Effects of Laser Treatment of Terbium-Doped Indium Oxide Thin Films and Transistors.

In this study, a KrF excimer laser with a high-absorption coefficient in metal oxide films and a wavelength of 248 nm was selected for the post-processing of a film and metal oxide thin film transistor (MOTFT). Due to the poor negative bias illumination stress (NBIS) stability of indium gallium zinc oxide thin film transistor (IGZO-TFT) devices, terbium-doped Tb:In2O3 material was selected as the target of this study. The XPS test revealed the presence of both Tb3+ and Tb4+ ions in the Tb:In2O3 film. It was hypothesized that the peak of the laser thermal effect was reduced and the action time was prolonged by the f-f jump of Tb3+ ions and the C-T jump of Tb4+ ions during the laser treatment. Studies related to the treatment of Tb:In2O3 films with different laser energy densities have been carried out. It is shown that as the laser energy density increases, the film density increases, the thickness decreases, the carrier concentration increases, and the optical band gap widens. Terbium has a low electronegativity (1.1 eV) and a high Tb-O dissociation energy (707 kJ/mol), which brings about a large lattice distortion. The Tb:In2O3 films did not show significant crystallization even under laser energy density treatment of up to 250 mJ/cm2. Compared with pure In2O3-TFT, the doping of Tb ions effectively reduces the off-state current (1.16 × 10-11 A vs. 1.66 × 10-12 A), improves the switching current ratio (1.63 × 106 vs. 1.34 × 107) and improves the NBIS stability (ΔVON = -10.4 V vs. 6.4 V) and positive bias illumination stress (PBIS) stability (ΔVON = 8 V vs. 1.6 V).

Editorial: Management of PJI/SSI after joint arthroplasty.

The management of periprosthetic joint infection (PJI) and surgical site infection (SSI) after joint arthroplasty poses a major challenge in orthopedic surgery. This Editorial provides an overview of the studies published in the special issue "Management of PJI/SSI after Joint Arthroplasty", summarizing the key findings from these studies, which cover a wide range of topics, including stringent preventive strategies, comprehensive diagnostic methods, and personalized treatment modalities. The authors concluded the editorial with their perspectives regarding the status quo of research in this field and future directions for research, such as the development of novel antibiotics, biofilm research, patient-specific risk factors, and the integration of technological advancements (such as machine learning and artificial intelligence) into clinical practice. The authors emphasized the need for continued research, interdisciplinary collaboration, and the application of innovative technologies to enhance patient outcomes and mitigate the burden of these infections on healthcare systems.

Dexmedetomidine Attenuates Inflammation in Elderly Patients Following Major Hepatobiliary and Pancreatic Surgery: A Randomized Clinical Trial.

Background: Dexmedetomidine (Dex) may have anti-inflammatory properties and potentially reduce the incidence of postoperative organ injury. Objective: To investigate whether Dex protects pulmonary and renal function via its anti-inflammatory effects in elderly patients undergoing prolonged major hepatobiliary and pancreatic surgery. Design and Setting: Between October 2019 and December 2020, this randomized controlled trial was carried out at a tertiary hospital in Chongqing, China. Patients: 86 patients aged 60-75 who underwent long-duration (> 4 hrs) hepatobiliary and pancreatic surgery without significant comorbidities were enrolled and randomly assigned into two groups at a 1:1 ratio. Interventions: Patients were given either Dex or an equivalent volume of 0.9% saline (Placebo) with a loading dose of 1 µg kg-1 for 10 min, followed by 0.5 µg kg-1 hr-1 for maintenance until the end of surgery. Main Outcome Measures: The changes in serum concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were primary outcomes. Results: At one hour postoperatively, serum IL-6 displayed a nine-fold increase (P<0.05) in the Placebo group. Administration of Dex decreased IL-6 to 278.09 ± 45.43 pg/mL (95% CI: 187.75 to 368.43) compared to the Placebo group (P=0.019; 432.16 ± 45.43 pg/mL, 95% CI: 341.82 to 522.50). However, no significant differences in TNF-α were observed between the two groups. The incidence of postoperative acute kidney injury was twice as high in the Placebo group (9.30%) compared to the Dex group (4.65%), and the incidence of postoperative acute lung injury was 23.26% in the Dex group, lower than that in the Placebo group (30.23%), although there was no statistical significance between the two groups. Conclusion: Dex administration in elderly patients undergoing major hepatobiliary and pancreatic surgery reduces inflammation and potentially protects kidneys and lungs. Registration: Chinese Clinical Trials Registry, identifier: ChiCTR1900024162, on 28 June 2019.

