Outcomes of 2-SSRS plus bevacizumab therapy strategy for brainstem metastases (BSM) over 2 cm3: a multi-center study.

Despite 2-staged stereotactic radiosurgery (2-SSRS) has been reported to provide patients with improved survival and limited toxicity, 2-SSRS for brainstem metastases (BSM) larger than 2 cm3 remains challenging. We tried to find out the effectiveness and safety of 2-SSRS plus bevacizumab therapy for BSMs over 2 cm3 and prognostic factors that related to the tumor local control. Patients that received 2-SSRS plus bevacizumab therapy from four gamma knife center were retrospectively studied from Jan 2014 to December 2023. Patients' domestic characteristics and the tumor features were evaluated before and after the treatment. Cox regression model was used to find out prognostic factors for tumor local control. 53 patients with 63 lesions received the therapy. The median peri-tumor edema volume greatly reduced at the end of therapy (P < 0.01), the median tumor volume dramatically reduced (P < 0.01) and patients' KPS score improved significantly (P < 0.05) 3 months after the therapy. Patients' median OS was 12.8 months. The tumor local control rate at 3, 6, and 12 months was 98.4%, 93.4%, and 85.2%. The incidence side effects were mainly oral and nasal hemorrhage (5.7%, 3/53), and radiation necrosis (13.2%, 7/53). Patients with primary lung adenocarcinoma, therapeutic dose over 12 Gy at second-stage SRS, primary peri-tumor edema volume less than 2.3 cm³, primary tumor volume less than 3.7 cm³ would enjoy longer tumor local control. These results suggested that 2-SSRS plus bevacizumab therapy was effective and safe for BSMs over 2 cm3. However, it is important for patients with BSM to receive early diagnosis and treatment to achieve good tumor local control.

Association of low-level blood lead with plasma homocysteine in US children and adolescents.

Although research in adults has revealed a positive relationship between blood lead levels (BLLs) and homocysteine (Hcy) levels in adults, few studies have investigated this relationship in children and adolescents. We evaluated the relationship between lowlevel blood lead and Hcy levels in US children and adolescents. A total of 8,313 children and adolescents aged 8-19 participated in this study via the National Health and Nutrition Examination Survey 1999-2006. Multivariable linear regression analyses were performed to examine the association between continuous BLLs and Hcy levels. The dose-dependent relationship between continuous BLLs and Hcy levels was analyzed using smooth curve fitting. The average age of participants was 14.1 ± 3.3 years (50.3% male). The mean values of BLLs and Hcy levels were 1.45 µg/dL and 5.77 µmol/L, respectively. In a multivariable adjusted model, an increase in 1.0 µg/dL of BLLs was associated with an elevation of 0.06 µmol/L in Hcy levels (ß = 0.06, 95%CI:0.02-0.10, P = 0.001). A linear relationship between BLLs and Hcy levels was discovered using smooth curve fitting (P non-linearity = 0.464). The relationship between low-level blood lead and Hcy levels was stronger on participants with lower serum folate levels (P for interaction = 0.002). Low BLLs were positively associated with plasma Hcy levels in children and adolescents, which varies depending on the levels of folate, vitamin B, and dietary supplements involved in Hcy metabolism.

OLIG2 expression level could be used as an independent prognostic factor for patients with cerebellar Glioblastoma (cGBM).

