ccRCC to immunotherapy. Therefore, it is necessary to further research and construct corresponding clinical prediction models to predict the efficacy of Immune checkpoint inhibitors. We integrated PBRM1 mutation data, transcriptome data, endogenous retrovirus data, and gene copy number data from 123 patients with advanced ccRCC who participated in prospective clinical trials of PD-1 inhibitors (including CheckMate 009, CheckMate 010, and CheckMate 025 trials). We used AI to optimize mutation data interpretation and established clinical prediction models for survival (for overall survival AUC: 0.931; for progression-free survival AUC: 0.795) and response (ORR AUC: 0.763) to immunotherapy of ccRCC. The models were internally validated by bootstrap. Well-fitted calibration curves were also generated for the nomogram models. Our models showed good performance in predicting survival and response to immunotherapy of ccRCC.

AZ-628 delays osteoarthritis progression via inhibiting the TNF-α-induced chondrocyte necroptosis and regulating osteoclast formation.

As a degenerative disease, the pathogenesis and treatment of osteoarthritis (OA) are still being studied. The prevailing view is that articular cartilage dysfunction plays an essential role in the development of osteoarthritis. Similarly, dynamic bone remodeling dramatically influences the development of osteoarthritis. The inflammatory response is caused by the overexpression of inflammatory factors, among which tumor necrosis factor-α is one of the main causes of OA, and its sources include the secretion of chondrocytes themselves and osteoclast secretion of subchondral bone. Moreover, TNF-α-induced activation of RIP1, RIP3, and MLKL has been shown to play an important role in cell necroptosis and inflammatory responses. In vitro, AZ-628 alleviates chondrocyte inflammation and necroptosis by inhibiting the NF-κB signaling pathway and RIP3 activation instead of RIP1 activation. AZ-628 also reduces osteoclast activity, proliferation and differentiation, and release of inflammatory substances by inhibiting autophagy, MAPK, and NF-κB pathways. Similarly, the in vivo study demonstrated that AZ-628 could inhibit chondrocyte breakdown and lower osteoclast formation and bone resorption, thereby slowing down subchondral bone changes induced by dynamic bone remodeling and reversing the progression of osteoarthritis in mice. The results of this study indicate that AZ-628 could be used to treat OA byinhibiting chondrocyte necroptosis and regulating osteoclast formation.

Neratinib exerts dual effects on cartilage degradation and osteoclast production in Osteoarthritis by inhibiting the activation of the MAPK/NF-κB signaling pathways.

Osteoarthritis (OA) is a degenerative disease caused by the progressive destruction of cartilage and subchondral bone [1]. Studies have shown that by inhibiting the degradation of cartilage cells and the loss of subchondral bone, OA can be prevented and treated. Neratinib, as a small molecule compound with anti-inflammatory and anti-tumor properties, is a very effective inhibitor of IL-1ß-induced chondrocyte inflammation and anabolic metabolism. By investigating the effect of neratinib in ATDC5 chondrocytes, the study finds that neratinib reduces inflammation by inhibiting the MAPK and NF-κB signaling pathways, and at the same time reduces pyrolysis (indicated by the results of reverse transcription quantitative PCR and western blotting). For anabolic metabolism, after high-density cell culture, IL-1ß-induced catalytic changes and degradation of the extracellular matrix were evaluated by toluidine blue staining. Since osteoclasts are key participants in the process of subchondral bone remodeling in OA, we also studied the effect of neratinib on the maturation of osteoclasts. The results showed that neratinib also acts as an anti-osteoclast agent in vitro. By inhibiting the NF-κB and MAPK pathways, it reduces the expression of osteoclast-related genes, thereby inhibiting RANKL-induced osteoclastogenesis. The results of in vivo animal experiments supported the conclusions from the experiments in vitro. Neratinib inhibited both the destruction of medial meniscus induced cartilage degradation and osteoclast formation, which proves that neratinib has a dual effect, protecting cartilage and inhibiting osteoclast formation. These results indicate that neratinib can be a brand-new latent strategy for the treatment of OA.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Endoscopic and Robotic Parotidectomy for the Treatment of Parotid Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND: The goal of this review was to introduce endoscopic/robotic parotidectomy (EP/RP) and compare EP/RP against conventional parotidectomy (CP) regarding the intraoperative and postoperative parameters in the treatment of parotid tumors. METHODS: A systematic literature search of medical databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) was performed from inception to November 2020 to generate relevant studies. RESULTS: A total of 13 eligible studies (572 patients) were included for systematic review, and 7 out of 13 comparable studies for the quantitative synthesis of outcomes. Patients who underwent EP were characterized by less intraoperative bleeding volume, shorter incision length, and higher satisfaction postoperatively (WMD, 95% CI, -42.80; - 58.23 to -27.37; p < 0.01; WMD, 95% CI, -5.64; -7.88 to -3.39; p < 0.01; SMD, 95% CI, 1.88; 1.46 to 2.31; p < 0.01, respectively). However, operative time and risk of facial palsy exhibited no significant differences (WMD, 95% CI, -11.17; -26.71 to 4.34; p = 0.16; OR, 95% CI,0.71; 0.39 to 1.32; p = 0.28, respectively). CONCLUSIONS: Our findings suggest that the current evidence does not adequately support EP is equally safe and effective as CP. In certain selected cases, endoscopic technology has its unique advantages. For patients with strong cosmetic needs, endoscopic or robotic techniques may be an alternative through adequate preoperative evaluations. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews, identifier CRD42020210299.

