The preferred surgical choice for intermediate-risk papillary thyroid cancer: total thyroidectomy or lobectomy? a systematic review and meta-analysis.

BACKGROUND: The optimal surgical approach for intermediate-risk papillary thyroid carcinoma (IR-PTC) (according to ATA definition), whether total thyroidectomy (TT) or lobectomy (LT), has remained a contentious clinical grey area for several decades. This systematic review and meta-analysis aim to provide robust evidence and address this clinical dilemma comprehensively. MATERIALS AND METHODS: A comprehensive literature search was conducted in Pubmed, Embase, Web of Science, and the Cochrane Library from 1st January 2009 to 29th December 2023 to evaluate the impact of different surgical options (TT or LT) on patients with IR-PTC. The primary outcomes included survival, recurrence rates, and postoperative complications. I2 and sensitivity analysis was used to explore the heterogeneity. RESULTS: A total of 8 studies involving 2984 participants were included in this meta-analysis and systematic review. The results indicated that LT was a superior choice for mitigating complications compared to TT (RR, 0.32; 95%CI, 0.24-0.44, P<0.01), particularly for transient complications (RR, 0.24; 95%CI, 0.08-0.65, P<0.01), such as the transient parathyroid dysfunction (RR, 0.04; 95%CI, 0.01-0.15, P<0.01). However, TT did not increase the risk of recurrent laryngeal nerve palsy (RR, 0.78; 95%CI, 0.24-2.47, P=0.67), hemorrhage/seroma (RR, 0.77; 95%CI, 0.48-1.25, P=0.30) and permanent complications (RR, 0.18; 95%CI, 0.02-1.42, P=0.10). Besides, both LT and TT presented similar effect on survival outcomes (Overall Survival: RR, 1.00; 95%CI, 0.97-1.03, P=0.92, Disease-Specific Survival: RR, 0.99; 95%CI, 0.97-1.02, P=0.69, Recurrence-Free Survival: RR, 1.00; 95%CI, 0.96-1.05, P=0.86), recurrence (RR, 1.05; 95%CI, 0.76-1.46, P=0.76). CONCLUSION: The present meta-analysis revealed that TT did not yield improved outcomes in IR-PTC patients, but was associated with an increased incidence of temporary complications. In light of these findings, it may be advisable to consider LT as the optimal choice for IR-PTC patients.

Bibliometric research on the developments of artificial intelligence in radiomics toward nervous system diseases.

Background: The growing interest suggests that the widespread application of radiomics has facilitated the development of neurological disease diagnosis, prognosis, and classification. The application of artificial intelligence methods in radiomics has increasingly achieved outstanding prediction results in recent years. However, there are few studies that have systematically analyzed this field through bibliometrics. Our destination is to study the visual relationships of publications to identify the trends and hotspots in radiomics research and encourage more researchers to participate in radiomics studies. Methods: Publications in radiomics in the field of neurological disease research can be retrieved from the Web of Science Core Collection. Analysis of relevant countries, institutions, journals, authors, keywords, and references is conducted using Microsoft Excel 2019, VOSviewer, and CiteSpace V. We analyze the research status and hot trends through burst detection. Results: On October 23, 2022, 746 records of studies on the application of radiomics in the diagnosis of neurological disorders were retrieved and published from 2011 to 2023. Approximately half of them were written by scholars in the United States, and most were published in Frontiers in Oncology, European Radiology, Cancer, and SCIENTIFIC REPORTS. Although China ranks first in the number of publications, the United States is the driving force in the field and enjoys a good academic reputation. NORBERT GALLDIKS and JIE TIAN published the most relevant articles, while GILLIES RJ was cited the most. RADIOLOGY is a representative and influential journal in the field. "Glioma" is a current attractive research hotspot. Keywords such as "machine learning," "brain metastasis," and "gene mutations" have recently appeared at the research frontier. Conclusion: Most of the studies focus on clinical trial outcomes, such as the diagnosis, prediction, and prognosis of neurological disorders. The radiomics biomarkers and multi-omics studies of neurological disorders may soon become a hot topic and should be closely monitored, particularly the relationship between tumor-related non-invasive imaging biomarkers and the intrinsic micro-environment of tumors.

