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1.
Org Biomol Chem ; 22(11): 2226-2230, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38363281

ABSTRACT

An efficient intermolecular annulation of indazole aldehydes with propargylic amines has been developed for the synthesis of pyrazinoindazoles under catalyst- and additive-free conditions. This straightforward methodology was found to feature a wide substrate scope, high atom economy and environmental advantages. The bioactivity results of these new pyrazino[1,2-b]indazoles showed that some of them exhibited significant antifungal activity.

2.
Mater Today Bio ; 22: 100788, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37680584

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a pressing clinical issue that impedes wound healing. Pro-inflammatory M1 macrophages is required to clear bacteria and recruit various cell types during the initial phase of wound healing, but timing of this process is crucial. Herein, a microenvironment-responsive nanofibrous dressing capable of timely macrophage phenotype transition in vivo is constructed by coating copper ions (Cu2+)-polydopamine (PDA) networks on poly (ε-caprolactone) fiber (PCL-fiber) membrane. During the initial post-implantation period, the nanofibrous dressing show pH-sensitive Cu2+ release in the acidic infection microenvironment. The release Cu2+ have a direct killing effect on MRSA, and promote the proinflammatory M1 phenotype of macrophages to enhance the antibacterial macrophage response. Later, PDA to become a reactive oxygen species (ROS) scavenger when in microenvironments with elevated ROS levels, which conferred the dressing with an immunomodulatory activity that convert M1 macrophages into M2 macrophages. In vivo examination in an MRSA infected full-thickness skin wounds of rat model demonstrates that this dressing significantly facilitated infection eradication and wound healing through modulating local inflammatory phenotype. Overall, this study offers a simple and effective approach for timely manipulation of inflammation progression to promote infected wound healing.

3.
Small ; 19(44): e2302575, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37394717

ABSTRACT

Osteosarcoma (OS) is the most frequent osseous neoplasm among young people aged 10-20. Currently, the leading treatment for osteosarcoma is a combination of surgery and chemotherapy. However, the mortality remains high due to chemoresistance, metastasis, and recurrence, attributing to the existence of cancer stem cells (CSCs) as reported. To target CSCs, differentiation therapy attracts increasing attention, inducing CSCs to bulk tumor cells with elevated reactive oxygen species (ROS) levels and less chemoresistance. Moreover, increasing studies have implied that ferroptosis is a promising approach to eliminating cancer cells through eliciting oxidative damage and subsequent apoptosis, effectively bypassing chemoresistance. Here, a cancer-cell-membrane-decorated biocompatible formulation (GA-Fe@CMRALi liposome) is constructed to combat OS efficiently by combining distinct differentiation and ferroptosis therapies through magnified ROS-triggered ferroptosis and apoptosis with homologous target capability to tumor sites. The combinational approach exhibited favorable therapeutic efficacy against OS in vitro and in vivo. Impressively, the potential mechanisms are revealed by mRNA sequencing. This study provides a tactical design and typical paradigm of the synergized differentiation and ferroptosis therapies to combat heterogeneous OS.


Subject(s)
Bone Neoplasms , Ferroptosis , Osteosarcoma , Humans , Adolescent , Reactive Oxygen Species , Apoptosis , Osteosarcoma/drug therapy , Bone Neoplasms/drug therapy , Cell Differentiation , Cell Line, Tumor
4.
Bone ; 176: 116839, 2023 11.
Article in English | MEDLINE | ID: mdl-37454963

ABSTRACT

X-linked hypophosphatemia (XLH) is caused by dominant inactivating mutations in the phosphate regulating endopeptidase homology, X-linked (PHEX), resulting in elevated fibroblast growth factor 23 (FGF23), hypophosphatemia, rickets and osteomalacia. PHEX variants are identified in approximately 85 % of individuals with XLH, which leaves a substantial proportion of patients with negative DNA-based genetic testing. Here we describe a 16-year-old male who had typical features of XLH on clinical and radiological examination. Genomic DNA sequencing of a hypophosphatemia gene panel did not reveal a pathogenic variant. We therefore obtained a urine sample, established cell cultures and obtained PHEX cDNA from urine-derived cells. Sequencing of exon-spanning PCR products demonstrated the presence of an 84 bp pseudoexon in PHEX intron 21 due to a deep intronic variant (c.2147+1197A>G), which created a new splice donor site in intron 21. The corresponding PHEX protein would lack 33 amino acids on the C-terminus and instead include an unrelated sequence of 17 amino acids. The patient and his affected mother both had this variant. This report highlights that individuals with the typical clinical characteristics of XLH and negative genomic DNA sequence analysis can have deep intronic PHEX variants that are detectable by PCR-based RNA diagnostics.


