R2-ISS staging combined with circulating plasma cells improves risk stratification for newly diagnosed multiple myeloma: a single-center real-world study.

We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

Histone deacetylase 6 as a novel promising target to treat cardiovascular disease.

Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular disease. Recent studies have focused on the crucial role of HDAC6 in regulating cardiovascular diseases such as atherosclerosis, myocardial infarction, myocardial hypertrophy, myocardial fibrosis, hypertension, pulmonary hypertension, and arrhythmia. Here, we review the association between HDAC6 and cardiovascular disease, the research progress of HDAC6 inhibitors in the treatment of cardiovascular disease, and discuss the feasibility of combining HDAC6 inhibitors with other therapeutic agents to treat cardiovascular disease.

Compressive Properties of Basalt Fibers and Polypropylene Fiber-Reinforced Lightweight Concrete.

With the development of high-rise and large-scale modern structures, traditional concrete has become a design limitation due to its excessive dead weight. High-strength lightweight concrete is being emphasized. Lightweight concrete has low density and the characteristics of a brittle material. This is an important factor affecting the strength and ductility of the lightweight concrete. To improve these shortcomings and proffer solutions, a three-phase composite lightweight concrete was prepared using a combination of tumbling and molding methods. This paper investigates the various influencing factors such as the stacking volume fraction of GFR-EMS, the type of fiber, and the content and length of fiber in the matrix. Studies have shown that the addition of fibers significantly increases the compressive strength of the concrete. The compressive strength of concrete with a 12 mm basalt fiber (BF) (1.5%) admixture is 9.08 MPa, which is 62.43% higher than that of concrete without the fiber admixture. The compressive strength was increased by 27.53 and 21.88% compared to concrete containing 3 mm BF (1.5%) and 0.5% BF (12 mm), respectively. Fibers can fill the pore defects within the matrix. Mutually overlapping fibers easily form a network structure to improve the bond between the cement matrix and the aggregate particles. The compressive strength of lightweight concrete with the addition of BF was 16.71% higher than that with the addition of polypropylene fiber (PPF) with the same length and content of fibers. BF has been shown to be more effective in improving the mechanical properties of concrete. In this work, the compressive mechanism and optimum preparation parameters of a three-phase composite lightweight concrete were analyzed through compression tests. This provides some insights into the development of lightweight concrete.

Phases of (2+1)D SO(5) Nonlinear Sigma Model with a Topological Term on a Sphere: Multicritical Point and Disorder Phase.

Novel critical phenomena beyond the Landau-Ginzburg-Wilson paradigm have been long sought after. Among many candidate scenarios, the deconfined quantum critical point (DQCP) constitutes the most fascinating one, and its lattice model realization has been debated over the past two decades. Here we apply the spherical Landau level regularization upon the exact (2+1)D SO(5) nonlinear sigma model with a topological term to study the potential DQCP therein. We perform a density matrix renormalization group (DMRG) simulation with SU(2)_{spin}×U(1)_{charge}×U(1)_{angular-momentum} symmetries explicitly implemented. Using crossing point analysis for the critical properties of the DMRG data, accompanied by quantum Monte Carlo simulations, we accurately obtain the comprehensive phase diagram of the model and find various novel quantum phases, including Néel, ferromagnet (FM), valence bond solid (VBS), valley polarized (VP) states and a gapless quantum disordered phase occupying an extended area of the phase diagram. The VBS-disorder and Néel-disorder transitions are continuous with non-Wilson-Fisher exponents. Our results show the VBS and Néel states are separated by either a weakly first-order transition or the disordered region with a multicritical point in between, thus opening up more interesting questions on the two-decade long debate on the nature of the DQCP.

Up-regulation of miR-126 via DNA methylation in hypoxia-preconditioned endothelial cells may contribute to hypoxic tolerance of neuronal cells.

