A novel complex coupling agent for enhancing the compatibility between collagen fiber and natural rubber: A utilization strategy for leather wastes.

Leather shavings are generated as solid waste in the leather industry and may cause environmental pollution if not disposed judiciously. These solid wastes, primarily composed of collagen fibers (CFs), can be recycled as biomass composites. However, CFs are incompatible with natural rubber (NR) due to its hydrophilicity. Conventionally, the compatibility has been improved by utilizing silane coupling agents (SCAs) along with a large number of organic solvents, which further contribute to environmental pollution. In this study, we developed a novel complex coupling agent (CCA) to enhance the compatibility between CF and NR. The CCA was synthesized through a coordination reaction between Cr(III) and α-methacrylic acid (MAA). Cr(III) in the coupling agent coordinates with the active groups in CFs, while the unsaturated double bonds in MAA facilitate covalent crosslinking between the CCA and NR, improving compatibility. The coordination bonding between CF and NR exhibits strong interfacial interaction, endowing the composites with desirable mechanical properties. Moreover, the proposed method is an economical and green approach that can be used to synthesize CF-based composites without requiring organic solvents. Herein, a strategy promoted sustainable development in the leather industry has been established.

Reviving Intervertebral Discs: Treating Degeneration Using Advanced Delivery Systems.

Intervertebral disc degeneration (IVDD) is commonly associated with many spinal problems, such as low back pain, and significantly impacts a patient's quality of life. However, current treatments for IVDD, which include conservative and surgical methods, are limited in their ability to fully address degeneration. To combat IVDD, delivery-system-based therapy has received extensive attention from researchers. These delivery systems can effectively deliver therapeutic agents for IVDD, overcoming the limitations of these agents, reducing leakage and increasing local concentration to inhibit IVDD or promote intervertebral disc (IVD) regeneration. This review first briefly introduces the structure and function of the IVD, and the related pathophysiology of IVDD. Subsequently, the roles of drug-based and bioactive-substance-based delivery systems in IVDD are highlighted. The former includes natural source drugs, nonsteroidal anti-inflammatory drugs, steroid medications, and other small molecular drugs. The latter includes chemokines, growth factors, interleukin, and platelet-rich plasma. Additionally, gene-based and cell-based delivery systems are briefly involved. Finally, the limitations and future development of the combination of therapeutic agents and delivery systems in the treatment of IVDD are discussed, providing insights for future research.

Is CaMKII friend or foe for cell apoptosis in eye?: A narrative review.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) controls cell proliferation, differentiation, apoptosis, and other biological processes that have an essential role in eye diseases. However, it seems that previous studies have generated conflicting conclusions about the effect of CaMKII on cell apoptosis. In this review, we explore the positive and potentially deleterious effects of CaMKII on eye cell apoptosis. We can safely conclude that the early elevation of CaMKII could be viewed as a promoter of cell apoptosis. Overexpression of CaMKII by transfection or pretreatment with drugs helped combat cell apoptosis.

Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis.

This study investigated the function of telomerase RNA component (TERC) in spinal cord injury (SCI). SCI models were established in rats via laminectomy and PC-12 cells were treated with lipopolysaccharide (LPS). TERC and miR-34a-5p expressions in cells and rat spinal cords were detected by quantitative reverse transcription polymerase chain reaction, followed by overexpression/knockdown of TERC/miR-34a-5p. Spinal cord histopathological changes were examined via hematoxylin-eosin staining. miR-34a-5p' relation with TERC and XBP-1 was predicted by TargetScan and checked by dual-luciferase reporter/RNA immunoprecipitation assays. Cell biological behaviors were assessed by Cell counting kit-8, wound healing, Transwell, and flow cytometry assays. XBP-1 and inflammation/apoptosis-related protein expressions were analyzed by western blot. TERC was upregulated and miR-34a-5p was low-expressed in SCI tissues and LPS-induced PC-12 cells. TERC-knockdown alleviated histopathological abnormalities yet upregulated miR-34a-5p in SCI tissues. In LPS-induced PC-12 cells, TERC knockdown promoted cell viability, migration, invasion, and inhibited apoptosis, while TERC overexpression ran oppositely. TERC knockdown downregulated the XBP-1, IL-6, TNF-α, Bax, p-p38/t-p38, and cleaved caspase-9/-3, but upregulated Bcl-2 and p-Akt/t-Akt. TERC targeted miR-34a-5p, which further targeted XBP-1. miR-34a-5p downregulation exerted effects opposite to and offset TERC knockdown-induced effects. TERC knockdown facilitated the regeneration of neuron tissues yet inhibited inflammation in SCI through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis.