Subject(s)
Familial Hypophosphatemic Rickets , Genetic Diseases, X-Linked , Hypophosphatemia , Male , Humans , Adolescent , Familial Hypophosphatemic Rickets/genetics , Familial Hypophosphatemic Rickets/metabolism , RNA , Genetic Diseases, X-Linked/genetics , Mutation/genetics , Hypophosphatemia/genetics , Polymerase Chain Reaction , PHEX Phosphate Regulating Neutral Endopeptidase/genetics
5.
J Bone Miner Res ; 38(8): 1125-1134, 2023 08.
Article in English | MEDLINE | ID: mdl-37293821

ABSTRACT

DNA sequencing is a reliable tool for identifying genetic variants in osteogenesis imperfecta (OI) but cannot always establish pathogenicity, particularly in variants altering splicing. RNA sequencing can provide functional evidence of the effect of a variant on the transcript but requires cells expressing the relevant genes. Here, we used urine-derived cells (UDC) to characterize genetic variants in patients with suspected or confirmed OI and provide evidence on the pathogenicity of variants of uncertain significance (VUS). Urine samples were obtained from 45 children and adolescents; UDC culture was successful in 40 of these participants (age range 4-20 years, 21 females), including 18 participants with OI or suspected OI who had a candidate variant or VUS on DNA sequencing. RNA was extracted from UDC and sequenced on an Illumina NextSeq550 device. Principal component analysis showed that the gene expression profiles of UDC and fibroblasts (based on Genotype Tissue Expression [GTEx] Consortium data) clustered close together and had less variability than those of whole blood cells. Transcript abundance was sufficient for analysis by RNA sequencing (defined as a median gene expression level of ≥10 transcripts per million) for 25 of the 32 bone fragility genes (78%) that were included in our diagnostic DNA sequencing panel. These results were similar to GTEx data for fibroblasts. Abnormal splicing was identified in 7 of the 8 participants with pathogenic or likely pathogenic variants in the splice region or deeper within the intron. Abnormal splicing was also observed in 2 VUS (COL1A1 c.2829+5G>A and COL1A2 c.693+6T>G), but no splice abnormality was observed in 3 other VUS. Abnormal deletions and duplications could also be observed in UDC transcripts. In conclusion, UDC are suitable for RNA transcript analysis in patients with suspected OI and can provide functional evidence for pathogenicity, in particular of variants affecting splicing. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Subject(s)
Osteogenesis Imperfecta , Child , Female , Adolescent , Humans , Child, Preschool , Young Adult , Adult , Osteogenesis Imperfecta/diagnosis , Osteogenesis Imperfecta/genetics , Osteogenesis Imperfecta/pathology , Collagen Type I, alpha 1 Chain , Mutation , Collagen Type I/genetics , Sequence Analysis, RNA
6.
Spine (Phila Pa 1976) ; 48(16): 1148-1154, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37026738