Prognostic predictive value of intracranial pressure and cerebral oxygen metabolism monitoring in patients with spontaneous intracerebral hemorrhage.

OBJECTIVE: Our study aimed to investigate the predictive value of intracranial pressure (ICP) and cerebral oxygen metabolism monitoring in the postoperative prognosis of patients with spontaneous intracerebral hemorrhage (SICH). METHODS: The clinical data of 55 patients with SICH treated by neurosurgery were analyzed retrospectively. These patients were divided into two groups based on postoperative Glasgow Outcome Scale (GOS) scores, i.e., the poor prognosis group (GOS I-III) and the good prognosis group (GOS IV and V). Next, the ICP and cerebral oxygen metabolism indexes, such as brain temperature (BT), cerebral perfusion pressure (CPP), internal jugular venous oxygen saturation (SjvO2), and arterial partial pressure of carbon dioxide (PaCO2), were recorded after the operation. Further, the prognostic differences between the two groups were compared, and the predictive values were evaluated using the receiver operating characteristic curve (ROC) and area under the curve (AUC). RESULTS: The results showed that the average ICP and BT in the good prognosis group were lower than those in the poor prognosis group. However, the CPP and SjvO2 in the good prognosis group were higher than those in the poor prognosis group. Moreover, the incidence of low PaCO2 in the poor prognosis group was higher than that in the good prognosis group. CONCLUSIONS: Our results demonstrated that the average ICP, BT, CPP, SjvO2, and arterial PaCO2 may reflect the changes in brain function and cerebral blood flow, which are significantly correlated with the prognosis of patients. Further, our findings indicated that the combined postoperative ICP levels with cerebral oxygen metabolism indexes could guide clinical treatments and predict prognosis.

The prognostic significance of PD-L1 expression in patients with glioblastoma: A meta-analysis.

Background: Glioblastoma (GBM) is a malignant brain tumor associated with high morbidity and mortality rates with a poor prognosis. In recent years, studies on prognostic markers such as programmed death ligand 1 (PD-L1) have increased; however, their conclusions remain controversial. Here, relevant literature was reviewed and a meta-analysis was performed to clarify the correlation between PD-L1 expression and overall survival (OS) in GBM. Methods: The non-foundational literature on PD-L1 expression associated with OS in GBM up to February 2022 was searched in the PubMed, Metstr, Cochrane, and Web of Science databases. Literature was rigorously screened according to inclusion and exclusion criteria, the total hazard ratio (HR), and corresponding 95% confidence intervals (CIs). Results: Calculating the combined HR value and corresponding 95% CI of HR=1.124 (95% CI: 1.047-1.201, P=0.000, I2 (I-squared)=48.8%), it was shown that PD-L1 expression was significantly associated with low OS in GBM patients. Although I2 = 48.8% < 50%, to make the results more credible, in the cutoff values ≥10% subgroup HR=1.37 (95% CI: 1.07-1.67, P=0.000, I2 = 0%), which was also the result found in the first meta-analysis. In contrast, in the cutoff value ≥5% subgroup HR=1.14 (95% CI: 0.98-1.30, P=0.000, I2 = 59.8%) and in the cutoff value median PD-L1 expression levels subgroup HR=1.05 (95% CI: 0.92-1.18, P=0.000, I2 = 0%), indicating that PD-L1 expression was not associated with low OS in GBM. Furthermore, in four studies, we found no significant correlation between PD-L1 expression and the progression-free survival of GBM (HR=1.14, 95% CI:0.40-1.88, P=0.03, I2 = 29.3%). Conclusion: PD-L1 expression was significantly associated with low OS in GBM patients; however, this result needs to be interpreted with caution and requires a large, multicenter clinical study in patients with similar baseline data for further evaluation.

Characterization of Different Subtypes of Immune Cell Infiltration in Glioblastoma to Aid Immunotherapy.

