Development, validation, and visualization of a web-based nomogram to predict the effect of tubular microdiscectomy for lumbar disc herniation

ObjectiveThe purpose of this study was to retrospectively collect the relevant clinical data of lumbar disc herniation (LDH) patients treated with the tubular microdiscectomy (TMD) technique, and to develop and validate a prediction model for predicting the treatment improvement rate of TMD in LDH patients at 1 year after surgery.MethodsRelevant clinical data of LDH patients treated with the TMD technology were retrospectively collected. The follow-up period was 1 year after surgery. A total of 43 possible predictors were included, and the treatment improvement rate of the Japanese Orthopedic Association (JOA) score of the lumbar spine at 1 year after TMD was used as an outcome measure. The least absolute shrinkage and selection operator (LASSO) method was used to screen out the most important predictors affecting the outcome indicators. In addition, logistic regression was used to construct the model, and a nomogram of the prediction model was drawn.ResultsA total of 273 patients with LDH were included in this study. Age, occupational factors, osteoporosis, Pfirrmann classification of intervertebral disc degeneration, and preoperative Oswestry Disability Index (ODI) were screened out from the 43 possible predictors based on LASSO regression. A total of 5 predictors were included while drawing a nomogram of the model. The area under the ROC curve (AUC) value of the model was 0.795.ConclusionsIn this study, we successfully developed a good clinical prediction model that can predict the effect of TMD for LDH. A web calculator was designed on the basis of the model (https://fabinlin.shinyapps.io/DynNomapp/)

White Matter Injury After Intracerebral Hemorrhage

Spontaneous intracerebral hemorrhage (ICH) accounts for 15% of all stroke cases. ICH is a devastating form of stroke associated with high morbidity, mortality, and disability. Preclinical studies have explored the mechanisms of neuronal death and gray matter damage after ICH. However, few studies have examined the development of white matter injury (WMI) following ICH. Research on WMI indicates that its pathophysiological presentation involves axonal damage, demyelination, and mature oligodendrocyte loss. However, the detailed relationship and mechanism between WMI and ICH remain unclear. Studies of other acute brain insults have indicated that WMI is strongly correlated with cognitive deficits, neurological deficits, and depression. The degree of WMI determines the short- and long-term prognosis of patients with ICH. This review demonstrates the structure and functions of the white matter in the healthy brain and discusses the pathophysiological mechanism of WMI following ICH. Our review reveals that the development of WMI after ICH is complex; therefore, comprehensive treatment is essential. Understanding the relationship between WMI and other brain cells may reveal therapeutic targets for the treatment of ICH

Polymeric Systems Containing Supramolecular Coordination Complexes for Drug Delivery

Cancer has become a common disease that seriously endangers human health and life. Up to now, the essential treatment method has been drug therapy, and drug delivery plays an important role in cancer therapy. To improve the efficiency of drug therapy, researchers are committed to improving drug delivery methods to enhance drug pharmacokinetics and cancer accumulation. Supramolecular coordination complexes (SCCs) with well-defined shapes and sizes are formed through the coordination between diverse functional organic ligands and metal ions, and they have emerged as potential components in drug delivery and cancer therapy. In particular, micelles or vesicles with the required biocompatibility and stability are synthesized using SCC-containing polymeric systems to develop novel carriers for drug delivery that possess combined properties and extended system tunability. In this study, the research status of SCC-containing polymeric systems as drug carriers and adjuvants for cancer treatment is reviewed, and a special focus is given to their design and preparation

Polymeric Systems Containing Supramolecular Coordination Complexes for Drug Delivery

Cancer has become a common disease that seriously endangers human health and life. Up to now, the essential treatment method has been drug therapy, and drug delivery plays an important role in cancer therapy. To improve the efficiency of drug therapy, researchers are committed to improving drug delivery methods to enhance drug pharmacokinetics and cancer accumulation. Supramolecular coordination complexes (SCCs) with well-defined shapes and sizes are formed through the coordination between diverse functional organic ligands and metal ions, and they have emerged as potential components in drug delivery and cancer therapy. In particular, micelles or vesicles with the required biocompatibility and stability are synthesized using SCC-containing polymeric systems to develop novel carriers for drug delivery that possess combined properties and extended system tunability. In this study, the research status of SCC-containing polymeric systems as drug carriers and adjuvants for cancer treatment is reviewed, and a special focus is given to their design and preparation

