IGF2BP3 regulates the expression of RRM2 and promotes the progression of rheumatoid arthritis via RRM2/Akt/MMP-9 pathway.

BACKGROUND: Rheumatoid arthritis (RA) is a common inflammatory and autoimmune disease. Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) is a crucial and a rate-limiting enzyme responsible for deoxynucleotide triphosphate(dNTP) production. We have found a high expression level of RRM2 in patients with RA, but the molecular mechanism of its action remains unclear. METHODS: We analyzed the expression of hub genes in RA using GSE77298 datasets downloaded from Gene Expression Omnibus database. RRM2 and insulin-like growth factor-2 messenger ribonucleic acid (mRNA)-binding protein 3 (IGF2BP3) gene knockdown was achieved by infection with lentiviruses. The expression of RRM2, IGF2BP3, matrix metalloproteinase (MMP)-1, and MMP-9 were detected via western blotting assay. Cell viability was detected via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MeRIP-qRT-PCR was performed to test the interaction of IGF2BP3 and RRM2 mRNA via m6A modification. Cell proliferation was determined by clone formation assay. Migration and invasion assays were performed using transwell Boyden chamber. RESULTS: RRM2 and IGF2BP3 were highly expressed in clinical specimens and tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1ß-stimulated synovial cells. RRM2 and IGF2BP3 knockdown inhibited the proliferation, migration, and invasion of MH7A cells. The inhibitory effects of IGF2BP3 knockdown were effectively reversed by simultaneously overexpressing RRM2 in MH7A cells. By analyzing N6-methyladenosine (m6A)2Target database, five m6A regulatory target binding sites for IGF2BP3 were identified in RRM2 mRNA, suggesting a direct relationship between IGF2BP3 and RRM2 mRNA. Additionally, in RRM2 small hairpin (sh)RNA lentivirus-infected cells, the levels of phosphorylated Akt and MMP-9 were significantly decreased compared with control shRNA lentivirus-infected cells. CONCLUSION: The present study demonstrated that RRM2 promoted the Akt phosphorylation leading to high expression of MMP-9 to promote the migration and invasive capacities of MH7A cells. Overall, IGF2BP promotes the expression of RRM2, and regulates the migration and invasion of MH7A cells via Akt/MMP-9 pathway to promote RA progression.

Synergistic electrochemical catalysis by high-entropy metal phosphide in lithium-sulfur batteries.

The shuttle effect and sluggish redox kinetics of polysulfides have hindered the development of lithium-sulfur batteries (LSBs) as premier energy storage devices. To address these issues, a high-entropy metal phosphide (NiCoMnFeCrP) was synthesized using the sol-gel method. NiCoMnFeCrP, with its rich metal species, exhibits strong synergistic effects and provides numerous catalytic active sites for the conversion of polysulfides. These active sites, possessing significant polarity, can bond with polysulfides. In situ ultraviolet-visible were conducted to monitor the dynamic changes in species and concentrations of polysulfides, validating the ability of NiCoMnFeCrP to facilitate the conversion of polysulfides. The batteries with the NiCoMnFeCrP catalyst as functional separators exhibited minimal capacity decay rates of 0.04 % and 0.23 % after 100 cycles at 0 °C and 60 °C, respectively. This indicates that the NiCoMnFeCrP catalyst possesses good thermal stability. Meanwhile, its area capacity can reach 4.78 mAh cm-2 at a high sulfur load of 4.54 mg cm-2. In conclusion, NiCoMnFeCrP achieves the objective of mitigating the shuttle effect and accelerating the kinetics of the redox reaction, thereby facilitating the commercialization of LSBs.

A 1.5 mm2 4-Channel EEG/BIOZ Acquisition ASIC With 15.2-Bit 3-Step ADC Based on a Signal-Dependent Low-Power Strategy.

