Human Chorionic Gonadotropin Regulates the Smad Signaling Pathway by Antagonizing TGF-ß in Giant Cell Tumor of Bone.

BACKGROUND: Giant cell tumor of bone (GCTB) is a locally aggressive bone tumour aggravated by stromal cell proliferation and metastasis. OBJECTIVE: We investigated the mechanism of action of human chorionic gonadotropin (HCG) in mediating GCTB proliferation and invasion. METHODS: The expression of HCG was quantified using quantitative real-time PCR. After the primary stromal cells were isolated and identified, the function of HCG in GCTB was estimated using the cell counting kit-8, flow cytometry, scratch experiment, transwell assay, Western blot, and immunofluorescence. Moreover, the mechanism of HCG was assessed through western blotting. RESULTS: HCG expression was decreased in clinical tissue samples from patients with GCTB. We validated that HCG repressed stromal cell proliferation, migration, invasion, autophagy, and epithelial- mesenchymal transition (EMT) and promoted cell apoptosis in GCTB. We also verified that HCG repressed the autophagy and EMT of stromal cells through the Smad signaling axis in GCTB. HCG inhibited the transduction of the Smad signaling pathway by restraining the binding of the TGF-ß II receptor to ligand Activin A. CONCLUSION: HCG restrained the Smad signaling pathway by antagonizing TGF-ß signaling in GCTB. HCG may serve as a useful patent to treat GCTB.

CP-25 inhibits the hyperactivation of rheumatic synoviocytes by suppressing the switch in Gαs-Gαi coupling to the ß2-adrenergic receptor.

In essence, the ß2 adrenergic receptor (ß2AR) plays an antiproliferative role by increasing the intracellular cyclic 3',5'-adenosine monophosphate (cAMP) concentration through Gαs coupling, but interestingly, ß2AR antagonists are able to effectively inhibit fibroblast-like synoviocytes (FLSs) proliferation, thus ameliorating experimental RA, indicating that the ß2AR signalling pathway is impaired in RA FLSs via unknown mechanisms. The local epinephrine (Epi) level was found to be much higher in inflammatory joints than in normal joints, and high-level stimulation with Epi or isoproterenol (ISO) directly promoted FLSs proliferation and migration due to impaired ß2AR signalling and cAMP production. By applying inhibitor of receptor internalization, and small interfering RNA (siRNA) of Gαs and Gαi, and by using fluorescence resonance energy transfer and coimmunoprecipitation assays, a switch in Gαs-Gαi coupling to ß2AR was observed in inflammatory FLSs as well as in FLSs with chronic ISO stimulation. This Gαi coupling was then revealed to be initiated by G protein coupled receptor kinase 2 (GRK2) but not ß-arrestin2 or protein kinase A-mediated phosphorylation of ß2AR. Inhibiting the activity of GRK2 with the novel GRK2 inhibitor paeoniflorin-6'-O-benzene sulfonate (CP-25), a derivative of paeoniflorin, or the accepted GRK2 inhibitor paroxetine effectively reversed the switch in Gαs-Gαi coupling to ß2AR during inflammation and restored the intracellular cAMP level in ISO-stimulated FLSs. As expected, CP-25 significantly inhibited the hyperplasia of FLSs in a collagen-induced arthritis (CIA) model (CIA FLSs) and normal FLSs stimulated with ISO and finally ameliorated CIA in rats. Together, our findings revealed the pathological changes in ß2AR signalling in CIA FLSs, determined the underlying mechanisms and identified the pharmacological target of the GRK2 inhibitor CP-25 in treating CIA. Video Abstract.

Dry suction versus wet suction technique of endoscopic ultrasound-guided fine-needle biopsy for diagnosis of solid pancreatic lesions: study protocol of a multicenter randomized controlled non-inferiority trial.