ABSTRACT

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To verify the clinical efficacy of a novel transoral stepwise release technique (TSRT) for the treatment of irreducible atlantoaxial dislocations (IAAD). SUMMARY OF BACKGROUND DATA: Anterior release for IAAD remains challenging, with a 3.2 times higher complication rate than posterior release. However, there are some patients who cannot achieve successful reduction from a posterior approach and require the higher-risk anterior release. Our work presents a novel anterior release technique that aims to minimize iatrogenic injury and associated complications from an anterior release. MATERIALS AND METHODS: IAAD cases who were treated with TSRT were retrospectively studied. Primary outcomes included fusion rate, complications, and neurological function over the course of a minimum 1-year follow-up. Radiographic differences between preoperative and postoperative imaging were also considered. A preoperative prediction model for the actual release grade was developed using multivariate logistic regression based on demographic factors and the craniovertebral abnormalities identified on preoperative images, evaluating the need for higher-grade TSRT release. RESULTS: We included 201 IAAD cases, with 42% (84/201) demonstrating degeneration of the atlantoaxial joint or anterior-hook-like dens. The reduction was achieved in all cases, with 80% (160/201) of cases only requiring relatively low-grade or grade I types TSRT release. Degeneration of the atlantoaxial joint was significantly associated with the need for higher-grade TSRT release (odds ratio:16.68, CI: 2.91-94.54, P = 0.002). The overall complication rate was 4.5% (9/201). Over the course of follow-up, the fusion rate reached 98.5%, and the American Spinal Injury Association and Japanese Orthopedic Association scores were significantly improved to 97.28 and 16.25 ( P < 0.01 and P < 0.01), respectively. CONCLUSION: This study demonstrated that our novel TSRT anterior release technique demonstrated complication rates similar to those published in the literature for posterior release. TSRT can be used as an alternative to posterior release techniques for refractory cases or when a posterior approach is not considered viable.


Subject(s)
Atlanto-Axial Joint , Joint Dislocations , Spinal Fusion , Humans , Retrospective Studies , Spinal Fusion/methods , Treatment Outcome , Atlanto-Axial Joint/diagnostic imaging , Atlanto-Axial Joint/surgery , Atlanto-Axial Joint/injuries , Decompression, Surgical/methods , Joint Dislocations/surgery
7.
Front Bioeng Biotechnol ; 11: 1041973, 2023.
Article in English | MEDLINE | ID: mdl-37034256

ABSTRACT

Finite element analysis (FEA) is a widely used tool in a variety of industries and research endeavors. With its application to spine biomechanics, FEA has contributed to a better understanding of the spine, its components, and its behavior in physiological and pathological conditions, as well as assisting in the design and application of spinal instrumentation, particularly spinal interbody cages (ICs). IC is a highly effective instrumentation for achieving spinal fusion that has been used to treat a variety of spinal disorders, including degenerative disc disease, trauma, tumor reconstruction, and scoliosis. The application of FEA lets new designs be thoroughly "tested" before a cage is even manufactured, allowing bio-mechanical responses and spinal fusion processes that cannot easily be experimented upon in vivo to be examined and "diagnosis" to be performed, which is an important addition to clinical and in vitro experimental studies. This paper reviews the recent progress of FEA in spinal ICs over the last six years. It demonstrates how modeling can aid in evaluating the biomechanical response of cage materials, cage design, and fixation devices, understanding bone formation mechanisms, comparing the benefits of various fusion techniques, and investigating the impact of pathological structures. It also summarizes the various limitations brought about by modeling simplification and looks forward to the significant advancement of spine FEA research as computing efficiency and software capabilities increase. In conclusion, in such a fast-paced field, the FEA is critical for spinal IC studies. It helps in quantitatively and visually demonstrating the cage characteristics after implanting, lowering surgeons' learning costs for new cage products, and probably assisting them in determining the best IC for patients.

8.
Nanotechnology ; 34(31)2023 May 16.
Article in English | MEDLINE | ID: mdl-37116479

ABSTRACT

The growth of artificial synthesis two-dimensional (2D) materials usually demands for suitable substrate due to their rare bulk allotropies. Borophene, as a typical artificial synthetic material, has been proved its substrate-growth on metal or nonmetals and its high theoretical specific capacity (1720 mAh g-1) for next-genatration electrode material, but structural instability and transfer difficulties have hindered the development of its applications. Here, a structurally stable and freestanding AA-stacked-α'-4H-borophene sheets have been synthesized byin situlithium eutectic salt-assisted synthetic method to realize the application of borophene in lithium-ion battery. The atomic structure of AA-α'-4H-borophene with interlayer VdWs was established by comparing the experimental observation with DFT optimal calculation. Different stacking configurations (AA- and AB-) of borophene was realized by a temperature-structure-photoluminescence intensity relationship, and the AA-stacked borophene exhibits higher specific capacity than AB structure. Based on electrochemical performance, the AA-borophene exhibits excellent rate capability and cycling performance due to its non-collapsible stacking configurations, which dominates great initial coulombic efficiency of 87.3% at 200 mA g-1superior to that of black phosphorus-based and borophene/graphene. Meanwhile, it still maintains the coulombic efficiency of 99.13% after 1000 cycles. It also shows a reversible capacity of 181 mAh g-1at 10 mA g-1between the voltage window of 0.01 and 2 V, which improves the reported capacity (43 mAh g-1) of bulk boron anode by over 430%. This work brings fantastic new view of fabricating stable, stacking and freestanding borophene and provides a significative idea on applications of borophene in energy storage domain.