BACKGROUND: Endothelial cells (ECs) can confer neuroprotection by secreting molecules. This study aimed to investigate whether DNA methylation contributes to the neuroprotective gene expression induced by hypoxia preconditioning (HPC) in ECs and to clarify that the secretion of molecules from HPC ECs may be one of the molecular mechanisms of neuroprotection. METHODS: Human microvascular endothelial cell-1 (HMEC-1) was cultured under normal conditions (C), hypoxia(H), and hypoxia preconditioning (HPC), followed by the isolation of culture medium (CM). SY5Y cell incubated with the isolated CM from HMEC-1 was exposed to oxygen-glucose deprivation (OGD). The DNA methyltransferases (DNMTs), global methylation level, miR-126 and its promotor DNA methylation level in HMEC-1 were measured. The cell viability and cell injury in SY5Y were detected. RESULTS: HPC decreased DNMTs level and global methylation level as well as increased miR-126 expression in HMEC-1. CM from HPC treated HMEC-1 also relieved SY5Y cell damage, while CM from HMEC-1 which over-expression of miR-126 can reduce injury in SY5Y under OGD condition. CONCLUSIONS: These findings indicate EC may secrete molecules, such as miR-126, to execute neuroprotection induced by HPC through regulating the expression of DNMTs.

Association between coronary artery stenosis and myocardial injury in patients with acute pulmonary embolism: A case-control study.

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE. METHODS: In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation. RESULTS: The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243-5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056-5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792-30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467-8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288-36.484) were independently associated with elevated hs-cTnI. CONCLUSIONS: CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Increased expression of keratin 17 in oral lichen planus and its correlation with disease severity.

Background/purpose: Oral lichen planus (OLP) is a chronic inflammatory disease with unknown mechanisms of pathogenesis. Keratin 17 (KRT17) is a protein that regulates numerous cellular processes. This study aimed to explore the expression of KRT17 in OLP and its correlation with the severity of OLP. Materials and methods: RNA sequencing using epithelium from 5 OLP patients and 5 health control (HC) was performed, followed by functional analysis. The validation cohort of 20 OLP and 20 HC tissues were used to investigate positive area value of KRT17 by immunohistochemical analysis. Reticular, erosive and ulcerative (REU) scores were used for measuring the severity of OLP. Results: A total of 15493 genes were detected, of which 1492 genes were significantly up-regulated in OLP and 622 were down-regulated. The mRNA expression of KRT17 was elevated by 13.09-fold in OLP compared to that in HC. Pathway analysis demonstrated high KRT17 expression was associated with multiple biological processes. The median of percentage of KRT17 positive area value was 19.30 % in OLP and 0.01 % in HC (P < 0.001). Percentage of KRT17 positive area value was higher in erosive OLP patients (27.25 %) compared to that in non-erosive patients (15.02 %, P = 0.006). REU scores were positively correlated with percentage of KRT17 positive area value (r = 0.628, P = 0.003). Conclusion: The mRNA expression of KRT17 was elevated in OLP tissues compared to that in HC. KRT17 was positively correlated with the severity of OLP, indicating KRT17 might play a vital role in the pathogenesis of OLP.

Effect of force direction and impaction angulation during dilaceration impacted central incisor traction: a finite element analysis.

BACKGROUND: The effects of traction forces at different angles on impacted central incisors(ICI)with varying inverted angles (IA) may be different. The objective of this study was to analyze the biomechanical effects of different force directions (FD) on developmentally inverted ICI with multi-angle variations and to offer insights and guidance for the treatment of inverted ICI. METHODS: Three-dimensional finite element method was employed to simulate clinical scenarios of inverted ICI traction. As such, 0.2 N of force (direction: antero-superior angles of 90°, 100°, 110°, 120°, and 130° relative to the long axis of the inverted ICI crown) was applied to the inverted ICI with inverse angles (IA) of 40°, 30°, 20°, 10° and 0°. Inverted ICI apical displacement and Von Mises stress on periodontal ligament (PDL) and alveolar bone were compared. RESULTS: IA and FD showed minimal influence on the stress distribution in the PDL, as higher stresses were concentrated in the apical region. The higher stresses in the alveolar bone are focused on the cervical and apical regions of the tooth. In particular, IA exerts a more significant impact on stress distribution in the alveolar bone than FD. The influence of IA on the apical displacement of inverted ICI is larger than that of FD. CONCLUSIONS: To promote the health of the root and periodontal tissues, it is recommended to use an angle of 100°-110° relative to the long axis of the ICI crown when dealing with a large IA (> 20°) developmentally inverted ICI. Conversely, an angle of 110°-120° can be used.