ROC1 promotes the malignant progression of bladder cancer by regulating p-IκBα/NF-κB signaling.

BACKGROUND: Regulator of cullins 1 (ROC1) is an important catalytic subunit of cullin-RING E3 ligase. Nuclear factor-kappa B (NF-κB) signaling is closely related to tumor invasion and metastasis. Earlier, we reported that ROC1 was associated with a poor prognosis in patients with bladder cancer (BCa). However, it is unclear whether ROC1 is involved in the NF-κB signaling associated with malignant BCa progression. METHODS: The expression of ROC1 and p65 in bladder cancer and paracancerous tissues were detected by immunohistochemistry (IHC). Pearson correlation was used to assess correlation between ROC1 and p65 protein expressions. The wound-healing and transwell assays were used to monitor cell invasion and migration. The effect of ROC1 on the expression of key proteins in the NF-κB signaling was determined by immunofluorescence and western blot (WB). Cycloheximide (CHX), MG132 and immunoprecipitation assays were used to evaluate the effect of ROC1 on the ubiquitination of phosphorylated inhibitor of kappa B alpha (p-IκBα). A lung metastasis mouse model was generated to detect the role of ROC1 in tumor metastasis. RESULTS: We found that ROC1 was up-regulated in BCa tissues and cell lines, and high ROC1 levels were positively correlated with higher tumour grade, lymph node metastasis, distant metastasis and poor prognosis. Linear-regression analysis showed significant a Pearson correlation between ROC1 and nuclear p65 expression in BCa tissue microarray (TMA) samples. Functional studies demonstrated that ROC1 promoted BCa cell invasion and migration. In vitro and in vivo experiments showed that ROC1 activated NF-κB signaling by enhancing the ubiquitination of p-IκBα, which caused p65 nuclear translocation and promoted the transcription of some metastasis-related target genes, such as urokinase-type plasminogen activator receptor (uPAR), intracellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and matrix metalloproteinase 9 (MMP9), resulting in promoting BCa metastasis. CONCLUSION: ROC1 plays an important role in the progression of BCa and serves as a potential diagnostic and therapeutic target for patients with BCa.

Platelet-Derived Growth Factor-BB Inhibits Intervertebral Disc Degeneration via Suppressing Pyroptosis and Activating the MAPK Signaling Pathway.

Platelet-derived growth factor-BB (PDGF-BB) is a cytokine involved in tissue repair and tumor progression. It has been found to have expression differences between normal and degenerative intervertebral discs. However, it is not clear whether PDGF-BB has a protective effect on intervertebral disc degeneration (IDD). In this experiment, we treated nucleus pulposus cells (NPCs) with IL-1ß to simulate an inflammatory environment and found that the extracellular matrix (ECM) anabolic function of NPCs in an inflammatory state was inhibited. Moreover, the induction of IL-1ß also enhanced the expression of NLRP3 and the cleavage of caspase-1 and IL-1ß, which activated the pyroptosis of NPCs. In this study, we studied the effect of PDGF-BB on IL-1ß-treated NPCs and found that PDGF-BB not only significantly promotes the ECM anabolism of NPCs, but also inhibits the occurrence of pyroptosis and the production of pyroptosis products of NPCs. Consistent with this, when we used imatinib to block the PDGF-BB receptor, the above-mentioned protective effect disappeared. In addition, we found that PDGF-BB can also promote the ECM anabolism of NPCs by regulating the ERK, JNK, PI3K/AKT signaling pathways, but not the P38 signaling pathway. In vivo studies, mice that blocked PDGF-BB receptors showed more severe histological manifestations of intervertebral disc degeneration. In summary, our results indicate that PDGF-BB participates in inhibiting the occurrence and development of IDD by inhibiting pyroptosis and regulating the MAPK signaling pathway.