9.
Nanotechnology ; 34(20)2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36753755

ABSTRACT

Multilayer borophene was predicted to have a similar semiconductor property to its monolayer arise from the weak van der Waals interactions between the layers. Besides, multilayer borophene has a higher carrier mobility than monolayer ones, so it is placed great hopes in applications of photoelectric and photovoltaic devices. However, its preparation and application in experiments of multilayer borophene are still lacking. Here, multilayerα'-4H-borophene was synthesized on semiconductingn-type GaAs substrates using NaBH4source as precursor and hydrogen as the carrier gas under controlled temperature and pressure conditions. The experimental results of the borophene are in good agreement with those of its theoretical prediction. The borophene is a semiconductor with a bandgap of 2.48 eV. To demonstrate the device application potential of the borophene, a near-infrared photodetector composed ofp-type borophene andn-type GaAs was fabricated. The photodetector shows a high photoresponsivity of 0.31 mA·W-1, a high specific detectivity of108Jones, and a fast response or recovery speed of 117 or 109 ms under the irradiation with the wavelength of 940 nm at zero bias. The results prove that theα'-4H-borophene/GaAs photodetector can show high sensitivity and zero consumption, which is of great value in meeting the appeal of sustainable development of society.

10.
Front Surg ; 9: 995662, 2022.
Article in English | MEDLINE | ID: mdl-36238865

ABSTRACT

Study Design: Technical report. Objective: Evaluate technical feasibility of extreme lateral interbody fusion (XLIF) at the L5-S1 level and provide an elaborate description of the surgical technique. Summary of Background Data: With the development of surgical techniques, the indications for oblique lumbar interbody fusion (OLIF) surgery have been broadened to the L5/S1 segment. However, this technique also has limitations. Different from OLIF, the L5/S1 segment used to be considered the main contraindication for XLIF. To date, no authors have reported the application of XLIF at the L5/S1 level. Methods: Only patients whose preoperative lumbar MRI showed the position of the psoas major muscles and blood vessels at the L5/S1 level were similar to those seen at supra-L5 levels were seleted. By folding the operating table, the iliac crest was moved downward to expose the L5/S1 intervertebral space during the operation. The remaining surgical procedures were consistent with routine XLIF surgery. Results: 8 patients successfully underwent XLIF at the L5/S1 level. The L5/S1 disk spaces were always exposed sufficiently for disk preparation and cage insertion. The post operative radiographs showed a satisfactory L5/S1 reconstruction with good cage position. Only 1 patient (12.5%) felt thigh numbness, and the symptoms gradually resolved after surgery and were no longer present in a month. There were no cases of psoas hematoma, retrograde ejaculation or vascular injury. The postoperative VAS score showed that all the patients achieved satisfactory results. Conclusions: XLIF at L5-S1 is feasible in strictly selected cases after thorough preoperative preparation and careful intraoperative procedures. However, we did not recommend XLIF as a routine surgical option at the L5/S1 level.

