Analysis of new-onset seizures following use of COVID-19 vaccinations in children based on VAERS.

BACKGROUND: Recently, there have been some reports of seizures related with COVID-19 vaccinations. However, no studies have systematically investigated the relationship between seizures and various COVID-19 vaccines. RESEARCH DESIGN AND METHODS: This research aimed to analyze the characteristics and risk signals of new-onset seizures in children caused by various COVID-19 vaccines based on the data of the Vaccine Adverse Event Reporting System (VAERS). To identify potential risk signals, a disproportionality analysis was conducted. The reporting odds ratio (ROR) and the Proportional Reporting Ratio (PRR) were used to detect signals. RESULTS: A total of 695 children with new-onset seizures events associated with COVID-19 vaccinations were retrieved from the VAERS database. Compared with influenza vaccinations, the percentage and rate of COVID-19 vaccinations related seizures was all reduced. The median onset time of seizures was 1 day after COVID-19 vaccines. No signal was detected for an association between the COVID-19 vaccines and new-onset seizures, neither when compared with influenza vaccines nor with non-COVID-19 vaccines. CONCLUSION: No statistically significant risk signal of COVID-19 vaccine-related seizures was found in this study. However, it is still necessary to monitor the possibility of new-onset seizures when children are immunized with COVID-19 vaccines.

Real-world data for the availability of pediatric medicines in Chinese hospitals: a multi-center survey and analysis.

Aim: No information exists on the availability of pediatric medicines in China. This study aimed to access the availability of different types of pediatric medicine and determine their ratio in medical institution drug catalogs. Methods: Based on drug instructions, an expert meeting method was used to divide pediatric medicines into five categories: child-specific medicine (CSM), co-use medicine for adults and children (CMAC), other pediatric medicines (OCM), off-label medicine use (OMU), and non-child medicine (NM). Results: A total of 60 hospitals nationwide participated in this survey, namely, 20 children's hospitals (C-hosp), 14 maternal and child healthcare hospitals (MCHC-hosp), and 26 general hospitals (G-hosp). The average number of drug catalogs in G-hosp was significantly higher than that in C-hosp and MCHC-hosp. CSM accounted for 9.77% of the C-hosp catalog, 7.12% of the MCHC-hosp catalog, and 1% of the G-hosp catalog. The availability rate of CMAC was 49.63% in C-hosp and 40.87% and 31% in MCHC-hosp and G-hosp, respectively. The proportion of OCM in C-hosp (27.28%) was higher than that in MCHC-hosp (13.4%) and G-hosp (5%). The OMU occupied ratio in C-hosp, MCHC-hosp, and G-hosp is not negligible, which was 12.06%, 8.7%, and 10% respectively. The proportion of NM in C-hosp was almost negligible but was 29.91% and 53% in MCHC-hosp and G-hosp, respectively. Compared to the CSM and CMAC listed in China, the share of CSM in C-hosp was close to 40%, which was much higher than that of G-hosp and MCHC-hosp. In contrast, the share of CMAC in G-hosp was nearly 30%, which was significantly higher than that in C-hosp and MCHC-hosp. Health insurance covers most of these five types of pediatric medicines, with the proportion of insured medicines reaching close to 80% in C-hosp and approximately 85% in MCHC-hosp and G-hosp. Discussion: The availability of specific medicines suitable for use in children is generally low, and even CSM in specialized hospitals such as C-hosp cannot meet the relatively high accessibility level of WHO evaluation standards. Policies and measures should be implemented to boost the research and development of pediatric medicines, as well as supplement safety information lacking in instruction manuals.

Deletion of mesencephalic astrocyte-derived neurotrophic factor delays and damages the development of white pulp in spleen.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) stress-induced protein, and it has been reported that ER stress and unfolded protein response (UPR) are closely related to the immune system. The spleen is an important immune organ and we have shown in our previous research that MANF is expressed in human spleen tissues. However, there have been limited studies about the effect of MANF on spleen development. In this study, we detected MANF expression in spleen tissues and found that MANF was expressed in the red pulp and marginal zone. Additionally, MANF was localized in the CD68+ and CD138+ cells of adult rat spleen tissues, but not in the CD3+ cells. We performed immunohistochemical staining to detect MANF expression in the spleen tissues of rats that were different ages, and we found that MANF+ cells were localized together in the spleen tissues of rats that were 1-4 weeks old. MANF was also expressed in CD68+ cells in the spleen tissues of rats and mice. Furthermore, we found that MANF deficiency inhibited white pulp development in MANF knockout mice, thus indicating that MANF played an important role in the white pulp development of rodent spleen tissues.

