Machine learning identifies novel coagulation genes as diagnostic and immunological biomarkers in ischemic stroke.

BACKGROUND: Coagulation system is currently known associated with the development of ischemic stroke (IS). Thus, the current study is designed to identify diagnostic value of coagulation genes (CGs) in IS and to explore their role in the immune microenvironment of IS. METHODS: Aberrant expressed CGs in IS were input into unsupervised consensus clustering to classify IS subtypes. Meanwhile, key CGs involved in IS were further selected by weighted gene co-expression network analysis (WGCNA) and machine learning methods, including random forest (RF), support vector machine (SVM), generalized linear model (GLM) and extreme-gradient boosting (XGB). The diagnostic performance of key CGs were evaluated by receiver operating characteristic (ROC) curves. At last, quantitative PCR (qPCR) was performed to validate the expressions of key CGs in IS. RESULTS: IS patients were classified into two subtypes with different immune microenvironments by aberrant expressed CGs. Further WGCNA, machine learning methods and ROC curves identified ACTN1, F5, TLN1, JMJD1C and WAS as potential diagnostic biomarkers of IS. In addition, their expressions were significantly correlated with macrophages, neutrophils and/or T cells. GSEA also revealed that those biomarkers may regulate IS via immune and inflammation. Moreover, qPCR verified the expressions of ACTN1, F5 and JMJD1C in IS. CONCLUSIONS: The current study identified ACTN1, F5 and JMJD1C as novel coagulation-related biomarkers associated with IS immune microenvironment, which enriches our knowledge of coagulation-mediated pathogenesis of IS and sheds light on next-step in vivo and in vitro experiments to elucidate the relevant molecular mechanisms.

Tuberous sclerosis complex: a case report and literature review.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with different initial symptoms and complex clinical manifestations. A 14-year-old female patient presented with persistent fever and severe headache. Medical imaging examinations revealed multiple abnormal intracranial lesions. The patient had previously been misdiagnosed with "encephalitis and acute disseminated encephalomyelitis" after visiting numerous hospitals. Eventually, by combing the characteristics of the case and genetic testing results, the patient was diagnosed with TSC accompanied by Mycoplasma pneumoniae infection. The purpose of this case report and literature review is to improve understanding of the clinical diagnosis and treatment of TSC so as to avoid misdiagnosis, missed diagnosis, and overtreatment.

The "island sign" on diffusion-weighted imaging predicts early neurological deterioration in penetrating artery territory infarctions: a retrospective study.

BACKGROUND: Early neurological deterioration (END) sometimes occurs in patients with penetrating artery territory infarction (PATI) and leads to poor prognosis. In this study, we analyzed clinical and neuroimaging characteristics of PATI, and focused on the infarct patterns on diffusion-weighted imaging (DWI). We tried to investigate whether the "island sign" pattern is associated with END. METHODS: We enrolled consecutive patients admitted with acute PATI within 48 h after onset from May 2020 to July 2022. They were divided into with and without the "island sign" pattern on DWI. According to infarct location, all the patients were classified into two groups: the territories of the lenticulostriate arteries (LSA) and paramedian pontine arteries (PPA). The patients in each group were further divided into two groups according to whether they developed END or not. Through analyzing the clinical and neuroimaging characteristics of the patients, we tried to identify the factors that might associated with the "island sign" pattern and the potential predictors of END within the LSA and PPA groups. RESULTS: Out of the 113 patients enrolled in this study, END was found in 17 patients (27.9%) in the LSA group and 20 patients (38.5%) in the PPA group. The "island sign" was found in 26 (23%) patients. In the multivariate analysis, the independent predictors of END in the LSA group were the "island sign" (OR 4.88 95% CI 1.03-23.2 P = 0.045) and high initial National Institute of Health Stroke Scale (NIHSS) (OR 1.79 95% CI 1.08-2.98 P = 0.024) and in the PPA group was the presence of lesions extending to the ventral pontine surface (OR 7.53 95% CI 1.75-32.37 P = 0.007). CONCLUSIONS: The predictive factors for END were different in the LSA and PPA groups. The "island sign" was particularly associated with END in the LSA group.

Analysis of Metagenomic Next-Generation Sequencing (mNGS) in the Diagnosis of Herpes Simplex Virus (HSV) Encephalitis with Normal Cerebrospinal Fluid (CSF).