Blockage of TRPV4 Downregulates the Nuclear Factor-Kappa B Signaling Pathway to Inhibit Inflammatory Responses and Neuronal Death in Mice with Pilocarpine-Induced Status Epilepticus.

The blockage of transient receptor potential vanilloid 4 (TRPV4) inhibits inflammation and reduces hippocampal neuronal injury in a pilocarpine-induced mouse model of temporal lobe epilepsy. However, the underlying mechanisms remain largely unclear. NF-κB signaling pathway is responsible for the inflammation and neuronal injury during epilepsy. Here, we explored whether TRPV4 blockage could affect the NF-κB pathway in mice with pilocarpine-induced status epilepticus (PISE). Application of a TRPV4 antagonist markedly attenuated the PISE-induced increase in hippocampal HMGB1, TLR4, phospho (p)-IκK (p-IκK), and p-IκBα protein levels, as well as those of cytoplasmic p-NF-κB p65 (p-p65) and nuclear NF-κB p65 and p50; in contrast, the application of GSK1016790A, a TRPV4 agonist, showed similar changes to PISE mice. Administration of the TLR4 antagonist TAK-242 or the NF-κB pathway inhibitor BAY 11-7082 led to a noticeable reduction in the hippocampal protein levels of cleaved IL-1ß, IL-6 and TNF, as well as those of cytoplasmic p-p65 and nuclear p65 and p50 in GSK1016790A-injected mice. Finally, administration of either TAK-242 or BAY 11-7082 greatly increased neuronal survival in hippocampal CA1 and CA2/3 regions in GSK1016790A-injected mice. Therefore, TRPV4 activation increases HMGB1 and TLR4 expression, leading to IκK and IκBα phosphorylation and, consequently, NF-κB activation and nuclear translocation. The resulting increase in pro-inflammatory cytokine production is responsible for TRPV4 activation-induced neuronal injury. We conclude that blocking TRPV4 can downregulate HMGB1/TLR4/IκK/κBα/NF-κB signaling following PISE onset, an effect that may underlie the anti-inflammatory response and neuroprotective ability of TRPV4 blockage in mice with PISE.

Walkability assessment of metro catchment area: A machine learning method based on the fusion of subject-objective perspectives.

China's metro system is developing rapidly. Walking is the most frequently adopted mode to connect to the metro, the attributes of the pedestrian-built environment around the stations directly influence people's willingness to use the metro. However, few studies have paid attention to the comprehensive assessments of the built environment in the metro catchment area. Thus, this paper attempts to construct a walkability evaluation model that combines subjective and objective perspectives. We collected field data of the built environment factors affecting on walkability in the 800 m buffer zone of eight case metro stations in Dalian city, China. We also collected on-site interviews from 867 passengers to evaluate the walkability. A machine learning-based approach was developed to calculate the weights of walkability variables, followed by constructing a Score-Effectiveness framework to identify the built environment factors in the metro catchment area that need to be improved. The study found that the shading facilities, obstacle barriers, and resting seats around pedestrian walkways are the most efficient and imbalanced variables recognized by the crowd. The convenience of overpasses and underpasses are additional efficient imbalance-type variables for leisure and commuting populations, respectively. This indicates that the current level of construction of the above five built environment factors is relatively low, but the construction has a significant impact on the degree of friendliness in supporting pedestrian walkability. In this paper, improvement measures are proposed in a targeted manner in order to achieve the effect of effectively improving the current level of metro catchment area's walkability. The results of the study can provide references to provide strategies for precise pedestrian planning in the metro catchment area, leading to a pedestrian environment with high walking quality.

Analysis of strategy and efficacy clinical treatments of Kümmell disease: a cohort study.