BACKGROUND: Studies have shown that the wet suction technique in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) generates better histological diagnostic accuracy and specimen quality than the dry suction technique. However, conclusions of wet suction on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) are still controversial. Besides, the optimal number of passes for EUS-FNB has not been determined. We aimed to design a large multicenter randomized trial to compare the diagnostic accuracy of dry suction versus wet suction technique in solid pancreatic lesions (SPLs) using 22G Franseen needles and determine the optimal number of passes required for EUS-FNB. METHODS: This is a multi-center open-label, randomized controlled non-inferiority trial with two parallel groups. Two hundred patients with SPLs will undergo EUS-FNB using 22G Franseen needles in 4 tertiary hospitals in China and will be randomly assigned to the dry suction group and wet suction group in a ratio of 1:1. The primary endpoint is diagnostic accuracy. Secondary endpoints include the optimal number of needle passes, sensitivity, specificity, specimen quality, cytological diagnoses, time of the procedure, and incidence of complications. DISCUSSION: This study has been designed to determine (i) whether EUS-FNB using 22G Franseen needle with dry suction is non-inferior to wet suction in terms of diagnostic accuracy and (ii) the optimal number of passes during EUS-FNB of SPLs using 22G Franseen needle. TRIAL REGISTRATION: ClinicalTrials.gov NCT05549856. Registered on September 22, 2022.

Anti-Her2 affibody-decorated arsenene nanosheets induce ferroptosis through depleting intracellular GSH to overcome cisplatin resistance.

Ferroptosis, a form of regulated cell death induced by excessive accumulation of reactive oxygen species and lipid peroxidation, has recently attracted extensive attention due to its ability to effectively suppress tumors and overcome drug resistance. Unlike previously reported metal nanomaterials that induce ferroptosis via the Fenton reaction, arsenene nanosheets can effectively deplete intracellular glutathione and then induce ferroptosis by inhibiting glutathione peroxidase 4. In this study, we designed target-modified arsenene nanosheets loaded with cisplatin (Her2-ANs@CDDP), which are capable of selective uptake by tumor cells. Her2-ANs@CDDP promotes both apoptosis and ferroptosis through a reciprocal cascade reaction between cisplatin and the carrier, respectively, and we demonstrate that it can significantly inhibit the activity of drug-resistant cells. Arsenene nanosheets kill drug-resistant tumor cells by inducing ferroptosis and restoring the sensitivity of drug-resistant cells to cisplatin. Cisplatin-loaded arsenene nanosheets can be prepared simply, and exert synergistic effects that overcome drug resistance. They show great potential for applications in the clinical treatment of chemotherapy-insensitive osteosarcoma, expanding the uses of arsenic in the treatment of solid tumors.

Construction of Osteosarcoma Diagnosis Model by Random Forest and Artificial Neural Network.

Osteosarcoma accounts for 28% of primary bone malignancies in adults and up to 56% in children and adolescents (<20 years). However, early diagnosis and treatment are still inadequate, and new improvements are still needed. Missed diagnoses exist due to fewer traditional diagnostic methods, and clinical symptoms are often already present before diagnosis. This study aimed to develop novel and efficient predictive models for the diagnosis of osteosarcoma and to identify potential targets for exploring osteosarcoma markers. First, osteosarcoma and normal tissue expression microarray datasets were downloaded from the Gene Expression Omnibus (GEO). Then we screened the differentially expressed genes (DEGs) in the osteosarcoma and normal groups in the training group. Next, in order to explore the biologically relevant role of DEGs, Metascape and enrichment analyses were also performed on DEGs. The "randomForest" and "neuralnet" packages in R software were used to select representative genes and construct diagnostic models for osteosarcoma. The next step is to validate the model of the artificial neural network. Then, we performed an immune infiltration analysis by using the training set data. Finally, we constructed a prognostic model using representative genes for prognostic analysis. The copy number of osteosarcoma was also analyzed. A random forest classifier identified nine representative genes (ANK1, TGFBR3, TNFRSF21, HSPB8, ITGA7, RHD, AASS, GREM2, NFASC). HSPB8, RHD, AASS, and NFASC were genes we identified that have not been previously reported to be associated with osteosarcoma. The osteosarcoma diagnostic model we constructed has good performance with areas under the curves (AUCs) of 1 and 0.987 in the training and validation groups, respectively. This study opens new horizons for the early diagnosis of osteosarcoma and provides representative markers for the future treatment of osteosarcoma. This is the first study to pioneer the establishment of a genetic diagnosis model for osteosarcoma and advance the development of osteosarcoma diagnosis and treatment.