Motivational simulated teaching of clinical skills using formative assessment methods for medical undergraduate students: between-group evaluation of a simulated course in a Chinese medical college.

OBJECTIVES: Teaching clinical skills is an important component of educational programmes for medical undergraduates. However, the extension of the interval between the completion of the course and qualification examination affects the performance of students in the skill examination. This study established a multisource evaluation system to determine whether formative assessment can enhance the instruction of clinical skills. METHODS: Formative assessment was introduced to the entire training course on clinical skills, in which diversified methods were used to observe the performance of students during training. Students in the experimental group received training for clinical skills using formative assessment (class of 2019, n=128), while students in the control group received traditional training without formative assessment (class of 2018, n=123). Both groups participated in the Objective Structured Clinical Examination (OSCE) conducted by Tongji Medical College, and the exam scores were taken as the objective measure of course outcome. After completing the course, all students in the experimental group were instructed to fill in a questionnaire to evaluate their experience in the training programme, as a subjective measure of course outcome. RESULTS: Compared with the control group, students in the experimental group received significantly better practical scores in the four clinical skills tested by the OSCE. The questionnaire results revealed that the majority of students who were trained using formative assessment methods considered the course helpful for learning, and appreciated the course for the clinical skills they had gained, and the opportunity to receive and give feedback to the instructors. CONCLUSIONS: The findings of this study suggest that formative assessment methods are beneficial for learning clinical skills through simulated teaching, as shown by the improved objective clinical skills evaluated by the structured clinical examination, and the self-reported satisfaction with the learning process.

A bone-conserving revision stem for unstable intertrochanteric fractures of the geriatric osteoporotic population.

PURPOSE: Primary hemiarthroplasty is gaining popularity for the treatment of unstable intertrochanteric fractures in geriatric patients with severe osteoporosis. This study evaluated early clinical and radiographic outcomes by using a bone-conserving revision stem for unstable intertrochanteric fractures in the geriatric osteoporotic population. METHODS: A retrospective study involving 31 patients with unstable intertrochanteric fractures was conducted. The patients were aged 82.1 years on average. All patients underwent primary hemiarthroplasty using bone-conserving, fully porous-coated revision stem. The operative time, intraoperative blood loss, length of hospitalization, and need for blood transfusion were noted during the hospital stay. Postoperative complications, including dislocations, deep venous thrombosis, infections, peri-prosthetic fractures, and frontal thigh pain were also recorded. Koval's category was used to quantify activity level, and Harris hip score (HHS) was used for functional assessment. Radiographic outcomes, including osteolysis, bone ingrowth, subsidence of the femoral component, lower limb length discrepancy, and heterotopic ossification, were collected at each follow-up. RESULTS: The 31 patients were followed for an average time of 23 months postoperatively. The average operative time lasted for 74.2 min, while the mean intraoperative blood loss was 200.1 ml, with an average hemoglobin decrease of 11.1 g/L after the procedure. The mean visual analog scale (VAS) score for pain dropped from 7.4 preoperatively to 2.4 at the 4-week follow-up. At the latest follow-up, the mean Harris hip score was 82.1, and the VAS was 1.7. No intraoperative or postoperative peri-prosthetic fractures were noted. Postoperative complications included one case of thrombosis formation in the posterior tibial vein and one case of congestive heart failure. Both patients were discharged uneventfully after treatment. Radiographically, none of the hips had evidence of stem loosening or osteolysis. Within the follow-up period of 23 months, the mortality rate was 3.2% (1/31), and no revision surgeries were required. CONCLUSION: Primary hemiarthroplasty using a bone-conserving, cementless revision stem could serve as a reliable alternative for the treatment of unstable intertrochanteric fractures in the geriatric population with osteoporosis.

