MicroRNA-125a-3p Modulate Amyloid ß-Protein through the MAPK Pathway in Alzheimer's Disease.

BACKGROUND: MicroRNA (miR)-125a-3p is reported to play an important role in some central nervous system diseases, such as Alzheimer's disease (AD). However, a study has not been conducted on the mechanism of miR-125a-3p in the pathological process of AD. METHODS: First, we assessed the expression of miR-125a-3p in AD cohort. Subsequently, we altered the expressions of miR-125a-3p to assess its role in cell viability, cell apoptosis, amyloid-ß (Aß) metabolism, and synaptic activity. Finally, we identified its potential mechanism underlying AD pathology. RESULTS: This study unveiled the potential function of miR-125a-3p through modulating amyloid precursor protein processing. Additionally, miR-125a-3p influenced cell survival and activated synaptic expression through the modulation of Aß metabolism in the mitogen-activated protein kinase (MAPK) pathway via fibroblast growth factor receptor 2. CONCLUSION: Our study indicates that targeting miR-125a-3p may be an applicable therapy for AD in the future. However, more in vitro and in vivo studies with more samples are needed to confirm these results.

The Ex vivo Preparation of Spinal Cord Slice for the Whole-Cell Patch-Clamp Recording in Motor Neurons During Spinal Cord Stimulation.

Spinal cord stimulation (SCS) can effectively restore locomotor function after spinal cord injury (SCI). Because the motor neurons are the final unit to execute sensorimotor behaviors, directly studying the electrical responses of motor neurons with SCS can help us understand the underlying logic of spinal motor modulation. To simultaneously record diverse stimulus characteristics and cellular responses, a patch-clamp is a good method to study the electrophysiological characteristics at a single-cell scale. However, there are still some complex difficulties in achieving this goal, including maintaining cell viability, quickly separating the spinal cord from the bony structure, and using the SCS to successfully induce action potentials. Here, we present a detailed protocol using patch-clamp to study the electrical responses of motor neurons to SCS with high spatiotemporal resolution, which can help researcher improve their skills in separating the spinal cord and maintaining the cell viability at the same time to smoothly study the electrical mechanism of SCS on motor neuron and avoid unnecessary trial and mistake.

A novel scoring system for assessing adult syringomyelia associated with CM I treatment outcomes.

BACKGROUND: A specific scoring system for syringomyelia is lacking. Our objective was to investigate the value of a novel scoring system (Syringomyelia Outcome Scale of Xuanwu hospital, SOS-XW) in assessing surgical outcomes in the treatment of syringomyelia (SM) associated with Chiari malformation type I (CM I). METHODS: A quantitative evaluation system (SOS-XW) of SM includes 4 parameters: pain (P), sensation (S), movement (M), and syringomyelia tension index (STI). The clinical data of 88 patients with CM I-related syringomyelia treated by foramen magnum and Magendie dredging (FMMD) from January 2018 to January 2019 were retrospectively analysed with a mean follow-up of 14.3 months, and the SOS-XW score was used to assess the efficacy. RESULTS: The higher the SOS-XW score, the more severe was the SM and related symptoms. The mean preoperative score was 5.97, and the postoperative score was 2.66. The symptom improvement rates were 77.78% for P, 69.01% for S, 31.82% for M, and 95.06% for the syringomyelia tension index (STI). The symptom improvement rate of the PSM score was weakly correlated with the improvement rate of STI, R2 = 0.0016. The percentage of PSM (P + S + M) improvement was lower in patients with an STI of 0. The postoperative SOS-XW score was positively correlated with the postoperative JOA score, R2 = 0.8314. The positive detection rate of SOS-XW was higher than that of the JOA score. CONCLUSIONS: To evaluate the surgical procedure efficacy in the treatment of syringomyelia, the SOS-XW score can provide a more objective, detailed, and comprehensive analysis, especially STI. A reduction in STI is the practical standard for assessing the effectiveness of surgery.

Population PK/PD model of tacrolimus for exploring the relationship between accumulated exposure and quantitative scores in myasthenia gravis patients.