Background: Metagenomic next-generation sequencing (mNGS) is becoming increasingly extensive in diagnosing herpes simplex encephalitis (HSE). However, many HSE patients with normal cerebrospinal fluid (CSF) diagnosed by mNGS have been found during the clinical application. This study aimed to summarize and analyze the clinical characteristics, supplementary examinations, and prognosis of patients with HSE whose cerebrospinal fluid was confirmed to be normal by mNGS. Methods: This retrospective study evaluated the clinical characteristics, auxiliary examinations, and patient prognosis of patients with HSE that were diagnosed by mNGS but had normal CSF. Clinical data collected included baseline information, signs and symptoms upon admission, and risk factors for infection. Auxiliary examinations included indirect immunofluorescence assay (IIF), cell-based assay (CBA), and CSF testing. Prognosis was evaluated based on hospital stay and patient survival. Results: Seven of the nine patients (77.8%) experienced headaches, and four (44.4%) had a fever of 38°C or higher. The average leukocyte count in the CSF was 2.6 ± 2.3/L. According to the mNGS, the median sequence count of HSV was 2 (1, 16). Magnetic resonance imaging (MRI) revealed one bilateral temporal lobe lesion (11.1%), two isolated bilateral frontal lobe lesions (22.2%), and one bilateral cingulate gyrus lesion (11.1%). One patient (11.1%) was admitted to the intensive care unit and passed away in the hospital. The remaining patients (88.9%) had a positive prognosis upon discharge. Conclusion: Patients with HSE who had normal CSF were typically middle-aged women with normal immune function. They showed typical HSE clinical features, such as fever, headache and epilepsy, that did not differ from those of other HSE patients. A normal CSF result is generally associated with a low viral load and the body's ability to mount an effective immune response. Most of these patients have a favorable prognosis.

Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of VZV-Associated Rhombencephalitis.

BACKGROUND: Rhombencephalitis (RE) is a general term for a group of inflammatory diseases of the rhombencephalon caused by different etiologies. Patients of RE caused by the varicella-zoster virus (VZV) are sporadic in medical practice. The VZV-RE is easily misdiagnosed and causes a poor prognosis for patients. METHODS: In this study, we analyzed the clinical symptoms and imaging features of five patients with VZV-RE diagnosed by the next-generation sequencing (NGS) technique of cerebrospinal fluid. Magnetic resonance imaging (MRI) examination was used to characterize the imaging of the patients. The McNemar test was used to analyze the cerebrospinal fluid testing (CSF) values and MRI test of the 5 patients. RESULTS: We finally used NGS technology to confirm the diagnosis in 5 patients with VZV-RE. MRI revealed T2/FLAIR high signal lesions in the patients' medulla oblongata, pons, and cerebellum. All patients had early signs of cranial nerve palsy; some had herpes or pain in the corresponding cranial nerve distribution areas. The patients develop headaches, fever, nausea, vomiting, and other signs and symptoms of brainstem cerebellar involvement. McNemar's test showed no statistical difference between multi-mode MRI and CSF values for diagnosing VZV-RE (p = 0.513). CONCLUSIONS: This study showed that patients with herpes in the skin and mucous membranes at the distribution area of the cranial nerves and with the underlying disease were prone to RE. We suggest that the NGS analysis should be considered and selected based on the level of parameters, such as MRI lesion characteristics.

Predictive value of ApoB/ApoA-I for recurrence within 1 year after first incident stroke.

Background: ApoB/ApoA-I ratio is a reliable indicator of cholesterol balance, particularly in the prediction of ischemic events risk. The aim of this study was to investigate the prognostic value of ApoB/ApoA-I for stroke recurrence within 1 year after the first incident. Methods: We retrospectively included patients who were first diagnosed with acute (<7 days after onset) ischemic stroke. Blood samples were collected on admission, and serum ApoB and ApoA-I concentrations were measured. We analyzed the relationship between ApoB/ApoA-I ratio and ischemic stroke recurrence within 1 year. Results: A total of 722 patients with acute ischemic stroke were included, of whom 102 experienced stroke recurrence within 1 year, with a recurrence rate of 14.1%. Serum ApoB/ApoA-I concentrations on admission were higher in patients with stroke recurrence at 1 year compared with those with a good prognosis (P < 0.001). The Kaplan-Meier survival curve revealed a significant difference in cumulative stroke recurrence rates across ApoB/ApoA-I tertiles (log-rank P-value < 0.001). A positive correlation between the ApoB/ApoA-I ratio and the risk of stroke recurrence within 1 year was demonstrated using Cox regression analysis, which remained significant after adjusting for traditional risk factors [hazard ratio (HR) 4.007, 95% confidence interval (CI) 1.661-9.666]. This relationship was particularly strong in patients with LAA stroke (HR 4.955, 95% CI 1.591-15.434). Subgroup analysis further revealed that a high ApoB/ApoA-I ratio was strongly associated with stroke recurrence regardless of whether patients had high or low LDL-C levels. Discussion: ApoB/ApoA-I ratio, measured during the acute phase of the first stroke, was positively correlated with the risk of stroke recurrence within 1 year.

