Causal role of peripheral immune cells in epilepsy: A large-scale genetic correlation study.

BACKGROUND: While an increasing number of researchers have focused on the correlation between the immune system and epilepsy, the precise causal role of immune cells in epilepsy continues to elude scientific understanding. The aim of the study was to examine the causal relationship between peripheral immune phenotypes and epilepsy. METHODS: Mendelian randomization (MR) analysis and linkage disequilibrium score regression (LDSC) were utilized to determine the causal relationship between 731 immune cell traits and various types of epilepsy in this study. RESULTS: LDSC revealed that 80 immunophenotypes showed genetic correlation with epilepsy, including 58 immunophenotypes associated with a single type of epilepsy (72.5 %),14 immunophenotypes associated with two types of epilepsy (17.5 %),7 immunophenotypes with 3 types of epilepsy (8.75 %) and 1 immunophenotype with 5 types of epilepsy (1.25 %). Although none of the types of epilepsy had a statistically significant effect on immunophenotypes, it is noteworthy that the MR revealed the protective effects of five immunophenotypes on epilepsy: CD45RA+CD8br AC (OR:0.86, 95 %CI:0.80-0.93), FSC-A on myeloid DC (OR:0.95, 95 %CI:0.91-0.98）, CM CD8br AC (OR:0.69, 95 %CI:0.59--0.82), CD33 on CD66b++ Myeloid cell (OR:0.88, 95 %CI:0.83-0.93) and CD127 on CD28- CD8br (OR:0.97, 95 %CI:0.95-0.98). Additionally, harmful effects were observed for two immunophenotypes on epilepsy:CD4 Treg %CD4 (OR:1.04, 95 %CI:1.02-1.06) and SSC-A on plasmacytoid DC (OR:1.01, 95 %CI:1.00-1.02). CONCLUSION: Our research has demonstrated the causal connections between immune cells and epilepsy, potentially providing valuable insights for future clinical studies.

Pulmonary embolism following severe polytrauma: a retrospective study from a level I trauma center in China.

BACKGROUND: Trauma patients are at high risk of Venous thromboembolism (VTE), but compared to well-established deep venous thrombosis (DVT), data specifically evaluating post-traumatic pulmonary embolism (PE) are scarce. The aim of this study is to assess whether PE represents a distinct clinical entity with injury pattern, risk factors, and prophylaxis strategy different from DVT, among severe poly-trauma patients. PATIENTS AND METHODS: We retrospectively enrolled patients admitted to our level I trauma center from January 2011 to December 2021 who were diagnosed with severe multiple traumatic injuries and identified thromboembolic events among them. We regarded four groups as None (without thromboembolic events), DVT only, PE only, and PE with DVT. Demographics, injury characteristics, clinical outcomes, and treatments were collected and analyzed in individual groups. Patients were also classified according to the occurring time of PE, and indicative symptoms and radiological findings were compared between early PE (≤ 3 days) and late PE (> 3 days). Logistic regression analyses were conducted to explore independent risk factors for different VTE patterns. RESULTS: Among 3498 selected severe multiple traumatic patients, there were 398 episodes of DVT only, 19 of PE only, and 63 of PE with DVT. Injury variables associated with PE only included shock on admission and severe chest trauma. Severe pelvic fracture and mechanical ventilator days (MVD) ≥ 3 were the independent risk factors for PE with DVT. There were no significant differences in the indicative symptoms and location of pulmonary thrombi between the early and late PE groups. Obesity and severe lower extremity injury might have an impact on the incidence of early PE, while patients with a severe head injury and higher ISS are particularly at risk for developing late PE. CONCLUSION: Occurring early, lacking association with DVT, and possessing distinct risk factors warrant PE in severe poly-trauma patients special attention, especially for its prophylaxis strategy.

Impact of White Matter Hyperintensity and Age on Gait Parameters in Patients With Cerebral Small Vessel Disease.