Progression of the PI3K/Akt signaling pathway in chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) is a chronic respiratory disease characterized by a slow progression and caused by the inhalation of harmful particulate matter. Cigarette smoke and air pollutants are the primary contributing factors. Currently, the pathogenesis of COPD remains incompletely understood. The PI3K/Akt signaling pathway has recently emerged as a critical regulator of inflammation and oxidative stress response in COPD, playing a pivotal role in the disease's progression and treatment. This paper reviews the association between the PI3K/Akt pathway and COPD, examines effective PI3K/Akt inhibitors and novel anti-COPD agents, aiming to identify new therapeutic targets for clinical intervention in this disease.

Serum TSH Levels are Associated with Hyperactivity Behaviors in Children with Attention Deficit/Hyperactivity Disorder.

Objective: Previous studies indicated that maternal thyroid dysfunction increase the offspring's risk for attention deficit/hyperactivity disorder (ADHD). However, the relationship between thyroid function and symptoms in children with ADHD remains unclear. Methods: A total of 49 children with ADHD were enrolled. The Conners 3 scale was used to estimate the symptoms associated with ADHD. Correlation between thyroid hormones and the scores of the Conners 3 scale was evaluated by Pearson correlation analysis. Then, ADHD children were divided into two groups according to the hyperactivity index (HI) of the Conners 3 scale: ADHD children with hyperactivity behaviors (HB) (HI > 1.5) and ADHD children without HB (HI < 1.5). The demographic characteristics, thyroid hormones, and routine laboratory parameters between the two groups were collected. To distinguish HI-related factors, a univariate analysis and a binary logistic regression predictive model were used. The discriminative ability of thyroid stimulating hormone (TSH) in predicting ADHD children with HB from ADHD children without HB was investigated using the receiver operating characteristic (ROC) curve method. Results: The levels of TSH were positively correlated to the scores of the Conners 3 scale (r = 0.338, P = 0.033) and HI (r = 0.371, P = 0.019). Moreover, the levels of TSH, serum ferritin, and lactic acid were significantly increased in ADHD children with HB compared to ADHD children without HB (all P < 0.05). Furthermore, the results of binary logistic regression found that TSH (OR 2.243 (CL 1.052-4.783)) and lactic acid (OR 1.018 (CI 1.003-1.032)) were independently associated with HI. Additionally, ROC analysis indicated the potential diagnostic value of TSH in discriminating ADHD children with HB from ADHD children without HB with an AUC of 0.684. Conclusion: These results suggested that the serum TSH levels may be related to the HB in children with ADHD.

Pan-Cancer analysis shows that ACO2 is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including hepatocellular carcinoma.

Background: Recent evidence increasingly suggests key roles for the tricarboxylic acid cycle and fatty acid metabolism in tumor progression and metastasis. Aconitase 2 (ACO2) is a component of the tricarboxylic acid cycle and represents a key cellular metabolic hub that promotes de novo fatty acid biosynthesis. However, there have been few reports on the role of ACO2 in tumorigenesis and cancer progression. Methods: Through the comprehensive use of datasets from The Cancer Genome Atlas, Genotype-Tissue Expression Project, cBioPortal, Human Protein Atlas, UALCAN, Gene Expression Profiling Interactive Analysis, DNA Methylation Interactive Visualization Database, and TIMER2, we adopted bioinformatics methods to uncover the potential carcinogenic roles of ACO2, including by analysing ACO2 expression and correlations between prognosis, genetic mutations, immune cell infiltration, DNA methylation, tumor mutational burden, and microsatellite instability in different tumors. Additionally, the expression level and tumor-promoting effect of ACO2 were verified in hepatocellular carcinoma (HCC) cells. To explore the underlying mechanisms of ACO2 in human cancer, ACO2-related gene enrichment analysis and lipid metabolomics were performed using LM3 cells with or without ACO2 knockdown. Results: The results indicated that ACO2 was highly expressed in most cancers, showing early diagnostic value in six tumor types, and was positively or negatively associated with prognosis in different tumors. Moreover, ACO2 expression was associated with immune cell infiltration, such as CD8+ T cells and tumor-associated neutrophils, in some cancers. For most cancer types, there was a significant association between immune checkpoint-associated genes and ACO2 expression. Compared with normal hepatocytes, ACO2 was upregulated in HCC cells, which promoted their proliferation and migration. Furthermore, to explore the underlying molecular mechanism, we performed KEGG pathway enrichment analysis of ACO2-associated genes and lipidomics using LM3 cells with or without ACO2 knockdown, which screened 19 significantly altered metabolites, including 17 with reduced levels and 2 with increased levels. Conclusion: Through pan-cancer analysis, we discovered for the first time and verified that ACO2 could be a useful diagnostic biomarker for cancer detection. Additionally, ACO2 could be used as an auxiliary prognostic marker or as a marker for immunotherapy in some tumor types.

