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1.
Sci Rep ; 14(1): 12637, 2024 06 02.
Article in English | MEDLINE | ID: mdl-38825605

ABSTRACT

Osteoporosis (OP) is a bone metabolism disease that is associated with inflammatory pathological mechanism. Nonetheless, rare studies have investigated the diagnostic effectiveness of immune-inflammation index in the male population. Therefore, it is interesting to achieve early diagnosis of OP in male population based on the inflammatory makers from blood routine examination. We developed a prediction model based on a training dataset of 826 Chinese male patients through a retrospective study, and the data was collected from January 2022 to May 2023. All participants underwent the dual-energy X-ray absorptiometry (DXEA) and blood routine examination. Inflammatory markers such as systemic immune-inflammation index (SII) and platelet-to-lymphocyte ratio (PLR) was calculated and recorded. We utilized the least absolute shrinkage and selection operator (LASSO) regression model to optimize feature selection. Multivariable logistic regression analysis was applied to construct a predicting model incorporating the feature selected in the LASSO model. This predictive model was displayed as a nomogram. Receiver operating characteristic (ROC) curve, C-index, calibration curve, and clinical decision curve analysis (DCA) to evaluate model performance. Internal validation was test by the bootstrapping method. This study was approved by the Ethic Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (Ethic No. JY2023012) and conducted in accordance with the relevant guidelines and regulations. The predictive factors included in the prediction model were age, BMI, cardiovascular diseases, cerebrovascular diseases, neuropathy, thyroid diseases, fracture history, SII, PLR, C-reactive protein (CRP). The model displayed well discrimination with a C-index of 0.822 (95% confidence interval: 0.798-0.846) and good calibration. Internal validation showed a high C-index value of 0.805. Decision curve analysis (DCA) showed that when the threshold probability was between 3 and 76%, the nomogram had a good clinical value. This nomogram can effectively predict the incidence of OP in male population based on SII and PLR, which would help clinicians rapidly and conveniently diagnose OP with men in the future.


Subject(s)
Inflammation , Nomograms , Osteoporosis , Humans , Male , Osteoporosis/diagnosis , Osteoporosis/blood , Middle Aged , Retrospective Studies , Aged , Inflammation/blood , Inflammation/diagnosis , China/epidemiology , Risk Factors , Biomarkers/blood , Absorptiometry, Photon , ROC Curve , Adult , Risk Assessment/methods
2.
Nature ; 630(8015): 84-90, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38840015

ABSTRACT

Direct and precise monitoring of intracranial physiology holds immense importance in delineating injuries, prognostication and averting disease1. Wired clinical instruments that use percutaneous leads are accurate but are susceptible to infection, patient mobility constraints and potential surgical complications during removal2. Wireless implantable devices provide greater operational freedom but include issues such as limited detection range, poor degradation and difficulty in size reduction in the human body3. Here we present an injectable, bioresorbable and wireless metastructured hydrogel (metagel) sensor for ultrasonic monitoring of intracranial signals. The metagel sensors are cubes 2 × 2 × 2 mm3 in size that encompass both biodegradable and stimulus-responsive hydrogels and periodically aligned air columns with a specific acoustic reflection spectrum. Implanted into intracranial space with a puncture needle, the metagel deforms in response to physiological environmental changes, causing peak frequency shifts of reflected ultrasound waves that can be wirelessly measured by an external ultrasound probe. The metagel sensor can independently detect intracranial pressure, temperature, pH and flow rate, realize a detection depth of 10 cm and almost fully degrade within 18 weeks. Animal experiments on rats and pigs indicate promising multiparametric sensing performances on a par with conventional non-resorbable wired clinical benchmarks.


Subject(s)
Hydrogels , Intracranial Pressure , Wireless Technology , Animals , Wireless Technology/instrumentation , Rats , Swine , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Hydrogels/chemistry , Male , Ultrasonic Waves , Female , Hydrogen-Ion Concentration , Injections/instrumentation , Brain/physiology , Brain/diagnostic imaging , Temperature , Absorbable Implants , Rats, Sprague-Dawley
3.
Pathol Res Pract ; 258: 155349, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38772115

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and non-motor symptoms. Emerging evidence suggests that inflammation plays a crucial role in the pathogenesis of PD, with the NLRP3 inflammasome implicated as a key mediator. Nfon-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have recently garnered attention for their regulatory roles in various biological processes, including inflammation. This review aims to provide a mechanistic insight into how ncRNAs function as regulators of inflammatory pathways in PD, with a specific focus on the NLRP3 inflammasome. We discuss the dysregulation of miRNAs and lncRNAs in PD pathogenesis and their impact on neuroinflammation through modulation of NLRP3 activation, cytokine production, and microglial activation. Additionally, we explore the crosstalk between ncRNAs, alpha-synuclein pathology, and mitochondrial dysfunction, further elucidating the intricate network underlying PD-associated inflammation. Understanding the mechanistic roles of ncRNAs in regulating inflammatory pathways may offer novel therapeutic targets for the treatment of PD and provide insights into the broader implications of ncRNA-mediated regulation in neuroinflammatory diseases.


