Advanced Smart Biomaterials for Regenerative Medicine and Drug Delivery Based on Phosphoramidite Chemistry: From Oligonucleotides to Precision Polymers.

Over decades of development, while phosphoramidite chemistry has been known as the leading method in commercial synthesis of oligonucleotides, it has also revolutionized the fabrication of sequence-defined polymers (SDPs), offering novel functional materials in polymer science and clinical medicine. This review has introduced the evolution of phosphoramidite chemistry, emphasizing its development from the synthesis of oligonucleotides to the creation of universal SDPs, which have unlocked the potential for designing programmable smart biomaterials with applications in diverse areas including data storage, regenerative medicine and drug delivery. The key methodologies, functions, biomedical applications, and future challenges in SDPs, have also been summarized in this review, underscoring the significance of breakthroughs in precisely synthesized materials.

Spinal Clear Cell Meningiomas: Clinical Features and Factors Predicting Recurrence.

OBJECTIVE: As a World Health Organization grade II tumor of the nervous system, clear cell meningioma (CCM) is an uncommon histologic variant of meningioma. Spinal CCMs are even rarer, with <100 spinal CCMs reported in the English literature. We present this study to characterize clinical manifestations of spinal CCMs and determine the factors predicting recurrence. METHODS: A literature search was performed for relevant case reports and series in PubMed and Embase until September 1, 2019. These articles were reviewed to identify clinical features, treatment modalities, and prognosis of patients with spinal CCMs. RESULTS: Eighty-four spinal CCMs were analyzed. Of these patients, 36 (42.9%) were young (age ≤18 years), and the mean age at resection was 24 years. Fifty-three patients (63.1%) were female and 31 (36.9%) were male. Most of the tumors (56/84, 66.7%) were located in the lumbar region. In 31 patients (36.9%) >2 segments in the craniocaudal direction were involved (number of involved segments ≥3 levels). Gross tumor resection was performed in 77 patients (91.7%). Twenty patients (23.8%) showed radiographic evidence of recurrence during follow-up. Recurrence-free survival at 1, 5, and 10 years after resection of spinal CCM was 87%, 71%, and 47%, respectively. Multivariate analysis showed that age ≤18 years (hazard ratio [HR], 3.64; P = 0.024), subtotal resection (HR, 3.43; P = 0.031), and segments involving ≥3 levels (HR, 5.66; P = 0.002) were associated with increased recurrence. CONCLUSIONS: Spinal CCMs have their own unique clinical features compared with conventional spinal meningiomas and intracranial CCMs. Spinal CCMs have a predilection to affect younger patients, are prone to appear in the lumbar region, and have a high recurrence rate. Age ≤18 years, subtotal resection, and involvement of long segments (≥3 levels) are positive predictors of recurrence.

Intracranial Clear Cell Meningiomas: Study on Clinical Features and Predictors of Recurrence.

OBJECTIVE: Clear cell meningioma (CCM) is a rare histologic subtype of meningioma that is classified as World Health Organization grade II tumor. We conducted the present study to characterize clinical features of intracranial CCM and investigate the prognostic factors associated with surgical recurrence-free survival of the patients. METHODS: PubMed and Embase were searched for case reports and series relevant to CCM. For each included study, relevant data were extracted, including patients' characteristics, pathology findings, therapeutic modality, and outcome. RESULTS: A total of 146 intracranial CCMs patients were included, comprising 73 females and 73 males. The median age of the patients at surgery was 32 years. Most tumors (58.2%) were located in the skull base region. Ninety-nine (67.8%) patients underwent gross total resection (GTR), and 47 (32.2%) patients underwent subtotal resection (STR). Seventy-four (50.7%) patients had tumor recurrence during the follow-up. Recurrence-free survival rates at 1 and 5 years after resection were 86% and 37%, respectively. Multivariate analysis showed that STR (hazard ratio [HR], 4.13; P < 0.001) and male gender (HR, 1.69; P = 0.030) were associated with increased recurrence while postoperative radiotherapy (HR, 0.51; P = 0.040) was related to decreased recurrence. CONCLUSIONS: The results suggest that intracranial CCM has its own unique clinical features compared with the other 2 types of grade II meningiomas. Patients with subtotally resected tumors, males, or those who did not receive postoperative radiotherapy are at greater risk of recurrence. GTR should be the primary goal in the surgical management of intracranial CCMs. Our data also highlight the value of radiotherapy in intracranial CCM patients.

Role of interleukin-6 to differentiate sepsis from non-infectious systemic inflammatory response syndrome.

Differentiating between sepsis and non-infectious systemic inflammatory response syndrome (SIRS) poses a great challenge. Several potential bloodstream biomarkers including Interleukin 6 (IL-6) have been investigated for their ability to diagnose sepsis. We conducted the present meta-analysis to evaluate the diagnostic quality of IL-6 in differentiating sepsis from non-infectious SIRS in adults. We also compared its accuracy with procalcitonin (PCT) and C-reactive protein (CRP). PubMed and EMBASE were systematically searched for studies published up to January 18, 2016. Twenty articles containing 22 studies and 2680 critically ill patients were included, of which, 21 studies also involved PCT and 14 involved CRP. Quantitative synthesis of studies showed that the pooled sensitivity/specificity of IL-6 and PCT were 0.68/0.73 and 0.78/0.67. The area under the curve (AUC) of IL-6, PCT and CPR for diagnosis of sepsis was 0.80, 0.83, and 0.71, respectively. This meta-analysis provides evidence that the IL-6 test has moderate diagnostic performance in differentiating sepsis from non-infectious SIRS in adults. IL-6 and PCT test has similar diagnostic value but higher than CRP. Considering its relatively high specificity, we recommend the use of IL-6 as a diagnostic aid to confirm infection rather than exclude infection in patients with SIRS.