A case report of acute intermittent porphyria leading to severe disability.

Acute intermittent porphyria (AIP) is a rare inherited metabolic disorder resulting from increased production of porphyrins and their precursors, δ-aminolevulinic acid (ALA) and porphobilinogen (PBG), due to deficiencies in the enzymatic activity of the heme synthesis pathway. The disease is typically characterized by a triad of abdominal pain, neurologic impairment symptoms, and psychiatric abnormalities. However, only a small percentage of patients present with this classic triad of symptoms. Our female patient, aged 23, was admitted to the hospital with a 4-year history of abnormal mood episodes and weakness in the limbs for over 1 week. She had a previous medical history of intestinal obstruction. After admission, a cranial MRI revealed reversible posterior leukoencephalopathy imaging manifestations, and the patient exhibited weakness of the extremities, respiratory failure, seizures, and severely reduced serum sodium concentration. The diagnosis of AIP was ultimately confirmed by a positive urine PBG-sunlight test and analysis of HMBS gene variants. The absence of typical triadic signs in acute attacks of AIP can make early recognition of the disease challenging. We present a case with multiple typical clinical manifestations of AIP in the hope of aiding clinicians in fully recognizing acute intermittent porphyria.

An unusual case of subacute combined degeneration due to nitrous oxide abuse, which relapsed after bariatric surgery: A case report.

RATIONALE: Several studies have reported subacute combined degeneration (SCD) induced by nitrous oxide (N2O) abuse. However, few studies have reported that N2O-induced SCD recurred because of sleeve gastrectomy after neurological symptoms improved. PATIENT CONCERNS: We report the case of an 18-year-old woman who developed paresthesia, weakness in 4 limbs, and an unstable gait after frequent, excessive N2O inhalation. DIAGNOSIS: The patient was diagnosed as having SCD. INTERVENTIONS AND OUTCOMES: Nineteen days after intravenous mecobalamin and supplementation with other kinds of vitamin B, her weakness and paresthesia resolved. However, 7 months after discharge, the patient experienced recurrence following sleeve gastrectomy. Blood biochemistry revealed low vitamin B12 levels. After a 22-day treatment, similar to the first hospitalization, her residual numbness and unsteady gait improved. LESSONS: This case highlights that patients, especially those at high risk of vitamin B12 deficiency, undergoing sleeve gastrectomy require careful nutritional follow-up and routine monitoring of micronutrients such as vitamin B12 and homocysteine. Continuous vigilance is essential for patients with common and rare neurological complications.

N­acetyl cysteine prevents ambient fine particulate matter­potentiated atherosclerosis via inhibition of reactive oxygen species­induced oxidized low density lipoprotein elevation and decreased circulating endothelial progenitor cell.

Ambient fine particulate matter (PM) serves an important role in the development of cardiovascular disease, including atherosclerosis. Antioxidant N­acetyl cysteine (NAC) has protective effects in the cardiovascular system. However, it is unknown if NAC prevents PM­potentiated atherosclerosis in hyperlipidemia. Low­density lipoprotein (LDL) receptor knockout mice were pretreated with 1 mg/ml NAC in drinking water for 1 week and continued to receive NAC, high­fat diet and intranasal instillation of PM for 1 week or 6 months. Blood plasma was collected for lipid profile, oxidized (ox­)LDL, blood reactive oxygen species (ROS) and inflammatory cytokine (TNF­α, IL­1ß and IL­6) measurement. Blood cells were harvested for endothelial progenitor cell (EPC) population and intracellular ROS analysis. Murine aorta was isolated for atherosclerotic plaque ratio calculation. NAC treatment maintained circulating EPC level and significantly decreased blood ox­LDL and ROS, inflammatory cytokines, mononuclear and EPC intracellular ROS levels as well as aortic plaque ratio. NAC prevented PM­potentiated atherosclerosis by inhibiting plasma ROS­induced ox­LDL elevation, mononuclear cell and EPC intracellular ROS­induced circulating EPC reduction and inflammatory cytokine production.

Delayed multiple intracranial aneurysms caused by left atrial myxoma: a case report and literature review.