11.
Acta Biomater ; 153: 108-123, 2022 11.
Article in English | MEDLINE | ID: mdl-36115651

ABSTRACT

Insufficient vascularization is a major challenge in the repair of critical-sized bone defects. Deferoxamine (DFO) has been reported to play a potential role in promoting the formation of H-type blood vessels, a specialized vascular subtype with coupled angiogenesis and osteogenesis. However, whether DFO promotes the expression of H-type vessels in critical femoral defects with complete periosteal damage remains unknown. Moreover, stable drug loading systems need to be designed owing to the short half-life and high-dose toxic effects of DFO. In this study, we developed an injectable DFO-gelatin microspheres (GMs) hydrogel complex as a stable drug loading system for the treatment of critical femoral defects in rats. Our results showed that sustained release of DFO in critical femoral defects stimulated the generation of functional H-type vessels. The DFO-GMs hydrogel complex effectively promoted proliferation, formation, and migration of human umbilical vein endothelial cells in vitro. In vivo, the application of the DFO-GMs hydrogel complex expanded the distribution range and prolonged the expression time of H-type vessels in the defect area and was positively correlated with the number of osterix+ cells and new bone tissue. Topical application of the HIF-1α inhibitor PX-478 partially blocked the stimulation of H-type vessels by DFO, whereas the osteogenic potential of the latter was also weakened. Our results extended the local application of DFO and provided a theoretical basis for targeting H-type vessels to treat large femoral defects. STATEMENT OF SIGNIFICANCE: Abundant functional blood vessels are essential for bone repair. The H-type blood vessel is a functional subtype with angiogenesis and osteogenesis coupling potential. A drug loading system with long-term controlled release was first used to investigate the formation of H-type blood vessels in critical femoral defects and promotion of bone repair. Our results showed that the application of DFO-GMs hydrogel complex expanded the distribution range and expression time of H-type vessels, and was positively correlated with the number of osteoblasts and volume of new bone tissue. These results expanded the local application approach of DFO and provide a theoretical basis for targeting H-type vessels to treat large femoral defects.


Subject(s)
Deferoxamine , Hydrogels , Humans , Rats , Animals , Hydrogels/pharmacology , Deferoxamine/pharmacology , Microspheres , Temperature , Bone and Bones , Gelatin/pharmacology , Osteogenesis , Human Umbilical Vein Endothelial Cells , Bone Regeneration
12.
Int Orthop ; 46(10): 2329-2337, 2022 10.
Article in English | MEDLINE | ID: mdl-35773531

ABSTRACT

PURPOSE: Transoral approach can accomplish ventral decompression directly. However, surgical site infection (SSI) cannot be ignored. This paper aims to review the prevalence of infection and conduct advice for the treatment of SSI in the cervical spine following the transoral approach. METHODS: A retrospective analysis of patients with SSI after transoral atlantoaxial reduction plate (TARP) surgery was performed. SSI was classified into three kinds according to the modified American CDC criteria. RESULTS: 2.9% (17/581) patients who underwent TARP surgery, experienced SSI, of which five had superficial SSI (SI), eight had deep SSI (DI), and four had organ/space SSI (O/SI). The patients with SI underwent intravenous antibiotic treatment and were ultimately cured. Among the remaining 12 patients with DI and O/SI, 11 underwent reoperation for TARP system removal and subsequently one-stage posterior occipitocervical fixation, and one patient experienced infection two months post-operatively and died without receiving treatment. Among patients who underwent revision surgery, three experienced intracranial infection due to intra-operative dural tears, and continuous lumbar cerebrospinal fluid drainage and intrathecal injection of antibiotics were used as effective and appropriate treatments, with outcomes of one recovery and two deaths. All patients with SSI were begun on intravenous antibiotics with conversion to oral antibiotics. CONCLUSIONS: The incidence of SSI was 2.9% (17/581). Adequate peri-operative preparation, early diagnosis, and appropriate treatment of SSI require further research.