Endoscopic-Assisted Transoral Thyroglossal Cyst Resection.

Sistrunk procedure is the standard method for thyroglossal duct cyst resection. While this procedure is successful and safe, it results in postoperative scars on the front of neck. We propose a total transoral technique without external incision that starts with careful separation of the floor of the mouth and genioglossus muscle followed by the exact localization of the cyst using methylene blue. Simultaneously, the hyoid bone connected to the cyst and tract was removed. Finally, routine hemostasis is conducted, and the operative cavity is closed. All patients who received this operation in our department recovered successfully without experiencing severe intraoperative or postoperative complications.

Cochlear implantation in prelingually deaf children with white matter lesions.

OBJECTIVE: White matter lesions (WMLs) are the most common central nervous system changes observed during cochlear implant evaluation. However, its clinical significance in cochlear implantation (CI) remains unclear. The purpose of this study is to explore the effects of WMLs on hearing and speech rehabilitation of prelingually deaf children after CI. METHODS: The data of forty-five children with WMLs who received CI from 2011 to 2014 were retrospectively reviewed. All patients underwent magnetic resonance imaging examination preoperatively. The categories of auditory performance (CAP) and speech intelligibility rating (SIR) scales were used to evaluate changes in the auditory and speech abilities of the patients, and the Fazekas scale was adopted to assess the extent of WMLs. The degree of WMLs was divided into four grades (none, mild, moderate, severe). We assessed hearing and speech abilities at the following time points: 6, 12, 24, 36, 48 and 60-months post-operation. RESULTS: No significant differences in CAP scores were observed between WMLs groups and the control group at 12 months post-CI (p = 0.099), but marked between-group differences were found at 6, 24, 48- and 60-months post-CI. (p < 0.05). Similarly, no significant differences in the SIR scores were observed at 6 months post-CI (p = 0.087), but marked between-group differences were found at 12, 24, 48- and 60- months post-CI. (p < 0.05). Analysis of stratified group results revealed improvements in hearing and speech development for all the subgroups, including the severe WMLs subgroup following CI. However, hearing and speech ability of the severe WMLs subgroup was much slower than that of other groups. CONCLUSIONS: The auditory and speech abilities of prelingually deaf children with WMLs and those without WMLs can improve after CI. Therefore, WMLs should not be considered a contraindication for CI. However, the decision to perform CI in such patients needs a comprehensive evaluation because the post-surgery effects on children with severe WMLs are not ideal.

Influence of family environment on the development of speech and language in pre-lingually deaf children after cochlear implantation.

OBJECTIVE: To investigate the influence of family environment on the development of speech and language in pre-school children after cochlear implantation. METHODS: A total of 88 pre-lingually deaf children, aged 2-5 years, who received cochlear implantation, were included in this study. All families completed a self-report family environment questionnaire (FES). The deaf children's linguistic progress was assessed by Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) at 0, 3, 6 and 12 months after implantation. RESULTS: The family environment was the significant factor associated with CAP and SIR at 6 months post-implantation. The children in families with higher levels of Cohesion, Intellectual-Cultural Orientation and the ability to express emotion effectively had better auditory and speech abilities, while children in families with low intimacy and high incompatibility exhibited a delay in the development of auditory speech (P < .05). CONCLUSIONS: The development of speech and language in pre-lingually deaf children after cochlear implantation can be influenced by family environment and parents' roles.

Myringotomy and tube insertion combined with balloon eustachian tuboplasty for the treatment of otitis media with effusion in children.

OBJECTIVE: This study aimed to clarify the role and safety of balloon eustachian tuboplasty (BET) in the treatment of otitis media with effusion (OME) in children. METHODS: This retrospective study was performed between January 2017 and February 2018. The study covered 25 OME patients treated with BET combined with myringotomy and tube insertion (MTI), designated as the BET group, and 24 OME patients treated with MTI during the same period considered as the controls. In addition, all patients received adenoidectomy if found with adenoid hypertrophy. The air-bone conduction gap (ABG) and curative effect were compared between the two groups. Tubomanometry (TMM) results were recorded preoperatively to confirm existence of eustachian tube dysfunction (ETD). Otologic history and examination results of all patients were carefully recorded before the operation, at 6, 12 and 18 months postoperatively. RESULTS: Six months after surgery, ABG difference between the two groups was less than 1 dB HL. At 12 months after the operation, ABG in the BET group was smaller than that in the control group. There was a marked ABG deterioration (from 10.1 to 15.9 dB HL) in the control group compared to that in BET. Statistically significant differences in ABG difference between the two groups were observed 18 months after surgery with cured and total effective rates of BET at 76.1 and 93.5%, respectively. In the control group, these rates were 60.9 and 89.1% respectively. No serious complications and tympanic perforations were found in all subjects. CONCLUSION: MTI combined with BET is effective and safe in the treatment of children with OME. Compared to simple MTI, application of BET can effectively extend improvement period and increase cured rate, especially after removal of the ventilation tube. Directly benefit from the ventilation tube, the curative effect was close during the period of tube retention. Considering the sample size and follow-up time of this study, related studies targeting large cohorts are needed in the future to validate the benefits of BET in children with OME.