An experimental study on stress-shielding effects of locked compression plates in fixing intact dog femur.

BACKGROUND: In orthopedic application, stress-shielding effects of implant materials cause bone loss, which often induces porosis, delayed bone healing, and other complications. We aimed to compare the stress-shielding effects of locked compression plate (LCP) and limited-contact dynamic compression plate (LC-DCP) in dogs with plate-fixed femurs. METHODS: Bilateral intact femurs of 24 adult dogs were fixed by adult forearm 9-hole titanium plates using minimally invasive plate osteosynthesis (MIPPO) technology, with LCP on the left and LC-DCP on the right femurs. Dogs were sacrificed at 6 weeks, 12 weeks, and 24 weeks after surgery, and bone specimens were used to evaluate the efficacies of different fixing methods on bones through X-ray, dual-energy X-ray absorptiometry (DEXA), histology, MicroCT, and biomechanics analyses. RESULTS: X-ray results showed significant callus formation and periosteal reaction in the LC-DCP group. Bone cell morphology, degree of osteoporosis, and bone mineral density (BMD) changes of the LCP group were significantly better than that of the LC-DCP group. MicroCT results showed that the LCP group had significantly reduced degree of cortical bone osteoporosis than the LC-DCP group. Tissue mineral density (TMD) in the LCP group was higher than that in the LC-DCP group at different time points (6 weeks, 12 weeks, and 24 weeks). Biomechanics analyses demonstrated that the compressive strength and flexural strength of bones fixed by LCP were better than that by LC-DCP. CONCLUSIONS: Stress-shielding effects of LCP are significantly weaker than that of LC-DCP, which is beneficial to new bone formation and fracture healing, and LCP can be widely used in clinic for fracture fixation.

Relationship between the use of statins and patient survival in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Studies have indicated that statins influence the risks and mortality rates of several types of solid tumors. However, the association between statin use and survival in patients with colorectal cancer (CRC) remains unclear. METHODS: We searched the PubMed and Embase databases for relevant studies published up to September 2014 that assessed statin use and CRC prognosis. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). The secondary outcomes were disease-free survival (DFS) and recurrence-free survival (RFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled with Mantel-Haenszel random-effect modeling. All statistical tests were two-sided. RESULTS: Four studies on post-diagnosis statin therapy and five studies on pre-diagnosis statin use were included in our meta-analysis of 70,608 patients. Compared with the non-users, the patients with post-diagnosis statin use gained survival benefits for OS (HR 0.76; 95% CI: 0.68 to 0.85, P<0.001) and CSS (HR 0.70; 95% CI: 0.60 to 0.81, P<0.001). In addition, we observed that pre-diagnosis statin use prolonged the survival of patients with CRC for OS (HR 0.70; 95% CI: 0.54 to 0.91, P=0.007) and CSS (HR 0.80; 95% CI: 0.74 to 0.86, P<0.001). However, we did not observe a survival benefit for DFS (HR 1.13; 95% CI: 0.78 to 1.62, P=0.514) or RFS (HR 0.98; 95% CI: 0.36 to 2.70, P=0.975) in the CRC patients with post-diagnosis statin use. CONCLUSIONS: Statin use before or after cancer diagnosis is related to reductions in overall and cancer-specific mortality in colorectal cancer survivors.

Cimetidine attenuates vinorelbine-induced phlebitis in mice by militating E-selectin expression.