Tacrolimus is an important immunosuppressant used in the treatment of myasthenia gravis (MG). However, the population pharmacokinetic (PK) characteristics together with the exposure-response of tacrolimus in the treatment of MG remain largely unknown. In this study, we aimed to develop a population PK/pharmacodynamic (PK/PD) model of tacrolimus in patients with MG, in order to explore the relationships among tacrolimus dose, exposure, and its therapeutic efficacy. The genotype of CYP3A5, Osserman's classification, and status of thymus, as well as demographic characteristics and other biomarkers from laboratory testing were tested as covariate, and simulations were performed based on the final model. The population PK model was described using a one-compartment model with first-order elimination and fixed absorption parameters. CYP3A5 genotype significantly influenced the apparent clearance, and total protein (TP) influenced the apparent volume of distribution as covariates. The quantitative MG scores were characterized by the cumulated area under curve of tacrolimus in a maximum effect function. Osserman's classification was a significant covariate on the initial score of patients with MG. The simulations demonstrated that tacrolimus showed an unsatisfying effect possibly due to insufficient exposure in some patients with MG. A starting dose of 2 mg/d and even higher dose for patients with CYP3A5 *1/*1 and *1/*3 and lower TP level were required for the rapid action of tacrolimus. The population PK/PD model quantitatively described the relationships among tacrolimus dose, exposure, and therapeutic efficacy in patients with MG, which could provide reference for the optimization of tacrolimus dosing regimen at the individual patient level.

An imbalance of netrin-1 and DCC during nigral degeneration in experimental models and patients with Parkinson's disease.

AIMS: Multiple guidance cues, such as netrin-1 (NTN-1)/deleted in colorectal carcinoma (DCC), control the guidance of axons and help establish functional neural circuits during development. However, the function of these guidance molecules during the neurodegenerative process is unclear. METHODS: To access the alterations of NTN-1 and DCC during the onset and progression of PD, we first established two subacute and one chronic PD model. Then, we investigated the relationship between the NTN-1/DCC pathway and cell death in SH-SY5Y cells. Finally, we conducted correlation studies between plasma NTN-1 and parkinsonian symptoms in patients to understand how this pathway contributes to PD. RESULTS: We found that the imbalance of NTN-1 and DCC was a common feature of nigral DA neuron injury in PD mouse models. We investigated that MPP+ inhibited NTN-1 expression and increased DCC expression in a concentration- and time-dependent manner. We further discovered a significant decrease in plasma NTN-1 levels and a positive correlation with UPDRS scores in PD patients. CONCLUSION: Our findings confirmed the imbalance of NTN-1/DCC signaling during nigral degeneration in experimental PD models and found for the first time a correlation of plasma NTN-1 with PD symptoms in patients.

Application of a count data model to evaluate the anti-metastatic efficacy of QAP14 in 4T1 breast cancer allografts.

Dopamine D1 receptor (D1DR) is proved to be a promising target to prevent tumor metastasis, and our previous studies showed that QAP14, a potent anti-cancer agent, exerted inhibitory effect on lung metastasis via D1DR activation. Therefore, the purpose of the study was to establish count data models to quantitatively characterize the disease progression of lung metastasis and assess the anti-metastatic effect of QAP14. Data of metastatic progression were collected in 4T1 tumor-bearing mice. Generalized Poisson distribution best described the variability of metastasis counts among the individuals. An empirical PK/PD model was developed to establish mathematical relationships between steady plasma concentrations of QAP14 and metastasis growth dynamics. The latency period of metastasis was estimated to be 12 days after tumor implantation. Our model structure also fitted well to other D1DR agonists (fenoldopam and l-stepholidine) which had inhibitory impact on breast cancer lung metastasis likewise. QAP14 40 mg/kg showed the best inhibitory efficacy, for it provided the longest prolongation of metastasis-free periods compared with fenoldopam or l-stepholidine. This study provides a quantitative method to describe the lung metastasis progression of 4T1 allografts, as well as an alternative PD model structure to evaluate anti-metastatic efficacy.

Comparison of 3D-printed Navigation Template-assisted Pedicle Screws versus Freehand Screws for Scoliosis in Children and Adolescents: A Systematic Review and Meta-analysis.