Glioblastoma multiforme (GBM) has been identified as a frequently occurring adult primary brain cancer that is highly aggressive. Currently, the prognostic outcome for GBM patients is dismal, even with intensive treatment, and the median overall survival (OS) is 14.6 months. Immunotherapy, which is specific at the cellular level and can generate persistent immunosurveillance, is now becoming a promising tool to treat diverse cancers. However, the complicated nature of the tumor microenvironment (TME) makes it challenging to develop anti-GBM immunotherapy because several cell types, cytokines, and signaling pathways are involved in generating the immunosuppressive environment. Novel immunotherapies can illustrate novel tumor-induced immunosuppressive mechanisms. Here, we used unsupervised clustering analysis to identify different subtypes of immune cell infiltration that actuated different prognoses, biological actions, and immunotherapy responses. Gene cluster A, with a hot immune cell infiltration phenotype, had high levels of immune-related genes (IRGs), which were associated with immune pathways including the interferon-gamma response and interferon-alpha response, and had low IDH1 and ATRX mutation frequencies. Gene cluster B, a cold immune cell infiltration subtype, exhibited a high expression of the KCNIP2, SCRT1, CPLX2, JPH3, UNC13A, GABRB3, ARPP21, DLGAP1, NRXN1, DLL3, CA10, MAP2, SEZ6L, GRIA2, and GRIA4 genes and a low expression of immune-related genes, i.e., low levels of immune reactivity. Our study highlighted the complex interplay between immune cell infiltration and genetic mutation in the establishment of the tumor immune phenotype. Gene cluster A was identified as an important subtype with a better prognosis and improved immunotherapy response.

Factors Affecting Development of Infection After Implantation of Ventriculoperitoneal Shunts in Patients with Posttraumatic Hydrocephalus.

BACKGROUND: Patients with posttraumatic hydrocephalus (PTH) have a high incidence of infection after ventriculoperitoneal shunt (VPS). In this study, we investigated different risk factors affecting infection after VPS in PTH patients. METHODS: Clinical data on PTH patients with VPS in Shaanxi Provincial People's Hospital from March 2012 to November 2020 were collected and analyzed retrospectively. We evaluated the relevance of patients' sex, age, cause of hydrocephalus, severity of hydrocephalus, types of hydrocephalus, hypertension, diabetes, decompressive craniectomy (DC), abdominal surgery, and duration of VPS surgery in the development of postoperative infection. Predictive values of different risk factors for the development of postoperative infection were analyzed using the receiver operating characteristic curve. RESULTS: Shunt infection occurred in 38 patients (10.2% of cases). We found that patients >60 years of age with severe hydrocephalus, hypertension, diabetes, DC, and duration of surgery for VPS >60 minutes were at a significantly higher risk of developing an infection after VPS (P < 0.05). The area under the curve was used to predict shunt infection using age (0.611), severe hydrocephalus (0.589), hypertension (0.641), diabetes (0.657), DC (0.640), and duration of operation (0.600) as independent risk factors. The area under the curve of shunt infection predicted by whole index was 0.871. CONCLUSIONS: Age, severe hydrocephalus, hypertension, diabetes, DC, as well as duration of operation for VPS (>60 minutes) were factors that significantly and independently correlated with the incidence of infection after VPS. The receiver operating characteristic curve that we have developed can predict the occurrence of shunt infection.

Analysis of Gene Co-Expression Network to Identify the Role of CD8 + T Cell Infiltration-Related Biomarkers in High-Grade Glioma.