This article presents a multichannel EEG/BIOZ acquisition application specific integrated circuit (ASIC) with 4 EEG channels and a BIOZ channel, a switch resistor low-pass filter (SR-LPF). Each EEG channel includes a frontend, and a 4-channel multiplexed analog-to-digital converter (ADC), while the BIOZ channel features a pseudo sine current generator and a pair of readout paths with multiplexed SR-LPF and ADC. The ASIC is designed for size and power minimization, utilizing a 3-step ADC with a novel signal-dependent low power strategy. The proposed ADC operates at a sampling rate of 1600 S/s with a resolution of 15.2 bits, occupying only 0.093 mm2. With the help of the proposed signal-dependent low-power strategy, the ADC's power dissipation drops from 32.2 µW to 26.4 µW, resulting in an 18% efficiency improvement without performance degradation. Moreover, the EEG channels deliver excellent noise performance with a NEF of 7.56 and 27.8 nV/√Hz at the expense of 0.16 mm2 per channel. In BIOZ measurement, a 5-bit programmable current source is used to generate pseudo sine injection current ranging from 0 to 22 µApp, and the detection sensitivity reaches 2.4 mΩ/√Hz. Finally, the presented multichannel EEG/BIOZ acquisition ASIC has a compact active area of 1.5 mm2 in an 180nm CMOS technology.

Different femoral tunnel placement in posterior cruciate ligament reconstruction: a finite element analysis.

BACKGROUND: At present, there is no consensus on the optimal biomechanical method for Posterior cruciate ligament (PCL) reconstruction, and the "critical corner" that is produced by the femoral tunnel is currently considered to be one of the main reasons for PCL failure. Thus, the purpose of this study was to identify one or several different tunnels of the femur, thereby reducing the influence of the "critical corner" without reducing the posterior stability of the knee. METHODS: CT and MRI data of the knee joint of a healthy adult man were collected, and computer-related software was used to reconstruct the finite element model of the knee joint, to provide different properties to different materials and to allow for the performance of a finite element analysis of the reconstructed model. The position of the femoral tunnel was positioned and partitioned according to anatomical posture, and three areas were divided (the antero-proximal region, the antero-distal region and the posterior region). In addition, we applied a posterior tibial load of 134 N to the reconstructed model, recorded and compared different tunnels of the femur, conducted peak stress at the flexion of the knee joint of 0°, 30°, 60° and 90°, and elicited the displacement of the proximal tibia. RESULTS: Among the 20 different femoral tunnels, the graft peak stress was lower in tunnels 4, 12 and 18 than in the PCL anatomical footpath tunnel 13, especially at high flexion angles (60° and 90°). These three tunnels did not increase the posterior displacement of the proximal tibia compared with the anatomical footpath tunnel 13. CONCLUSION: In summary, among the options for PCL reconstruction of the femoral tunnel, the tunnels located 5 mm distal to the footprint and 5 mm anterior to the footprint could reduce the peak stress of the graft; additionally, it may reduce the "critical corner" and was shown to not reduce the posterior stability of the knee joint.

Direct Anterior Approach in Lateral Decubitus Position Versus Supine Position for Unilateral Total Hip Arthroplasty: A Comparative Study.

OBJECTIVE: To compare the clinical efficacy of the direct anterior approach in lateral decubitus position (L-DAA) and supine position (S-DAA) for unilateral total hip arthroplasty. METHODS: A retrospective study was conducted on 89 patients who underwent primary unilateral total hip arthroplasty in our department between August 2016 and December 2017. There were 46 patients who underwent L-DAA and 43 patients who underwent S-DAA. The body mass index (BMI), operation time, blood loss, preoperative Hb, first day and third day postoperative Hb, incision length, hospital stay, preoperative and postoperative Harris score, preoperative and postoperative visual analogue scale (VAS) score, radiological evaluation, intraoperative and postoperative complication, postoperative absolute length difference of lower extremity were recorded and analyzed. P < 0.05 was set as the significant difference. RESULTS: All patients were followed up for 8-23 months, with an average of 15.6 months. No significant differences were found in preoperative and postoperative Harris scores, preoperative Hb, incision lengths, radiological evaluations, preoperative and postoperative VAS scores, and hospital stay (P > 0.05). However, significant differences were detected in BMI, blood loss, first day and third day postoperative Hb, and operation time (P < 0.05). There were no postoperative complications in the L-DAA and S-DAA groups. During the operation, two cases of proximal femoral fracture occurred in the L-DAA group, four in the S-DAA group, and the difference was statistically significant. There were significant differences found in the postoperative absolute length difference of lower extremity between the two groups. CONCLUSION: Compared with the S-DAA approach, the L-DAA approach had the advantages of shorter operation time and less blood loss. Compared with S-DAA, it was easier to expose the proximal femur, and lower BMI was required in L-DAA. However, it was more difficult to compare the length of both lower extremities in the L-DAA approach than in the S-DAA approach.