BACKGROUND: There is a lack of attention to screw placement techniques for surgical treatment of scoliosis in children and adolescents. This meta-analysis aims to compare the accuracy and safety of pedicle screw placement between the 3D-printed navigation template technique and the freehand technique during corrective surgery for scoliosis in children and adolescents. METHODS: A comprehensive search was conducted for relevant articles up to December 2021 in databases including PubMed, Embase, MEDLINE, Cochrane, and Web of Science. The systematic meta-analysis compared the efficacy of pedicle screw placement between the two techniques, including accuracy of pedicle screw placement, complication rate, operation time, blood loss, mean placement time per screw, and mean times for fluoroscopy. RESULTS: The seven articles analyzed in this study involved 229 patients altogether. A total of 2,805 pedicle screws were placed by the two methods. Our results revealed that the 3D-printed guide template technique was more accurate than the freehand technique in pedicle screw placement (odds ratio [OR] =2.96; 95% confidence interval [CI]: 2.24-3.91; p < 0.000) with a lower complication rate (OR = 0.21; 95% CI: 0.06-0.78; p = 0.02). The operation time (mean difference [MD] = -34.37; 95% CI: -67.47 to -1.28; p = 0.04) and mean placement time per screw (MD = -3.11; 95% CI: -6.13 to -0.09; p = 0.04) and mean times for fluoroscopy (MD = -6.60; 95% CI: -8.66 to -4.55; p < 0.000) significantly decreased among patients in the 3D-printed navigation template group compared with those in the freehand technique group. In addition, the two techniques had no significant statistical difference in blood loss. CONCLUSIONS: Compared with the traditional freehand technique, the 3D-printed guide template is a promising technique with higher accuracy and safety in screw placement for surgical treatment of scoliosis in children and adolescents, and is worth popularizing and validating through more prospective clinical studies.

An integrated PK/PD model investigating the impact of tumor size and systemic safety on animal survival in SW1990 pancreatic cancer xenograft.

Survival is one of the most important endpoints in cancer therapy, and parametric survival analysis could comprehensively reveal the overall result of disease progression, drug efficacy, toxicity as well as their interactions. In this study we investigated the efficacy and toxicity of dexamethasone (DEX) combined with gemcitabine (GEM) in pancreatic cancer xenograft. Nude mice bearing SW1990 pancreatic cancer cells derived tumor were treated with DEX (4 mg/kg, i.g.) and GEM (15 mg/kg, i.v.) alone or in combination repeatedly (QD, Q3D, Q7D) until the death of animal or the end of study. Tumor volumes and net body weight (NBW) were assessed every other day. Taking NBW as a systemic safety indicator, an integrated pharmacokinetic/pharmacodynamic (PK/PD) model was developed to quantitatively describe the impact of tumor size and systemic safety on animal survival. The PK/PD models with time course data for tumor size and NBW were established, respectively, in a sequential manner; a parametric time-to-event (TTE) model was also developed based on the longitudinal PK/PD models to describe the survival results of the SW1990 tumor-bearing mice. These models were evaluated and externally validated. Only the mice with good tumor growth inhibition and relatively stable NBW had an improved survival result after DEX and GEM combination therapy, and the simulations based on the parametric TTE model showed that NBW played more important role in animals' survival compared with tumor size. The established model in this study demonstrates that tumor size was not always the most important reason for cancer-related death, and parametric survival analysis together with safety issues was also important in the evaluation of oncology therapies in preclinical studies.

Starting dose selection of palbociclib in Chinese patients with breast cancer based on population kinetic-pharmacodynamic model of neutropenia.