[Effect of combined application of organic and chemical fertilizers on yield and quality of Epimedium pubescens].

To investigate the effects of different ratios of organic and chemical fertilizers on the yield and quality of Epimedium pubescens,so as to provide a scientific basis for the fertilization of high-yield and high-quality E. pubescens cultivation. In this experiment,a field plot test was conducted,and CK(without fertilizer) was set as the control group,with five treatment groups with different ratios of organic fertilizers and chemical fertilizers set up,namely OF0(100% chemical fertilizers),OF25(25% organic fertilizers),OF50(50% organic fertilizers),OF75(75% organic fertilizers),and OF100(100% organic fertilizers). The effects of different fertilization patterns on the agronomic traits,yield,effective component content,nutrient accumulation,and soil physicochemical properties of E. pubescens were determined,and the yield and quality of the medicinal herb were comprehensively evaluated by using the CRITIC weights method. It was found that the herb yield of each treatment group was significantly increased compared with the CK group,although the yield of the groups with both organic fertilizer and chemical fertilizer was slightly lower than that of OF0. However,there was no significant difference,which indicated that the organic fertilizer combined with chemical fertilizer could ensure the herb yield. With the increase in organic fertilizer ratios,the medicinal components epimedin A,epimedin B,and epimedin C showed a tendency of first increasing and then decreasing,with the highest content in the OF25,while icariin showed a rising trend,with the best in the OF100. However,overall,the total flavonol glycosides ABCI accumulated the most in the OF25. The results of the CRITIC method showed that the top three fertilization treatments in terms of the comprehensive scores of the medicinal herb were OF25,OF50,and OF75. Organic fertilizer combined with chemical fertilizer is conducive to improving the soil's fertilizer holding and supply capacity,and the soil indexes are optimal in OF100. The soil enzyme activity is the highest in OF75. Meanwhile,organic fertilizer combined with chemical fertilizer can help the plant's uptake and accumulation of nutrients,and OF25 shows the most obvious effect.By comprehensively considering the influence of different ratios of organic and chemical fertilizers on the yield,effective component content,nutrient accumulation,and other indexes of E. pubescens,it is recommended that a 25% ratio(7 500 kg·hm~(-2)) of organic fertilizers and chemical fertilizers should be used in E. pubescens production in the first year,so as to promote the E. pubescens industry to increase yield and improve quality.

Neighborhood Walkability Is Associated With Lower Burden of Cardiovascular Risk Factors Among Cancer Patients.

Background: Modifiable cardiovascular risk factors constitute a significant cause of cardiovascular disease and mortality among patients with cancer. Recent studies suggest a potential link between neighborhood walkability and favorable cardiovascular risk factor profiles in the general population. Objectives: This study aimed to investigate whether neighborhood walkability is correlated with favorable cardiovascular risk factor profiles among patients with a history of cancer. Methods: We conducted a cross-sectional study using data from the Houston Methodist Learning Health System Outpatient Registry (2016-2022) comprising 1,171,768 adults aged 18 years and older. Neighborhood walkability was determined using the 2019 Walk Score and divided into 4 categories. Patients with a history of cancer were identified through International Classification of Diseases-10th Revision-Clinical Modification codes (C00-C96). We examined the prevalence and association between modifiable cardiovascular risk factors (hypertension, diabetes, smoking, dyslipidemia, and obesity) and neighborhood walkability categories in cancer patients. Results: The study included 121,109 patients with a history of cancer; 56.7% were female patients, and 68.8% were non-Hispanic Whites, with a mean age of 67.3 years. The prevalence of modifiable cardiovascular risk factors was lower among participants residing in the most walkable neighborhoods compared with those in the least walkable neighborhoods (76.7% and 86.0%, respectively). Patients with a history of cancer living in very walkable neighborhoods were 16% less likely to have any risk factor compared with car-dependent-all errands neighborhoods (adjusted OR: 0.84, 95% CI: 0.78-0.92). Sensitivity analyses considering the timing of events yielded similar results. Conclusions: Our findings demonstrate an association between neighborhood walkability and the burden of modifiable cardiovascular risk factors among patients with a medical history of cancer. Investments in walkable neighborhoods may present a viable opportunity for mitigating the growing burden of modifiable cardiovascular risk factors among patients with a history of cancer.