Key Role of Heat Shock Protein Expression Induced by Ampicillin in Citrus Defense against Huanglongbing: A Transcriptomics Study

Citrus Huanglongbing (HLB) is a serious disease for the citrus industry. Earlier studies showed that ampicillin (Amp) can reduce titers of the pathogen which causes HLB and the bacteria Candidatus Liberibacter asiaticus (CLas) in HLB-affected citrus. CLas has not yet been cultured, so the mechanisms of Amp against CLas are unclear. Some chemicals were demonstrated to trigger citrus defense systems against CLas. Therefore, we hypothesize that Amp may induce citrus defenses against CLas. Here we applied three nano-formulations of varying droplet sizes to HLB-affected citrus to achieve different accumulated concentrations of Amp (high, medium, low) in the plants. We then used RNA-seq to analyze induction of gene expression of citrus defense systems against CLas in response to different concentrations of Amp. The results indicated that at all accumulated concentrations of Amp can significantly suppress CLas titer and mitigate HLB symptoms. Transcriptomic analyses showed that Amp treatment induced expression of heat shock proteins (Hsps) in HLB-affected citrus, and these Hsps were significantly related to several defense genes encoding R proteins, transcription factors, splicing factors, RNA-binding proteins, RNA-dependent RNA polymerase, Gibberellic acid methyltransferase 2, L-ascorbate peroxidase 2, and ferruginol synthase that confer tolerance to CLas in citrus plants. Taken together, these results suggest that Amp treatment of citrus plants can trigger expression of Hsps and related defense genes to respond to CLas infection. These findings are valuable for developing novel strategies to combat citrus HLB

Key Role of Heat Shock Protein Expression Induced by Ampicillin in Citrus Defense against Huanglongbing: A Transcriptomics Study

Citrus Huanglongbing (HLB) is a serious disease for the citrus industry. Earlier studies showed that ampicillin (Amp) can reduce titers of the pathogen which causes HLB and the bacteria Candidatus Liberibacter asiaticus (CLas) in HLB-affected citrus. CLas has not yet been cultured, so the mechanisms of Amp against CLas are unclear. Some chemicals were demonstrated to trigger citrus defense systems against CLas. Therefore, we hypothesize that Amp may induce citrus defenses against CLas. Here we applied three nano-formulations of varying droplet sizes to HLB-affected citrus to achieve different accumulated concentrations of Amp (high, medium, low) in the plants. We then used RNA-seq to analyze induction of gene expression of citrus defense systems against CLas in response to different concentrations of Amp. The results indicated that at all accumulated concentrations of Amp can significantly suppress CLas titer and mitigate HLB symptoms. Transcriptomic analyses showed that Amp treatment induced expression of heat shock proteins (Hsps) in HLB-affected citrus, and these Hsps were significantly related to several defense genes encoding R proteins, transcription factors, splicing factors, RNA-binding proteins, RNA-dependent RNA polymerase, Gibberellic acid methyltransferase 2, L-ascorbate peroxidase 2, and ferruginol synthase that confer tolerance to CLas in citrus plants. Taken together, these results suggest that Amp treatment of citrus plants can trigger expression of Hsps and related defense genes to respond to CLas infection. These findings are valuable for developing novel strategies to combat citrus HLB

Metagenomic Analysis Reveals the Mechanism for the Observed Increase in Antibacterial Activity of Penicillin against Uncultured Bacteria Candidatus Liberibacter asiaticus Relative to Oxytetracycline in Planta