OBJECTIVES: The incidence of cerebellar Glioblastoma Multiforme (cGBM) is rare. Database like TCGA have not distinguish cGBM from GBM, our knowledge on cGBM gene expression characteristics is limited. The expression status of Oligodendrocyte Lineage Transcription factor 2 (OLIG2) and its clinical significance in cGBM is still unclear. METHODS: The clinical data and tissue specimens of 73 cGBM patients were retrospectively studied. The association between OLIG2 expression level and the demographic characteristics of cGBM patients was identified by the Chi-Square test. The survival curves were drawn by Kaplan-Meier analysis. The independent prognostic factors was calculated according to Cox regression analysis. RESULTS: The OLIG2 high expression was observed in about 57.5% (42/73) of the cGBM patients. Patients with high OLIG2 expression levels had a higher alive ratio at the end of follow-up (alive ratio: 70.6% vs. 29.4%, p = 0.04). The median survival time was 21 months and 13 months for high and low expression of OLIG2 (p < 0 .05). Univariate analysis and Multivariate analysis indicated that EOR (HR = 3.89, 95% CI 1.23‒12.26, p = 0.02), low OLIG2 expression (HR = 5.26, 95% CI 1.13‒24.59, p = 0.04), and without adjuvant therapy (HR = 4.95, 95% CI 1.22‒20.00, p = 0.03) were independent risk factors for the OS of cGBM patients. CONCLUSION: High expression level of OLIG2 could be used as an independent favorable prognosis indicator in cGBM patients and be recognized as a characteristic biomarker of cGBM.

On the possibility of using the Ti@Si16 superatom as a novel drug delivery carrier for different drugs: A DFT study.

The potential application of an experimentally synthesized superatom Ti@Si16 as a novel drug carrier for cisplatin (DDP), isoniazid (INH), acetylsalicylic acid (ASA), 5-fluorouracil (5-Fu), and favipiravir (FPV) has been explored by density functional theory. It is observed that the Pt atom of DDP can be effectively absorbed on Ti@Si16 via a "donation-back donation" electron transfer mechanism, resulting in a moderate adsorption energy of -19.95 kcal/mol for DDP@[Ti@Si16]. As for INH, it prefers to combine with Ti@Si16 via the N atom of pyridine ring by forming a strongly polar N-Si bond. Differently, the interaction between Ti@Si16 and the ASA, 5-Fu, and FPV drugs is dominated by the Van der Waals interaction. Our results reveal that DDP@[Ti@Si16] possesses a moderate recovery time under body temperature, which benefits the desorption of DDP from Ti@Si16. More importantly, the release of DDP drug from the Ti@Si16 surface can be effectively controlled by exerting small orientation external electric fields on the DDP@[Ti@Si16] complex. Therefore, this study demonstrates that Ti@Si16 can serve as a promising drug carrier for DDP, and thus will further expand its practical applications in the biomedical field.

OLIG2 expression level could be used as an independent prognostic factor for patients with cerebellar Glioblastoma (cGBM)

Abstract Objectives: The incidence of cerebellar Glioblastoma Multiforme (cGBM) is rare. Database like TCGA have not distinguish cGBM from GBM, our knowledge on cGBM gene expression characteristics is limited. The expression status of Oligodendrocyte Lineage Transcription factor 2 (OLIG2) and its clinical significance in cGBM is still unclear. Methods: The clinical data and tissue specimens of 73 cGBM patients were retrospectively studied. The association between OLIG2 expression level and the demographic characteristics of cGBM patients was identified by the Chi-Square test. The survival curves were drawn by Kaplan-Meier analysis. The independent prognostic factors was calculated according to Cox regression analysis. Results: The OLIG2 high expression was observed in about 57.5% (42/73) of the cGBM patients. Patients with high OLIG2 expression levels had a higher alive ratio at the end of follow-up (alive ratio: 70.6% vs. 29.4%, p = 0.04). The median survival time was 21 months and 13 months for high and low expression of OLIG2 (p < 0 .05). Univariate analysis and Multivariate analysis indicated that EOR (HR = 3.89, 95% CI 1.23−12.26, p = 0.02), low OLIG2 expression (HR = 5.26, 95% CI 1.13−24.59, p = 0.04), and without adjuvant therapy (HR = 4.95, 95% CI 1.22−20.00, p = 0.03) were independent risk factors for the OS of cGBM patients. Conclusion: High expression level of OLIG2 could be used as an independent favorable prognosis indicator in cGBM patients and be recognized as a characteristic biomarker of cGBM.