Reconstruction of Tumor-Induced Pelvic Defects With Customized, Three-Dimensional Printed Prostheses.

Background: Reconstruction of pelvis girdle stability after tumor-induced hemipelvectomy remains challenging. We surgically treated 13 patients with custom-made, three-dimensional printed hemipelvic prostheses. We aim to identify the preliminary outcomes for patients who have been managed with more mixed regions of prosthetic pelvic reconstruction and the feasibility of two reconstructive systems. Methods: Seven male patients and 6 female patients treated at our center between January 2019 and May 2021 were included. There were 11 primary sarcomas and 2 solitary bone metastases. After en bloc tumor resection, two types of personalized, three-dimensional printed prostheses were fixed to restore the stability and rebuild the load transfer. The position of the reconstructed hemipelvis was evaluated on an anteroposterior plain radiograph. The complications and outcomes were traced. One amputation specimen was discovered through histological analysis of the porous structure. Results: The operative duration was 467 ± 144 min, and the blood loss was 3,119 ± 662 ml. During a follow-up of 22.4 ± 8.5 months, two patients had delayed wound healing and one had a second-stage flap transfer. One patient with osteosarcoma died of pulmonary metastasis 27 months after surgery. Two patients with marginal resection suffered from local recurrence and had extra surgeries. One patient had traumatic hip dislocation 2 months after surgery and manipulative reduction was performed. The acetabular inclination of the affected side was 42.2 ± 4.3°, compared with 42.1 ± 3.9° on the contralateral side. The horizontal distance between the center of the femoral head and the middle vertical line was 10.4 ± 0.6 cm, while the reconstructed side was 9.8 ± 0.8 cm. No significant difference in acetabular position after surgery was found (p > 0.05). The amputation specimen harvested from one patient with local recurrence demonstrated bone and soft tissue ingrowth within the three-dimensional printed trabecular structure. Walking ability was preserved in all patients who are still alive and no prosthesis-related complications occurred. The MSTS score was 22.0 ± 3.7. Conclusions: Both types of custom-made, three-dimensional printed prostheses manifested excellent precision, mechanical stability, and promising functional rehabilitation. The porous structure exhibited favorable histocompatibility to facilitate the ingrowth of bone and soft tissue.

Case Report: 3D-Printed Prosthesis for Limb Salvage and Joint Preservation After Tibial Sarcoma Resection.

Introduction: Reconstruction of massive tibial defects in ankle joint-preserving surgery remains challenging though biological and prosthetic methods have been attempted. We surgically treated a patient with only 18-mm distal tibia remaining and reconstructed with a unique three-dimensional printed prosthesis. Case Presentation Intervention and Outcomes: A 36-year-old male presented to our clinic with complaints of gradually swelling left calf and palpable painless mass for five months. Imageological exam indicated a lesion spanning the entire length of the tibia and surrounding the vascular plexus. Diagnosis of chondrosarcoma was confirmed by biopsy. Amputation was initially recommended but rejected, thus a novel one-step limb-salvage procedure was performed. After en-bloc tumor resection and blood supply rebuilding, a customized, three-dimensional printed prosthesis with porous interface was fixed that connected the tumor knee prosthesis and distal ultra-small bone segment. During a 16-month follow-up, no soft tissue or prosthesis-related complications occurred. The patient was alive with no sign of recurrence or metastasis. Walking ability and full tibiotalar range of motion were preserved. Conclusions: Custom-made, three-dimensional printed prosthesis manifested excellent mechanical stability during the follow-up in this joint-preserving surgery. Further investigation of the durability and rate of long-term complications is needed to introduce to routine clinical practice.

Pharmacodynamics and pharmacokinetics of PLGA-based doxorubicin-loaded implants for tumor therapy.

