Factors influencing postoperative visual improvement in 208 patients with tuberculum sellae meningiomas.

OBJECTIVE: Tuberculum sellae meningiomas (TSMs) usually compress the optic nerve and optic chiasma, thus affecting vision. Surgery is an effective means to remove tumors and improve visual outcomes. On a larger scale, this study attempted to further explore and confirm the factors related to postoperative visual outcomes to guide the treatment of TSMs. METHODS: Data were obtained from 208 patients with TSMs who underwent surgery at our institution between January 2010 and August 2022. Demographics, ophthalmologic examination results, imaging data, extent of resection, radiotherapy status, and surgical approaches were included in the analysis. Univariate and multivariate logistic regressions were used to assess the factors that could lead to favorable visual outcomes. RESULTS: The median follow-up duration was 63 months, and gross total resection (GTR) was achieved in 174 (83.7%) patients. According to our multivariate logistic regression analysis, age < 60 years (odds ratio [OR] = 0.310; P = 0.007), duration of preoperative visual symptoms (DPVS) < 10 months (OR = 0.495; P = 0.039), tumor size ≤ 27 mm (OR = 0.337; P = 0.002), GTR (OR = 3.834; P = 0.006), and a tumor vertical-to-horizontal dimensional ratio < 1 (OR = 2.593; P = 0.006) were found to be significant independent predictors of favorable visual outcomes. CONCLUSION: Age, DPVS, tumor size, GTR, and the tumor vertical-to-horizontal dimensional ratio were found to be powerful predictors of favorable visual outcomes. This study may help guide decisions regarding the treatment of TSMs.

Polymer Nanoparticles with 2-HP-ß-Cyclodextrin for Enhanced Retention of Uptake into HCE-T Cells.

Triamcinolone acetonide (TA), a medium-potency synthetic glucocorticoid, is primarily employed to treat posterior ocular diseases using vitreous injection. This study aimed to design novel ocular nanoformulation drug delivery systems using PLGA carriers to overcome the ocular drug delivery barrier and facilitate effective delivery into the ocular tissues after topical administration. The surface of the PLGA nanodelivery system was made hydrophilic (2-HP-ß-CD) through an emulsified solvent volatilization method, followed by system characterization. The mechanism of cellular uptake across the corneal epithelial cell barrier used rhodamine B (Rh-B) to prepare fluorescent probes for delivery systems. The triamcinolone acetonide (TA)-loaded nanodelivery system was validated by in vitro release behavior, isolated corneal permeability, and in vivo atrial hydrodynamics. The results indicated that the fluorescent probes, viz., the Rh-B-(2-HP-ß-CD)/PLGA NPs and the drug-loaded TA-(2-HP-ß-CD)/PLGA NPs, were within 200 nm in size. Moreover, the system was homogeneous and stable. The in vitro transport mechanism across the epithelial barrier showed that the uptake of nanoparticles was time-dependent and that NPs were actively transported across the epithelial barrier. The in vitro release behavior of the TA-loaded nanodelivery systems revealed that (2-HP-ß-CD)/PLGA nanoparticles could prolong the drug release time to up to three times longer than the suspensions. The isolated corneal permeability demonstrated that TA-(2-HP-ß-CD)/PLGA NPs could extend the precorneal retention time and boost corneal permeability. Thus, they increased the cumulative release per unit area 7.99-fold at 8 h compared to the suspension. The pharmacokinetics within the aqueous humor showed that (2-HP-ß-CD)/PLGA nanoparticles could elevate the bioavailability of the drug, and its Cmax was 51.91 times higher than that of the triamcinolone acetonide aqueous solution. Therefore, (2-HP-ß-CD)/PLGA NPs can potentially elevate transmembrane uptake, promote corneal permeability, and improve the bioavailability of drugs inside the aqueous humor. This study provides a foundation for future research on transocular barrier nanoformulations for non-invasive drug delivery.