The potential and pitfalls of using a large language model such as ChatGPT, GPT-4, or LLaMA as a clinical assistant.

OBJECTIVES: This study aims to evaluate the utility of large language models (LLMs) in healthcare, focusing on their applications in enhancing patient care through improved diagnostic, decision-making processes, and as ancillary tools for healthcare professionals. MATERIALS AND METHODS: We evaluated ChatGPT, GPT-4, and LLaMA in identifying patients with specific diseases using gold-labeled Electronic Health Records (EHRs) from the MIMIC-III database, covering three prevalent diseases-Chronic Obstructive Pulmonary Disease (COPD), Chronic Kidney Disease (CKD)-along with the rare condition, Primary Biliary Cirrhosis (PBC), and the hard-to-diagnose condition Cancer Cachexia. RESULTS: In patient identification, GPT-4 had near similar or better performance compared to the corresponding disease-specific Machine Learning models (F1-score ≥ 85%) on COPD, CKD, and PBC. GPT-4 excelled in the PBC use case, achieving a 4.23% higher F1-score compared to disease-specific "Traditional Machine Learning" models. ChatGPT and LLaMA3 demonstrated lower performance than GPT-4 across all diseases and almost all metrics. Few-shot prompts also help ChatGPT, GPT-4, and LLaMA3 achieve higher precision and specificity but lower sensitivity and Negative Predictive Value. DISCUSSION: The study highlights the potential and limitations of LLMs in healthcare. Issues with errors, explanatory limitations and ethical concerns like data privacy and model transparency suggest that these models would be supplementary tools in clinical settings. Future studies should improve training datasets and model designs for LLMs to gain better utility in healthcare. CONCLUSION: The study shows that LLMs have the potential to assist clinicians for tasks such as patient identification but false positives and false negatives must be mitigated before LLMs are adequate for real-world clinical assistance.

[Occurrence and Risk Assessment of Microplastics in the Coastal Seawater of Guangdong Province].

Microplastics （MPs） are ubiquitous in the marine environment and have become an emerging pollutant that is attracting great attention. To reveal the pollution characteristics of MPs in surface seawater of coastal waters in Guangdong Province, nine bays （estuaries） were selected from Jiangmen to Shantou. The distribution and compositional characteristics of MPs were investigated through field sampling, oxidation digestion, and visual and compositional identification, and their potential sources were analyzed. The ecological risks were assessed by combining the pollution load index and the polymer risk index. The results showed that MPs were detected in all 30 surface seawater samples from the coastal waters of Guangdong Province, with an abundance range of 70-920 n·m-3 and an average abundance of （295.3 ±175.3） n·m-3. The highest MPs abundance was found in the Pearl River estuary, and the lowest abundance was found in Shenquan bay. The distribution patterns were mainly influenced by human activities and ocean currents. The dominant polymer types included polypropylene （31.2%）, phenol resin （16.0%）, polyethylene terephthalate （15.3%）, and polyethylene （10.9%）. The main shape, color, and size categories of MPs were fiber （57.5%）, transparent （72.0%）, and 0.5-1 mm （32.8%）, respectively. The possible sources of MPs mainly included aquaculture, fishing, navigation, tourism, municipal sewage discharge, and ocean current transportation. The model assessment results showed that the pollution load risk of MPs was relatively low, but the polymer risk was at a medium-high level. This study provides a data basis for the action plan of plastic pollution control in Guangdong Province and supports the prevention and control of marine MPs pollution.

Deferoxamine alleviates chondrocyte senescence and osteoarthritis progression by maintaining iron homeostasis.