Subject(s)
Cervical Vertebrae , Surgical Wound Infection , Anti-Bacterial Agents/therapeutic use , Cervical Vertebrae/surgery , Humans , Incidence , Retrospective Studies , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology
13.
BMC Musculoskelet Disord ; 23(1): 353, 2022 Apr 12.
Article in English | MEDLINE | ID: mdl-35413830

ABSTRACT

BACKGROUND: The study aimed to (1) create a series of pedicle injectors with different number of holes on the sheath especially for the Chinese elderly patients and (2) further investigate the effects of the injectors on the augmentation of pedicle screw among osteoporotic lumbar pedicle channel. METHODS: This study used the biomechanical test module of polyurethane (Pacific Research Laboratory Corp, USA) to simulate the mechanical properties of human osteoporotic cancellous bone. The bone cement injectors were invented based on anatomical parameters of lumbar pedicle in Chinese elderly patients. Mechanical test experiments were performed on the bone cement injectors according to the three groups, namely, a local augmentation group, a full-length augmentation group, and a control group. The local augmentation group included three subgroups including 4-hole group, 6-hole group, and 8-hole group. All holes were laterally placed. The full-length augmentation group was a straight-hole injector. The control group was defined that pedicle screws were inserted without any cement augmentation. Six screws were inserted in each group and the maximum insertion torque was recorded. After 24 h of injecting acrylic bone cement, routine X-ray and CT examinations were performed to evaluate the distribution of bone cement. The axial pull-out force of screws was tested with the help of the material testing system 858 (MTS-858) mechanical tester. RESULTS: The bone cement injectors were consisted of the sheaths and the steel rods and the sheaths had different number of lateral holes. The control group had the lowest maximum insertion torque as compared with the 4-hole, 6-hole, 8-hole, and straight pore groups (P < 0.01), but the differences between the 4-hole, 6-hole, 8-hole, and straight pore groups were no statistical significance. The control group had the lowest maximum axial pull-out force as compared with the other four groups (P < 0.01). Subgroup analysis showed the 8-hole group (161.35 ± 27.17 N) had the lower maximum axial pull-out force as compared with the 4-hole group (217.29 ± 49.68 N), 6-hole group (228.39 ± 57.83 N), and straight pore group (237.55 ± 35.96 N) (P < 0.01). Bone cement was mainly distributed in 1/3 of the distal end of the screw among the 4-hole group, in the middle 1/3 and distal end of the screw among the 6-hole group, in the proximal 1/3 of the screw among the 8-hole group, and along the long axis of the whole screw body in the straight pore group. It might indicate that the 8-hole and straight-hole groups were more vulnerable to spinal canal cement leakage. After pullout, bone cement was also closely connected with the screw without any looseness or fragmentation. CONCLUSIONS: The bone cement injectors with different number of holes can be used to augment the pedicle screw channel. The pedicle screw augmented by the 4-hole or 6-hole sheath may have similar effects to the straight pore injector. However, the 8-hole injector may result in relatively lower pull-out strength and the straight pore injector has the risks of cement leakage as well as cement solidarization near the screw head.


Subject(s)
Pedicle Screws , Aged , Biomechanical Phenomena , Bone Cements/adverse effects , China , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Polymethyl Methacrylate
14.
ACS Appl Mater Interfaces ; 13(27): 31808-31815, 2021 Jul 14.
Article in English | MEDLINE | ID: mdl-34213879

ABSTRACT

The emergence of borophene has triggered soaring interest in the investigation of its superior structural anisotropy, a novel photoelectronic property for diverse potential applications. However, the structural instability and need of a metal substrate for depositing borophene restrict its large-scale applications toward high-performance electronic and optoelectric devices. van der Waals epitaxy is regarded as an efficient technique for growing superb two-dimensional materials onto extensive functional substrates, but the preparation of stable and controllable borophene on nonmetallic substrates is still not reported. Here, we demonstrate that borophene films can be synthesized onto a mica substrate by van der Waals epitaxy, where hydrogen and NaBH4 are respectively used as the carrier gas and the boron source. The lattice structure of the as-synthesized borophene coincides with the predicted α'-boron sheet. The borophene-based photodetector shows an excellent photoresponsivity of 1.04 A W-1 and a specific detectivity of 1.27 × 1011 Jones at a reversed bias of 4 V under illumination of a 625 nm light-emitting diode, which are remarkably superior to those of reported boron nanosheets. This work facilitates further studies of borophene toward its attractive properties and applications in novel optoelectronic devices and integrated circuits.