Telemedicine in patients with obsessive-compulsive disorder after deep brain stimulation: a case series.

Background: Patients suffering from refractory obsessive-compulsive disorder (OCD) who have undergone deep brain stimulation (DBS) surgery require repeated in-person programming visits. These sessions could be labor-intensive and may not always be feasible, particularly when in-person hospital visits are restricted. Telemedicine is emerging as a potential supplementary tool for post-operative care. However, its reliability and feasibility still require further validation due to the unconventional methods of interaction. Methods: A study was conducted on three patients with refractory OCD who had undergone DBS. Most of their programming sessions were completed via a remote programming system. These patients were recruited and monitored for a year. Changes in their clinical symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale-Second Edition (Y-BOCS-II), the Hamilton Anxiety Scale-14 (HAMA), the Hamilton Depression Scale-17 (HAMD), and the Short Form 36 Health Survey Questionnaire (SF-36). The scores from these assessments were reported. Results: At the last follow-up, two out of three patients were identified as responders, with their Y-BOCS-II scores improving by more than 35% (P1: 51%, P3: 42%). These patients also experienced some mood benefits. All patients observed a decrease in travel expenses during the study period. No severe adverse events were reported throughout the study. Conclusion: The group of patients showed improvement in their OCD symptoms within a 1-year follow-up period after DBS surgery, without compromising safety or benefits. This suggests that telemedicine could be a valuable supplementary tool when in-person visits are limited.

A long-term follow-up study of adults with Chiari malformation type I combined with syringomyelia.

Background: There is a considerable amount of controversy regarding the treatment and prognosis of adult patients with Chiari malformation type I (CM-I) at home and abroad; furthermore, no large-sample, long-term, follow-up studies have examined CM-I patients with syringomyelia (SM) comparing posterior fossa decompression with resection of tonsils (PFDRT) vs. posterior fossa decompression with duraplasty (PFDD). Objective: This study retrospectively analyzed the factors affecting the treatment and long-term prognosis of adults with CM-I combined with SM. Methods: We retrospectively analyzed data from 158 adult CM-I patients combined with SM who underwent PFDRT or PFDD, including 68 patients in group PFDRT and 90 patients in group PFDD. We examined the clinical manifestations, imaging features, and follow-up data of patients. Clinical outcomes were assessed using the Chicago Chiari Outcomes Scale (CCOS), and radiographic outcomes were indicated by the syrinx remission rate. Multivariate logistic regression analysis and multiple linear regression analysis were used to explore the relevant factors affecting the long-term prognosis of patients. Results: This study showed that compared with preoperative patients in the PFDRT group and PFDD group, the sensory impairment, cough-related headache, and movement disorder were significantly improved (p < 0.01); meanwhile, the diameter of the syrinx and the volume of the syrinx decreased significantly (p < 0.001). Additionally, the study found that there were significant differences in the syrinx remission rate (p = 0.032) and the clinical cure rates (p = 0.003) between the two groups. Multivariate logistic regression analysis showed that age (p = 0.021), cerebellar-related symptoms (p = 0.044), preoperative cisterna magna volume (p = 0.043), and peak systolic velocity (p = 0.036) were independent factors for clinical outcomes. Multiple linear regression analysis showed that different surgical procedures were positively correlated with the syrinx remission rate (p = 0.014), while preoperative syrinx diameter (p = 0.018) and age (p = 0.002) were negatively correlated with the syrinx remission rate. Conclusion: In conclusion, this study suggested that, in a long-term follow-up, although both surgical procedures are effective in treating patients with CM-I and SM, PFDRT is better than PFDD; age and cerebellar-related signs independently affect the patient's prognosis. Additionally, an effective prognosis evaluation index can be developed for patients, which is based on imaging characteristics, such as preoperative cisterna magna volume, preoperative syrinx diameter, and preoperative cerebrospinal fluid (CSF) hydrodynamic parameters to guide clinical work.