The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based DOX-loaded implant and to evaluate the efficacy and drug metabolism distribution of the implant in intratumoral chemotherapy for osteosarcoma (OS). In this study, implants containing DOX, poly(d,l-lactide-co-glycolide), and polyethylene glycol 4000 were prepared by melt-molding method. Then, the antitumor activity and systemic drug distribution of the implants were tested in a K7M2 OS bearing mouse model. The scanning electron microscope images showed that DOX was uniformly dispersed in the polymer matrix. Both the in vitro and in vivo release profiles of implants are characterized by three-phase release. Implantation of DOX-loaded implants into tumors can inhibit tumor growth in a dose-dependent manner. The pharmacokinetic behavior shows that intratumor chemotherapy through implants has a much higher drug concentration in tumors than in normal tissues, which may be the reason for improving antitumor activity and reducing systemic side effects. In summary, the drug release of the implants prepared in this study is sustained and stable, which promotes long-term local accumulation of drugs in tumors, improves the efficacy of chemotherapy and has low toxicity to normal tissues.

Reconstruction with 3D-printed prostheses after type I + II + III internal hemipelvectomy: Finite element analysis and preliminary outcomes.

Background: Prosthetic reconstruction after type I + II+ III internal hemipelvectomy remains challenging due to the lack of osseointegration and presence of giant shear force at the sacroiliac joint. The purpose of this study was to evaluate the biomechanical properties of the novel 3D-printed, custom-made prosthesis with pedicle screw-rod system and sacral tray using finite element analysis. Methods: Four models that included one intact pelvis were established for validation. Forces of 500 N and 2,000 N were applied, respectively, to simulate static bipedal standing and the most loaded condition during a gait cycle. Biomechanical analysis was performed, and the results were compared; the preliminary outcomes of four patients were recorded. Results: For the reconstructed hemipelvis, stress was mainly concentrated on the sacral screws, bone-prosthesis interface, and upper endplate of the L5 vertebra. The optimization of the design with the sacral tray structure could decrease the peak stress of the sacral screws by 18.6%, while the maximal stress of the prosthesis increased by 60.7%. The addition of the lumbosacral pedicle-rod system further alleviated stress of the sacral screws and prosthesis by 30.2% and 19.4%, respectively. The site of peak stress was contemporaneously transferred to the connecting rods within an elastic range. In the retrospective clinical study, four patients who had undergone prosthetic reconstruction were included. During a follow-up of 16.6 ± 7.5 months, the walking ability was found preserved in all patients who are still alive and no prosthesis-related complications had occurred except for one hip dislocation. The Musculoskeletal Tumor Society (MSTS) score was found to be 19.5 ± 2.9. Conclusion: The novel reconstructive system yielded favorable biomechanical characteristics and demonstrated promising preliminary outcomes. The method can be used as a reference for reconstruction after type I + II + III hemipelvectomy.

TNF-α impairs EP4 signaling through the association of TRAF2-GRK2 in primary fibroblast-like synoviocytes.

Our previous study showed that chronic treatment with tumor necrosis factor-α (TNF-α) decreased cAMP concentration in fibroblast-like synoviocytes (FLSs) of collagen-induced arthritis (CIA) rats. In this study we investigated how TNF-α impairs cAMP homeostasis, particularly clarifying the potential downstream molecules of TNF-α and prostaglandin receptor 4 (EP4) signaling that would interact with each other. Using a cAMP FRET biosensor PM-ICUE3, we demonstrated that TNF-α (20 ng/mL) blocked ONO-4819-triggered EP4 signaling, but not Butaprost-triggered EP2 signaling in normal rat FLSs. We showed that TNF-α (0.02-20 ng/mL) dose-dependently reduced EP4 membrane distribution in normal rat FLS. TNF-α significantly increased TNF receptor 2 (TNFR2) expression and stimulated proliferation in human FLS (hFLS) via ecruiting TNF receptor-associated factor 2 (TRAF2) to cell membrane. More interestingly, we revealed that TRAF2 interacted with G protein-coupled receptor kinase (GRK2) in the cytoplasm of primary hFLS and helped to bring GRK2 to cell membrane in response of TNF-α stimulation, the complex of TRAF2 and GRK2 then separated on the membrane, and translocated GRK2 induced the desensitization and internalization of EP4, leading to reduced production of intracellular cAMP. Silencing of TRAF2 by siRNA substantially diminished TRAF2-GRK2 interaction, blocked the translocation of GRK2, and resulted in upregulated expression of membrane EP4 and intracellular cAMP. In CIA rats, administration of paroxetine to inhibit GRK2 effectively improved the symptoms and clinic parameters with significantly reduced joint synovium inflammation and bone destruction. These results elucidate a novel form of cross-talk between TNFR (a cytokine receptor) and EP4 (a typical G protein-coupled receptor) signaling pathways. The interaction between TRAF2 and GRK2 may become a potential new drug target for the treatment of inflammatory diseases.