Effects of General Anesthesia on Changes of Serum Hepatitis B Virus-DNA Levels in Infected Patients Underwent Non-Hepatobiliary Minimally Invasive Surgery: A Pilot Observational Study.

Objective: To investigate the effects of different general anesthesia methods on the changes of serum hepatitis B virus deoxyribonucleic acid (HBV-DNA) levels in the hepatitis B virus (HBV) infected patients. Methods: This pilot prospective observational study was carried out from March 2021 to January 2022. Forty patients infected by HBV, who underwent non-hepatobiliary minimally invasive surgery, were allocated into an intravenous anesthesia group maintained with propofol (Group P, n = 20) and an inhalation anesthesia group maintained with sevoflurane (Group S, n = 20) by a random envelope method. Patient's blood was drawn before operation (Tbaseline), at 24 hours (Tpost 24hrs) and 48 hours (Tpost 48hrs) after operation to detect the serum HBV-DNA levels and analyze the subset levels of T, B lymphocytes and NK cells (TBNK) in two groups. The serum HBV-DNA level was used as the major outcome, and it was analyzed by repeated-measures analysis of variance after natural logarithm transformation. Results: In Group P and Group S, compared with the baseline, the serum HBV-DNA levels decreased significantly at Tpost 24hrs and Tpost 48hrs, P<0.05. The total ratio of CD4+T cells and the ratio of CD4+T to CD8+T cells (CD4+/CD8+) were lower at Tpost 24hrs, P<0.05, and the total ratio of B cells was significantly increased at Tpost 24hrs, P<0.05. Compared with the values at Tpost 24hrs, the total ratio of CD4+ T cells, CD4+/CD8+ T cells, and the total ratio of B cells were significantly increased at Tpost 48hrs in both groups, P<0.05. However, there were no statistical differences between Group P and Group S. Conclusion: The levels of serum HBV-DNA decreased within 48 hours after general anesthesia. There were no significant differences between the effects of intravenous and inhalation anesthesia on the serum HBV-DNA levels. Trial Registration: This study has been prospectively registered in the Clinical Trials Registry (NCT02038088, 1/28/2015).

Femoral head metastases from primary mucinous lung adenocarcinoma with left hip pain: A case report and literature review.

Background: Primary mucinous lung adenocarcinoma, a subtype of lung adenocarcinoma, is extremely rare. Currently, as there are no specific diagnostic features, it is easy to delay the diagnosis or even to misdiagnose when atypical symptoms are present. Case summary: This case details a patient with primary mucinous lung adenocarcinoma and metastasis to the femoral head. The sole symptom was left hip pain and the initial diagnosis was isolated femoral head necrosis. Conclusions: By presenting this rare case report and the experiences learned from it, we hope to assist clinicians to identify bone metastasis cases with non-typical symptoms in order to make the correct diagnosis as soon as possible.

CircHGF suppressed cell proliferation and osteogenic differentiation of BMSCs in ONFH via inhibiting miR-25-3p binding to SMAD7.

Steroid-induced osteonecrosis of the femoral head (ONFH) is a common and devastating bone disorder, which often results in progressive collapse of the femoral head and subsequent osteoarthritis. The proliferation ability and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) play critical roles in maintaining the structural and functional integrity of the femoral head to prevent ONFH. Until now, little has been known about the underlying mechanism of BMSCs differentiation disorder during ONFH progression. Circular RNAs (circRNAs) are considered to be vital non-coding RNAs functionally involved in various human diseases. However, whether and how circRNA regulates the proliferation and osteogenic differentiation of BMSCs in ONFH remain unclear. In this study, we analyzed the circRNA expression profile of five samples of BMSCs in ONFH and five samples of control by using circRNA microarray assays. We identified 182 differentially expressed circRNAs, among which 108 circRNAs were upregulated. We further investigated the effects of a significantly upregulated circRNA, circHGF, on the proliferation and osteogenic differentiation of BMSCs in vitro. Results showed that circHGF suppressed the proliferation and osteogenic differentiation of BMSCs in ONFH by targeting miR-25-3p/SMAD7 axis. Our findings provided a potential diagnostic and therapeutic strategy for ONFH.

DBGAN: A dual-branch generative adversarial network for undersampled MRI reconstruction.