Subject(s)
Parkinson Disease , RNA, Untranslated , Parkinson Disease/genetics , Parkinson Disease/pathology , Parkinson Disease/metabolism , Humans , RNA, Untranslated/genetics , RNA, Untranslated/metabolism , Inflammasomes/metabolism , Animals , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Inflammation/genetics , Inflammation/pathology , Inflammation/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Neuroinflammatory Diseases/pathology , Neuroinflammatory Diseases/genetics , Neuroinflammatory Diseases/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism
4.
Aging (Albany NY) ; 16(9): 8198-8216, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38738994

ABSTRACT

Disulfidptosis, a newly recognized cell death triggered by disulfide stress, has garnered attention for its potential role in osteoporosis (OP) pathogenesis. Although sulfide-related proteins are reported to regulate the balance of bone metabolism in OP, the precise involvement of disulfidptosis regulators remains elusive. Herein, leveraging the GSE56815 dataset, we conducted an analysis to delineate disulfidptosis-associated diagnostic clusters and immune landscapes in OP. Subsequently, vertebral bone tissues obtained from OP patients and controls were subjected to RNA sequencing (RNA-seq) for the validation of key disulfidptosis gene expression. Our analysis unveiled seven significant disulfidptosis regulators, including FLNA, ACTB, PRDX1, SLC7A11, NUBPL, OXSM, and RAC1, distinguishing OP samples from controls. Furthermore, employing a random forest model, we identified four diagnostic disulfidptosis regulators including FLNA, SLC7A11, NUBPL, and RAC1 potentially predictive of OP risk. A nomogram model integrating these four regulators was constructed and validated using the GSE35956 dataset, demonstrating promising utility in clinical decision-making, as affirmed by decision curve analysis. Subsequent consensus clustering analysis stratified OP samples into two different disulfidptosis subgroups (clusters A and B) using significant disulfidptosis regulators, with cluster B exhibiting higher disulfidptosis scores and implicating monocyte immunity, closely linked to osteoclastogenesis. Notably, RNA-seq analysis corroborated the expression patterns of two disulfidptosis modulators, PRDX1 and OXSM, consistent with bioinformatics predictions. Collectively, our study sheds light on disulfidptosis patterns, offering potential markers and immunotherapeutic avenues for future OP management.


Subject(s)
Osteoporosis , Sequence Analysis, RNA , rac1 GTP-Binding Protein , Humans , Osteoporosis/genetics , Osteoporosis/immunology , rac1 GTP-Binding Protein/genetics , rac1 GTP-Binding Protein/metabolism , Filamins/genetics , Female , Amino Acid Transport System y+/genetics , Amino Acid Transport System y+/metabolism , Nomograms , Male , Peroxiredoxins
5.
World J Surg Oncol ; 22(1): 137, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38790064

ABSTRACT

BACKGROUND: Craniopharyngiomas (CPs) are generally derived from the craniopharyngeal duct epithelium, accounting for 38% and 24.5% of mortality in pediatric and adult patients, respectively. At present, the widespread application of the endoscopic endonasal transsphenoidal approach (EEA) has led to controversy between the traditional microscopic transcranial approach (TCA) and EEA in relation to the surgical management of CPs. OBJECT AND METHOD: We performed a systematic review and meta-analysis comparing the complications, surgical outcomes, and endocrine functions of patients with CPs to provide evidence-based decision-making in their surgical management. RESULT: Overall, 11 observational studies with 12,212 participants were included in the meta-analysis, in which five of them only included an adult population, three of them only included a child population, and the other three studies included a mixed population (adult and child). In pediatric patients, the EEA achieved a higher gross total resection (GTR) rate (odds ratio (OR) = 5.25, 95%CI: 1.21-22.74), lower recurrence rate (OR = 0.54, 95%CI: 0.31-0.94, p = 0.030), and less hypopituitarism (OR = 0.34, 95%CI: 0.12-0.97, p = 0.043). In adult patients, EEA significantly improved mortality (OR = 0.09, 95%CI: 0.06-0.15, p < 0.001) and visual outcomes (visual improvement: OR = 3.42, 95%CI: 1.24-9.40, p = 0.017; visual deficit: OR = 0.30, 95%CI: 0.26-0.35) with decreases in postoperative stroke (OR = 0.58, 95%CI: 0.51-0.66, p < 0.001), hydrocephalus, and infections (OR = 0.32, 95%CI: 0.24-0.42, p < 0.001). CONCLUSION: Compared with the traditional TCA in primary CP resection, the development and wide application of EEA optimistically decreased the recurrence rate of CP, alleviated hypopituitarism with improvement in the GTR rate of pediatric patients, and significantly improved the visual outcomes, hydrocephalus, postoperative stroke, survival, and infection rates of the patients. Therefore, EEA is an optimal approach for primary CP resection.