Background: Most clinical reports on the surgical treatment of kümmell disease lack consistency between classification and treatment protocol. In this study, we investigate the most appropriate and effective clinical treatment strategies according to the characteristics of different types of Kümmell disease. Methods: A retrospective analysis was performed of 48 patients with Kümmell disease treated in Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China for which complete follow-up data were available. All cases were classified into six types: type I, vertebral body height loss less than 20% and no intervertebral disc degeneration from adjacent segments; type II, vertebral body height loss more than 20% and accompanied by degeneration or mild instability of intervertebral discs at adjacent segments; type III, posterior vertebral cortical rupture and dural sac compression, and some accompanied by spinal cord nerve injury. Type III includes type IIIA (recoverable stable type), type IIIB (recoverable unstable type), type IIIC (spinal stenosis type), and type IIID (kyphosis type). Methods of surgery: patients of types I, II, and IIIA were treated with percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP), type IIIB were treated with posterior fixation and fusion, type IIIC were treated with posterior decompression and fixation fusion, and type IIID were treated with posterior osteotomy, orthopedic fixation, and fusion. All patients were followed up for 10-44 months (mean, 20.5±4.5 months). The preoperative and postoperative visual analog scale (VAS) scores, Owestry disability index (ODI) scores, secondary height loss and kyphosis, and neurological improvement were followed up and statistically analyzed. Results: The VAS and ODI scores of all cases were improved compared with those pre-surgery (P<0.05). A total of 8 cases showed loss of vertebral height or secondary kyphosis. The American Spinal Injury Association (ASIA) grades of patients with neural impairment were all improved at the last follow-up. Conclusions: According to the characteristics of different types of Kümmell disease, appropriate clinical treatment strategies can achieve satisfactory curative effects and reduce the occurrence of complications. This study is only a retrospective study, lacks a control group, and the sample size is small. Therefore, it has limitations and does not provide guidance.

Repeated inhibition of sigma-1 receptor suppresses GABAA receptor expression and long-term depression in the nucleus accumbens leading to depressive-like behaviors.

Sigma-1 receptor (σ1R) downregulation in male mice is known to cause a depressive-like phenotype. The nucleus accumbens (NAc), a region associated with affective regulation, has high levels of σ1R. Here, we investigated the effect of repeated inhibition of σ1R in the NAc on depressive-like behaviors and synaptic plasticity by microinjecting σ1R antagonist NE-100 into NAc nuclei in mice (NE-100 mice); this was followed by behavioral tests and field potentials recordings. We first examined the effect of NE-100 administration on σ1R expression and found that cell surface levels of σ1R were significantly reduced in the NAc of NE-100 mice. Compared to control mice, NE-100 mice exhibited significantly prolonged immobility in forced swim test (FST) and tail suspension test (TST), impaired long-term depression (LTD) as well as multi-spike waveform field excitatory postsynaptic potential (fEPSP) with an extended duration and an increased paired-pulse ratio (PPR). Reduced levels of GABAA receptor (GABAAR)-α1, -α2, -ß2, and -ß3 subunits, membrane D2R, and PKC phosphorylation in the NAc were observed in NE-100 mice. Activation of GABAAR by muscimol corrected the extended fEPSP duration and increased PPR, restored LTD maintenance as well as alleviated depressive-like behaviors in NE-100 mice. The decline of PKC phosphorylation in the NAc of NE-100 mice was corrected by injecting NAc with quinpirole, a D2R agonist. Injections of quinpirole or PMA (a PKC activator) into NAc of NE-100 mice rescued the expression levels of GABAAR, and alleviated the increase in PPR and impairment in LTD; these effects were sensitive to GF109203X, a PKC inhibitor. Furthermore, injecting NAc with quinpirole or PMA relieved depressive-like behaviors in NE-100 mice. Collectively, these results indicate that repeated inhibition of σ1R in the NAc reduces D2R-mediated PKC phosphorylation and suppresses GABAAR expression, thus impairing LTD maintenance and leading to depressive-like behaviors.

[Unilateral biportal endoscopic discectomy for high-grade migrated lumbar disc herniation].