Cisplatin inhibits the proliferation of Saos-2 osteosarcoma cells via the miR-376c/TGFA pathway.

The transforming growth factor alpha (TGFA) gene is involved in the proliferation and metastasis of various tumors, but its role in cell sensitivity to cisplatin chemotherapy is unclear. In this study, we investigated the mechanism underlying inhibitory effects of cisplatin on growth and proliferation of osteosarcoma cells. Osteosarcoma and normal skeletal muscle tissues were collected from 26 patients by biopsy. TGFA was silenced or overexpressed in Saos-2 osteosarcoma cells by transfection with TGFA-shRNA or TGFA ORF clone, respectively. MiR-376c was inhibited or overexpressed by transfection of Saos-2 cells with miR-376c sponge or miR-376c mimics, respectively. Cell growth was analyzed by MTT assay and cell proliferation by BrdU assay. MiR-376c and TGFA mRNA expression was detected by quantitative reverse transcription PCR and TGFA protein expression by Western blot. The target relationship between miR-376c and TGFA was assessed by luciferase reporter assay. Both in osteosarcoma tissues and Saos-2 cells, miR-376c expression was significantly decreased and TGFA mRNA expression was significantly increased compared with control. Transfection of Saos-2 cells with TGFA-shRNA silenced TGFA expression and significantly inhibited cell growth and proliferation. TGFA mRNA and protein expression in Saos-2 cells significantly decreased with increasing cisplatin concentrations (2.5-10 mg/L). Transfection with TGFA ORF clone reversed the inhibitory effects of cisplatin on Saos-2 cell proliferation. Compared with cisplatin (10 mg/L) treatment alone, the combined treatment with cisplatin and miR-376c mimics inhibited the proliferation of Saos-2 cells more significantly. MiR-376c suppressed TGFA expression by directly interacting with its 3' UTR region. Overall, cisplatin inhibited the proliferation of Saos-2 cells by upregulating miR-376c and downregulating TGFA expression.

Knockdown of hsa_circ_0037658 inhibits the progression of osteoarthritis via inducing autophagy.

Osteoarthritis (OA) is a chronic musculoskeletal degeneration disease that can result in chronic pain and functional disability. Circular RNAs (CirRNAs) are known to be involved in OA. It was reported that hsa_circ_0037658 was notably upregulated in OA tissues; however, the biological role of hsa_circ_0037658 in OA remains unclear. To investigate the function of hsa_circ_0037658 in OA, CHON-001 cells were treated with IL-1ß. The effect of hsa_circ_0037658 knockdown on cell growth was tested by CCK-8 and immunofluorescence staining. In addition, the correlation between hsa_circ_0037658 and autophagy was explored by LC3 staining and western blot. The results indicated that hsa_circ_0037658 was significantly upregulated in IL-1ß-treated CHON-001 cells. The silencing of hsa_circ_0037658 could protect CHON-001 cell injury against IL-1ß. Moreover, hsa_circ_0037658 shRNA reversed IL-1ß-induced cell growth inhibition via inducing cell autophagy. Furthermore, knockdown of hsa_circ_0037658 notably alleviated the symptom of OA in vivo. To sum up, knockdown of hsa_circ_0037658 suppressed the progression of OA via inducing autophagy. Thus, hsa_circ_0037658 might serve as a potential target for the treatment of OA.

Cold atmospheric plasma­activated Ringer's solution inhibits the proliferation of osteosarcoma cells through the mitochondrial apoptosis pathway.