Subject(s)
Craniopharyngioma , Pituitary Neoplasms , Humans , Craniopharyngioma/surgery , Craniopharyngioma/pathology , Pituitary Neoplasms/surgery , Pituitary Neoplasms/pathology , Postoperative Complications/etiology , Prognosis , Treatment Outcome , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/pathology , Endoscopy/methods
6.
Toxicol Appl Pharmacol ; 487: 116969, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38744347

ABSTRACT

Cysteine and glycine-rich protein 2 (CSRP2) is expressed differently in numerous cancers and plays a key role in carcinogenesis. However, the role of CSRP2 in glioma is unknown. This study sought to determine the expression profile and clinical significance of CSRP2 in glioma and explore its biological functions and mechanisms via lentivirus-mediated CSRP2 silencing experiments. Increased CSRP2 was frequently observed in gliomas, which was associated with clinicopathological characteristics and an unfavourable prognosis. Decreasing CSRP2 led to the suppression of malignant proliferation, metastasis and stemness in glioma cells while causing hypersensitivity to chemotherapeutic drugs. Mechanistic investigations revealed that CSRP2 plays a role in mediating the Notch signalling cascade. Silencing CSRP2 decreased the levels of Notch1, cleaved Notch1, HES1 and HEY1, suppressing the Notch signalling cascade. Reactivation of Notch markedly diminished the tumour-inhibiting effects of CSRP2 silencing on the malignant phenotypes of glioma cells. Notably, CSRP2-silencing glioma cells exhibited reduced potential in the formation of xenografts in nude mice in vivo, which was associated with an impaired Notch signalling cascade. These results showed that CSRP2 is overexpressed in glioma and has a crucial role in sustaining the malignant phenotypes of glioma, suggesting that targeting CSRP2 could be a promising strategy for glioma treatment.


Subject(s)
Glioma , Mice, Nude , Signal Transduction , Humans , Glioma/pathology , Glioma/metabolism , Glioma/genetics , Animals , Cell Line, Tumor , Mice , Male , Cell Proliferation , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Brain Neoplasms/genetics , Female , Phenotype , Receptors, Notch/metabolism , Receptors, Notch/genetics , Receptor, Notch1/metabolism , Receptor, Notch1/genetics , Mice, Inbred BALB C , Middle Aged , Gene Expression Regulation, Neoplastic , Xenograft Model Antitumor Assays
7.
Research (Wash D C) ; 7: 0376, 2024.
Article in English | MEDLINE | ID: mdl-38741604

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 Omicron variants still causes neurological complications in elderly individuals. However, whether and how aging brains are affected by Omicron variants in terms of neuroinvasiveness and neurovirulence are unknown. Here, we utilize resected paracarcinoma brain tissue from elderly individuals to generate primary brain spheroids (BSs) for investigating the replication capability of live wild-type (WT) strain and Omicron (BA.1/BA.2), as well as the mechanisms underlying their neurobiological effects. We find that both WT and Omicron BA.1/BA.2 are able to enter BSs but weakly replicate. There is no difference between Omicron BA.1/BA.2 and WT strains in neurotropism in aging BSs. However, Omicron BA.1/BA.2 exhibits ameliorating neurological damage. Transcriptional profiling indicates that Omicron BA.1/BA.2 induces a lower neuroinflammatory response than WT strain in elderly BSs, suggesting a mechanistic explanation for their attenuated neuropathogenicity. Moreover, we find that both Omicron BA.1/BA.2 and WT strain infections disrupt neural network activity associated with neurodegenerative disorders by causing neuron degeneration and amyloid-ß deposition in elderly BSs. These results uncover Omicron-specific mechanisms and cellular immune responses associated with severe acute respiratory syndrome coronavirus 2-induced neurological complications.