OBJECTIVES: This study aimed to investigate the effect of white matter hyperintensity (WMH), a common cerebral small vessel disease (CSVD) imaging marker, and age on gait parameters in middle-aged and geriatric populations. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 1076 participants (62.9% female; age 61.0 ± 9.3 years), who visited the neurology clinic or obtained a physical check-up from the Affiliated Hospital of Guizhou Medical University. In total, 883 patients with WMH and 193 healthy controls were included in this study. METHODS: The Fazekas scores of patients with CSVD were used to assess the burden of WMH. Based on the Fazekas scores, all participants were divided into 4 groups: 553 patients with Fazekas I, 257 patients with Fazekas II, 73 patients with Fazekas III, and 193 controls. Gait parameters, including step speed, frequency, length, width, stance time, and swing time, were quantitatively assessed using a vision-based artificial intelligence gait analyzer (SAIL system). The relationships among the Fazekas scores, age, and gait parameters were analyzed. RESULTS: Step speed, step length, step width, stance time, and swing time were significantly different among the 4 groups. Furthermore, Fazekas scores and age were both associated with gait parameters, including step speed, step length, stance time, and swing time. The Fazekas scores were associated with step width, whereas age was not. Age was associated with step frequency, whereas Fazekas scores were not. CONCLUSIONS AND IMPLICATIONS: Fazekas score and age are useful for evaluating gait parameters in patients with CSVD. Emerging WMH (such as Fazekas Ⅰ) could be a clinical warning sign of gait disturbance in a geriatric population.

Association between admission serum phosphate and risk of acute kidney injury in critically ill patients with rhabdomyolysis: A retrospective study based on MIMIC-â ¢.

BACKGROUND: The incidence of acute kidney injury (AKI) is high in critically ill patients with rhabdomyolysis. Limited evidence was proved of the association between serum phosphate levels at intensive care unit (ICU) admission and the subsequent risk of AKI. Our study aims to assess if serum phosphate levels at admission were independently associated with AKI risk in these patients. METHODS: This study extracted and analyzed data from Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ, version1.4). Rhabdomyolysis was defined as a peak creatine kinase (CK) level higher than 1000 U/L. Serum phosphate was measured within the first day into the ICU and was categorized to 4 groups (<2.6, 2.6-3.4, 3.5-4.5, >4.5mg/dl). AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) guidelines. Adjusted smoothing spline plots and multivariable logistic regressions were carried out to explode the association between serum phosphate and risk of AKI. Subgroup analyse was applied to verify the consistency of the association. RESULTS: Three hundred and twenty-one patients (68% male) diagnosed as rhabdomyolysis were eligible for this analysis. AKI occurred in 204 (64%) patients of total. Incidence of AKI with admission serum phosphate groups<2.6, 2.6-3.4, 3.5-4.5 and>4.5mg/dl were 53%, 57%, 68% and 76%, respectively. Smoothing spline curve showed that there was a positive curve between the elevated phosphate values and increasing risk of AKI, and there was no threshold saturation effect. In multivariable logistic regression, OR was 1.2 (95%CI 1.0-1.5, P=0.035, P trend=0.041) after adjusting confounders. Subgroup analyses proved the consistency of the relationship in these patients, possibly, except in the strata of potassium. CONCLUSION: In rhabdomyolysis patients admitted to ICU, serum phosphate levels at admission were independently associated with an increased risk of AKI. As phosphate levels rise, the risk of AKI increased.

Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China.

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.

Mixed cerebrovascular disease in an elderly patient with mixed vascular risk factors: a case report.