A machine learning-based integrated clinical model for predicting prognosis in atypical meningioma patients.

PURPOSE: Atypical meningioma (AM) recurs in up to half of patients after surgical resection and may require adjuvant therapy to improve patient prognosis. Various clinicopathological features have been shown to have prognostic implications in AM, but an integrated prediction model is lacking. Thus, in this study, we aimed to develop and validate an integrated prognostic model for AM. METHODS: A retrospective cohort of 528 adult AM patients surgically treated at our institution were randomly assigned to a training or validation group in a 7:3 ratio. Sixteen baseline demographic, clinical, and pathological parameters, progression-free survival (PFS), and overall survival (OS) were analysed. Sixty-five combinations of machine learning (ML) algorithms were used for model training and validation to predict tumour recurrence and patient mortality. RESULTS: The random survival forest (RSF) model was the best model for predicting recurrence and death. Primary or secondary tumour, Ki-67 index, extent of resection, tumour size, brain involvement, tumour necrosis, and age contributed significantly to the model. The C-index value of the RSF recurrence prediction model reached 0.8080. The AUCs for 1-, 3-, and 5-year PFS were 0.83, 0.82, and 0.86, respectively. The C-index value of the RSF death prediction model reached 0.8890. The AUCs for 3-year and 5-year OS were 0.88 and 0.89, respectively. CONCLUSION: A high-performing integrated RSF predictive model for AM recurrence and patient mortality was proposed that may guide therapeutic decision-making and long-term monitoring.

Emerging role of aging in the progression of NAFLD to HCC.

With the aging of global population, the incidence of nonalcoholic fatty liver disease (NAFLD) has surged in recent decades. NAFLD is a multifactorial disease that follows a progressive course, ranging from simple fatty liver, nonalcoholic steatohepatitis (NASH) to liver cirrhosis and hepatocellular carcinoma (HCC). It is well established that aging induces pathological changes in liver and potentiates the occurrence and progression of NAFLD, HCC and other age-related liver diseases. Studies of senescent cells also indicate a pivotal engagement in the development of NAFLD via diverse mechanisms. Moreover, nicotinamide adenine dinucleotide (NAD+), silence information regulator protein family (sirtuins), and mechanistic target of rapamycin (mTOR) are three vital and broadly studied targets involved in aging process and NAFLD. Nevertheless, the crucial role of these aging-associated factors in aging-related NAFLD remains underestimated. Here, we reviewed the current research on the roles of aging, cellular senescence and three aging-related factors in the evolution of NAFLD to HCC, aiming at inspiring promising therapeutic targets for aging-related NAFLD and its progression.

Coronary artery disease risk factors affected by RNA modification-related genetic variants.

Background: Single nucleotide polymorphisms that affect RNA modification (RNAm-SNPs) may have functional roles in coronary artery disease (CAD). The aim of this study was to identify RNAm-SNPs in CAD susceptibility loci and highlight potential risk factors. Methods: CAD-associated RNAm-SNPs were identified in the CARDIoGRAMplusC4D and UK Biobank genome-wide association studies. Gene expression and circulating protein levels affected by the RNAm-SNPs were identified by QTL analyses. Cell experiments and Mendelian randomization (MR) methods were applied to test whether the gene expression levels were associated with CAD. Results: We identified 81 RNAm-SNPs that were associated with CAD or acute myocardial infarction (AMI), including m6A-, m1A-, m5C-, A-to-I- and m7G-related SNPs. The m6A-SNPs rs3739998 in JCAD, rs148172130 in RPL14 and rs12190287 in TCF21 and the m7G-SNP rs186643756 in PVT1 were genome-wide significant. The RNAm-SNPs were associated with gene expression (e.g., MRAS, DHX36, TCF21, JCAD and SH2B3), and the expression levels were associated with CAD. Differential m6A methylation and differential expression in FTO-overexpressing human aorta smooth muscle cells and peripheral blood mononuclear cells of CAD patients and controls were detected. The RNAm-SNPs were associated with circulating levels of proteins with specific biological functions, such as blood coagulation, and the proteins (e.g., cardiotrophin-1) were confirmed to be associated with CAD and AMI in MR analyses. Conclusion: The present study identified RNAm-SNPs in CAD susceptibility genes, gene expression and circulating proteins as risk factors for CAD and suggested that RNA modification may play a role in the pathogenesis of CAD.