Compressed sensing magnetic resonance imaging (CS-MRI) greatly accelerates the acquisition process and yield considerable reconstructed images. Deep learning was introduced into CS-MRI to further speed up the reconstruction process and improve the image quality. Recently, generative adversarial network (GAN) using two-stage cascaded U-Net structure as generator has been proven to be effective in MRI reconstruction. However, previous cascaded structure was limited to few feature information propagation channels thus may lead to information missing. In this paper, we proposed a GAN-based model, DBGAN, for MRI reconstruction from undersampled k-space data. The model uses cross-stage skip connection (CSSC) between two end-to-end cascaded U-Net in our generator to widen the channels of feature propagation. To avoid discrepancy between training and inference, we replaced classical batch normalization (BN) with instance normalization (IN) . A stage loss is involved in the loss function to boost the training performance. In addition, a bilinear interpolation decoder branch is introduced in the generator to supplement the missing information of the deconvolution decoder. Tested under five variant patterns with four undersampling rates on different modality of MRI data, the quantitative results show that DBGAN model achieves mean improvements of 3.65 dB in peak signal-to-noise ratio (PSNR) and 0.016 in normalized mean square error (NMSE) compared with state-of-the-art GAN-based methods on T1-Weighted brain dataset from MICCAI 2013 grand challenge. The qualitative visual results show that our method can reconstruct considerable images on brain and knee MRI data from different modality. Furthermore, DBGAN is light and fast - the model parameters are fewer than half of state-of-the-art GAN-based methods and each 256 × 256 image is reconstructed in 60 milliseconds, which is suitable for real-time processing.

Sex difference in the correlation between carotid artery diameter and prevalence of stroke: Insights from a Chinese population.

BACKGROUND: The atherosclerotic process can cause compensatory enlargement of artery diameter. However, the association between common carotid artery (CCA) diameter and stroke remains unclear. METHODS: This cross-sectional study included 5668 participants ≥40 years of age residing in rural northeast China, in whom the inter-adventitial diameter of CCA was measured. The association between CCA diameter and stroke prevalence was explored using multivariate logistic regression and concentration-response relationship in females and males, respectively. RESULTS: CCA diameter (mm) was greater in stroke than in non-stroke populations in both males (7.73 versus [vs.] 7.49; P < 0.05) and females (7.69 vs. 7.13; P < 0.001). Among males, when dividing CCA diameters into quartiles, the second quartile (6.86-7.5 mm) had a 1.64 times higher risk for stroke than the bottom quartile (≤6.85 mm) (P < 0.05) in the adjusted model. In females, the top quartile (>7.95 mm) had a 2.08 (1.07-4.04) times higher risk than the bottom quartile (≤6.50 mm) (P < 0.01) (overall trend 1.19 [1.00-1.43]). Moreover, dose-response relationship confirmed correlations between CCA diameter and stroke in females (P < 0.05). The net reclassification index (NRI) and integrated discrimination index (IDI) confirmed the incremental value of CCA diameter in predicting probability of stroke in females (NRI 0.353 [95% confidence interval (CI) 0.198-0.497], P < 0.001; IDI 0.004 [95% CI 0.001-0.006], P < 0.01) and males (NRI 0.201 [95% CI 0.158-0.241], P < 0.001; IDI 0.005 [95% CI 0.001-0.009], P < 0.01). CONCLUSIONS: This study highlighted the incremental value of CCA diameter in optimizing risk classification and stroke prevention in a Chinese population.

Effectiveness of a patient-specific guide for femoral stem implantation in primary total hip arthroplasty: a randomized control trial.