Objective: To investigate the effectiveness of the unilateral biportal endoscopy (UBE) technique in the treatment of high-grade migrated lumbar disc herniation (LDH). Methods: Between January 2020 and February 2021, 23 cases of high-grade migrated LDH were treated with discectomy via UBE. There were 14 males and 9 females, with a mean age of 48.7 years (range, 32-76 years). All patients had low back and leg pain. The disease duration ranged from 2 months to 7 years (median, 13 months). Lesion segments were L 3, 4 in 2 cases, L 4, 5 in 15 cases, and L 5, S 1 in 6 cases. The operation time, intraoperative blood loss, the time when the patients started to move off the floor, and postoperative complications were recorded. The effectiveness was evaluated using the visual analogue scale (VAS) score, the modified Oswestry disability index (ODI), and the modified MacNab criteria. Results: All operations were completed successfully, and no complication such as dural tear, epidural hematoma, nerve injury, or vascular injury occurred. The operation time ranged from 53 to 96 minutes, with an average of 71.0 minutes. The intraoperative blood loss ranged from 32 to 56 mL, with an average of 39.3 mL. All patients were removed the drainage tube and wore a lumbar brace to move off the floor around 1 to 2 days after operation. All patients were followed up 3-12 months after operation, with an average of 5.7 months. The VAS scores of low back pain and leg pain and the modified ODI at all postoperative time points were lower than those before operation, and the differences were significant ( P<0.05). The differences were significant ( P<0.05) when comparing the above indexes between the time points after operation. At last follow-up, the effectiveness was evaluated according to the modified MacNab criteria, and 17 cases were excellent, 4 cases were good, and 2 cases were fair, with an excellent and good rate of 91.3%. There was no recurrence of LDH during follow-up. Conclusion: Discectomy via UBE is an effective method for the treatment of high-grade migrated LDH because of its flexibility, clear view, and wide range of intraoperative exploration, which can effectively reduce the risk of residual nucleus pulposus after operation.

Analysis of the Clinical Significance and Safety of Interferon in the Treatment of Chronic Myeloproliferative Tumors.

Objective: To investigate the clinical significance and safety of interferon in the treatment of chronic myeloproliferative tumors (MPN). Methods: In this prospective study, a total of 120 patients with advanced chronic MPN admitted to our hospital between April 2016 and August 2020 were assessed for eligibility and recruited, including 62 patients with JAK2V617F mutation-positive ET (ET group) and 58 patients with JAK2V617F mutation-positive PV (PV group). 62 patients with JAK2V617F mutation-positive ET were assigned (1 : 1) to receive interferon-α (IFN-α) or hydroxyurea (HU). A similar subgrouping method for treatment of IFN-α and HU was introduced to patients with JAK2V617F mutation-positive PV. Outcome measures included efficacy and adverse reactions. Results: For patients with JAK2V617F mutation-positive ET and PV, there were no significant differences in the overall response rate between the groups treated with IFN-α or HU (P > 0.05); however, the patients treated with IFN-α had a significantly higher 5-year progression-free survival (PFS) than those treated with HU (P < 0.05). IFN-α was associated with a significantly lower incidence of disease progression, thrombotic events, splenomegaly, myelofibrosis, nausea, and vomiting and a higher incidence of hematological adverse reactions and flu-like symptoms versus HU (P < 0.05). After six months of treatment, the PV group had 12 cases of hematological response both in the IFN-α subgroup and the HU subgroup and fewer PV patients treated with IFN-α required phlebotomy versus those treated with HU (P < 0.05), in which 4 patients in the IFN-α subgroup had no hematological response and 6 patients in the HU subgroup had no hematological response. There was no significant difference in the number of cases with phlebotomy between the two subgroups of PV patients without hematological response (P > 0.05). Conclusion: The use of IFN in the treatment of JAK2V617F mutation-positive ET and PV patients yields a prominent clinical effect by prolonging PFS and avoiding phlebotomy for JAK2V617F mutation-positive PV patients.

Involvement of TRPV4 in changes in rapidly inactivating potassium channels in the early stage of pilocarpine-induced status epilepticus in mice.