Citrus huanglongbing (HLB) is a devastating disease for the citrus industry. The previous studies demonstrated that oxytetracycline and penicillin are effective antibiotics against Candidatus Liberibacter asiaticus (CLas). However, since CLas is uncultured, the mechanisms of action of antibiotics against CLas are still unclear. It was recently reported that the endophytic microbial communities are associated with the progression of citrus HLB after oxytetracycline and penicillin treatment. Therefore, we hypothesize that penicillin has greater antibacterial activity against CLas than oxytetracycline, which may be associated with the alteration of the structure and function of endophytic microbial communities in HLB-affected citrus in response to these antibiotics. To test this hypothesis, the microbiome of HLB-affected citrus leaves treated with these two antibiotics was analyzed using a metagenomic method. Our results indicate that the microbial structure and function in HLB-affected citrus were altered by these two antibiotics. The relative abundance of beneficial bacterial species, including Streptomyces avermitilis and Bradyrhizobium, was higher in penicillin-treated plants compared to those treated with oxytetracycline, and the relative abundance of the bacterial species (such as Propionibacterium acnes and Synechocystis sp PCC 6803) associated with CLas survival was lower for penicillin-treated plants compared to oxytetracycline-treated plants. These results indicate that penicillin has greater antibacterial activity against CLas. Based on the metagenomic analysis, this study elucidated the mechanism for the observed increase in antibacterial activity of penicillin against CLas. The data presented here are not only invaluable for developing eco-friendly and effective biocontrol strategies to combat citrus HLB, but also provide a method for revealing mechanism of antimicrobial against uncultured bacteria in host

Evaluation of Thermotherapy against Huanglongbing (Citrus Greening) under Laboratory Conditions

Huanglongbing (HLB, citrus greening) is the most destructive disease of citrus. The disease is associated with “Candidatus Liberibacter asiaticus”. Few management options are available, besides preventive measures such as the removal of affected plants, planting disease-free stock and maintaining vector-free production in quarantine areas. In this study, we assessed the efficacy of thermotherapy against the disease under controled laboratory conditions. A total of sixty, 2-year old graft-infected Citrus reticulate Blanco seedlings were used for the study. The plants were randomly divided into 3 treatment groups (45, 48°C, and untreated), with 5 plants/rep, 4 reps/trt. The treated plants were placed in temperature chambers for a 4-h treatment sessions, repeated weekly 3 times. Disease remission was observed beginning 8 weeks post-treatment. Real-time PCR assays revealed that pathogen “Ca. L. asiaticus” concentration of all HLB-affected seedlings were significantly reduced except for 8 plants under 45 and 48°C treatments at 4 weeks after treatment. In contrast, pathogen concentration in the untreated control plants exhibited a significant increase, with the highest increase of about 30-fold compared to the initial pathogen concentration (pre-treatment). Except for 7 plants (7 out of 40 total plants), pathogen concentration in the new flushes of the treated plants decreased 90% at ca. 8 weeks after treatment, compared to the initial pathogen concentration. Nested and real-time PCR were used for confirmation of HLB infection in the seedlings, and for pathogen titer assessment.Although the result is considered preliminary, it provides a foundation for further work in developing the technique for HLB management. Complementary work will include exploration of additional exposure time and temperature combinations as well as treatments using commercial field settings

Activation of Nurr1 with Amodiaquine Protected Neuron and Alleviated Neuroinflammation after Subarachnoid Hemorrhage in Rats

Background. Nurr1, a member of the nuclear receptor 4A family (NR4A), played a role in neuron protection, anti-inflammation, and antioxidative stress in multidiseases. We explored the role of Nurr1 on subarachnoid hemorrhage (SAH) progression and investigated the feasibility of its agonist (amodiaquine, AQ) as a treatment for SAH. Methods. SAH rat models were constructed by the endovascular perforation technique. AQ was administered intraperitoneally at 2 hours after SAH induction. SAH grade, mortality, weight loss, neurological performance tests, brain water content, western blot, immunofluorescence, Nissl staining, and qPCR were assessed post-SAH. In vitro, hemin was introduced into HT22 cells to develop a model of SAH. Results. Stimulation of Nurr1 with AQ improved the outcomes and attenuated brain edema. Nurr1 was mainly expressed in neuron, and administration of AQ alleviated neuron injury in vivo and enhanced the neuron viability and inhibited neuron apoptosis and necrosis in vitro. Besides, AQ reduced the amount of IL-1β+Iba-1+ cells and inhibited the mRNA level of proinflammatory cytokines (IL-1β and TNF-α) and the M1-like phenotype markers (CD68 and CD86). AQ inhibited the expression of MMP9 in HT22 cells. Furthermore, AQ reduced the expression of nuclear NF-κB and Nurr1 while increased cytoplasmic Nurr1 in vivo and in vitro. Conclusion. Pharmacological activation of Nurr1 with AQ alleviated the neuron injury and neuroinflammation. The mechanism of antineuroinflammation may be associated with the Nurr1/NF-κB/MMP9 pathway in the neuron. The data supported that AQ might be a promising treatment strategy for SAH