15.
Front Pharmacol ; 12: 582309, 2021.
Article in English | MEDLINE | ID: mdl-33967746

ABSTRACT

To test the pharmacokinetics and toxicology of whole organs and tissues after intradiscal injection of simvastatin in rabbits. To provide the information needed to support human clinical trials. Twelve male and twelve female rabbits were randomly divided into four groups: control group (0 mg/ml), low dose group (0.1 mg/ml), medium dose group (1 mg/ml) and high dose group (10 mg/ml). Simvastatin at different concentrations of 10 µl was injected into L3/4, L4/5 and L5/6 intervertebral discs in each group. Poly (ethylene glycol) -poly (lactic-co-glycolic acid) -poly (ethylene glycol) (PEG-PLGA-PEG) polymer as the drug carrier. The pharmacokinetics of blood samples were measured by LC-MS/MS. Cerebrospinal fluid was obtained and the drug concentration was measured. Blood routine, blood biochemistry and urine of all animals were analyzed and evaluated. The heart, kidney, liver and spleen of each animal were observed and weighed. The intervertebral disc tissues were stained with hematoxylin and hematoxylin (H&E), and then qualitatively analyzed by optical microscopy. 28 days after intradiscal injection of simvastatin, 28 days after simvastatin intradiscal injection, there was no significant difference between the weight, food residue, blood routine, blood biochemistry, urine routine results and the weight of each organ in the four groups (p > 0.05). The serum concentration of simvastatin is lower than the lowest measurable concentration. The histological score of the intervertebral disc in the high-dose group was significantly higher than that in the other three groups at 28 days (p < 0.05). Three doses of simvastatin were injected into male and female animals respectively, showing no toxic effects. Microscopic histological evaluation of the intervertebral disc showed that the high dose group (10 mg/ml) had damage to the intervertebral disc tissue.

16.
Front Neurosci ; 15: 642436, 2021.
Article in English | MEDLINE | ID: mdl-33815046

ABSTRACT

To study the effect of intradiscal injection of simvastatin on discogenic pain in rats and its possible mechanism, 30 adult female rats were used in this experiment. Twenty rats were randomly divided into sham operation group (Control group), intervertebral disk degeneration group (DDD group), intervertebral disk degeneration + hydrogel group (DDD + GEL group), and intervertebral disk degeneration + simvastatin group (DDD + SIM group). The mechanical pain threshold and cold sensation in rats were measured. The contents of NF-kappa B1, RelA, GAP43, SP, CGRP, TRPM 8, IL-1ß, and TNF-α in the intervertebral disk (IVD), the corresponding contents of dorsal root ganglion (DRG) and plantar skin GAP43 and TRPM 8 were quantitatively detected by PCR. The corresponding IVDs were stained to detect their degeneration. There was no significant difference in the mechanical pain threshold between the groups at each time point. From the first day to the 8th week after surgery, the cold-sensing response of the DDD group was significantly higher than that of the Control group (P < 0.05). At 7 and 8 weeks postoperatively, the cold-sensing response of the DDD + SIM group was significantly lower than that of the DDD + GEL group (P < 0.05). The levels of NF-κB1, RelA, GAP43, SP, CGRP, TRPM8, IL-1ß, and TNF-α in the IVD of DDD + SIM group were significantly lower than those in DDD group (P < 0.05). The content of GAP43 and TRPM8 in rat plantar skin decreased significantly and TRPM8 in DRG decreased significantly (P < 0.05).