The rapidly inactivating potassium current (IA ) is important in controlling neuronal action potentials. Altered IA function and K+ channel expression have been found in epilepsy, and activation of the transient receptor potential vanilloid 4 (TRPV4) channel is involved in epilepsy pathogenesis. This study examined whether TRPV4 affects Kv4.2 and K+ channel interacting protein (KCHIP) expression and IA changes following pilocarpine-induced status epilepticus (PISE) in mice. Herein, hippocampal protein levels of Kv4.2 and KCHIP2 increased 3 h-3 d and decreased 7-30 d; that of KCHIP1 increased 3-24 h and decreased 3-30 d post-PISE. The TRPV4 antagonist HC-067047 attenuated the increased protein levels of Kv4.2 and KCHIP2 but not that of KCHIP1 post-PISE. The TRPV4 agonist GSK1016790A increased hippocampal protein levels of Kv4.2 and KCHIP2 but had no effect on KCHIP1 expression. HC-067047 attenuated the increased IA in hippocampal pyramidal neurons 24 h and 3 d post-PISE. GSK1016790A increased IA in hippocampal pyramidal neurons, shifting the voltage-dependent inactivation curve toward depolarization. The GSK1016790A-induced increase of IA was blocked by protein kinase A and calcium/calmodulin-dependent kinase II antagonists but was unaffected by protein kinase C antagonists. We conclude that TRPV4 activation may be responsible for the increases of Kv4.2 and KCHIP2 expression in hippocampi and IA in hippocampal pyramidal neurons in PISE mice, which are likely compensatory measures for hyperexcitability at the early stage of epilepsy.

Feasibility of anterior pedicle screw fixation in lumbosacral spine: a radiographic and cadaveric study.

BACKGROUND: The anterior pedicle screw (APS) technique for L5 and S1 is crucial for proper anterior lumbar interbody fusion (ALIF). This study aimed to determine the projection, screw trajectory angle, and bone screw passageway length (BSPL), as well as the screw insertion regularity and the operating area within which it is safe to perform insertion. METHODS: Forty patients with low back pain, all of whom had lumbar computed tomography scans available, was included in this retrospective analysis. Radiographic parameters were measured, including: the distances from the projection to the upper endplate, lower endplate, and midline; the transverse and sagittal screw angles; and the BSPL. In addition, 10 fresh adult cadaveric lumbosacral spine segments were selected to determine the safe anatomic area in which to operate. Finally, APSs were inserted in L5 and S1 to determine the regularity of APS insertion. RESULTS: We measured the anterior projection parameters, including: the distances to the upper endplate (L5: 12.5±1.3 mm; S1: 4.54±0.87 mm), lower endplate (L5: 17.3±1.6 mm), and midline (L5: 6.6±0.7 mm; S1: 6.6±0.6 mm); the screw trajectory angle, including the transverse screw angle (L5: 25.3±2.8°; S1: 25.7±2.6°), sagittal screw angle (L5: 17.1±1.7°; S1: 22.4±1.1°); and the BSPL (L5: 48.6±3.5 mm; S1: 48.0±3.5 mm). The regularity of APS insertion in L5 and S1 was determined. Upon the needle reaching a point in the lateral view, it reached the corresponding point in the anteroposterior (AP) view. The anatomic parameters of the safe operating area were as follows: the distance from the abdominal aortic bifurcation to the L5 lower edge (40.50±9.40 mm); the distance from the common iliac vein confluence to the L5 lower edge (27.80±8.60 mm); and the horizontal distance from the inner edge of the common iliac vein to the L5 lower edge (37.50±1.30 mm). We also determined the distance between S1 holes (29.30±1.30 mm), the L5/S1 intervertebral height (17.20±1.50 mm), and the safe operating area (2,058.20±84.30 mm2). CONCLUSIONS: This study has determined the projection, screw trajectory angle, and BSPL of APSs in L5 and S1, their insertion regularity, and the area in which the operation can be safely performed.

Benzo(a)pyrene exposure in utero exacerbates Parkinson's Disease (PD)-like α-synucleinopathy in A53T human alpha-synuclein transgenic mice.