Lnc524369 promotes hepatocellular carcinoma progression and predicts poor survival by activating YWHAZ-RAF1 signaling.

BACKGROUND: Liver cancer is one of the most highly malignant cancers, characterized by easy metastasis and chemoradiotherapy resistance. Emerging evidence indicates that long noncoding RNAs (LncRNAs), including Lnc524369, are highly involved in the initiation, progression, radioresistance, and chemoresistance of hepatocellular carcinoma (HCC). However, the function of Lnc524369 remains unclear. AIM: To explore the function of Lnc524369 in HCC. METHODS: To investigate the effect of Lnc524369, tissue from 41 HCC patients were analyzed using CCK8, migration, and invasion assays. Lnc524369 and YWHAZ (also named 14-3-3ζ) mRNA were detected by qPCR, and YWHAZ and RAF1 proteins were detected by western blot in liver cancer cell lines and human HCC tissues. The Cancer Cell Line Encyclopedia (CCLE) databases, STRING database, Human Protein Atlas database, and the TCGA database were used for bioinformatic analysis. RESULTS: Lnc524369 was significantly upregulated in the nucleus of liver cancer cells and human HCC tissues. Overexpression of Lnc524369 was associated with the proliferation, migration, and invasion of liver cancer cells. YWHAZ and RAF1 proteins and YWHAZ mRNA were overexpressed in liver cancer, which could be attenuated by overexpression of Lnc524369. Lnc524369 and its downstream target YWHAZ and RAF1 proteins were negatively associated with overall survival time. CONCLUSION: Lnc524369 might be a promising target of HCC as it can enhance liver cancer progression and decrease the overall survival time of HCC by activating the YWHAZ/RAF1 pathway.

Seasonal SUHI Analysis Using Local Climate Zone Classification: A Case Study of Wuhan, China.

The surface urban heat island (SUHI) effect poses a significant threat to the urban environment and public health. This paper utilized the Local Climate Zone (LCZ) classification and land surface temperature (LST) data to analyze the seasonal dynamics of SUHI in Wuhan based on the Google Earth Engine platform. In addition, the SUHI intensity derived from the traditional urban-rural dichotomy was also calculated for comparison. Seasonal SUHI analysis showed that (1) both LCZ classification and the urban-rural dichotomy confirmed that Wuhan's SHUI effect was the strongest in summer, followed by spring, autumn and winter; (2) the maximum SUHI intensity derived from LCZ classification reached 6.53 °C, which indicated that the SUHI effect was very significant in Wuhan; (3) LCZ 8 (i.e., large low-rise) had the maximum LST value and LCZ G (i.e., water) had the minimum LST value in all seasons; (4) the LST values of compact high-rise/midrise/low-rise (i.e., LCZ 1-3) were higher than those of open high-rise/midrise/low-rise (i.e., LCZ 4-6) in all seasons, which indicated that building density had a positive correlation with LST; (5) the LST values of dense trees (i.e., LCZ A) were less than those of scattered trees (i.e., LCZ B) in all seasons, which indicated that vegetation density had a negative correlation with LST. This paper provides some useful information for urban planning and contributes to the healthy and sustainable development of Wuhan.

Transient increase in international normalized ratio (INR) and bleeding risk following Alendronate sodium in elderly patients on warfarin: Two case reports.