PURPOSE: We investigated E-selectin expression in mice and rabbits with vinorelbine-induced phlebitis and the effect of cimetidine. To find the relationship between E-selectin expression and vinorelbine-induced phlebitis. METHODS: Mouse and rabbit model of vinorelbine-induced phlebitis was established by intravenous infusion of vinorelbine. Pathological observation, molecular-biological determination of E-selectin and protein function of it was evaluated. RESULTS: Grossly, we observed swelling, edema and cord-like vessel changes in mice receiving vinorelbine but only mild edema in mice pretreated with cimetidine. Pathological scoring yielded a total score of 37 for vinorelbine-treated mice and 17 for mice pretreated with cimetidine (P < 0.05). ELISA revealed that rabbits treated with vinorelbine had markedly higher serum contents of E-selectin than normal saline (NS) controls (vinorelbine 1.534 ± 0.449 vs. NS 0.746 ± 0.170 ng/mL, P < 0.05), which was markedly attenuated by cimetidine (cimetidine 0.717 ± 0.468 vs. vinorelbine 1.534 ± 0.449 ng/mL, P < 0.05). Rose Bengal staining assays showed that vinorelbine markedly increased the adhesion rate of neutrophils for endothelial cells (vinorelbine 38.70 ± 8.34% vs. controls 8.93 ± 4.85%, P < 0.01), which, however, was significantly suppressed by cimetidine (9.93 ± 5.91%, P < 0.01 vs. vinorelbine). In E-selectin knockout mice, we found no apparent difference in tail swelling in mice receiving vinorelbine or cimetidine and vinorelbine. CONCLUSIONS: In conclusion, cimetidine attenuates vinorelbine-induced phlebitis in mice probably by suppressing increased expression of E-selectin.

Mechanical and biocompatible influences of chitosan fiber and gelatin on calcium phosphate cement.

Calcium phosphate cement (CPC) is a widely used bone substitute in the clinic; however, the low strength of CPC limits its utilization. In this study, we investigated mechanical influences of chitosan fiber combined with gelatin on CPC, and examined the biocompatibility of the new composite with rat bone marrow stromal cells. Compared to the fiber impregnated in phosphate buffered saline (80.5 MPa), our study showed that tensile strength of chitosan fiber increased 106 and 114% with the impregnation of gelatin at the mass fraction 5 and 10%, although this increase was not statistically significant. It was demonstrated by Fourier transform infrared spectroscopy that the characteristic absorption bands of chitosan were changed with the addition of gelatin. The optimal flexural strength enhancement was obtained when CPC was reinforced with fiber at volume fraction of 30% and gelatin at mass fraction of 5% (maximum: 12.31 MPa). The fiber morphology was more compact when the chitosan fibers impregnated with gelatin at mass fraction of 5 or 10% than chitosan alone. The fracture analysis showed that the new CPC-chitosan fiber-gelatin composite presented many remnants of CPC adhered to fibers. Short minimum essential medium extract test showed no cell growth inhibition after the addition of the new composite. Rat bone marrow stromal cells retain the ability to spread and grow on the composite. Our studies demonstrated that the flexural strength is greatly increased by using CPC incorporated with proper ratio of CF and gelatin. More over, the new composite demonstrated biocompatibility in vitro.

[Prospect of the foveola formation in the bovine trabecular bone under fatigue process].

This study aims at the mechanism of foveola formation in bovine trabecular bone under fatigue process and its relation with biomechanical pathogenesis of senile osteoporosis. The scanning electron microscope equipped with fatigue stage was used to observe fatigue micro injury accumulation of cancellous bone. The massive foveola formation in the laminal bone of vertical trabeculae was found in the tensile fatigue test. There existed the collagen avulsion in the foveola. The massive foveola formation was also observed in the lamina bone of the horizontal trabeculae in the compressive fatigue test. The bone collagen fibers were protracted, debound with hydroxyapatite crystal, and then avulsed under tensile and bending stresses. Finally the retraction of the avulsed collagen fibers brought on the massive formation of foveolae in lamina bone. The mechanical capacity of bone also declined greatly. We infer that the direct mineralization of avulsed collagen and foveola in lamina bone would be one of the main processes of self repair in vivo, which brings on the increase in fragility and stiffness of trabeculae of senile osteoporotic bone along with the agelong accumulation of collagen fatigue injury and foveola formation in the lamina bone.