BACKGROUND: Previous work indicated that benzo[a]pyrene (B(a)P) exposure in utero might adversely affect neurodevelopment and cause Parkinson's Disease (PD)-like symptoms. However, the effect of utero exposure to B(a)P on PD-like α-synucleinopathy and the mechanism under are unclear. OBJECTIVE: The A53T human alpha-synuclein (α-syn) transgenic mice (M83+/-) were used in this study to gain insights into the role of B(a)P exposure in utero in the onset of α-syn pathology and neuronal damage. METHOD: Timed-pregnant M83+/- dams were exposed to 1) corn oil (vehicle) or 2) 5 mg/kg bw/d B(a)P or 3) 20 mg/kg bw/d B(a)P at gestational day 10-17 by oral gavage and then the SNCA transcription, α-syn accumulation and aggregation, neuroinflammation and nigral dopaminergic neurodegeneration of 60-day-old pups were evaluated. RESULT: SNCA mRNA and α-syn protein expression in the midbrain of 60 days adult mice were found to be remarkably elevated after B(a)P exposure in utero, the protein degradation capacity was injured (in 20 mg/kg dose group) and α-syn aggregation could be observed in the substantia nigra (SN); Enhanced Iba1 expression in the midbrain and microglial activation (in 20 mg/kg dose group) in the SN were also figured out; Besides, dopaminergic neurons in the SN of 60 days adult mice were significantly decreased. CONCLUSIONS: Our findings demonstrated that B(a)P exposure in utero could exacerbate α-syn pathology and induce activation of microglia which might further lead to dopaminergic neuronal loss in the SN.

miRNA-93-5p Promotes Gemcitabine Resistance in Pancreatic Cancer Cells by Targeting the PTEN-Mediated PI3K/Akt Signaling Pathway.

OBJECTIVE: To investigate the role and potential underlying mechanism of miR-93-5p in the carcinogenesis and gemcitabine resistance of pancreatic cancer (PC) cells. METHODS: We generated a gemcitabine-resistant PC cell line Bxpc-3/GemR following prolonged gemcitabine exposure to its parental gemcitabine-sensitive counterpart Bxpc-3/Par. Cell viability was monitored by MTS assay. Transfection was performed using Lipofectamine 3000 reagent. Cell apoptosis and rhodamine 123 fluorescence were detected by flow cytometry. Luciferase activities were measured using the luciferase reporter gene assay. Expression analysis was carried out by qRT-PCR and western blot. RESULTS: Significantly increased viability and enhanced expression of the multi-drug resistance-1 (MDR1) gene were observed in Bxpc-3/GemR cells, in which miR-93-5p is considerably upregulated, compared with Bxpc-3/Par cells. Downregulation of miR-93-5p inhibited cell viability, induced cell apoptosis, and decreased MDR1 expression in Bxpc-3/GemR cells, whereas upregulation essentially reversed these properties in Bxpc-3/Par cells. We further confirmed that PTEN was a direct target of miR-93-5p, and overexpression of miR-93-5p was accompanied by a significant increase in the phosphorylation of Akt expression in the Bxpc-3/Par cells. Moreover, inhibition of PI3K/Akt signaling diminished MDR1 expression. CONCLUSION: These observations suggest that miR-93-5p modulates tumorigenesis and gemcitabine resistance in PC cells via targeting the PTEN/PI3K/Akt signaling pathway.

[Current advances in research of semaphorin 3A:a potential target for the treatment of nospecific low back pain].

Nonspecific low back pain is closely associated with afferent nerve ingrowth into degenerated IVDs and increasing the inflammatory response. Members of the class 3 semaphorins signal their response through two prominent receptors; the NRP (Neuropilin-1) and the Plexin A. Sema3A (Semaphorin3A) is primarily known for their role in modulating neuronal survival as well as neurite outgrowth and guidance via regulation of Sema3A-NRP-1-plexinA signal pathway. Also, sema3A is shown to be conductive to innervate the inner painful degenerated IVDs (Intervertebral discs). Furthermore, sema3A is thought to act as a barrier to endothelial cells survival and migration on vascular endothelial growth factor (VEGF) and inhibition of KLF5-induced (Krüppel-like factor 5) inflammatory mediators within degenerated IVDs. Therefore, Sema3A produce a new perspective of dual-action therapeutic agent for attenuating the regulator of innervation and angiogenesis into degenerated IVDs and inhibition of KLF5-induced inflammation.

Application of Intelligent Computer-Assisted Taylor 3D External Fixation in the Treatment of Tibiofibular Fracture: Retrospective Case Study.