INTRODUCTION: Alendronate sodium is used to reduce the risk of bone fracture in aged osteoporosis patients. However, its side effects should be recognized, especially for those aged patients with one or more basic cardiovascular diseases. PATIENT CONCERNS: A 90-year-old and a 75-year-old male patient were admitted to our department. These 2 patients were examined by dual energy X-ray absorptiometry (DXA). DIAGNOSIS: Both patients were diagnosed with osteoporosis, they also had history of atrial fibrillation (AF) and had long term use of warfarin. INTERVENTIONS: Alendronate sodium was prescribed to the two patients at 70 mg once a week. OUTCOMES: The 2 patients had experienced dramatic increase of international normalized ratio (INR) to 4.69∼4.86 within 24 hours and gradual decrease in the next 5 days. Both patients experienced spontaneous ecchymoses and petechiae in the skin at the first 72 hours. CONCLUSION: Alendronate sodium can transiently increase the INR over 50%, induce spontaneous ecchymoses and petechiae in the skin of aged male osteoporosis patients with AF who took warfarin. Clinicians should pay enough attention when using alendronate sodium on these kinds of patients and be aware of the consequent potential bleeding risk.

Efficacy and Safety of Gamma Knife Radiosurgery for Meningiomas in Patients with Neurofibromatosis Type 2: A Long-Term Follow-Up Single-Center Study.

OBJECTIVE: To explore the efficacy and safety of Gamma Knife radiosurgery (GKRS) for meningiomas in patients with neurofibromatosis type 2 (NF2). METHODS: A series of 35 consecutive patients with 99 meningiomas in our department were retrospectively included from January 2000 to December 2015. Clinical records, magnetic resonance images, and follow-up data were reviewed. RESULTS: A total of 35 patients (25 women and 10 men) with 99 NF2-associated meningiomas were identified. All patients initially received GKRS. The patients' median age at the time of GKRS was 40 years (range, 16-61 years). The median prescription dose at the tumor margin was 13 Gy (range, 12-15 Gy). The median follow-up time was 96 months (range, 25-224 months). Twenty-nine patients received GKRS only once, and 6 patients received it multiple times. Six patients (17.1%) had radiation-related complications 7.5 ± 2.4 months after GKRS. Local control rates at 1, 3, and 5 years were 100%, 97.1%, and 90.6%, respectively. Distant control rates at 1, 3, and 5 years were 88.5%, 55.9%, and 45.5%, respectively. Five patients died of concomitant neurologic symptoms. No malignant transformation was observed during the follow-up periods in all 35 patients. CONCLUSIONS: GKRS represents an effective and safe management strategy with minimal invasion for patients with NF2-associated meningiomas. Our data showed a high local control rate of NF2-associated meningiomas by GKRS; however, the distant control rate is low, especially in young patients. For these patients, retreatment with GKRS may still be the advisable method.

Occult community acquired Klebsiella pneumoniae purulent meningitis in an adult: A case report.

RATIONALE: Klebsiella pneumonia (K. pneumonia), primarily a hospital-acquired pathogen, can cause a variety of deep-seated infections with significant morbidities. However, in the current scenario of global rise in antibiotic abuse, unexpected infection could be caused by K. pneumoniae. PATIENT CONCERNS: A 56-year-old male who presented with intermittent headache and low fever was admitted, he had transsphenoidal surgery for pituitary adenoma 3 years ago. Routine laboratory tests revealed an elevated WBC count of 10.12 × 10/L and C-reactive protein (CRP) 12.9 mg/L. computed tomography (CT) revealed the sellar region with suspicious hemorrhage. DIAGNOSES: The patient was initially diagnosed with acute residual tumor hemorrhage. But the consequent diagnose of Klebsiella pneumoniae purulent meningitis was made based on the cerebrospinal fluid lab test and cerebrospinal fluid (CSF) and blood culture, and CT scan. INTERVENTIONS: Lumbar puncture examination was made and the antibiotics were adjusted to meropenem and vancomycin according to the antibiotic sensitivity test. But because of the patient's unstable vital signs, his family refuse further lateral ventricular drainage. OUTCOMES: The infection was out of control and the patient died of spontaneous breath and heartbeat arrest. LESSONS: Through this case, we could learn that any clue of suspicious intracranial infection should be carefully considered in the current scenario of global rise in antibiotic abuse. The manifestation of intermittent headache and mild fever could be potential signs of fatal infection, and prompt appropriate measures should be taken timely.