Induction of Ferroptosis in Glioblastoma and Ovarian Cancers by a New Pyrrole Tubulin Assembly Inhibitor.

We synthesized new aroyl diheterocyclic pyrrole (ARDHEP) 15 that exhibited the hallmarks of ferroptosis. Compound 15 strongly inhibited U-87 MG, OVCAR-3, and MCF-7 cancer cells, induced an increase of cleaved PARP, but was not toxic for normal human primary T lymphocytes at 0.1 µM. Analysis of the levels of lactoperoxidase, malondialdehyde, lactic acid, total glutathione, and ATP suggested that the in vivo inhibition of cancer cell proliferation by 15 went through stimulation of oxidative stress injury and Fe2+ accumulation. Quantitative polymerase chain reaction analysis of the mRNA expression in U-87 MG and SKOV-3 tumor tissues from 15-treated mice showed the presence of Ptgs2/Nfe2l2/Sat1/Akr1c1/Gpx4 genes correlated with ferroptosis in both groups. Immunofluorescence staining revealed significantly lower expressions of proteins Ki67, CD31, and ferroptosis negative regulation proteins glutathione peroxidase 4 (GPX4) and FTH1. Compound 15 was found to be metabolically stable when incubated with human liver microsomes.

Case report: Meningoencephalocele and recurrent bacterial meningitis in chronic idiopathic intracranial hypertension.

BACKGROUND: Meningoencephalocele is a rare malformation caused by congenital and acquired lesions. The association between recurrent bacterial meningitis and meningoencephaloceles with cerebrospinal fluid (CSF) leak is reported in the literature. We report a rare case of meningoencephalocele secondary to chronic idiopathic intracranial hypertension as a result of hospitalization repeatedly for meningitis due to the lack of CSF leak. CASE PRESENTATION: This study presents a case of a patient with a decade of recurrent meningitis. With clinical symptoms and imaging examination with chronic idiopathic intracranial hypertension, this patient was diagnosed with meningoencephalocele. With the treatment of acetazolamide to decrease CSF product, the patient had no recurrence of meningitis over the 6-months follow-up period. CONCLUSION: In patients with recurrent intracranial infections but no history of immunodeficiency, cranial trauma, or neurosurgery, the possibility of meningitis should be considered appropriately, even in the absence of CSF otorrhea or rhinorrhea.

[Finite element analysis of the effect of plate placement angle on cervical spine stability in anterior cervical fusion surgery].

OBJECTIVE: Using the method of finite element analysis, to compare the biomechanical properties between the plate deviating from the long axis of the cervical spine and the standard placement of the plate in the anterior cervical fusion surgery. METHODS: A healthy female volunteer was selected and CT scan (C1-T1) was performed. Using Mimics 19.0, Geomagic Studio 2015, Solidworks 2018, Ansys Workbench 17.2 to establish a lower cervical spine (C3-C7) model and to verify the reliability of the model. Subsequently, anterior cervical plates of different angles and lengths were placed to establish an anterior cervical discectomy fusion (ACDF) model. Applying 73.6 N axial pressure and 1 NM pure moment on C3 to make the model produce flexion, extension, lateral bending and rotation activities, observed the model stress cloud diagram and recorded the maximum stress value of the instrument and the intervertebral mobility. RESULTS: The lower cervical spine (C3-C7) finite element model was established and verified against the published literature on the range of motion (ROM) of cervical spine. Effect of steel plate offset axis on stress distribution, maximum stress value and intervertebral ROM of internal fixation apparatus was minimal, and the mechanical effect of steel plate offset was less in double section steel plate than in single section steel plate. CONCLUSION: Little effect on the mechanical stability of the cervical spine was anticipated when the anterior cervical plate was not perfectly aligned with the long axis of the cervical spine. If the tilt of the plate in clinical surgery is less than 20°, there is no need to readjust the position of the plate.

Durable clinical benefit from pyrotinib combined with carboplatin in HER2-positive relapsed breast cancer previously treated with taxanes, anthracyclines, and trastuzumab.