BACKGROUND: With the development of modern society, severe and complex tibial fractures caused by high-energy injuries such as traffic accidents have gradually increased. At present, the commonly used methods for the treatment of tibial fractures include plate fixation, intramedullary nail fixation, and external fixation. Most of these fractures are open wounds with severe soft tissue injury and wound contamination, and some involve bone defects, which makes internal fixation treatment difficult. OBJECTIVE: This study aims to explore the use of intelligent computer-assisted Taylor 3D external fixation for the treatment of tibiofibular fractures. METHODS: In total, 70 patients were included and divided into the Taylor 3D external fixation (TSF) group (28 patients with severe tibial fractures treated with TSF) and the internal fixation group (42 patients with complicated tibiofibular fractures treated by internal fixation). After the treatment, the follow-up evaluation of TSF for the treatment of tibiofibular fractures noted the incidence of complications, as well as the efficacy and occurrence of internal fixation for the treatment of tibial fractures in our hospital. RESULTS: The results showed that TSF was superior to orthopedics in the treatment of tibiofibular fractures in terms of efficacy and complications. CONCLUSIONS: TSF for the treatment of tibiofibular fractures is more effective than internal fixation and the incidence of complications is low. This is a new technology for the treatment of tibiofibular fractures that is worthy of clinical promotion.

Transient receptor potential vanilloid 4 activation inhibits the delayed rectifier potassium channels in hippocampal pyramidal neurons: An implication in pathological changes following pilocarpine-induced status epilepticus.

Activation of transient receptor potential vanilloid 4 (TRPV4) can increase hippocampal neuronal excitability. TRPV4 has been reported to be involved in the pathogenesis of epilepsy. Voltage-gated potassium channels (VGPCs) play an important role in regulating neuronal excitability and abnormal VGPCs expression or function is related to epilepsy. Here, we examined the effect of TRPV4 activation on the delayed rectifier potassium current (IK ) in hippocampal pyramidal neurons and on the Kv subunits expression in male mice. We also explored the role of TRPV4 in changes in Kv subunits expression in male mice following pilocarpine-induced status epilepticus (PISE). Application of TRPV4 agonists, GSK1016790A and 5,6-EET, markedly reduced IK in hippocampal pyramidal neurons and shifted the voltage-dependent inactivation curve to the hyperpolarizing direction. GSK1016790A- and 5,6-EET-induced inhibition of IK was blocked by TRPV4 specific antagonists, HC-067047 and RN1734. GSK1016790A-induced inhibition of IK was markedly attenuated by calcium/calmodulin-dependent kinase II (CaMKII) antagonist. Application of GSK1016790A for up to 1 hr did not change the hippocampal protein levels of Kv1.1, Kv1.2, or Kv2.1. Intracerebroventricular injection of GSK1016790A for 3 d reduced the hippocampal protein levels of Kv1.2 and Kv2.1, leaving that of Kv1.1 unchanged. Kv1.2 and Kv2.1 protein levels as well as IK reduced markedly in hippocampi on day 3 post PISE, which was significantly reversed by HC-067047. We conclude that activation of TRPV4 inhibits IK in hippocampal pyramidal neurons, possibly by activating CaMKII. TRPV4-induced decrease in Kv1.2 and Kv2.1 expression and IK may be involved in the pathological changes following PISE.

Dexamethasone Suppresses Radicular Pain Through Targeting the L-PGDS/PI3K/Akt Pathway in Rats With Lumbar Disc Herniation.

PURPOSE: Lumbar disc herniation (LDH) is a frequently occurring disease with unknown etiology, which makes treatment a challenge. The aim of this study was to analyze the effects of dexamethasone on LDH and elucidate the underlying mechanisms. GENERAL METHODS: An LDH rat model was established by nucleus pulposus implantation. The activity of the lipocalin type prostaglandin D synthase (L-PGDS)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) axis was evaluated by Western blotting. Paw withdrawal threshold and paw withdrawal latency were assessed by the Von Frey hairs method and the thermal dolorimeter of Hargreaves, respectively. The 21-point Basso-Beattie-Bresnahan scale was used to assess the locomotor function of rats. Pathological changes in the affected region were analyzed by hematoxylin-eosin staining. Immunofluorescence was used to measure the expression of microtubule-associated protein (MAP-2). FINDINGS: Lumbar disc herniation markedly increased thermo-mechanical allodynia and induced dorsal root ganglion (DRG) degeneration by inactivating the L-PGS/PI3K/Akt pathway. Dexamethasone restored the L-PGDS/PI3K/Akt pathway and relieved LDH-induced thermo-mechanical allodynia. Furthermore, overexpression and knockdown of L-PGDS respectively attenuated and worsened LDH-triggered thermo-mechanical allodynia and tissue degeneration by modulating the PI3K/Akt pathway. Pretreatment with dexamethasone partially abrogated the effect of L-PGDS knockdown through PI3K/Akt activation. CONCLUSIONS: Dexamethasone relieves LDH-mediated radicular pain by exerting anti-inflammatory effects and reducing the suppression of L-PGDS induced by LDH. Meanwhile, the activity of the PI3K/Akt pathway was decreased, possibly due to the attenuated inflammation induced by dexamethasone. Our results revealed the underlying mechanism of dexamethasone, which might be helpful in reducing the side effects of dexamethasone and provide more focused therapy in LDH.