Follow-up results of microendoscopic discectomy compared to day surgery using percutaneous endoscopic lumbar discectomy for the treatment of lumbar disc herniation.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) is satisfactory for hospitalized patients with lumbar disc herniation (LDH). Currently, only a few studies have reported about the day surgery patients undergoing PELD. METHODS: A total of 267 patients with LDH underwent PELD during day surgery and were followed up for at least 3 years. Clinical outcomes were assessed using the visual analog scale (VAS) for leg and lower back pain (VAS-B and VAS-L, respectively) and the Oswestry disability index (ODI). The radiological outcomes, such as lumbar lordosis (LL), sacral slope (SS), the disc-height ratio, and disc instability, were recorded and compared. The clinical effects between patients treated by PELD during day surgery and microendoscopic discectomy (MED) for contemporaneous hospitalized 116 patients with LDH were compared. RESULTS: Patients treated by PELD had lower blood loss and shorter hospital stay (P <  0.001) compared to those treated by MED. VAS-L, VAS-B, and ODI decreased significantly after PELD than before the operation and 3 years postoperatively. The postoperative VAS-B in the PELD group was significantly decreased than in the MED group (P = 0.001). The complications rate was 9.4% in the PELD group and 12.1% in the MED group (P = 0.471). The 1-year postoperative recurrence rate in the PELD group was much higher than that in MED group (P = 0.042). The postoperative LL and SS in the PELD group improved significantly compared to the values in the MED group (P <  0.001). According to the disc-height ratio at 3-year follow-up, a significant height loss was observed in the MED group than in the PELD group (P = 0.014). CONCLUSIONS: Although the 1-year postoperative recurrence rate was relatively high, the day surgery for LDH undergoing PELD had advantages in terms of less blood loss intraoperatively, short hospital stay, efficacy for back pain, and efficiency to maintain lumbar physiological curvature.

Risk factors for femoral fracture in lateral decubitus direct anterior approach total hip arthroplasty using conventional stems: a retrospective analysis.

OBJECTIVE: To provide guidelines for surgery and reduce the incidence of fracture, this study analyzed the relationship between femoral fracture and related factors in direct anterior approach (DAA) total hip arthroplasty (THA) in the lateral decubitus position. METHOD: A retrospective series of 273 consecutive patients who underwent THA with the DAA in the lateral decubitus position was analyzed. Each surgery was performed by the same surgeon with a conventional operation bed and femoral stem. The correlations between the incidence of fracture and sex, age, body mass index (BMI), height, osteoporosis, the anterior superior iliac spine-greater trochanter distance (ASIS-GTD), and hip joint disease were analyzed by univariate analysis and logistic regression analysis. RESULTS: Among all hip arthroplasty procedures, 35 hips had femoral fractures, including 30 greater trochanter fractures, 4 proximal femoral splits, and 1 femoral perforation. The incidence of fracture was 12.82%. Univariate analysis showed no significant difference in the incidence of fracture by sex, BMI, or age. However, osteoporosis caused an increase in the incidence of fracture, while the incidence of fracture decreased as height and the ASIS-GTD increased. The incidence of femoral neck fracture was lower in cases of osteonecrosis of the femoral head than in cases of other diseases. Logistic regression showed a significant correlation between osteoporosis, the ASIS-GTD, and fractures. Patients with osteoporosis had a high possibility of fracture (OR = 2.414); the possibility of fracture decreased with increasing ASIS-GTD (OR = 0.938). CONCLUSION: Lateral decubitus DAA THA can be successfully performed using a conventional operation bed and stem, effectively saving medical resources. Osteoporosis and a shorter ASIS-GTD were independent risk factors for femoral fracture.