Neutropenia is the most common adverse event (AE) of palbociclib, an oral CDK4/6 inhibitor for breast cancer. Neutropenia increases the risk of infection and is even life threatening. Asian patients generally suffer more severe neutropenia from palbociclib treatment, but the label does not recommend a reduction in the starting dose for Asian patients. Therefore, the study aimed to explore the exposure-response (E-R) relationship in Chinese patients and preliminarily generate a scale for starting dose selection of palbociclib in Chinese patients. After comparing the kinetic-pharmacodynamic (K-PD) and the pharmacokinetic/pharmacodynamic (PK/PD) model, a semi-mechanistic K-PD model was selected and developed on the basis of real-world data from 28 patients with breast cancer to describe the time course of longitudinal absolute neutrophil counts (ANC). The longitudinal ANC data were well described by the population K-PD model with reasonable parameters: mean transit time (MTT) of 198 h, feedback parameter (γ) of 0.317, baseline ANC level (Circ0) of 3.36 × 109 L-1, drug effect coefficient (kd) of 0.0349, and drug effect power (ß) of 0.383. No covariate was included in the final model. The model showed that palbociclib dose-dependently reduced ANC levels in a Chinese population, and lower baseline ANC level was associated with more severe neutropenia. The dose selection scale suggested that palbociclib 125 mg daily was appropriate for Chinese patients with Circ0 higher than 3.75 × 109 L-1. In summary, the K-PD model of palbociclib well described the longitudinal ANC in Chinese patients. Besides, the starting dose selection scale may provide reference for clinicians during individualized therapy.

Neurological deterioration after posterior fossa decompression for adult syringomyelia: Proposal for a summarized treatment algorithm.

Background: Patients with syringomyelia who present with new neurological symptoms after posterior fossa decompression (PFD) are not uncommon. However, systematic reports on different pathologies are few in the literature. Objective: The purpose of this study was to summarize our experience for failed PFD. Methods: Between January 2015 and December 2019, 85 consecutive failed PFD patients were identified. The neurological courses were summarized with Klekamp J (KJ) or mJOA score system for all patients. Long-term results were summarized with Kaplan-Meier method. Results: Twenty-eight consecutive patients underwent FMDD (Foramen magnum and foramen of Magendie dredging) (Group I), extradural PFD and manipulation of tonsil was significantly associated with lower failure rates. Twenty patients underwent craniocervical fixation (Group II), nine underwent local spinal segment decompression (Group III), six underwent CSF diversion procedures, and one were treated for persistent pain by radiofrequency. Neuropathic pain was most significantly improved in Group I while swallowing improved in Group II within 1 year after the surgery. In the long term, late postoperative deterioration-free possibility in Group II was better than in Group I. All patients in Group III improved (P = 0.0088). Six cases of CSF diversion procedures were relieved in a short time. Pain in one patient persisted after PFD, and trial of radiofrequency failed. Conclusion: Not only does the recurrent cerebrospinal fluid flow obstruct the foramen magnum, but also spinal pathologies and craniocervical instabilities may occur. This study provides the largest summarized clinical experience that may assist surgeons with different therapeutic decisions for failed PFD.

Spinal Obstruction-Related vs. Craniocervical Junction-Related Syringomyelia: A Comparative Study.

Background: No prior reports have focused on spinal cord injury (SCI) characteristics or inflammation after destruction of the blood-spinal cord barrier by syringomyelia. This study aimed to determine the differences in syringomyelia-related central SCI between craniocervical junction (CCJ) syringomyelia and post-traumatic syringomyelia (PTS) before and after decompression. Methods: In all, 106 CCJ, 26 CCJ revision and 15 PTS patients (mean history of symptoms, 71.5 ± 94.3, 88.9 ± 85.5, and 32.3 ± 48.9 months) between 2015 and 2019 were included. The symptom course was analyzed with the American Spinal Injury Association ASIA and Klekamp-Samii scoring systems, and neurological changes were analyzed by the Kaplan-Meier statistics. The mean follow-up was 20.7 ± 6.2, 21.7 ± 8.8, and 34.8 ± 19.4 months. Results: The interval after injury was longer in the PTS group, but the natural history of syringomyelia was shorter (p = 0.0004 and 0.0173, respectively). The initial symptom was usually paraesthesia (p = 0.258), and the other main symptoms were hypoesthesia (p = 0.006) and abnormal muscle strength (p = 0.004), gait (p < 0.0001), and urination (p < 0.0001). SCI associated with PTS was more severe than that associated with the CCJ (p = 0.003). The cavities in the PTS group were primarily located at the thoracolumbar level, while those in the CCJ group were located at the cervical-thoracic segment at the CCJ. The syrinx/cord ratio of the PTS group was more than 75% (p = 0.009), and the intradural adhesions tended to be more severe (p < 0.0001). However, there were no significant differences in long-term clinical efficacy or peripheral blood inflammation markers (PBIMs) except for the red blood cell (RBC) count (p = 0.042). Conclusion: PTS tends to progress faster than CCJ-related syringomyelia. Except for the RBC count, PBIMs showed no value in distinguishing the two forms of syringomyelia. The predictive value of the neutrophil-to-lymphocyte ratio for syringomyelia-related inflammation was negative except in the acute phase.