8.
BMC Endocr Disord ; 24(1): 45, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622616

ABSTRACT

BACKGROUND: Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES. METHODS: A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache. RESULTS: In Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16-13.03, p = 0.028) and Hardy's grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups. CONCLUSIONS: Postoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis.


Subject(s)
Pituitary Neoplasms , Sinusitis , Humans , Pituitary Neoplasms/surgery , Retrospective Studies , Quality of Life , Treatment Outcome , Endoscopy/adverse effects , Headache/etiology , Headache/prevention & control , Nasal Lavage
9.
Article in English | MEDLINE | ID: mdl-38656317

ABSTRACT

CONTEXT: Precision medicine for pituitary neuroendocrine tumors (PitNETs) is limited by the lack of reliable research models. OBJECTIVE: To generate patient-derived organoids (PDOs), which could serve as a platform for personalized drug screening for PitNET patients. DESIGN: From July 2019 to May 2022, a total of 32 human PitNET specimens were collected for the establishment of organoids with an optimized culture protocol. SETTING: This study was conducted at Sun Yat-Sen University Cancer Center. PATIENTS: PitNET patients who were pathologically confirmed were enrolled in this study. INTERVENTIONS: Histological staining and whole-exome sequencing were utilized to confirm the pathologic and genomic features of PDOs. A drug response assay on PDOs was also performed. MAIN OUTCOME MEASURES: PDOs retained key genetic and morphological features of their parental tumors. RESULTS: PDOs were successfully established from various types of PitNET samples with an overall success rate of 87.5%. Clinical nonfunctioning PitNETs-derived organoids (22/23, 95.7%) showed a higher likelihood of successful generation compared to those from functioning PitNETs (6/9, 66.7%). Preservation of cellular structure, subtype-specific neuroendocrine profiles, mutational features, and tumor microenvironment heterogeneity from parental tumors was observed. A distinctive response profile in drug tests was observed among the organoids from patients with different subtypes of PitNETs. With the validation of key characteristics from parental tumors in histological, genomic, and microenvironment heterogeneity consistency assays, we demonstrated the predictive value of the PDOs in testing individual drugs. CONCLUSION: The established PDOs, retaining typical features of parental tumors, indicate a translational significance in innovating personalized treatment for refractory PitNETs.

10.
J Cell Mol Med ; 28(9): e18339, 2024 May.
Article in English | MEDLINE | ID: mdl-38687049

ABSTRACT

Glioma is the most prevalent malignant brain tumour. Currently, reshaping its tumour microenvironment has emerged as an appealing strategy to enhance therapeutic efficacy. As the largest group of transmembrane transport proteins, solute carrier proteins (SLCs) are responsible for the transmembrane transport of various metabolites and ions. They play a crucial role in regulating the metabolism and functions of malignant cells and immune cells within the tumour microenvironment, making them a promising target in cancer therapy. Through multidimensional data analysis and experimental validation, we investigated the genetic landscape of SLCs in glioma. We established a classification system comprising 7-SLCs to predict the prognosis of glioma patients and their potential responses to immunotherapy and chemotherapy. Our findings unveiled specific SLC expression patterns and their correlation with the immune-suppressive microenvironment and metabolic status. The 7-SLC classification system was validated in distinguishing subgroups within the microenvironment, specifically identifying subsets involving malignant cells and tumour-associated macrophages. Furthermore, the orphan protein SLC43A3, a core member of the 7-SLC classification system, was identified as a key facilitator of tumour cell proliferation and migration, suggesting its potential as a novel target for cancer therapy.


Subject(s)
Brain Neoplasms , Gene Expression Regulation, Neoplastic , Glioma , Solute Carrier Proteins , Tumor Microenvironment , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Humans , Glioma/genetics , Glioma/immunology , Glioma/pathology , Glioma/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Solute Carrier Proteins/genetics , Solute Carrier Proteins/metabolism , Prognosis , Cell Proliferation/genetics , Gene Expression Profiling , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Multiomics
11.
Biomed Pharmacother ; 175: 116571, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677248