18.
Spine (Phila Pa 1976) ; 46(22): 1542-1550, 2021 Nov 15.
Article in English | MEDLINE | ID: mdl-32049938

ABSTRACT

STUDY DESIGN: A retrospective study. OBJECTIVE: Investigate the diagnosis and surgery strategy for treatment of development spinal canal stenosis (DSSA) at atlas plane based on computerized tography (CT) image characters. SUMMARY OF BACKGROUND DATA: The occurrence of spinal canal stenosis in the atlas plane is relatively rare compared with lower cervical. METHODS: Fifteen patients diagnosed with DSSA were included from 2014 to 2018. They are divided into four subgroups based on the character of CT images: group I (small size atlas), group II (hypertrophy of posterior arch of the atlas [PAA]), group III (incurved of PAA), and group IV (hypertrophy odontoid). RESULTS: There are type I 7, type II 3, type III 2, and group IV 3 in the 15 cases. All the patients received different surgery procedures respectively: (1) posterior arch osteotomy were performed for group I/III//IV without atlantoaxial dislocation, (2) posterior arch resect and replantation were performed for group II, (3) occipital cervical fixation and fusion were added to the patients with associated atlantoaxial dislocation (AAD), (4) a new method of odontoid reduce and atlantoaxial fixation by transoral approach were performed for group IV with associated AAD. All cases underwent surgery successfully which included posterior occipitocervical fixation (OCF) + posterior arch resection (PAR) eight cases, PAR four cases, posterior arch remodeling and re-implantation (PARR) two cases, and Dens remodeling + trans-oral anterior reduction and plate fixation (DR+TARP) one case without severe complications. All patients show different improvement in the symptoms. Japanese orthopaedic association score improved from 9.2 to 14.7 in 1 year follow-up. CONCLUSION: DSSA could be easily diagnosed and divided into four subgroups according to the character of CT image, corresponding surgery strategy could receive a fine clinical result.Level of Evidence: 4.


Subject(s)
Atlanto-Axial Joint , Cervical Atlas , Joint Dislocations , Spinal Fusion , Cervical Atlas/diagnostic imaging , Cervical Atlas/surgery , Constriction, Pathologic , Humans , Retrospective Studies , Spinal Canal , Treatment Outcome
19.
Plant Physiol Biochem ; 157: 432-440, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33202322

ABSTRACT

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) is a nutritional crop, which has high rutin, and is good for health. Until now, plant genetic engineering is insufficient for Tartary buckwheat. Abscisic acid (ABA), as one of phytohormones, is involved in the regulation of plant growth and development, and responses to diverse environmental challenges. Although ABA receptors have been well characterized in Arabidopsis, it is little understood in Tartary buckwheat. In this study, we identified 12 ABA receptors, designated as FtRCAR1 through FtRCAR12 in Tartary buckwheat. FtRCARs are divided into three subfamily. Based on the similarity, we could predict that FtRCARs comprise of the monomeric (FtRCAR1, 3, 4, 5, 9, 10, 11 and 12) and the dimeric (FtRCAR2, 7 and 8) state in solution. The analysis of the transcript pattern indicated that most of FtRCARs were significantly variable among the root, stem, leaf, flower and seed, while FtRCAR4 transcript was undetectable under in all tissues. The transcript levels of FtRCARs under ABA treatment indicated that most FtRCARs transcripts were depressed, indicating a possible feedback regulation of ABA signaling. The analysis of rutin biosynthesis related-genes indicated that ABA up-graduated CHS, CHI, F3'H, F3H and FLS transcript levels, while transcripts of 4CL and PAL were down-regulated. In addition, the transcription factors that mediated the rutin biosynthesis related-genes were also regulated by exogenous ABA. Thus, the identification and the characterization of FtRCARs would enable us to further understand the role of ABA signal in Tartary buckwheat.


Subject(s)
Abscisic Acid/pharmacology , Fagopyrum , Plant Proteins/genetics , Rutin/biosynthesis , Fagopyrum/genetics , Signal Transduction
20.
Chempluschem ; 85(9): 2186-2196, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32989917

ABSTRACT

Borophenes (2D boron sheets) have triggered a surge of interest both theoretically and experimentally because of its distinct structural, optical and electronic properties for extensive potential applications. Although theoretical efforts have guided the research directions of borophene, only few synthetic borophene sheets have been demonstrated experimentally. Borophene sheets have been successfully synthesized experimentally on metal substrates until 2015. Afterwards, more efforts were put on the controlled synthesis of crystalline and semiconducting borophene sheets as well as on the investigation of their novel and fascinating physical properties. This report provides a brief review on theoretical and experimental progress in borophene research. Some typical structures and properties of borophenes have been reviewed. The focus is laid on summarizing the experimental synthesis of borophene in recent years, and on showing some ultrastable and semiconducting borophenes which have been applied in electronic information devices. Finally, the future challenges and opportunities regarding experimental realization and practical applications of borophenes are presented.

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