Over-expression of TSPO in the hippocampal CA1 area alleviates cognitive dysfunction caused by lipopolysaccharide in mice.

The translocator protein 18kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future.

A dorsally located giant posterior fossa neurenteric cyst in a Chinese woman.

Neurenteric cysts (NC) are rare, endodermal-derived intracranial lesions, commonly located anteriorly in the posterior cranial fossa. We describe a rare case of a giant posterior fossa NC (6.5 × 5.9 × 4.3cm) located dorsal to the brain stem in a Chinese woman with a 1 week history of cerebellar symptoms. To our knowledge, this is the largest documented cyst of this type and the third dorsally located NC in the posterior fossa.

Diagnostic accuracy of diffusion MRI with quantitative ADC measurements in differentiating glioma recurrence from radiation necrosis.

OBJECTIVE: Differentiating radiation necrosis from glioma recurrence remains a great challenge. Several advanced imaging modalities have been developed to differentiate between these two entities with disparate outcomes. We conducted a meta-analysis to evaluate the diagnostic quality of diffusion MRI in differentiating glioma recurrence from radiation necrosis. METHOD: PubMed, Embase and Chinese Biomedical databases were systematically searched to identify published articles about evaluation of diffusion MRI for the differential diagnosis of glioma recurrence from radiation necrosis. Pooled sensitivity (SEN), specificity (SPE), negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were calculated. RESULTS: Nine studies involving 284 patients (288 lesions) met all inclusion and exclusion criteria. Quantitative synthesis of studies showed that the pooled weighted values were determined to be SEN: 0.82 (95% CI: 0.75, 0.87); SPE: 0.84 (95% CI: 0.76, 0.91); PLR: 5.10 (95% CI: 3.27, 7.95); NLR: 0.21 (95% CI: 0.15, 0.29); and DOR: 23.90 (95% CI: 12.44, 45.89). CONCLUSIONS: This meta-analysis shows that diffusion MRI has moderate diagnostic performance in differentiating glioma recurrence from radiation necrosis using quantitative ADC. It is recommended not to use diffusion MRI alone in differentiating between glioma recurrence and radiation necrosis. Multimodal imaging trials should be implemented in the future.

Association of the macrophage migration inhibitory factor gene--173G/C polymorphism with inflammatory bowel disease: a meta-analysis of 4296 subjects.

A variety of epidemiologic studies have focused on the association between macrophage migration inhibitory factor (MIF) gene--173G/C polymorphism and inflammatory bowel disease (IBD). However, results in different studies have been inconsistent. In order to derive a more precise estimation of the associations, we performed this meta-analysis and systematic searches of electronic databases PubMed and Web of Science (up to April 30, 2013). Based on our search criteria, a total of seven eligible studies concerning the MIF--173G/C polymorphism and IBD risk were included in the final meta-analysis, comprising 2162 IBD cases and 2134 controls. Significant association was found between MIF--173G/C polymorphism and the risk of IBD when all studies were pooled into the meta-analysis (for C allele vs. G allele: OR=1.25, 95% CI=1.12-1.41, p=0.000; for C/C vs. G/G: OR=1.71, 95% CI=1.23-2.39, p=0.002; for C/C+G/C vs. G/G: OR=1.24, 95% CI=1.09-1.42, p=0.002; for C/C vs. G/C+G/G: OR=1.67, 95% CI=1.20-2.33, p=0.002). Heterogeneity and publication bias did not exist in the overall comparisons. The present meta-analysis suggests an association between the MIF--173G/C polymorphism and IBD risk. However, due to few studies and the selection bias existed in some studies, the results should be interpreted with caution.

Primary intracranial leiomyosarcoma: review of the literature and presentation of a case.

BACKGROUND: Primary intracranial leiomyosarcoma (LMS) is a rare tumor of the central nervous system and therefore has only been reported sporadically. METHODS: The MEDLINE database was searched for relevant case reports and series published in English from 1969 to March 2012. These papers were reviewed to identify clinical and histopathological features, treatment modalities, and prognoses of patients with primary intracranial LMS. RESULTS: We reviewed 37 patients, including our patient, with primary intracranial LMS. Of these cases, 16 (43.2%) involved immunosuppression, 4 (10.8%) involved radiation-induced LMS, 3 (8.1%) cases involved a potential leiomyosarcomatous transformation of a brain lesion, and 7 (18.9%) cases, including the presented case, had no specific medical history. The treatment for these cases included resection (33/37, 89.2%), postoperative radiotherapy (20/37, 54.1%), and chemotherapy (7/37, 18.9%). CONCLUSIONS: The best method for the treatment of LMS could not be determined due to the limited number of cases that have been reported. However, optimized surgical resection, postoperative radiotherapy, and sarcoma-based chemotherapy may improve treatment outcomes.