ABSTRACT

Diabetes can lead to a disorder of bone-fat balance, a significant cause of osteoporosis due to changes in environmental factors. Baicalin (Bai), an active ingredient of Scutellaria baicalensis, has been confirmed to possess antioxidant, hypoglycemic, and anti-osteoporotic effects. However, a comprehensive understanding of Bai's influence on diabetic osteoporosis (DOP), including its effects and underlying mechanisms, remains elusive. This study investigated Bai's impact on the bone-fat equilibrium in rats with DOP. The results indicated that Bai alleviated bone damage in DOP by promoting osteogenesis and inhibiting adipogenesis. Concurrently, through bioinformatics analysis, it was suggested that Bai's mechanism of action might involve the P38-MAPK pathway. In vitro, Bai was found to enhance the development of bone marrow mesenchymal stem cells (BMSCs) towards osteogenic lineages while suppressing their differentiation towards adipogenic lineages. It was discovered that Bai's promotion of BMSC osteogenic differentiation depends on the P38-MAPK pathway. Additionally, the synergistic effect mediated by Bai and P38-MAPK inhibitor suppressed BMSC adipogenic differentiation. Our research indicates that the P38-MAPK pathway play a role in Bai's effects on the osteogenic-adipogenic differentiation of BMSCs, showcasing the potential for DOP treatment. This study highlights Bai's ability to regulate the equilibrium between bone and fat, presenting a novel approach to adressing DOP.


Subject(s)
Adipogenesis , Cell Differentiation , Flavonoids , Mesenchymal Stem Cells , Osteogenesis , Osteoporosis , Rats, Sprague-Dawley , p38 Mitogen-Activated Protein Kinases , Animals , Flavonoids/pharmacology , Flavonoids/therapeutic use , p38 Mitogen-Activated Protein Kinases/metabolism , Osteoporosis/drug therapy , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Osteogenesis/drug effects , Adipogenesis/drug effects , Male , Rats , Cell Differentiation/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/complications , MAP Kinase Signaling System/drug effects , Bone and Bones/drug effects , Bone and Bones/metabolism , Bone and Bones/pathology , Cells, Cultured
12.
J Hazard Mater ; 469: 134059, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38503209

ABSTRACT

Heavy metal exposure is closely associated with gut microbe function and tolerance. However, intestinal microbe responses in children to different copper ion (Cu2+) concentrations have not yet been clarified. Here, in vitro cultivation systems were established for fecal microbe control and Cu2+-treated groups in healthy children. 16S rDNA high-throughput sequencing, meta-transcriptomics and metabolomics were used here to identify toxicity resistance mechanisms at microbiome levels. The results showed that Lactobacillus sp. and Lactococcus sp. exerted protective effects against Cu2+ toxicity, but these effects were limited by Cu2+ concentration. When the Cu2+ concentration was ≥ 4 mg/L, the abundance of Lactobacillus sp. and Lactococcus sp. significantly decreased, and the pathways of antioxidant activity and detoxification processes were enriched at 2 mg/L Cu2+, and beneficial metabolites accumulated. However, at high concentrations of Cu2+ (≥4 mg/L), the abundance of potential pathogen increased, and was accompanied by a downregulation of genes in metabolism and detoxification pathways, which meant that the balance of gut microbiota was disrupted and toxicity resistance decreased. From these observations, we identified some probiotics that are tolerant to heavy metal Cu2+, and warn that only when the concentration limit of Cu2+ in food is 2 mg/L, then a balanced gut microbiota can be guaranteed in children, thereby providing protection for their health.


Subject(s)
Lactobacillus , Microbiota , Child , Humans , Lactobacillus/genetics , Copper/toxicity , Lactococcus , Ions
13.
Microorganisms ; 12(2)2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38399796

ABSTRACT

Benzalkonium chloride (BC) is widely used for disinfection in the food industry. However, Listeria monocytogenes strains with resistance to BC have been reported recently. In L. monocytogenes, the Agr communication system consists of a membrane-bound peptidase AgrB, a precursor peptide AgrD, a histidine kinase (HK) AgrC, and a response regulator (RR) AgrA. Our previous study showed that the agr genes are significantly upregulated by BC adaptation. This study aimed to investigate the role of the Agr system in BC resistance in L. monocytogenes. Our results showed that the Agr system was involved in BC resistance. However, a direct interaction between BC and AgrC was not observed, nor between BC and AgrA. These results indicated that BC could induce the Agr system via an indirect action. Both AgrBD and AgrC were required for growth under BC stress. Nevertheless, when exposed to BC, the gene deletion mutant ∆agrA strain exhibited better growth performance than its parental strain. The RR Lmo1172 played a role in BC resistance in the ∆agrA strain, suggesting that Lmo1172 may be an alternative to AgrA in the phosphotransfer pathway. Phosphorylation of Lmo1172 by AgrC was observed in vitro. The cognate HK Lmo1173 of Lmo1172 was not involved in BC stress, regardless of whether it was as the wild-type or the ∆agrA mutant strain. Our evidence suggests that the HK AgrC cross-phosphorylates its noncognate RR Lmo1172 to cope with BC stress when the cognate RR AgrA is absent. In vivo, further studies will be required to detect phosphotransfer of AgrC/AgrA and AgrC/Lmo1172.