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer inevitably progressed after a short response to initial trastuzumab treatment, suggesting a possibility of acquired-resistance to trastuzumab. Pyrotinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor (TKI), has been reported as an effective and safe drug for the treatment of HER2-positive relapsed or metastatic breast cancer. Pyrotinib combined with capecitabine is widely used to treat HER2-positive metastatic breast cancer in patients who have been previously treated with anthracyclines, taxanes, and trastuzumab. However, the efficacy of pyrotinib combined with other chemotherapy drugs is still unclear. Here we report pyrotinib combined with carboplatin in treating a patient with HER2-positive relapsed breast cancer who had acquired resistance to trastuzumab. The patient received three cycles of treatments of pyrotinib (400 mg, orally once per day, days 1-21) combined with carboplatin (600 mg, iv drip, day 1, cycled every 21 days). The patient showed an excellent response to the therapy, including faded rashes on the skin of her breast, no obvious signs of recurrence from the breast magnetic resonance imaging (MRI), decreased skin thickness and cord shadow of the right breast, unchanged degree of right pleural effusion, and no enlarged LN. The patient had a stable disease time of more than four months. Our case provides evidence for the feasibility and efficacy of pyrotinib with carboplatin in treating patients with HER2-positive relapsed or metastatic breast cancer who may develop resistance to trastuzumab.

[Research progress on minimally invasive treatment of anterior pelvic ring fracture].

OBJECTIVE: To summarize the related research results of minimally invasive treatment of anterior pelvic ring fracture, and to improve the understanding of minimally invasive treatment of anterior pelvic ring fracture. METHODS: The literature of minimally invasive treatment of anterior pelvic ring fracture at domestic and overseas in recent years was reviewed, and the reduction and fixation methods of minimally invasive treatment were summarized and analyzed. RESULTS: The pelvic reduction frame may be an effective auxiliary method for minimally invasive reduction of pelvis. The fixation methods of anterior pelvic ring include percutaneous screw fixation, stent fixation, and percutaneous plate fixation. CONCLUSION: One kind of fixation is not applicable to all types of anterior pelvic ring fracture, and the fixation method should be selected according to the type of fracture and the patient's condition to minimize the complications.

[Progress of research on the relationship between calcitonin gene-related peptide and RANK/RANKL/OPG system in the bone reconstruction].

OBJECTIVE: To summarize the research progress on the calcitonin gene-related peptide (CGRP) and receptor activator of nuclear factor κB (RANK)/receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) system during bone reconstruction to provide theoretical basis for further research on the prevention and treatment of bone-related diseases. METHODS: The relevant research results at home and abroad in recent years were analyzed and summarized. RESULTS: CGRP and RANK/RANKL/OPG system play important regulatory roles in the bone reconstruction. CONCLUSION: At present, the research on the mechanism of CGRP and RANK/RANKL/OPG system in bone reconstruction is insufficient. Therefore, it is necessary to study further on the process and interrelation of CGRP and RANK/RANKL/OPG system in bone reconstruction to confirm their mechanism, which will bring new ideas and methods for the treatment of bone related diseases in clinic.

The synthesized transporter K16APoE enabled the therapeutic HAYED peptide to cross the blood-brain barrier and remove excess iron and radicals in the brain, thus easing Alzheimer's disease.

Alzheimer's disease (AD) is currently incurable and places a large burden on the caregivers of AD patients. In the AD brain, iron is abundant, catalyzing free radicals and impairing neurons. The blood-brain barrier hampers antidementia drug delivery via circulation to the brain, which limits the therapeutic effects of drugs. Here, according to the method described by Gobinda, we synthesized a 16 lysine (K) residue-linked low-density lipoprotein receptor-related protein (LRP)-binding amino acid segment of apolipoprotein E (K16APoE). By mixing this protein with our designed therapeutic peptide HAYED, we successfully transported HAYED into an AD model mouse brain, and the peptide scavenged excess iron and radicals and decreased the necrosis of neurons, thus easing AD.

[Research progress of lateral wall injury of intertrochanteric fracture].