Longitudinal and time-to-event modeling for prognostic implications of radical surgery in retroperitoneal sarcoma.

Retroperitoneal sarcoma (RPS) is a rare malignancy which can be difficult to manage due to the variety of clinical behaviors. In this study, we aimed to develop a parametric modeling framework to quantify the relationship between postoperative dynamics of several biomarkers and overall/progression-free survival of RPS. One hundred seventy-four patients with RPS who received surgical resection with curative intent at the Peking University Cancer Hospital Sarcoma Center were retrospectively included. Potential prognostic factors were preliminarily identified. Longitudinal analyses of body mass index (BMI), serum total protein (TP), and white blood cells (WBCs) were performed using nonlinear mixed effects models. The impacts of time-varying and time-invariant predictors on survival were investigated by parametric time-to-event (TTE) models. The majority of patients experienced decline in BMI, recovery of TP, as well as transient elevation in WBC counts after surgery, which significantly correlated with survival. An indirect-response model incorporating surgery effect described the fluctuation in percentage BMI. The recovery of TP was captured by a modified Gompertz model, and a semimechanistic model was selected for WBCs. TTE models estimated that the daily cumulative average of predicted BMI and WBC, the seventh-day TP, as well as certain baseline variables, were significant predictors of survival. Model-based simulations were performed to examine the clinical significance of prognostic factors. The current work quantified the individual trajectories of prognostic biomarkers in response to surgery and predicted clinical outcomes, which would constitute an additional strategy for disease monitoring and intervention in postoperative RPS.

SPECT Imaging of Acute Disc Herniation by Targeting Integrin α5ß1 in Rat Models.

Objective: Traditional morphological imaging of intervertebral disc herniation (IVDH) is challenging in early disease diagnosis. Aiming at the early diagnosis of IVD by non-invasive molecular imaging targeting of integrin α5ß1, we performed novel imaging in rats with acute IVDH for the first time. Methods: Animal models were prepared by conducting an established needle puncture procedure through the normal intervertebral disc (IVD). The disc-injured rats underwent SPECT/CT imaging of the 99mTc-3PisoDGR2 peptide at 1 day to 2 months postinjury. The expression change of integrin α5ß1 was determined by anti-integrin α5 and anti-integrin α5ß1 immunohistochemistry (IHC). Magnetic resonance imaging (MRI) was performed for comparison during disease progression. The morphological changes of the disc were determined by safranin-O staining. Results: Rats with acute IVDH showed gradually increased disc uptake of 99mTc-3PisoDGR2 from 1 to 7 days posttreatment, which was a significantly higher level than that of the normal disks in degenerative diseases. IHC results showed the expression of integrin α5ß1 on the surface of annulus fibrosus (AF) cells and nucleus pulposus (NP) cells, which agreed with the uptake data. MRI showed a progressively decreased T2 density and MRI index throughout the investigation. Hematoxylin and eosin (HE) staining and safranin-O staining revealed a disorganized structure of the IVD as well as loss of proteoglycans after puncture. Conclusions: The present study demonstrated a good correlation between integrin α5ß1 expression and acute disc herniation. The SPECT/CT imaging of 99mTc-3PisoDGR2 targeting integrin α5ß1 may diagnose IVDH in an acute phase for early disease management.

Oblique Lumbar Interbody Fusion Using a Stand-Alone Construct for the Treatment of Adjacent-Segment Lumbar Degenerative Disease.