14.
World Neurosurg ; 184: e237-e246, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38272303

ABSTRACT

BACKGROUND: The use of cement in pedicle screw augmentation (PSA) enhances the pullout force of pedicle screws in vertebrae affected by osteoporosis. Risks involved in the use of cement for PSA include nerve injury and vascular damage caused by cement leakage. METHODS: This study included all patients who received PSA for degenerative lumbar stenosis in osteoporotic vertebrae from January 2014 to May 2022. Postoperative computed tomography was used to assess cement leakage. Correlation analysis and logistic regression analyses were used to establish the associated clinical or radiological factors, which were then used to construct nomograms and web calculators. RESULTS: The study comprised 181 patients including 886 screws inserted into 443 vertebrae. Perivertebral cement leakage was significantly associated with female sex, decreased bone mineral density, solid screws, and scattered cement distribution. Cement leakage through segmental veins (type S, 72.1%), leakage through basivertebral veins (type B, 23.9%), and instrument-related leakage (type I, 13.9%) accounted for most cement leakage. Patients with lower bone mineral density and scattered cement distribution were more likely to experience type S or type B leakage. Our analysis data showed that cement augmentation with cannulated and fenestrated screws tended toward concentrated cement distribution. Creation and verification of each nomogram additionally showcased the prognostic capability and medical significance of the corresponding model. CONCLUSIONS: Nomograms and web-based calculators can accurately forecast the probability of cement leakage. PSA should be routinely performed using cannulated and fenestrated screws, along with a moderate amount of high-viscosity cement, with continuous monitoring using fluoroscopy.


Subject(s)
Pedicle Screws , Humans , Female , Pedicle Screws/adverse effects , Nomograms , Constriction, Pathologic , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Bone Cements/adverse effects
15.
Orthop Surg ; 16(2): 420-428, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38191985

ABSTRACT

OBJECTIVE: Foraminoplasty is an important step in transforaminal endoscopic lumbar discectomy (TELD). A trephine is widely used in foraminoplasty. However, foraminoplasty using a trephine alone sometimes fails to remove the resected bone, resulting in the bone remaining in the foramen or spinal canal, which can potentially cause neurological irritation or injury. The objective of this study is to introduce a self-designed tool, referred to as an anchoring drill, for use with a trephine in foraminoplasty in TELD and to evaluate its advantages. METHODS: A retrospective review was performed to identify patients who underwent L4-5 TELD between January 2019 to January 2022. Foraminoplasty was performed in all patients. Depending on whether the anchoring drill was used or not, patients were divided into two groups. Surgery-related parameters and complications were reviewed. Visual analog scale (VAS) and Japanese Orthopaedic Association (JOA) scores were also assessed for all patients. SPSS statistical software was used for statistical calculation. RESULTS: A total of 100 patients were included (55 in the anchoring drill group and 45 in the trephine group). The incidence of residual bone fragments after foraminoplasty of the anchoring drill group was 9.09%, which was lower than that of the trephine group, at 33.33% (p < 0.05). The mean endoscopic operation time of the anchoring drill group was shorter than that of the trephine group (p < 0.05). The mean fluoroscopy time and duration of foraminoplasty showed no significant differences between the two cohorts. The total perioperative complication incidence was lower in the anchoring drill group, in which the neural irritation incidence showed a significant difference (anchoring drill group: 3.64%, trephine group: 17.78%, p < 0.05). VAS and JOA scores were significantly improved after the operation for all patients (p < 0.001), however, no statistical differences were found between the two groups at each follow-up visit. CONCLUSION: The combination of a trephine with an anchor drill was demonstrated to be safe and effective in foraminoplasty in TELD, improving the success rate of foraminoplasty and reducing neurological complications compared to using trephine alone.