Objective: To summarize the general concept of lateral wall, the causes of lateral wall injury, and surgical strategies in order to improve the understanding of lateral wall and reduce the complications of operation. Methods: The related literature on lateral wall was extensively reviewed, summarized, and analyzed. Results: The superior extent of the lateral wall is vastus lateralis ridge and the inferior extent is the intersection between the lateral femoral cortex and a line drawn at a tangent to the inferior femoral neck. The integrity of the lateral wall is important to prevent the failure of fixation and reoperation of intertrochanteric fractures. The main causes of injury are that there is no suitable typing criteria as a guide, the fracture pattern shown by X-ray does not match with the actual situation of the fracture, the type of fracture is special, and the operation is improper. The main treatment is to reconstruct the lateral wall and choose different reconstruction methods according to different fracture patterns. Conclusion: The lateral wall is very important for the treatment of intertrochanteric fracture. Lateral wall fracture should be internal fixation in order to minimize the risk of reoperation.

Lower incisor intrusion with intraoral transosseous stainless steel wire anchorage in rabbits.

The purpose of this research was to investigate the potential use of intraoral transosseous stainless steel wires as anchorage for intrusion of the lower incisors using a rabbit model. Placement of intraoral transosseous stainless steel wires around incisors is similar to that of intraoral transosseous wiring of edentulous mandibular fractures. Ten male New Zealand rabbits, 9 +/- 1.5 months of age, average weight 1.8 +/- 0.3 kg, were used in this study. One lower incisor was intruded with a 50 g bilateral force using a coil spring for 10 weeks, while the other incisor served as the control. Clinical measurements of the distances between the occlusal edges of the incisors (EE) were performed weekly with a calliper. In addition to standard descriptive statistical calculations, a paired Student's t-test was used for comparison of the two groups. All surgical sites healed uneventfully after insertion of the wires. Significant differences were found in the change of EE between the experimental and control sides from 4 weeks onwards. Intrusion of the incisor, 4 +/- 0.58 mm, was seen on the test side, while EE on the control side remained unchanged. Within the limits of this animal study, it is concluded that the intraoral transosseous stainless steel wire anchorage system is a cost-effective method for intrusion of lower incisors when the use of other anchorage system is not possible.

{2,2'-[1,1'-(Ethyl-enedioxy-dinitrilo)diethyl-idyne]di-1-naphtholato}nickel(II).

In the title complex, [Ni(C(26)H(22)N(2)O(4))], the Ni(II) atom has a slight distortion toward tetra-hedral geometry from a square-planar structure, coordinated by two O and two N atoms of the tetra-dentate salen-type bis-oxime 2,2'-[1,1'-(ethyl-enedioxy-dinitrilo)diethyl-idyne]di-1-naphtholate (L(2-)) unit, with a mean deviation of 0.022 Šfrom the N(2)O(2) plane. The N- and O-donor atoms are mutually cis. The dihedral angle between two naphthalene systems of the L(2-) ligand is 67.59 (4)°. The crystal structure is stabilized by inter-molecular C-H⋯O and C-H⋯π inter-actions, which link neighbouring mol-ecules into extended chains along the b axis.

Use of a simple intraoral instrument to standardize film alignment and improve image reproducibility.

OBJECTIVE: A lot of instruments and devices were reported in standardized realignment of intraoral film. However, these instruments either are too cumbersome and time consuming to be used or require extensive fabrication. In this study we described a prototype of a instrument for realignment of intraoral film and evalated its reproducibility. STUDY DESIGN: A technique that uses this instrument was compared with a validated method serving as control. An adult human dry skull with full dentition was exposed for measuring the angular errors. Two types of angular errors were calculated. RESULTS: of the analysis of the alignment error caused by projection of the x-ray beam showed the mean horizontal angulation error (+/-SD) was 1.70 +/- 0.75 degrees and the vertical one was 1.32 +/- 0.44 degrees in the new instrument group, and 1.65 +/- 0.70 degrees and 1.40 +/- 0.61 degrees, respectively, in the control group. Bite block seating error was 2.12 +/- 0.55 degrees in the newly developed instrument and 2.01 +/- 0.49 degrees in the instrument with registration material. Statistical analysis showed no significant difference in the 2 instruments (P > .05). CONCLUSION: The prototype of the new instrument reported by the authors can produce almost identical radiographs in vitro with only slight angular errors. Clinical use of the advanced type of the instrument can be expected to show similar results.