PURPOSE: The purpose of the present study was to evaluate the efficacy and feasibility of a novel CT-based patient-specific femoral alignment guide (PSG) as compared with conventional pre-operative planning during THA. METHODS: From March 2020 to September 2020, patients receiving unilateral primary THA were enrolled and randomly allocated to the conventional pre-operative planning group and the PSG group. Primary outcomes were radiographic measurements including lower limb length, femoral offset, femoral anteversion and stem varus/valgus angle, and post-operative perception of leg length discrepancy (LLD). Secondary outcomes were surgical time, intra-operative blood loss, total blood loss, visual analogue scale (VAS), and Harris Hip Score (HHS). The occurrence of post-operative complications was also recorded. RESULTS: Of the 104 patients screened, 80 cases were enrolled for analysis. The demographics of the two groups were similar. The PSG group illustrated significant improvements (p < 0.001) in lower limb length, femoral offset, femoral anteversion, and stem varus/valgus angle. Patients in the PSG group showed more favourable HHS (p < 0.001) at seven day, four week, andthree month (p = 0.003) follow-up. Perception of LLD was found significantly lower in the PSG group at three tmonth (p = 0.043), six month (p = 0.025), and 12-month (p = 0.048) follow-up. Utilization of the PSG had no significant increase in operative time, intra-operative blood loss, total blood loss, or VAS. No complication was noted in either group. CONCLUSION: Relative to conventional pre-operative planning, the application with the PSG could potentially provide a simple and reliable solution for improving femoral prosthesis orientation in THA with high accessibility and low healthcare costs. TRN: ChiCTR2000031043 Date of registration: 2020/3/21.

Opening Wedge High Tibial Osteotomy with Combined Use of Patient-Specific 3D-Printed Plates and Taylor Spatial Frame for the Treatment of Knee Osteoarthritis.

BACKGROUND: High tibial osteotomy (HTO) is used to treat medial degeneration of the osteoarthritis (OA) knee. However, shortcomings still exist in the current procedure, like unprecise creation, inability to correct knee rotation, and internal fixed failure. Here, we reported a novel procedure: patient-specific 3D-printed plates for opening wedge high tibial osteotomy (OWHTO) combined with Taylor spatial frame (TSF). The detailed technique was described, and the clinical outcomes were evaluated. METHODS: We prospectively evaluate outcomes of patient-specific 3D-printed plates for OWHTO with use of TSF in 25 patients with knee OA and varus alignment. Postoperative efficacy was evaluated using the HSS knee score, pain visual simulation score (VAS), and knee joint motion (ROM), and lower limb alignment was evaluated by measuring femorotibial angle (FTA) and hip-knee-ankle (HKA). Results and Conclusion. All patients did not experience complications such as wound infection, nerve damage, or bone amputation. 25 patients were followed up for 6-18 months. The bony union at bone amputation was achieved in 3 months after surgery, and the pain symptoms were significantly alleviated or disappeared. The VAS score was significantly reduced in 6 months after surgery compared with preoperative; the HSSS score was significantly added in 6 months after surgery compared with preoperative. The ROM of knee joint increased significantly 6 months after operation compared with that before operation, and the difference was statically significant (P < 0.05). The FTA and HKA after operation were significantly superior to that before operation, and the difference was statically significant (P < 0.01). CONCLUSIONS: Our study showed that patient-specific 3D-printed plates for HTO with the use of TSF have the advantages of small trauma, few complications, simple operation, and fast recovery in treating knee OA and varus alignment.

Application of Laser Treatment in MOS-TFT Active Layer Prepared by Solution Method.

The active layer of metal oxide semiconductor thin film transistor (MOS-TFT) prepared by solution method, with the advantages of being a low cost and simple preparation process, usually needs heat treatment to improve its performance. Laser treatment has the advantages of high energy, fast speed, less damage to the substrate and controllable treatment area, which is more suitable for flexible and large-scale roll-to-roll preparation than thermal treatment. This paper mainly introduces the basic principle of active layer thin films prepared by laser treatment solution, including laser photochemical cracking of metastable bonds, laser thermal effect, photoactivation effect and laser sintering of nanoparticles. In addition, the application of laser treatment in the regulation of MOS-TFT performance is also described, including the effects of laser energy density, treatment atmosphere, laser wavelength and other factors on the performance of active layer thin films and MOS-TFT devices. Finally, the problems and future development trends of laser treatment technology in the application of metal oxide semiconductor thin films prepared by solution method and MOS-TFT are summarized.

Application of Amorphous Zirconium-Yttrium-Aluminum-Magnesium-Oxide Thin Film with a High Relative Dielectric Constant Prepared by Spin-Coating.