The present study aimed to investigate the effects of cold atmospheric plasma (CAP)­activated Ringer's solution on osteosarcoma cell lines MG63 and U2OS, and to identify the molecular mechanism underlying these effects. CAP­activated Ringer's solution was used to treat osteosarcoma cell lines MG63 and U2OS for 30 min. Cell viability was measured using the MTT method. The apoptosis rate was detected using Annexin­V and propidium iodide. The expression levels of cytochrome c, caspase­3 and polyADP ribose polymerase (PARP) in MG63 cells were analyzed via western blotting. The change in mitochondrial membrane potential was detected via the JC­1 dye method and verified by the level of reactive oxygen species (ROS). CAP­activated Ringer's solution inhibited the proliferation of MG63 and U2OS cells in a dose­ and time­dependent manner. Furthermore, CAP­activated Ringer's solution induced the apoptosis of MG63 cells, increased the intracellular ROS level, decreased the mitochondrial membrane potential level, and induced the release of cytochrome c. CAP­activated Ringer's solution inhibits osteosarcoma cell proliferation through intracellular ROS­mediated mitochondrial apoptosis.

LncRNA XLOC_003810 promotes T cell activation and inhibits PD-1/PD-L1 expression in patients with myasthenia gravis-related thymoma.

This study aimed to investigate the effect of long non-coding RNA XLOC_003810 on the activation of CD4+ T cells and expression of PD-1/PD-L1 in patients with myasthenia gravis-related thymoma (MG-T). Thymus specimens and thymic mononuclear cells were obtained from MG and MG-T patients or cardiac surgery patients undergoing thoracotomy who were selected as negative controls (NC). XLOC_003810 expression was examined using quantitative real-time PCR (qRT-PCR). Frequency of CD4+ T cells and proportion of CD4+ PD-1+ T cells and CD14+ PD-L1+ monocytes were quantified by flow cytometry. The release of inflammatory cytokines was measured by qRT-PCR and enzyme-linked immunosorbent assay. Compared with the NC group, expression of XLOC_003810, frequency of CD4+ T cells and the production of inflammatory cytokines were increased in patients with MG and MG-T. XLOC_003810 overexpression significantly increased the frequency of CD4+ T cells, facilitated the production of inflammatory cytokines and decreased the proportion of CD4+ PD-1+ T cells and CD14+ PD-L1+ monocytes in the thymic mononuclear cells. In contrast, XLOC_003810 knockdown exerted the opposite effect. Together, XLOC_003810 promotes T cell activation and inhibits PD-1/PD-L1 pathway in patients with MG-T.

Mini-subvastus versus medial parapatellar approach for total knee arthroplasty: a prospective randomized controlled study.

PURPOSE: Whether minimally invasive total knee arthroplasty (MIS-TKA) could offer better and faster recovery without the deviation of post-operative prosthesis position and limb alignment is still controversial. This prospective and randomized study was conducted to compare the clinical and radiological outcomes between patients who underwent the mini-subvastus approach of MIS-TKA and those who underwent the medial parapatellar approach of traditional TKA. METHODS: Fifty patients, including 50 knees, who required TKA due to osteoarthritis were randomized to the mini-subvastus group (group I) or the medial parapatellar group (group II). All patients accepted the same method of anaesthesia, equal support therapy and identical rehabilitation exercise after surgery. The evaluation system included operation time, tourniquet time, blood loss, skin incision length in flexion, straight leg raising time, the time of lower limb muscle strength up to grade 4, the time of walking with aid or without aid, the time of walking up and down the stairs, the active flexion angle, range of movement (ROM), the Knee Society Scores (KSS), visual analogue score for pain (VAS), hospital stays and radiographic outcomes. RESULTS: The mini-subvastus approach offered smaller skin incision length in flexion, but at the cost of operation time (P < 0.001). No significant difference was found in tourniquet time and blood loss. The patients in group I could achieve straight leg raising, the lower limb muscle strength up to grade 4, walking with or without aid, and walking up and down the stairs earlier (P < 0.001). The active flexion angle, ROM, VAS and KSS in group I were superior to those in group II until six months post-operatively (P < 0.001), but the differences was not apparent at 12 months post-operatively. More importantly, there was no significant difference between the two groups on radiological outcomes (P > 0.05). CONCLUSIONS: The mini-subvastus approach could offer faster recovery, less pain and shorter hospital stays without compromising the principles of proper prosthesis position and limb alignment compared with the medial parapatellar approach.

[The longitude study on the mental development of congenital hearing-impaired infants and toddlers].