Objective: Adjacent-segment disease (ASD) is common in patients undergone previous lumbar fusion. A typical revision treatment from posterior approach requires management of postoperative scar tissue and previously implanted instrumentation. An oblique lumbar interbody fusion (OLIF) approach allows surgeon to reduce the potential risk of posterior approach. This study aimed to analyze the clinical and radiographic efficacy of stand-alone OLIF for the treatment of lumbar adjacent-segment disease. Methods: A total of 13 consecutive patients who underwent stand-alone OLIF for the treatment of adjacent-segment disease from December 2016 to January 2019 were reviewed. Visual analog scale (VAS) of back pain and leg pain and the Oswestry Disability Index (ODI) before surgery and at last postoperative clinic visits were obtained. Radiography, CT and MRI before and at last follow-up after surgery was evaluated in all patients. Results: During the study period, 13 cases were successfully treated with stand-alone OLIF. The mean follow-up was 17.7 ± 8.3 months. The back pain VAS improved from 6.2 ± 1.0 to 2.0 ± 1.1 (P < 0.01), and the leg pain VAS improved from 7.0 ± 1.9 to 1.0 ± 0.9 (P < 0.01). ODI improved from 28.0 ± 7.5 to 10.8 ± 4.0 (P < 0.01). The disc height (DH) increased from 9 ± 2 to 12 ± 2 mm (P < 0.01), the cross-sectional area (CSA) of spinal canal increased from 85 ± 26 to 132 ± 24 mm2 (P < 0.01), the foraminal height increased from 17 ± 2 to 21 ± 3 mm (P < 0.01) and the CSA of foramen increased from 95 ± 25 to 155 ± 36 mm2 (P < 0.01). Cage subsidence was observed in 2 cases. Conclusions: Stand-alone OLIF provides a safe and effective alternative way to treat ASD.

Comparison of Clinical Efficacy of Epidural Injection With or Without Steroids in the Treatment of Degenerative Disc Disease: Meta-analysis.

BACKGROUND: Selective nerve root block has been widely used to treat degenerative disc disease (DDD), but no detailed research data is provided to compare the efficacy of epidural injection of anesthetics with or without steroids on the DDD treatment. OBJECTIVES: This study aimed to  provide the first comparison of steroids + local anesthetic (LA) or LA alone for the treatment of DDD. STUDY DESIGN: We systematically searched PubMed, Medline, Embase, and Cochrane. A systemic review and meta-analysis were performed to assess the clinical efficacy of both the steroids + LA group and the LA alone group, and subgroup analysis was also adopted. SETTING: A systematic review and meta-analysis using a random effects model on randomized controlled studies (RCTs). METHODS: After reviewing titles, abstracts, risk of bias, and full texts of 15,889 studies that were chosen following removal of duplicates after the initial database search, finally, 19 RCTs were included. Pain rating, functional score, follow-up period, and other-related data were extracted from these included works, and the effect size and statistical significance were calculated by the random effects model. The quality and level of the derived evidence were assessed by means of the  Grading of Recommendations Assessment, Development and Evaluation method. RESULTS: In terms of the Numeric Rating Scale (NRS-11) and Oswestry Disability Index (ODI) at one year, the combination of steroids + LA was obviously superior to LA. Subgroup analysis suggested that the combination of steroids + LA was more effective than LA alone in regard to the ODI in the lumbar group within 2 years. The opioids intake of patients treated by LA alone was less than that of the steroids + LA group within 3 months, and LA alone was more effective in pain score reduction, with more than 50% within 6 months in the interlaminar injection group. However, the combination of steroids + LA was more effective when alleviating the NRS-11 within 18 months in the caudal injection group. LIMITATIONS: Firstly, this analysis was inconsistent in technique, dosage, injection frequency, and follow-up period of epidural injections. Such differences may compromise the reported efficacy. Secondly, adverse reactions arising out of the 2 groups were not examined in that the included RCTs did not provide the data. Thirdly, different injection methods would compromise the outcomes, and no subgroup analysis was performed on different injection methods. Finally, these included articles that were mainly sourced from Manchikanti's team, and thus biased to some extent. CONCLUSIONS: The addition of steroids to anesthetic injectates was associated with a better NRS-11 and ODI compared with LA alone within one year in patients with DDD. Furthermore, the improvement of the ODI was observed within 2 years in patients with lumbar DDD.

The effect of local intraoperative corticosteroid application on postoperative dysphagia following anterior cervical spine surgery.