Identification of RNA modification-associated single-nucleotide polymorphisms in genomic loci for low-density lipoprotein cholesterol concentrations.

Introduction: Genome-wide association studies have identified approximately 1000 lipid-associated loci, but functional variants are less known. Materials & methods: The authors identified RNA modification-related single-nucleotide polymorphisms (RNAm-SNPs) in summary data from a genome-wide association study. By applying Mendelian randomization analysis, the authors identified gene expression levels involved in the regulation of RNAm-SNPs on low-density lipoprotein cholesterol (LDL-C) levels. Results: The authors identified 391 RNAm-SNPs that were significantly associated with LDL-C levels. RNAm-SNPs in NPC1L1, LDLR, APOB, MYLIP, LDLRAP1 and ABCA6 were identified. The RNAm-SNPs were associated with gene expression. The expression levels of 112 genes were associated with LDL-C levels, and some of them (e.g., APOB, SMARCA4 and SH2B3) were associated with coronary artery disease. Conclusion: This study identified many RNAm-SNPs in LDL-C loci and elucidated the relationship among the SNPs, gene expression and LDL-C.

Exploring the prognostic differences in patients of Chiari malformation type I with syringomyelia undergoing different surgical methods.

Background: The best surgical treatment of Chiari malformation patients with syringomyelia remains controversial, and whether cerebellar tonsillectomy should be performed has not been decided. Objective: To evaluate the efficacy of posterior fossa decompression with duraplasty (PFDD) and Posterior fossa decompression with resection of tonsils (PFDRT) in patients of Chiari malformation type I (CM-I) with syringomyelia and explore relevant factors affecting prognosis. Patients and methods: We retrospectively analyzed 182 adult patients of CM-I with syringomyelia who underwent PFDD or PFDRT over a 6-year period, and analyzed their clinical manifestations, imaging features, and follow-up data. Clinical outcomes were assessed using the Chicago Chiari Outcome Scale (CCOS), and imaging outcomes were assessed using the syrinx remission rate. Difference comparisons were performed to compare the differences between different surgical groups. Influencing factors associated with outcome were investigated using bivariate analysis and multiple linear regression analysis. Results: There were statistically significant differences in CCOS score (p = 0.034) and syrinx remission rates (p = 0.046) between the PFDRT group and the PFDD group after surgery. Regression analysis showed that preoperative motor dysfunction, cerebellar-related symptoms and different surgical methods may have influenced the CCOS score and that brainstem-related symptoms and age may have influenced the syrinx remission rates in the total patient group (p < 0.05). Regression analysis showed that the duration of symptoms, cerebellar-related symptoms and preoperative syrinx diameter may have influenced the CCOS score and that the preoperative cerebellar tonsillar hernia distance may have influenced the postoperative syrinx remission rate in the PFDRT group (p < 0.05). Age and length of hospital stay may have influenced the CCOS score, and brainstem-related symptoms and age may have influenced the syrinx remission rates in the PFDD group (p < 0.05). Conclusion: This study showed that the CCOS score in the PFDRT group was better than that in the PFDD group. Preoperative motor dysfunction, cerebellar-related symptoms, and different surgical methods in patients of CM-I with syringomyelia affected postoperative CCOS score. Both the duration of symptoms and the age of the patients should be actively considered as factors influencing prognosis. Symptomatic CM-I patients with syringomyelia should undergo surgical treatment as early as possible.