BACKGROUND: Osteoarthritis (OA) is a prevalent age-related disease characterized by the gradual deterioration of cartilage. The involvement of chondrocyte senescence is crucial in the pathogenesis of OA. Desferoxamine (DFO) is an iron chelator with therapeutic potential in various diseases. However, the relationship of chondrocyte senescence and iron homeostasis is largely unknown. METHODS: Chondrocyte senescence was induced using tert-butyl hydroperoxide (TBHP), and the impact of DFO on chondrocyte senescence and iron metabolism was assessed through techniques such as western blotting, qRT-PCR, and ß-Galactosidase staining. To assess the impact of DFO on chondrocyte senescence and the progression of osteoarthritis (OA), the surgical destabilization of the medial meniscus model was established. RESULTS: In chondrocytes, TBHP administration resulted in elevated expression of P16, P21, and P53, as well as alterations in SA-ß-gal staining. Nevertheless, DFO effectively mitigated chondrocyte senescence induced by TBHP, and reversed the decrease in collagen II expression and increase in MMP13 expression caused by TBHP. Mechanismly, TBHP induced NCOA4 expression and iron release in chondrocytes. Excessive iron could induce chondrocyte senescence, whereas, DFO could inhibit NCOA4 expression and restore ferritin level, and chelate excessive iron. Importantly, intra-articular injection of DFO enhanced collagen II expression and reduced expression of P16, P21, and MMP13 of cartilage in OA mice, and delayed cartilage degeneration. CONCLUSIONS: Overall, this study provides evidence that DFO has the potential to alleviate chondrocyte senescence induced by TBHP and slow down the progression of osteoarthritis (OA) by effectively chelating excessive iron. These findings suggest that iron chelation could be a promising therapeutic strategy for treating OA.

Nanoscale chestnut soil pore characteristics changes induced by non-growing season precipitation in a temperate grassland.

Changes in precipitation patterns during the non-growing season can affect soil moisture storage in temperate grasslands. However, there is a lack of comprehensive understanding regarding how these changes influence microscale soil pore characteristics and nutrient cycling in the context of climate change. Therefore, we carried out a 3-year artificial precipitation experiment during the non-growing season, along with N2 adsorption experiments of soil pore distribution and surveys of soil nutrient content. The aim was to clarify the influence of non-growing season precipitation variations on nanoscale soil pore characteristics and explore the potential correlations of the soil physicochemical properties. The results showed that: (1) The precipitation sheltering treatment during the non-growing season led to a significant 9.80 % increase in soil porosity at the 0-15 cm depth compared to the control. (2) Compared to the control, alterations in non-growing season precipitation (both increase and sheltering treatments) led to a significant increase in soil specific surface area (SSA), with an average increase of 23.2 %. Additionally, soil micropores, mesopores, macropores, and total pore volume (PV) increased by an average of 24.2 %, 14.0 %, 30.1 %, and 23.1 %, respectively. (3) Significant correlations were observed between soil microscale pore characteristics and soil C, soil organic matter (SOM), C: N ratio, and available P (AP). Redundancy analysis showed that soil microscale pore characteristics effectively accounted for the variations in soil nutrients with an explanatory degree of 94.23 %. (4) Influence pathways analysis by structural equation modeling indicated that dramatic variability in non-growing season precipitation promoted increases in mesopore and macropore volume, as well as the transformation of mesopores into macropores, thereby facilitating soil carbon accumulation. Our study suggests that soil microscale pore characteristics, acquired through adsorption experiments, assist in elucidating these potential synergistic mechanisms among physicochemical properties under varying non-growing season precipitation patterns. Given the escalating impacts of climate change, our findings provide novel insights and evidence for the assessment of climate change impacts in temperate arid grassland ecosystems.

IRF1 regulation of ZBP1 links mitochondrial DNA and chondrocyte damage in osteoarthritis.

BACKGROUND: Z-DNA binding protein 1 (ZBP1) is a nucleic acid sensor that is involved in multiple inflammatory diseases, but whether and how it contributes to osteoarthritis (OA) are unclear. METHODS: Cartilage tissues were harvested from patients with OA and a murine model of OA to evaluate ZBP1 expression. Subsequently, the functional role and mechanism of ZBP1 were examined in primary chondrocytes, and the role of ZBP1 in OA was explored in mouse models. RESULTS: We showed the upregulation of ZBP1 in articular cartilage originating from OA patients and mice with OA after destabilization of the medial meniscus (DMM) surgery. Specifically, knockdown of ZBP1 alleviated chondrocyte damage and protected mice from DMM-induced OA. Mechanistically, tumor necrosis factor alpha induced ZBP1 overexpression in an interferon regulatory factor 1 (IRF1)-dependent manner and elicited the activation of ZBP1 via mitochondrial DNA (mtDNA) release and ZBP1 binding. The upregulated and activated ZBP1 could interact with receptor-interacting protein kinase 1 and activate the transforming growth factor-beta-activated kinase 1-NF-κB signaling pathway, which led to chondrocyte inflammation and extracellular matrix degradation. Moreover, inhibition of the mtDNA-IRF1-ZBP1 axis with Cyclosporine A, a blocker of mtDNA release, could delay the progression of DMM-induced OA. CONCLUSIONS: Our data revealed the pathological role of the mtDNA-IRF1-ZBP1 axis in OA chondrocytes, suggesting that inhibition of this axis could be a viable therapeutic approach for OA.