Dysphagia is a common complication following anterior cervical spine surgery (ACSS). Although several literatures have reported the potential benefit of local corticosteroid application on dysphagia, its safety and efficacy are still unclear. A systematic review was performed aiming to evaluate the evidence of local corticosteroid application in prevention or treatment of postoperative dysphagia following ACSS. A systematic search was performed in September 2018 in PubMed and Embase database. The following information was extracted: study investigator, year of publication, number of patients, study design, inclusion/exclusion criteria, administration protocol of steroid, type of surgical procedure, number of levels performed, assessment methodology of dysphagia, radiologic assessment of prevertebral soft tissue swelling (PSTS), follow-up time points, outcome of dysphagia, and corticosteroid-related complications. Qualitative synthesis was performed. Finally, 5 studies met the inclusion/exclusion criteria. Four studies found that local corticosteroid application could decrease the incidence and magnitude of postoperative dysphagia while 1 study showed no effect on dysphagia significantly at 6 weeks and 3 months follow-up time. A total of 2325 patients received local corticosteroid intraoperatively; no early corticosteroid-related complication was reported. Totally, 4 adverse events occurred in long-term follow-up time, including 2 bone nonunion at 1.5 and 2.5 years postoperatively, 2 esophageal perforation at 2 months and 11 months of follow-up, respectively. Local corticosteroid application can reduce the incidence and severity of dysphagia following ACSS without increasing early corticosteroid-related complications. But further high-quality study is necessary to analyze potential delayed complications.

Identification of two tandem genes associated with primary rosette branching in flowering Chinese cabbage.

Branching is an important agronomic trait determining plant architecture and yield; however, the molecular mechanisms underlying branching in the stalk vegetable, flowering Chinese cabbage, remain unclear. The present study identified two tandem genes responsible for primary rosette branching in flowering Chinese cabbage by GradedPool-Seq (GPS) combined with Kompetitive Allele Specific PCR (KASP) genotyping. A 900 kb candidate region was mapped in the 28.0-28.9 Mb interval of chromosome A07 through whole-genome sequencing of three graded-pool samples from the F2 population derived by crossing the branching and non-branching lines. KASP genotyping narrowed the candidate region to 24.6 kb. Two tandem genes, BraA07g041560.3C and BraA07g041570.3C, homologous to AT1G78440 encoding GA2ox1 oxidase, were identified as the candidate genes. The BraA07g041560.3C sequence was identical between the branching and non-branching lines, but BraA07g041570.3C had a synonymous single nucleotide polymorphic (SNP) mutation in the first exon (290th bp, A to G). In addition, an ERE cis-regulatory element was absent in the promoter of BraA07g041560.3C, and an MYB cis-regulatory element in the promoter of BraA07g041570.3C in the branching line. Gibberellic acid (GA3) treatment decreased the primary rosette branch number in the branching line, indicating the significant role of GA in regulating branching in flowering Chinese cabbage. These results provide valuable information for revealing the regulatory mechanisms of branching and contributing to the breeding programs of developing high-yielding species in flowering Chinese cabbage.

Clinicoradiological characteristics of primary spinal cord H3 K27M-mutant diffuse midline glioma.

OBJECTIVE: Primary spinal cord H3 K27M-mutant diffuse midline glioma (DMG) is a rare and devastating pathological entity. However, little attention has been paid to this disease. As a result, its clinicoradiological characteristics have yet to be described. The aim of this study was to describe the clinicoradiological characteristics of primary intramedullary H3 K27M-mutant DMG and to compare this tumor with the H3 K27 wild-type to explore potential features that could differentiate the two. METHODS: A total of 59 patients with pathologically confirmed intramedullary astrocytoma were included in this study. The cohort was divided into an H3 K27M-mutant group and H3 K27 wild-type group based on the status of H3 K27M according to an immunohistochemistry method. Demographic data, MRI features, and molecular information were collected. Multivariate logistic regression was conducted to investigate variables that might have a role in differentiating an H3 K27M DMG from an H3 K27 wild-type tumor. RESULTS: Only symptom duration showed an independent association with the H3 K27M mutation (OR 0.82, 95% CI 0.68-0.94, p = 0.016). Patients with spinal cord H3 K27M-mutant DMG had a shorter symptom duration than patients with H3 K27 wild-type glioma. No significant difference was found in terms of MRI features between the H3 K27M-mutant and H3 K27 wild-type groups. Additionally, H3 K27M-mutant DMG frequently demonstrated overexpression of p53. Survival outcome did not show a statistical difference between the H3 K27-mutant subgroup and H3 K27 wild-type subgroup in histologically high-grade astrocytoma. CONCLUSIONS: Symptom duration was associated with an H3 K27M mutation in intramedullary astrocytoma. MRI features were heterogeneous, and no imaging feature was able to predict the H3 K27M mutation. The H3 K27M mutation did not impact survival outcome in spinal histologically high-grade astrocytoma.