Tanshinone­IIA inhibits myocardial infarct via decreasing of the mitochondrial apoptotic signaling pathway in myocardiocytes.

Myocardial ischemia triggers an inflammatory reaction and oxidative stress that increases apoptosis of myocardiocytes. It has been evidenced that tanshinone­IIA (Tan­IIA) protects against heart failure post­myocardial infarction via inhibition of the apoptotic pathway. The purpose of the present study was to investigate the therapeutic effect of Tan­IIA in a rat model of myocardial ischemia, and explore the possible mechanism of Tan­IIA in myocardiocytes. The rat model of myocardial ischemia was established by left anterior descending coronary artery and rats received treatment with either Tan­IIA (10 mg/kg) or PBS for 20 days continuously. The cardiac function in the experimental rat model was detected using the Sequoia 512 echocardiography system on day 21. The cell viability of myocardiocytes was assessed by CCK­8 assay. Apoptosis of myocardiocytes and myocardial tissue was evaluated by TUNEL assay. The infarct size of the myocardial ischemia rat was determined through 2,3,5­triphenyltetrazolium chloride (TTC) and Evan blue double staining assay. The expression levels of apoptotic factors were assessed by immunohistochemistry, western blotting and immunofluorescence. The results demonstrated that Tan­IIA reduced myocardial infarct size and improved the myocardial function in myocardial ischemia rats. Compared with PBS, Tan­IIA treatment decreased myocardial tissue apoptosis and the expression levels of caspase­3, Cyto c and Apaf­1 in myocardial tissue. Tan­IIA increased the viability of impaired myocardiocytes, inhibited apoptosis of impaired myocardiocytes and increased Bcl­2 and Bak expression in myocardiocytes. In addition, Tan­IIA increased Bim and CHOP, decreased TBARS, ROS and H2O2 production, decreased ATF4 and IRE1α expression, and reduced intracellular calcium and oxidative stress in myocardiocytes. Furthermore, caspase­3 overexpression blocked Tan­IIA­decreased apoptosis of myocardiocytes. In conclusion, the data in the present study indicated that Tan­IIA improved myocardial infarct and apoptosis via the endoplasmic reticulum stress­dependent pathway and mitochondrial apoptotic signaling pathway.

Increased Legumain/Smad3 expression in atherosclerotic plaque of rat thoracic aorta.

OBJECTIVES: The purpose of this study was to investigate the role of legumain in the formation and stability of atherosclerotic plaque, as well as to explore the association between legumain with Smad3 pathway in a rat atherosclerosis model. METHODS: Rat with thoracic aorta atherosclerosis was established and received treatment with statin (n = 15 each) or controls (n = 10). Serum level of legumain was determined by enzyme-linked immunosorbent assay. Legumain and Smad3 aortic expression levels were assessed by immunohistochemistry and fluorescence microscopy. Protein and mRNA levels were analyzed using Western blot analysis and reverse transcriptase coupled polymerase chain reaction, respectively. RESULTS: The atherosclerotic group showed higher serum legumain level than control and statin group. Expression of legumain and Smad3 in macrophages and foam cells was increased in atherosclerotic group compared to control and statin group. The protein and mRNA levels of legumain and Smad3 were significantly attenuated by statin treatment (p < 0.05). For all groups, legumain expression was correlated linearly with Smad3 at mRNA (coefficient: 0.94) and protein (coefficient: 097) level. CONCLUSIONS: Legumain and Smad3 expression is highly expressed in mainly atherosclerotic plaque macrophages and linearly related, which is attenuated by statin therapy, suggesting legumain a potential Smad3 pathway-related marker of atherosclerosis.

Clay Nanoparticles Elicit Long-Term Immune Responses by Forming Biodegradable Depots for Sustained Antigen Stimulation.