BACKGROUND: High-grade glioma is a type of heterogeneous lethal brain tumor most common in adults. At present, immune checkpoint inhibitors (ICIs) are being considered for first-line therapeutics for malignant GBM. Nonetheless, molecular markers for malignant GBM are unavailable at present. As a result, it is important to explore molecular markers related to immunity for GBM. MATERIALS AND METHODS: The present study adopted a deconvolution algorithm for quantifying immunocyte composition and measuring gene expression, and used weighted gene co-expression network analysis (WGCNA) to analyze GBM expression data obtained from Gene Expression Omnibus (GEO), Chinese Glioma Genome Atlas (CGGA), and the Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) databases. Thereafter, key CD8+ T cell infiltration-related genes and modules were identified, and database analysis was conducted to verify the therapeutic and immune features of the selected genes. RESULTS: From this study, CD8+ T cell-related modules were identified. By using consistent clustering analysis, two panels of genes (red and green) with the highest correlation with CD8+ T cells infiltration were used to construct high-, low-expression groups, silent and/or mixed group of T cell infiltrations. In the high and low CD8+ T cell infiltration groups, a total of 535 differential genes were obtained, of which ten genes (RPS5, RPS6, FAU, RPS19, RPS23, RPS15A, RPS29, RPS14, RPS16, RPS27A) were identified through protein-protein interactions and co-expression network analysis. Post Cox regression and Kaplan-Meier (K-M) survival analysis, RPS5, RPS6, and RPS16 were selected as candidate prognostic biomarkers related to CD8+ T cells. CONCLUSION: The three associated genes RPS5, RPS6, and RPS16 were markedly related to degree of T cell infiltration and immune-related activated. We identified their potential biomarkers and therapeutic targets associated with the extent of CD8+ T cell infiltration in GBM.

MicroRNA-374b promotes the proliferation and differentiation of neural stem cells through targeting Hes1.

Accumulating evidence has documented that microRNAs (miRNAs) are critical regulators of neural stem cell (NSC) proliferation and differentiation. MiRNA-374b (miR-374b) has been reported to play an important role in regulating various cellular processes, such as proliferation and differentiation. However, whether miR-374b is involved in NSC proliferation and differentiation remains unclear. In this study, we investigated the potential role of miR-374b in regulating NSC proliferation and differentiation to elucidate the underlying molecular mechanism. Our results showed that miR-374b expression was significantly upregulated during NSC differentiation. Functional experiments showed that overexpression of miR-374b promoted NSC proliferation and differentiation to neurons. By contrast, miR-374b inhibition showed the opposite effect. Hairy and enhancer of split 1 (Hes1), a master regulator of neurogenesis, was predicted as a potential target gene of miR-374b by bioinformatics analysis. Dual-luciferase reporter assays showed that miR-374b could directly target the 3'-untranslated region of Hes1. Further experiments showed that miR-374b negatively regulated the mRNA and protein expression of Hes1 in NSCs. Moreover, overexpression of Hes1 significantly reversed the miR-374b overexpression-mediated effect on NSC proliferation and differentiation. In addition, knockdown of Hes1 abrogated the miR-374b inhibition-mediated effect on NSC proliferation and differentiation. Taken together, these results demonstrate that miR-374b regulates the proliferation and differentiation of NSCs through targeting Hes1 and suggest that miR-374b is a potential target for modulating NSC-mediated neurogenesis.

MicroRNA-346 regulates neural stem cell proliferation and differentiation by targeting KLF4.

MicroRNAs have been shown to play an important role in stem cell fate determination and self-renewal. However, the role of miRNAs in neural stem cells (NSCs) remains poorly understood. In this study, we showed that miR-346, a less characterized microRNA, promoted NSCs proliferation, differentiation and apoptosis by targeting KLF4, a core transcriptional factor in stem cell fate determination. Our data suggested that miR-346 could directly target the 3'-untranslated region of KLF4. Overexpression of miR-346 decreased KLF4 expression at both mRNA and protein levels in NSCs. More importantly, Overexpression of miR-346 repressed NSC proliferation and induced the expression of lineage markers including GFAP and Tuj1. Additionally, overexpression of miR-346 promoted apoptosis of NSCs. In concert, suppressing its expression by an antisense RNA, anti-miR-346, promoted NSC proliferation, and meanwhile inhibited its differentiation and apoptosis. We also showed that the effects of miR-346 overexpression could be reversed by re-expression of KLF4. Taken together, Those data suggest that miR-346 is a novel miRNA that regulates NSC proliferation and differentiation by targeting KLF4.

Umbilical cord mesenchymal stem cells in neurological disorders: A clinical study.