Amorphous metal oxide has been a popular choice for thin film material in recent years due to its high uniformity. The dielectric layer is one of the core materials of the thin film transistor (TFT), and it affects the ability of charges storage in TFT. There is a conflict between a high relative dielectric constant and a wide band gap, so we solved this problem by using multiple metals to increase the entropy of the system. In this paper, we prepared zirconium-yttrium-aluminum-magnesium-oxide (ZYAMO) dielectric layers with a high relative dielectric constant using the solution method. The basic properties of ZYAMO films were measured by an atomic force microscope (AFM), an ultraviolet-visible spectrophotometer (UV-VIS), etc. It was observed that ZYAMO thin films had a larger optical band when the annealing temperature increased. Then, metal-insulator-metal (MIM) devices were fabricated to measure the electrical properties. We found that the leakage current density of the device is relatively lower and the ZYAMO thin film had a higher relative dielectric constant as the concentration went up. Finally, it reached a high relative dielectric constant of 56.09, while the leakage current density was no higher than 1.63 × 10-6 A/cm2@ 0.5 MV/cm at 1.0 M and 400 °C. Therefore, the amorphous ZYAMO thin films has a great application in the field of high permittivity request devices in the future.

Clinical characteristics and early prognosis of patients with SARS-CoV-2 infection undergoing joint arthroplasty during the COVID-19 pandemic.

ABSTRACT: The present study reported early clinical outcomes and perioperative precautions for medical staffs during joint arthroplasty procedures in SARS-CoV-2-infected patients.The medical records of 8 patients with SARS-CoV-2 infection who underwent joint arthroplasty from January 19 to September 24, 2020 were retrospectively reviewed and analyzed. Perioperative precautions and follow-up (time length varies from 6 month to 13 months, 11 months in average) for SARS-CoV-2 infection of medical staffs were reported.All patients recovered well from both the primary disease and SARS-CoV-2 infection. Significant improved Visual analogue scale was observed with no major complications or recurrence of the COVID-19 at discharge. There was no evidence indicating SARS-CoV-2 infection in any health providers.Elective joint arthroplasties for patients in recovery period of SARS-CoV-2 infection could be continued under comprehensive preoperative evaluation and appropriate medical protection. For patients with currently confirmed or highly suspected COVID-19, the operation should be carried out only if it was essential.

Transparent Flexible IGZO Thin Film Transistors Fabricated at Room Temperature.

Flexible and fully transparent thin film transistors (TFT) were fabricated via room temperature processes. The fabricated TFT on the PEN exhibited excellent performance, including a saturation mobility (µsat) of 7.9 cm2/V·s, an Ion/Ioff ratio of 4.58 × 106, a subthreshold swing (SS) of 0.248 V/dec, a transparency of 87.8% at 550 nm, as well as relatively good stability under negative bias stress (NBS) and bending stress, which shows great potential in smart, portable flexible display, and wearable device applications.

LncRNA CRNDE is activated by SP1 and promotes osteosarcoma proliferation, invasion, and epithelial-mesenchymal transition via Wnt/ß-catenin signaling pathway.

Long noncoding RNAs (lncRNAs) were identified as a vital part in the development and progression of cancer in recent years. Colorectal neoplasia differentially expressed (CRNDE), a lncRNA, functions as an oncogene in some malignant neoplasias, but its role in the progression of osteosarcoma (OS) is still poorly understood. To dissect the difference in the expression of CRNDE, quantitative real-time polymerase chain reaction was utilized to evaluate it in OS tissues and cell lines (U2OS, MG63, and MNNG/HOS) compared with that in the adjacent normal tissues/osteoblast cells (hFOB1.19). The role of CRNDE in OS lines was assessed using Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, flow cytometry, Transwell assays, and Western blot, respectively. The results demonstrated that the expression of CRNDE was high in OS tissues and cell lines, and partly induced by SP1. CRNDE knockdown attenuated OS cell proliferation and invasion and induced apoptosis and G0/G1 arrest. Moreover, the expression of mesenchymal markers N-cadherin, Vimentin and Snail were downregulated, while the expression of epithelial markers E-cadherin and ZO-1 were conversely upregulated due to CRNDE knockdown. The mechanistic investigations showed that CRNDE promoted glycogen synthase kinase-3ß phosphorylation to activate the Wnt/ß-catenin pathway. The results suggested that lncRNA CRNDE indeed contributed to OS proliferation, invasion, and epithelial-mesenchymal transition, working as an oncogene, demonstrating that lncRNA CRNDE may be a valid therapeutic target for the OS.