Subject(s)
Diskectomy, Percutaneous , Intervertebral Disc Displacement , Humans , Retrospective Studies , Intervertebral Disc Displacement/surgery , Treatment Outcome , Lumbar Vertebrae/surgery , Endoscopy/methods , Diskectomy/methods , Diskectomy, Percutaneous/methods
16.
WIREs Mech Dis ; 16(3): e1640, 2024.
Article in English | MEDLINE | ID: mdl-38253964

ABSTRACT

Liver disease represents a significant global burden, placing individuals at a heightened risk of developing cirrhosis and liver cancer. Viral infections act as a primary cause of liver diseases on a worldwide scale. Infections involving hepatitis viruses, notably hepatitis B, C, and E viruses, stand out as the most prevalent contributors to acute and chronic intrahepatic adverse outcome, although the hepatitis C virus (HCV) can be effectively cured with antiviral drugs, but no preventative vaccination developed. Hepatitis B virus (HBV) and HCV can lead to both acute and chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma (HCC), which are principal causes of worldwide morbidity and mortality. Other viruses, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), are capable of causing liver damage. Therefore, it is essential to recognize that virus infections and liver diseases are intricate and interconnected processes. A profound understanding of the underlying relationship between virus infections and liver diseases proves pivotal in the effective prevention, diagnosis, and treatment of these conditions. In this review, we delve into the mechanisms by which virus infections induce liver diseases, as well as explore the pathogenesis, diagnosis, and treatment of liver diseases. This article is categorized under: Infectious Diseases > Biomedical Engineering.


Subject(s)
Liver Diseases , Humans , Liver Diseases/virology , Liver Diseases/diagnosis , Liver Diseases/etiology , Liver Diseases/therapy , Virus Diseases/diagnosis , Virus Diseases/therapy , Virus Diseases/virology , Antiviral Agents/therapeutic use , Animals , Liver Neoplasms/diagnosis , Liver Neoplasms/virology , Liver Neoplasms/etiology , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/virology , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/therapy
17.
J Orthop Surg Res ; 19(1): 32, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38178207

ABSTRACT

BACKGROUND: There are no reports discussing anatomic distribution of basivertebral foramen (BVF) in the osteoporotic vertebral body, which is critical in the analysis of the risk of epidural cement leakage (ECL) after cement-augmented pedicle screw fixation (CAPSF). METHODS: 371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was used to determine the frequency, width, height, and depth of magistral BVF in T10~L5. Additionally, we measured the distance between BVF and the left/right borders of vertebral body as well as the distance between BVF and upper/lower endplates. Following CAPSF, the severity of ECL and the position of pedicle screws were determined by postoperative CT. Finally, significant risk factors for extensive ECL were identified through binary logistic regression analysis. RESULTS: Of 2968 vertebral bodies ranging from T10 to L5, 801 (42.2%) had a magistral BVF. From T10 to L5, the frequency of magistral BVF appeared to gradually increase. The magistral BVF was much closer to the upper endplate and the depth accounted for about a quarter of anteroposterior diameter of vertebral body. Overall, there were 19 patients (5.1%) and 32 screws (1.7%) with extensive ECL, nine of whom had neurological symptoms. The independent risk factors for extensive ECL were the magistral BVF (OR = 8.62, P < 0.001), more volume of cement injected (OR = 1.57, P = 0.031), reduced distance from screw tip to vertebral midline (OR = 0.76, P = 0.003) and vertebral posterior wall (OR = 0.77, P < 0.001) respectively. CONCLUSION: When planning a CAPSF procedure, it is important to consider anatomical distribution of BVF and improve screw implantation methods.


Subject(s)
Bone Cements , Pedicle Screws , Humans , Bone Cements/adverse effects , Pedicle Screws/adverse effects , Vertebral Body , Clinical Relevance , Case-Control Studies , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery
18.
World Neurosurg ; 183: e668-e676, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38181877

ABSTRACT

BACKGROUND: Traditional C3-C7 unilateral open-door laminoplasty (UOLP) often leads to various postoperative complications as a result of damage of cervical posterior muscles and nuchal ligaments. We aimed to thoroughly evaluate postoperative outcomes after our modified UOLP versus traditional UOLP in treating multilevel cervical spondylotic myelopathy (MCSM). METHODS: Seventy-six patients with MCSM who underwent the modified UOLP with C3 laminectomy and C7 upper hemilaminectomy (40 patients) or traditional C3-C7 UOLP (36 patients) were included. Preoperative and postoperative cervical radiologic parameters, as well as clinical and surgical outcomes, were evaluated. RESULTS: Postoperatively, Japanese Orthopaedic Association scores improved significantly more in the modified UOLP group than in the traditional UOLP group (P = 0.028), whereas visual analog scale scores and Neck Disability Index improved similarly in both groups. Follow-up scores for Japanese Orthopaedic Association, Neck Disability Index, and visual analog scale were not significantly different between the 2 groups. At the final follow-up, the C2-C7 sagittal vertical axis and T1 slope increased in the traditional UOLP group and did not change in the modified UOLP group and were unchanged in the modified UOLP group. The C2-C7 Cobb angle decreased significantly in the traditional UOLP group and did not change in the modified UOLP group. The modified UOLP group lost less cervical posterior muscle area compared with the traditional UOLP group (3.72% ± 3.54% vs. 6.67% ± 2.81%; P < 0.001). The range of motion in the modified UOLP group was significantly greater than in the traditional UOLP group at the final follow-up (P < 0.001). Also, the modified UOLP group experienced a notable reduction in operative time, blood loss volume, and postoperative hospital stay. CONCLUSIONS: We recommend performing our modified UOLP with C3 laminectomy and C7 upper hemilaminectomy instead of traditional C3-C7 UOLP.