BACKGROUND: Mixed cerebrovascular disease is a diagnostic entity that presents with hemorrhagic and ischemic stroke clinically and/or subclinically. Here, we report a patient with mixed vascular risk factors, who presented with multiple intracerebral hemorrhages and a simultaneously occurring cerebral infarction with hemorrhagic transformation. CASE PRESENTATION: A 63-year-old male with no history of trauma or prior neurological disease presented with a sudden onset of weakness in his right limbs, followed by an episode of focal seizure without impaired awareness. The patient had a 4-year history of deep vein thrombosis in the lower limbs, and a 2-year history of Raynaud's phenomenon in the hands. He also had a family history of hypertension and thrombophilia. Head computed tomography plain scans showed two high densities in the bilateral parietal lobes and one mixed density in the left frontal lobe. The patient was diagnosed with mixed cerebrovascular disease. In this report, we make a systematic clinical reasoning regarding the etiological diagnosis, and discuss the possible pathogenic mechanisms leading to mixed cerebrovascular disease. We exclude coagulopathy, endocarditis, atrial fibrillation, patent foramen ovale, brain tumor, cerebral venous thrombosis, cerebral vascular malformation, cerebral amyloid angiopathy and vasculitis as causative factors. We identify hypertension, hereditary protein S deficiency, hypercholesteremia and hyperhomocysteinemia as contributing etiologies in this case. CONCLUSION: This case presents complex underlying mechanisms of mixed cerebrovascular disease, in which hypertension and hyperhomocysteinemia are considered to play a central role.

Development of a SCAR (sequence-characterised amplified region) marker for acid resistance-related gene in Lactobacillus plantarum.

A sequence characterised amplified region marker was developed to determine an acid resistance-related gene in Lactobacillus plantarum. A random amplified polymorphic DNA marker named S116-680 was reported to be closely related to the acid resistance of the strains. The DNA band corresponding to this marker was cloned and sequenced with the induction of specific designed PCR primers. The results of PCR test helped to amplify a clear specific band of 680 bp in the tested acid-resistant strains. S116-680 marker would be useful to explore the acid-resistant mechanism of L. plantarum and to screen desirable malolactic fermentation strains.

The effect of alpha-fetoprotein on the activation and phagocytosis of granulocytes and monocytes.

BACKGROUND/AIMS: The peripheral blood mononuclear cells constitute the first line of innate immunity.Although restricted to embryonic expression and elevated in liver cancer, alpha-fetoprotein (AFP) has recently been recognized for its role in modulation immunity. The aim of this study is to examine the influence of alpha-fetoprotein on the activation and phagocytosis of granulocytes and monocytes in vitro. METHODOLOGY: The human peripheral blood granulocytes and monocytes were prepared from healthy volunteers. Blood cells were incubated with different levels of AFP and activation by oxidative burst and phagocytosis were measured by flow cytometry. RESULTS: First- ly, the percentage of monocytes producing reactive oxygen metabolites was higher in groups with exogenous AFP than the group without AFP exposure. Secondly, we assessed the phagocytosis levels of granulocytes and monocytes at different AFP levels. At certain regions of AFP (600-6000ng/mL), the granulocytes and monocytes gained increased capacity of bacteria phagocytosis. CONCLUSIONS: Alpha-fetoprotein level in the plasma is apparently related to monocyte activation. The results also suggested that alpha-fetoprotein can stimulate the phagocytosis of granulocytes and monocytes in vitro.

[Study on natural killer cell subset and activity in patients with depression].

OBJECTIVE: The study was to investigate natural killer cells subset and activity in patients with depression. METHODS: 46 outpatients with unipolar depression and 46 normal controls were recruited. Peripheral blood samples were drawn for natural killer cells subset and activity. And the results in patients with depression before and after therapy were compared with each other. Flow cytometer was used for natural killer cells subset and enzyme-released assay was used for their activity. RESULTS: Natural killer cells subset and activities (effect-target cell ratio: 20:1,10:1)in patients with depression were significantly lower than normal controls (P < 0.01). Natural killer cell activities were increased significantly after therapy (P < 0.01)but subset was not (P > 0.05). CONCLUSION: The study suggested that unipolar depression may impact natural killer cells count and function.