High NRBP1 expression promotes proliferation and correlates with poor prognosis in bladder cancer.

Nuclear receptor binding protein 1 (NRBP1) is an evolutionarily highly conserved adaptor protein with multiple domains. Recently, its role in cancers has received increasing attention. To investigate whether NRBP1 is involved in the development of bladder cancer, we used tissue microarray and analyzed the association between the expression levels of NRBP1 and clinico-pathological features of 56 patients diagnosed with bladder cancer. Subsequently, NRBP1 was silenced using siRNA in bladder cancer cell lines T24 and 5637, and cell phenotype such as proliferation and apoptosis were observed. Further, in vivo tumor formation assay was performed. The expression of apoptosis markers was detected by Western blot. A significant positive correlation between increased NRBP1 expression and tumor stage, and lymph node metastasis was observed in 56 patients. High expression of NRBP1 was associated with poor prognosis and NRBP1 knockdown significantly inhibited cell proliferation and induced intrinsic apoptosis in vitro. Moreover, we also found that NRBP1 knockdown significantly suppress tumor growth in xenograft mouse model. Taken together, these data suggest that NRBP1 plays a critical role in the development of bladder cancer and may represent a potential target for bladder cancer treatment.

Accumulation of fructose 1,6-bisphosphate protects clear cell renal cell carcinoma from oxidative stress.

Clear cell renal cell carcinoma (ccRCC) is characterized by the activation of hypoxia-inducible factors and enhanced aerobic glycolysis. In our previous study, metabolic profiling revealed a threefold increase of fructose 1,6-bisphosphate (FBP) in ccRCC tissue compared with normal kidney tissue. As an important intermediate metabolite, its role in cancer development remains unknown. We found that high levels of FBP were required for cancer growth because of its ability to affect the redox status. Mechanistically, FBP regulated the redox status partially by suppressing NADPH oxidase isoform NOX4 activity in ccRCC cells. ccRCC maintained high levels of FBP through the downregulation of aldolase B (ALDOB). Reduction of FBP levels in cancer cells by the ectopic expression of ALDOB disrupted redox homeostasis, arrested cancer proliferation, and sensitized ccRCC cells to a chemotherapy agent (paclitaxel). Furthermore, low expression of ALDOB portended significantly worse disease-free survival and overall survival in ccRCC patients. In summary, the downregulation of ALDOB and accumulation of FBP promote ccRCC growth by counteracting oxidative stress.

Transoral vestibule approach for thyroid disease: a systematic review.

OBJECTIVES: Transoral endoscopic/robotic thyroidectomy vestibule approach (TOETVA/TORTVA) is a novel technology that has been proposed for the treatment of thyroid disease. Its adoption has increased because of its satisfying cosmetic effects. The primary aim of this systematic review was to assess the feasibility and safety of this approach, and the secondary aim was to discuss the indications for this technology. MATERIALS AND METHODS: According to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, we searched Pubmed, Embase and the Cochrane databases for published studies on the feasibility and safety of TOETVA or TORTVA. RESULTS: 11 articles containing 864 patients met the inclusion criteria after full-text screening, of which two were reports of randomized controlled trial (RCT), two were retrospective cohort studies and the remaining seven studies were case series. Only studies that evaluated the feasibility and safety of this approach were included. TOETVA/TORTVA was successfully performed in 857 out of the 864 cases (99.2%). The mean operative time ranged from 60.4 to 265.4 min. In most articles, blood loss was less than 50 mL and the mean hospital stay ranged from 1.1 to 8.2 days. The safety outcomes were presented in all articles. The total incidence of adverse events was 14.5%, of which the main complications were transient hypoparathyroidism (5.6%) and transient recurrent laryngeal nerve (RLN) injury (3.1%). CONCLUSIONS: This review preliminarily suggests that TOETVA or TORTVA could be an effective and safe treatment for thyroidectomy. Due to the small sample size and low level of evidence, further large-scale, well-designed RCTs are required to validate our findings.