Dioscin inhibits the growth of human osteosarcoma by inducing G2/M-phase arrest, apoptosis, and GSDME-dependent cell death in vitro and in vivo.

Pyroptosis is a form of programmed cell death (PCD) that plays a vital role in immunity and diseases. Although it was recently reported that chemotherapy drugs can induce pyroptosis through caspase-3-dependent cleavage of gasdermin E (GSDME), the role of pyroptosis in osteosarcoma (OS) with dioscin is less understood. In this study, we explored the effects of dioscin on OS in vitro and in vivo and further elucidated the underlying molecular mechanisms and found that dioscin-triggered pyroptosis in GSDME-dependent cell death and that GSDME-N was generated by caspase-3. Furthermore, dioscin inhibited cancer cell growth by inducing G2/M arrest and apoptosis through the JNK/p38 pathway. In vivo, dioscin significantly inhibited OS proliferation. Taken together, our results demonstrate that dioscin can induce apoptosis through the JNK/p38 pathway and GSDME-dependent pyroptosis in OS, identifying it as a potential therapeutic drug for treatment of this disease.

Targeting the IL-1ß/IL-1Ra pathways for the aggregation of human islet amyloid polypeptide in an ex vivo organ culture system of the intervertebral disc.

Intervertebral disc degeneration (IDD) is characterized by excessive apoptosis of nucleus pulposus (NP) cells and hyperactive extracellular matrix (ECM) catabolism. Our previous studies revealed the relationship between human islet amyloid polypeptide (hIAPP) and NP cell apoptosis. However, the role of hIAPP aggregates in IDD has not yet been investigated. This study aimed to determine whether the accumulation of hIAPP aggregates promotes IDD progression. The aggregation of hIAPP increased in human NP tissues during IDD. The deposition of hIAPP aggravated the compression-induced IDD that promoted NP cell apoptosis and ECM degradation via IL-1ß/IL-1Ra signaling in an ex vivo rat disc model. Moreover, neutralizing IL-1ß augmented the protective effects of hIAPP overexpression by decreasing hIAPP aggregation in human NP cells. These results suggest that the aggregation of hIAPP promotes NP cell apoptosis and ECM degradation ex vivo and in vitro by disrupting the balance of IL-1ß/IL-1Ra signaling.

Fibronectin induced ITGß1/FAK-dependent apoptotic pathways determines the fate of degenerative NP cells.

Intervertebral disc (IVD) degeneration is caused by a decrease in nucleus pulposus (NP) cells, due mainly to apoptosis. Focal adhesion kinase (FAK) is involved in the integrin (ITG)-mediated control of cell adhesion and anoikis (apoptosis). To explore the involvement of ITGß1/FAK-dependent apoptotic pathways in disc degeneration, histological, and molecular biological studies on the protein expression of fibronectin (FN), ITGß1, and syndecan 4 (SYND4) in non-degenerative and degenerative NP tissues were conducted. Degenerative NP cells were isolated and cultured in the presence of SYND4 and/or ITGß1, with or without an FAK inhibitor. The effects of upregulation or knockdown of ITGß1 gene expression were also examined. The TUNEL assay was used to determine the percentage of apoptotic cells. Western blotting was used to detect the expression of SYND4, ITGß1, FAK, and downstream pathway proteins. The results showed that extracellular FN was degraded during the IVD degeneration process, detrimentally affecting the function, and survival of NP cells. The apoptotic rate was increased by ITGß1 activation, but partially reduced by FN. After ITGß1 knockdown, the FAK/PI3 K/AKT axis was activated in the ITGß1/FAK-dependent pathways, resulting in increased cell adherence capacity and decreased anoikis. FN rescued the degenerative NP cells from anoikis through the FAK-dependent signaling pathways. In conclusion, the extracellular matrix protein FN is essential for maintaining the function and survival of NP cells through ITGß1/FAK-dependent apoptotic pathways during disc degeneration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:439-448, 2019.