OBJECTIVE: To explore the effect of chronological age and acoustic device in cognitive development of congenital hearing-impaired infants and toddlers, and analyze the correlation of abilities in cognitive development with other factors. METHODS: Depending on chronological age (1 year old group and 2 years old group) and acoustic device (hearing aids and cochlear implantation), locomotor, personal-social, hearing and speech, hand and eye co-ordination, performance tests in Griffith Cognitive Development Scale were used to assess the cognitive development of 80 hearing-impaired infants and toddlers aged 0-2 years, including before intervention (0 month), after intervention (6, 12 months). Datas were analyzed by Repeated Measurements and Pearson Correlation Test. RESULTS: During 1 year hearing intervention and rehabilitation, hearing and speech, performance and cognitive were extremely significant difference for each phase of early intervention (P < 0.01), the development of locomotor, personal-social, hand and eye co-ordination were no significant difference (P > 0.05). Personal-Social in 1 year old group with hearing impairment was much higher than 2 years old group P < 0.05). Hearing and speech in cochlear implanted group with hearing loss was much higher than hearing aids group. Cognitive development was positive correlation with various region development P < 0.01), and was negatively correlated with chronological age (P > 0.05). CONCLUSIONS: Cognitive development is proportional to recovery time. The chronological age of early intervention obviously affect deaf children's cognitive development. The ability of hearing and speech in cochlear implanted children is superior to children with hearing aids in severe and profound hearing impaired children.

[Follow up study on auditory development of congenital hearing-impaired infants and toddlers].

OBJECTIVE: To study the characteristics of auditory ability development in hearing-impaired infants and toddlers under home-based early intervention, and provide the theoretical basis for the development of rehabilitation and assessment strategies. METHODS: The clinical data was collected from subjects from 5 provinces between 2012 and 2014 in China. A total of 80 subjects were enrolled and divided into 2 groups with 1 year interval according to chronological age. Initials, finals and disyllable words in Auditory Ability Test were used to assess the auditory development before intervention (0 month) and after intervention (6, 12, 18, 24 months). Data was analyzed by repeated measures analysis of variance. RESULTS: In 1 age group and 2 age group, the main effect of recovery time and chronological age were significantly different in initials, finals and disyllable (P<0.05). The recognition ability of initials, finals and disyllable words in 1 age group were less than 2 age group at 6- and 12-month after early intervention (P<0.05). After 2 years hearing intervention and rehabilitation, the recognition rates of initials, finals and disyllable words were 88%±11%, 90%±11% and 92%±9%, respectively. 18%, 30% and 47%, respectively, hearing-impaired children achieved full score in initials, finals and disyllable words. 70% hearing-impaired children reached more than 90% recognition ability in initials, finals and disyllable words. CONCLUSIONS: The chronological age and recovery time are principle factors for auditory development in hearing-impaired children; 70% hearing-impaired children have reached grade A after 2 years hearing intervention and rehabilitation, and performed well in hearing identification and speech intelligibility.

Effect of the PTEN gene on adhesion, invasion and metastasis of osteosarcoma cells.

The phosphatase and tensin homolog (PTEN) gene, an important tumor-suppressor gene, has been demonstrated to have the potential for inhibiting proliferation, migration and invasion in various types of cancer cells. The aim of the present study was to investigate the effect of PTEN expression on osteosarcoma (OS) cells. The wild-type PTEN plasmid was transfected into OS U2-OS cells. The effects of PTEN on the adhesion, migration and invasion of U2-OS cells were evaluated by cell adhesion analysis, in vitro scratch and Transwell assays, respectively. The levels of MMP-2 and MMP-9, and focal adhesion kinase (FAK) protein regulated by PTEN were detected via western blot analysis. Meanwhile, the level of intracellular FAK phosphorylation was observed. The results from the present study showed that overexpression of PTEN transcription and protein were observed in U2-OS cells following PTEN transfection. Furthermore, the migration, invasion and adhesion capabilities of the cells with PTEN transfection were significantly decreased compared to these capacities in the cells without PTEN. Meanwhile, it was shown that there was downregulation of MMP-9, FAK and p-FAK concomitant with the elevation of the intracellular PTEN level. It is therefore evident that the upregulation of PTEN may attenuate the adhesion, migration and invasion capabilities of OS cells. The mechanisms of the effects of PTEN on OS cells may be correlated with a reduction in the related genes by PTEN regulation.