Epilepsy surgery for children with epileptic spasms: A systematic review and meta-analysis with focus on predictors and outcomes.

To conduct a systematic review of the literature regarding rates and predictors of favorable seizure outcome after resective surgery for epileptic spasms (ES) in pediatric patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed. We searched PubMed, EMBASE, and Cochrane CENTRAL for articles published on the prevalence or incidence of epileptic spasm since 1985. Abstract, full-text review, and data extraction were conducted by two independent reviewers. Meta-analysis was performed to assess overall seizure freedom rate. Subject-level analysis was performed on a subset of studies to identify prognostic indicators. A total of 21 retrospective studies (n = 531) were included. Meta-analysis of all studies demonstrated a pooled seizure freedom rate of 68.8%. Subject-level analysis on 18 studies (n = 360) demonstrated a significant association between duration of spasms and recurrence of spasms after surgery, with an estimated increased risk of 7% per additional year of spasms prior to operation. Patients who underwent resective surgery that was not a hemispherectomy (i.e., lobectomy, lesionectomy, etc.) had an increased recurrence risk of 57% compared to patients who had undergone hemispherectomy. Resective surgery results in seizure freedom for the majority of pediatric patients with epileptic spasms. Patients who undergo hemispherectomy have lower risk of recurrence than patients who undergo other types of surgical resection. Increased duration of spasms prior to surgery is associated with increased recurrence risk after surgery. PLAIN LANGUAGE SUMMARY: Children with epileptic spasms (ES) that do not respond to medications may benefit from surgical treatment. Our study reviewed existing research to understand how effective surgery is in treating ES in children and what factors predict better outcomes. Researchers followed strict guidelines to search for and analyze studies published since 1985, finding 21 studies with a total of 531 patients. They found that, on average, nearly 70% of children became seizure-free after surgery. Further individual analysis of 360 patients showed that longer duration of spasms before surgery increased the risk of spasms returning by 7% per year. Additionally, children who had less extensive surgeries, such as removal of only a specific part of the brain, had a 57% higher risk of seizure recurrence compared to those who had a hemispherectomy, which removed or disconnected half of the brain. Overall, the study concludes that surgery can often stop seizures, especially when more extensive surgery is performed and when the surgery is done sooner rather than later.

Therapeutic effects of exendin-4 on spinal cord injury via restoring autophagy function and decreasing necroptosis in neuron.

AIMS: Necroptosis is one of programmed death that may aggravate spinal cord injury (SCI). We aimed to investigate the effect and mechanism of exendin-4 (EX-4) on the recovery of motor function and necroptosis after SCI. METHODS: The SD rats with left hemisection in the T10 spinal cord as SCI model were used. The behavior tests were measured within 4 weeks. The effects of EX-4 on necroptosis-associated proteins and autophagy flux were explored. In addition, the SHSY5Y cell model was introduced to explore the direct effect of EX-4 on neurons. The effect of lysosome was explored using mTOR activator and AO staining. RESULTS: EX-4 could improve motor function and limb strength, promote the recovery of autophagy flux, and accelerate the degradation of necroptosis-related protein at 3 d after injury in rats. EX-4 reduced lysosome membrane permeability, promoted the recovery of lysosome function and autophagy flux, and accelerated the degradation of necroptosis-related proteins by inhibiting the phosphorylation level of mTOR in the SHSY5Y cell model. CONCLUSION: Our results demonstrated that EX-4 may improve motor function after SCI via inhibiting mTOR phosphorylation level and accelerating the degradation of necroptosis-related proteins in neurons. Our findings may provide new therapeutic targets for clinical treatment after SCI.