Nanomaterials have been widely tested as new generation vaccine adjuvants, but few evoke efficient immunoreactions. Clay nanoparticles, for example, layered double hydroxide (LDH) and hectorite (HEC) nanoparticles, have shown their potent adjuvanticity in generating effective and durable immune responses. However, the mechanism by which clay nanoadjuvants stimulate the immune system is not well understood. Here, it is demonstrated that LDH and HEC-antigen complexes form loose agglomerates in culture medium/serum. They also form nodules with loose structures in tissue after subcutaneous injection, where they act as a depot for up to 35 d. More importantly, clay nanoparticles actively and continuously recruit immune cells into the depot for up to one month, and stimulate stronger immune responses than FDA-approved adjuvants, Alum and QuilA. Sustained antigen release is also observed in clay nanoparticle depots, with 50-60% antigen released after 35 d. In contrast, Alum-antigen complexes show minimal antigen release from the depot. Importantly, LDH and HEC are more effective than QuilA and Alum in promoting memory T-cell proliferation. These findings suggest that both clay nanoadjuvants can serve as active vaccine platforms for sustained and potent immune responses.

[Association of the polymorphism of synaptobrevins/vesicle-associated membrane proteins 8 gene with coronary heart disease in Chinese Han population].

OBJECTIVE: To investigate the association of synaptobrevins/vesicle-associated membrane proteins 8 (VAMP8) gene rs1010 polymorphism with coronary heart disease (CHD) in Chinese Han population. METHODS: The allele and genotype frequencies of the VAMP8 gene rs1010 locus in 185 CHD patients and 149 controls were analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. RESULTS: There was polymorphism of the VAMP8 gene rs1010 locus in the studied population. The distribution of VAMP8 genotypes was in Hardy-Weinberg equilibrium. The frequency of the A allele in the CHD group was significantly higher than that in control (67.3% vs 53.0%, P< 0.05). Multiple logistic regression analysis showed that genotypes AA and AG were independent risk factors of coronary heart disease. The odds ratio (OR) of (AA+AG) genotype versus GG genotype was 1.969,95% CI: 1.032-3.755. CONCLUSION: The VAMP8 rs1010 polymorphism was associated with CHD risk in Chinese Han population, the A allele might serve as a genetic risk factor of coronary heart disease.

[Study on the correlation between CETP TaqIB, KCNE1 S38G and eNOS T-786C gene polymorphisms for predisposition and non-valvular atrial fibrillation].

OBJECTIVE: To study whether CETP TaqIB,KCNE1 S38G and eNOS T-786C genetic polymorphisms are associated with non-valvular atrial fibrillation in the Han population from Zhejiang province. METHODS: Polymerase chain reaction restriction fragment length polymorphism assay was used to detect the distribution of alleles and genotypes of CETP TaqIB, KCNE1 S38G and eNOS T-786C in 147 patients with non-valvular atrial fibrillation and in 147 subjects as controls in Han population of Zhejiang province. RESULTS: (1) The frequency of CETP B1 allele in NVAF patients was higher than that of the control group and showing a statistically significant difference (OR = 1.763, 95% CI: 1.247-2.492, P = 0.002). (2) Results from logistic regression analysis revealed that: after adjustment of confounding variables such as sex, age, smoking, hypertension and body mass index, data from the binary logistic analysis showed a statistically significant difference in CETP TaqIB genetic polymorphism between patients and controls. (3) From multifactor dimensionality reduction analysis, results showed an interaction of CETP TaqIB, KCNE1 S38G and eNOS T-786C genetic polymorphisms. Odds ratio of the three simultaneously existing genetic polymorphisms was 1.849 times more than CETP TaqIB alone. CONCLUSION: CETP BI allele was an independent risk factor for predisposition to non-valvular atrial fibrillation. These findings suggested that the simultaneous existence of CETP B1, KCNE1 S38G and eNOS T-786C allele might be elevated with the predisposition to non-valvular atrial fibrillation in the Han population of Zhejiang province.