Appropriate insertion point for percutaneous pedicle screw placement in the lumbar spine using c-arm fluoroscopy: a cadaveric study.

BACKGROUND: We studied the characteristics and regularity of appropriate insertion points for percutaneous pedicle screw placement in the lumbar spine using C-arm X-ray fluoroscopy. The purpose of this study was to improve the accuracy of percutaneous pedicle screw placement and reduce the incidence of superior-level facet joint violation. METHODS: Six normal spinal specimens were included. Three different methods for placing percutaneous pedicle screws in the lumbar spine were applied, including the Roy-Camille method, Magerl method and Weinstein method. The relationships among the insertion point, pedicle projection and proximal facet joint on C-arm X-ray films were studied. The projection morphology of the vertebral pedicle in different segments of the lumbar spine was observed. The relationship between the outer edge of the pedicle projection and the outer edge of the cranial articular process was also studied. The distance between the insertion point and the facet joint (M1), the distance between the insertion point and outer edge of the cranial articular process (M2), and the distance between the insertion point and the projection center of the pedicle (M) were measured. RESULTS: In this study, we found that the projection shape of the vertebral pedicle differed across segments of the lumbar spine: the shape for L1-L3 was oval, and that for L4-L5 was round. The radiographic study showed that the outer edge of the cranial articular process was located on the lateral side of the outer edge of the pedicle projection and did not overlap with the pedicle projection. M for the Weinstein group was larger than that for the Roy-Camille group (P <  0.05). M1 for the Weinstein group was larger than that for the Roy-Camille and Magerl groups (P <  0.05). M2 for the Roy-Camille group was negative, M2 for the Magerl group was 0, and M2 for the Weinstein group was positive. CONCLUSION: Under C-arm X-ray fluoroscopy, we were able to accurately identify the characteristics and regularity of the appropriate insertion point for percutaneous pedicle screw placement in the lumbar spine, which was important for improving the accuracy of percutaneous pedicle screw placement and reducing the incidence of superior-level facet joint violation.

Double-stranded RNA-induced dopaminergic neuronal loss in the substantia nigra in the presence of Mac1 receptor.

BACKGROUND: The underlying mechanism of viral infection as a risk factor for Parkinson's disease (PD), the second most common neurodegenerative disease, remains unclear. OBJECTIVE: We used Mac-1-/- and gp91phox-/- transgene animal models to investigate the mechanisms by which poly I:C, a mimic of virus double-stranded RNA, induces PD neurodegeneration. METHOD: Poly I:C was stereotaxically injected into the substantia nigra (SN) of wild-type (WT), Mac-1-knockout (Mac-1-/-) and gp91 phox-knockout (gp91 phox-/-) mice (10 µg/µl), and nigral dopaminergic neurodegeneration, α-synuclein accumulation and neuroinflammation were evaluated. RESULT: Dopaminergic neurons in the nigra and striatum were markedly reduced in WT mice after administration of poly I:C together with abundant microglial activation in the SN, and the expression of α-synuclein was also elevated. However, these pathological changes were greatly dampened in Mac-1-/- and gp91 phox-/- mice. CONCLUSIONS: Our findings demonstrated that viral infection could result in the activation of microglia as well as NADPH oxidase, which may lead to neuron loss and the development of Parkinson's-like symptoms. Mac-1 is a key receptor during this process.