Efficacy analysis of two surgical treatments for thoracic and lumbar intraspinal tumours.

BACKGROUND: Surgery remains the main curative option for the treatment of intraspinal tumour. The purpose of the present study was to analyze the clinical outcomes of laminoplasty with process-lamina complex replantation compared with laminectomy with pedicle screw fixation for intraspinal tumours. METHODS: In our retrospective analysis, 27 patients received tumour resection surgery by laminoplasty with reconstruction plate fixation and 32 patients received laminectomy with pedicle screw fixation. All patients were followed up for at least 1 year. Data, including surgical time, blood loss, volume of drainage, drainage time, hospital stay, complications, and neurological status were compared. In addition, imaging evaluation was also included. RESULTS: Patients in the laminoplasty group had lower blood loss (laminoplasty group: 281.5 ± 130.2 mL; laminectomy group: 450.0 ± 224.3 mL; p = 0.001), shorter surgical time (laminoplasty group: 141.7 ± 26.2 min, laminectomy group: 175.3 ± 50.4 min; p = 0.003), lower volume of drainage (laminoplasty group: 1578.9 ± 821.7 mL, laminectomy group: 2621.2 ± 1351.0 mL; p = 0.001), shorter drainage time (laminoplasty group: 6.6 ± 2.5 days, laminectomy group: 9.7 ± 1.8 days; p = 0.000), and a shorter hospital stay (laminoplasty group: 16.9 ± 4.9 days, laminectomy group: 21.0 ± 4.4 days; p = 0.002) compared with patients in the laminectomy group. There were significant differences of oswestry dysfunction index (ODI) between the two groups at 12 months postoperatively (p = 0.034). The incidence of secondary spinal stenosis in the laminoplasty group was significantly reduced (p = 0.029). CONCLUSIONS: Laminoplasty in intraspinal tumour resection has a lower blood loss and volume of drainage, shorter surgical time and hospital stay as advantages over the standard laminectomy technique. Moreover, laminoplasty can effectively avoid iatrogenic spinal canal stenosis and thus enhancing functional recovery of spinal cord.

CPEB1 Expression Correlates with Severity of Posttraumatic Ankle Osteoarthritis and Aggravates Catabolic Effect of IL-1ß on Chondrocytes.

Most cases of posttraumatic ankle osteoarthritis (PTAOA) represent a sequela of ankle fractures. The cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is an RNA binding protein that controls protein expression. Here, we report the previously unappreciated association of CPEB1 with PTAOA. We found that CPEB1 was upregulated in articular cartilage from patients with PTAOA. Additionally, its expression level positively correlated with disease severity. In human primary chondrocytes cultured in vitro, CPEB1 was upregulated when treated with pro-inflammatory cytokines, i.e., IL-1ß and TNF-α, suggesting that the observed CPEB1 upregulation in articular cartilage of PTAOA patients may be attributed to local inflammatory milieu. Functionally, CPEB1 overexpression aggravated the catabolic effect of IL-1ß on chondrocytes in vitro, and vice versa, its knockdown reduced this effect, together implying a detrimental role of CPEB1 involved in OA progression. In sum, our study identifies CPEB1 as a potential regulator of disease progression of PTAOA.

Comparison of early complications between the use of a cannulated screw locking plate and multiple cancellous screws in the treatment of displaced intracapsular hip fractures in young adults: a randomized controlled clinical trial.