We investigated the intrathecally administrated unbilical cord mesenchymal stem cells (UC-MSCs) by lumbar puncture and assessed the technical difficulties and effects in various neurological conditions. One hundred patients underwent subarachnoid placement of UC-MSCs between December 2006 and May 2010 in the Affiliated Hospital of Medicine. Technical difficulties in patients in the form of localization of subarachnoid space, number of attempts, and post-procedural complications were evaluated. Functional evaluation was done using Hauser Ambulation Index (HAI) by the stem cell transplant team on a regular basis. All patients were followed-up for more than 1 yr after the treatment. Clinical symptoms, related biochemical index and photographic examinations were observed regularly. We encountered technical difficulties in 31 patients (31%) in the form of general anesthesia supplementation and difficulty localizing the lumbar space. Side effects (headache, low-grade fever, low back pain and lower limb pain) were observed in 22 (22%) patients, which were treated with symptomatic therapy within 48 h. One year after the treatment, functional indices improved in 47 patients (47%): 12 patients with spinal cord injury, 11 patients with cerebral palsy, 9 patients with post-traumatic brain syndrome, 9 patients with post-brain infarction syndrome, 3 patients with spinocerebellar ataxias, and 3 patients with motor neuron disease. In conclusion, intrathecal administration of UC-MSCs is a safe and effective way to treat neurological disorders. Our encouraging results of intrathecal administration of UC-MSCs indicate the potential of restoration of lost tissue and improvement of function in patients with profound neurological defects and inefficient conventional cure. These data support expanded double-blind, placebo-controlled studies for this treatment modality.

Notch signaling regulates CXCR4 expression and the migration of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have been used to repair injured tissues through immune-suppression and/or cell replace mechanisms. However, a significant barrier to MSC therapy is insufficient MSC engraftment in injured tissues after systemic administration. Here, we report that cell surface, total protein, and mRNA levels of CXCR4 were significantly increased in MSCs when Notch signaling was interrupted by γ-secretase inhibitor (GSI) or knockout of the transcription factor RBP-J, which mediates signaling from all four mammalian Notch receptors. The GSI-treated or RBP-J deficient MSCs showed stronger migration toward stromal cell-derived factor-1α (SDF-1α) than that of the control. In a mouse hepatic ischemia/reperfusion model, RBP-J deficient MSCs migrated into the injured liver tissues at a significantly higher efficiency than that of the control MSCs. Mice transfused with RBP-J deficient MSCs showed reduced liver damage. Therefore, Notch signaling regulates MSC migration and function, at least partially via the modulation of CXCR4 expression.

[Deferoxamine suppresses microglia activation and protects against secondary neural injury after intracerebral hemorrhage in rats].

OBJECTIVE: To investigate the effect of the iron chelator deferoxamine (DFA) in suppressing microglia activation and protecting against secondary neural injury in a rat model of intracerebral hemorrhage (ICH). METHODS: SD rats were randomly divided into sham-operated group, ICH group and DFA treatment group. ICH model was established by infusion of type IV collagenase into the right basal ganglia, and starting from 1 h after the operation, the rats received intraperitoneal DFA injections every 12 h for 7 days. The iron content in the perihematoma brain tissue was determined at different time points after DFA administration, and OX42 immunohistochemistry was used to observe the changes in the microglia. The contents of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the brain tissue were detected by ELISA. The neural death and neurological deficiency were measured using Nissl staining and neurological scores, respectively. RESULTS: The iron content in the brain tissues around the hematoma was significantly increased 3 days after ICH and maintained a high level till 28 days, accompanied by a marked increase of microglial cells as compared to the sham-operated group. DFA injection caused significantly decreased iron content in the brain tissue, reduced number of microglial cells, and lowered levels of IL-1ß and TNF-α. Neuronal loss around the hematoma was obviously reversed after DFA injections, which resulted in improved neurological deficiency. CONCLUSION: DFA can suppress microglia activation by removing iron overload from the perihematoma brain tissue, thus reducing secondary neuronal death and neurological deficiency in rats with ICH.