Subject(s)
Laminoplasty , Spinal Cord Diseases , Spondylosis , Humans , Treatment Outcome , Laminoplasty/methods , Spondylosis/complications , Spondylosis/diagnostic imaging , Spondylosis/surgery , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/surgery , Spinal Cord Diseases/complications , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Laminectomy/methods , Retrospective Studies
19.
Genet Test Mol Biomarkers ; 28(1): 22-32, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38294358

ABSTRACT

Purpose: Recently, apoptosis-related genes were shown to modulate cancer immunity. However, the role of apoptosis-related genes in the glioma immune microenvironment (GIME) remains unknown. This study aimed to explore the prognostic value of apoptosis-related genes in glioma. Methods: Doxorubicin was used to induce glioma cell apoptosis, and four differentially expressed apoptosis-related genes were identified: CREM, TNFSF12, PEA15, and PRKCD. Kaplan-Meier analyses, receiver operating characteristic curve analyses, and nomograms were established to determine the relationship between risk markers and the prognosis of patients with glioma. Results: Risk biomarkers were significantly associated with overall survival, immune cell infiltration, and immune checkpoints in patients with glioma. Somatic mutations and anti-PD-1/L1 immunotherapy were associated with worse prognosis in the high-risk group receiving anti-PD-1/L1 therapy. The expression of these four apoptosis-related genes was verified using quantitative polymerase chain reaction and immunohistochemistry, and the relationship between these four genes and apoptosis was examined using flow cytometry. Conclusions: This study suggests that apoptosis-related genes play a critical role in shaping the GIME. Assessing the apoptotic patterns of individual tumors will enhance our understanding of GIME infiltration features and lead to improved strategies for immunotherapy.


Subject(s)
Glioma , Humans , Prognosis , Glioma/genetics , Apoptosis/genetics , Doxorubicin , Flow Cytometry , Tumor Microenvironment/genetics , Apoptosis Regulatory Proteins
20.
Arch Orthop Trauma Surg ; 144(3): 1013-1020, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38078951

ABSTRACT

INTRODUCTION: In cement-augmented pedicle screw fixation (CAPSF), epidural cement leakage (CL) is a frequently reported complication with the potential for neural injury, especially when it is extensive. To date, there has been no reports discussing basivertebral foramen morphology and pedicle screw placement, which is critical in the analysis of the risk of extensive epidural CL. Thus, this study aimed to identify the incidence and risk factors for extensive epidural CL in osteoporotic patients with CAPSF. MATERIALS AND METHODS: 371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was utilized to characterize basivertebral foramen morphology. Following CAPSF, the severity of epidural CL, the implantation position of pedicle screw and cement extension within the vertebral body were determined by postoperative CT. In this study, significant risk factors for extensive epidural CL were identified through logistic regression analysis. RESULTS: There were 19 patients (5.1%) and 32 screws (1.7%) with extensive epidural CL. Nine patients (involving 19 screws) had neurological symptoms. The independent risk factors for patients with extensive epidural CL were decreased BMD and increased number of augmented screws. Significant predictors for extensive epidural CL were a magistral type of basivertebral foramen, more volume of cement injected, solid screw, a shallower screw implantation, and the smaller distance between the tip of the screw and the midline of vertebral body. CONCLUSION: Extensive epidural CL risk was significant in CAPSF when a magistral basivertebral foramen was present; solid screws and more volume of cement were used; and screw tip was implanted shallower or closer to the midline.


Subject(s)
Bone Cements , Pedicle Screws , Humans , Bone Cements/adverse effects , Pedicle Screws/adverse effects , Retrospective Studies , Incidence , Risk Factors , Lumbar Vertebrae/surgery
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