BACKGROUND: The incidence of early postoperative complications of displaced intracapsular hip fractures is high. The purpose of this study was to compare the early postoperative complications and assess the incidence of femoral neck shortening on using a newly designed proximal femoral cannulated screw locking plate (CSLP) versus multiple cancellous screws (MCS) in the treatment of displaced intracapsular hip fractures in young adults. METHODS: Sixty-eight young adult patients with displaced intracapsular hip fractures were randomly assigned to either the CSLP group or the MCS group and treated routinely by internal fixation with either the CSLP or the MCS. Harris Hip Score, nonunion, failure of fixation, overall complications, and femoral neck shortening were recorded and compared. RESULTS: Two patients (5.88%) in the CSLP group and eight (23.53%) in the MCS group had postoperative nonunion (P < 0.05). There was one case (2.94%) of fixation failure in the CSLP group and three cases (8.82%) in the MCS group (P > 0.05). Three patients (8.82%) in the CSLP group and 11 (32.35%) in the MCS group had overall complications (P < 0.05). Mean femoral neck shortening was 5.10 mm in the vertical plane and 5.11 mm in the horizontal plane in the CSLP group and 11.14 mm in the vertical plane and 10.51 mm in the horizontal plane in the MCS group. Severe femoral neck shortening (≥ 10 mm) did not occur in either the vertical or the horizontal plane in any patient of the CSLP group but occurred in 10 patients (28.57%) in the vertical plane and in 8 (22.86%) patients in the horizontal plane in the MCS group. CONCLUSIONS: Compared with MCS, the use of CSLP in the treatment of displaced intracapsular hip fractures in young adults can reduce the rates of postoperative nonunion and overall complications and minimize femoral neck shortening. TRIAL REGISTRATION: ChiCTR1800016032 . Registered 8 May 2018. Retrospectively registered.

Modification in aortic arch replacement surgery.

OBJECTIVE: We modified the conventional aortic arch replacement procedure to avoid circulation arrest and a prolonged extracorporeal circulation time, especially in cases of acute aortic dissection. We herein present our experience with a modified branch-first approach to acute aortic dissection, with anastomosis of the supra aortic vessels prior to commencing cardiopulmonary bypass. METHODS: Since 2012, 41 patients (aortic dissection, 36; arch aneurysm, 5) have undergone the modified procedure. Procedurally, the implanted graft was used as a landing zone for second-stage endovascular stent-graft deployment intended to manage the residual descending dissection. Antegrade and retrograde systemic perfusion was instituted during cardioplegic arrest. The brain was actively perfused via the graft throughout the procedure. RESULTS: Arch replacement surgery could generally be completed within approximately 4 h. During a 2-year period of aortic dissection or arch aneurysm treatment, only four anastomoses were required during the first stage of operation: two in the aorta, and one each in the innominate and left common carotid arteries. No patient died of surgical causes, and no stent grafts were deployed into the false lumen, a characteristic of procedures using traditionally antegrade deployment. CONCLUSION: We recommend that our procedure for acute aortic dissection be performed in two stages (graft replacement first and stent graft deployment second), particularly for patients underwent preoperative hypotesion. If malperfusion syndrome still exists after graft replacement, stent graft should be deployed in one stage. The arch aneurysm can be treated in one stage because there is no concern about false lumen deployment.

Noninvasive, targeted gene therapy for acute spinal cord injury using LIFU-mediated BDNF-loaded cationic nanobubble destruction.

Various gene delivery systems have been widely studied for the acute spinal cord injury (SCI) treatment. In the present study, a novel type of brain-derived neurotrophic factor (BDNF)-loaded cationic nanobubbles (CNBs) conjugated with MAP-2 antibody (mAbMAP-2/BDNF/CNBs) was prepared to provide low-intensity focused ultrasound (LIFU)-targeted gene therapy. In vitro experiments, the ultrasound-targeted tranfection to BDNF overexpressioin in neurons and efficiently inhibition neuronal apoptosis have been demonstrated, and the elaborately designed mAbMAP-2/BDNF/CNBs can specifically target to the neurons. Furthermore, in a acute SCI rat model, LIFU-mediated mAbMAP-2/BDNF/CNBs transfection significantly increased BDNF expression, attenuated histological injury, decreased neurons loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in SCI rats. LIFU-mediated mAbMAP-2/BDNF/CNBs destruction significantly increase transfection efficiency of BDNF gene both in vitro and in vivo, and has a significant neuroprotective effect on the injured spinal cord. Therefore, the combination of LIFU irradiation and gene therapy through mAbMAP-2/BDNF/CNBs can be considered as a novel non-invasive and targeted treatment for gene therapy of SCI.