Explore the role of CR1 genetic variants in late-onset Alzheimer's disease susceptibility.

BACKGROUND: Complement component (3b/4b) receptor 1 (CR1) is an interesting candidate gene which has a close connection with Alzheimer's disease, and its polymorphisms have been reported to link to the late-onset Alzheimer's disease (LOAD) susceptibility. However, the findings of these related studies are inconsistent. Objective To explore the effect of CR1 genetic variants in LOAD susceptibility. MethodsWe searched relevant studies for the period up to 1 November 2020. And odds ratios (ORs) and their 95% confidence intervals (CIs) were utilized to assess the strength of the association. In addition, we carried out a case-control association study to assess their genetic association. RESULTS: Finally, a total of 30 articles with 30108 LOAD cases and 37895 controls were included. Significant allele frequency between LOAD patients and controls was observed in rs3818361 and rs6656401 (rs3818361, T vs. C: OR,1.18; 95% CI, 1.13-1.23; rs6656401, A vs. G: OR, 1.23; 95% CI, 1.10-1.36). Moreover, these results remain significant in subgroup of rs3818361 in Asia or America (OR,1.26; 95% CI,1.06-1.45; OR, 1.18; 95% CI, 1.13-1.24, respectively) and rs6656401 in Europe (OR = 1.26; 95% CI, 1.09-1.42). In addition, the two single nucleotide polymorphisms were proved to significantly increase LOAD risk in the overall population under the dominant model (OR = 1.12; 95% CI, 1.02-1.21; OR = 1.18, 95% CI, 1.15-1.22, respectively). Our case-control study showed that the distribution of rs6656401 genotype was significant (P = 0.000; OR, 6.889; 95% CI, 2.709-17.520), suggesting the A allele of rs6656401 is the risk allele. CONCLUSION: These available data indicate that rs6656401 in CR1 is significant to increase LOAD risk.

Prognostic factors and nomogram prediction of survival probability in primary spinal cord astrocytoma patients.

OBJECTIVE: Knowledge on the management of spinal cord astrocytoma (SCA) remains scarce. Here, the authors constructed and validated a predictive nomogram, often used for individualized prognosis and evaluations, to estimate cancer-specific survival (CSS) and overall survival (OS) for patients with SCA. METHODS: Epidemiological characteristics were compared between low-grade SCA (LGSCA) and high-grade SCA (HGSCA) patients from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors for CSS and OS were determined using univariate and multivariate analyses and Kaplan-Meier curves. A nomogram was developed to individually predict the 3-, 5-, and 10-year CSS and OS rates. The clinical usefulness of the nomogram was assessed using calibration plots, the concordance index (C-index), and time-dependent receiver operating characteristic curves. RESULTS: A total of 468 LGSCA and 165 HGSCA patients were eligible for inclusion. LGSCA and HGSCA patients demonstrated differences in age, tumor extension, insurance status, adjuvant treatment, and survival. Multivariate analysis demonstrated that in the LGSCA group, tumor extension, surgery type, and adjuvant therapy were individually associated with CSS. The distance of tumor extension and WHO grade were individually associated with CSS in the HGSCA group. The prognostic variables were further demonstrated using the Kaplan-Meier method, which also suggested that adjuvant treatment provided no advantage to HGSCA patients. A nomogram was constructed, and the C-index for CSS was 0.84 by internal validation (95% CI 0.79-0.90). CONCLUSIONS: This research suggests that the distance of tumor extension, type of surgery, and adjuvant therapy are significant risk factors for CSS using multivariate analysis in the LGSCA group. Adjuvant treatment provided no advantages for CSS or OS in patients with HGSCAs. The nomogram may be clinically useful to healthcare providers.