Intracranial aneurysm may appear even after the removal of the cardiac myxoma. However, the pathogenesis and treatment of such aneurysm lesions are not clear. The study aimed to explore the clinical and imaging manifestation, hypothetical pathogenesis, and therapy in one case of left atrial myxoma causing multiple intracranial aneurysms. A 14-year-old male displayed a 3-hour history of episodic loss of consciousness and right hemiplegia after a leapfrog-like movement. The myxoma was diagnosed by a combination of clinical examination, leading to the diagnosis of mitral dynamic obstruction with a Grade III mitral diastolic murmur and tumor plop; magnetic resonance imaging, revealing multiple ischemic sites in both semi-oval centers; and transthoracic echocardiography, demonstrating a mitral valve obstruction. The myxoma was removed surgically; however, computed tomography angiography showed multiple intracranial aneurysms in both middle cerebral arteries 18 months after resection of the atrial myxoma. After conservative treatment, the patient had no neurological dysfunction symptoms for 5 years after myxoma resection. His condition is relatively stable. In conclusion, resection of the atrial myxoma may eliminate the early neurological symptoms, but it cannot ensure the nonoccurrence of delayed intracranial aneurysms. The neoplastic process theory was favored for explaining the aneurysm development in this case. According to the specific conditions of the patient, a combination of open surgery, chemotherapy, radiotherapy, and coil embolization is recommended.

Susac syndrome with the typical clinical triad: A case report and literature review.

Susac syndrome is an immune-mediated microvascular disease characterized by the clinical triad of acute multiple encephalopathies, branch retinal artery occlusion, and sensorineural hearing loss. However, the typical clinical triad is not seen in all patients at disease onset. In this study, a 29-year-old male was admitted to our hospital due to aggravation of headache accompanied by retarded reaction. After treatment for a diagnosis of possible central nervous system vasculitis, the patient's retarded reaction and neurological dysfunction were improved. One year after discharge, the patient had no abnormal clinical symptoms and he discontinued taking prednisone voluntarily five months after discharge. Two years later, the patient was admitted to our hospital again owing to a sudden visual field defect in the superonasal quadrant of the left eye for one week, and Susac syndrome was diagnosed. After treatment, the patient's condition became stabilized with no further progress, but the visual field defect did not recover. At the onset of Susac syndrome, the typical clinical triad of Susac syndrome is rare, so this disease is difficult to be recognized at the beginning. The case we report presented the clinical triad two years after the disease onset. We expect that this case report will increase physicians' understanding of Susac syndrome.

Differences in the reaction of hyperlipidemia on different endothelial progenitor cells based on sex.

The sex of a patient can affect the outcomes of several cardiovascular diseases, and men generally tend to experience earlier episodes of cardiovascular diseases compared with women. The progression of atherosclerosis during hyperlipidemia can be induced by reactive oxygen species (ROS) and oxidized-low-density lipoprotein (ox-LDL). By contrast, bone marrow (BM)-derived endothelial progenitor cells (EPCs) have been reported to serve a protective role against atherosclerosis. The aim of the present was to compare the effects of sex under conditions of hyperlipidemia on different populations of EPCs, and to identify the potential underlying mechanisms. EPC numbers and ROS levels in the blood and BM were measured using fluorescence activated cell sorting in male and female LDL receptor knock-out C57BL/6 mice maintained on a high-fat diet for 6 months, and in male and female wild type C57BL/6 mice following ox-LDL injection for 3 days. Female hyperlipidemic mice exhibited lower levels of plasma lipids, atherosclerotic plaque formation, intracellular EPC ROS formation and inflammatory cytokine levels. Furthermore, BM CD34+/ fetal liver kinase-1 (Flk-1+), CD34+/CD133+ and stem cell antigen-1+/Flk-1+, as well as all circulating EPCs, were maintained at higher levels in female hyperlipidemic mice. In addition, similar changes with regards to BM CD34+/Flk-1+, CD34+/CD133+, c-Kit+/CD31+ and circulating CD34+/Flk1+ and CD34+/CD133+ EPCs were observed in female mice following ox-LDL treatment. These sustained higher levels of BM and circulating EPCs in female mice with hyperlipidemia may be associated with reduced levels of ox-LDL as a result of reduced intracellular ROS formation in EPCs and decreased inflammatory cytokine production.

Clinical and Imaging Prognosis in Patients with Delayed Encephalopathy after Acute Carbon Monoxide Poisoning.

OBJECTIVE: To study the clinical manifestations, magnetic resonance imaging (MRI) findings, and prognosis of delayed encephalopathy after carbon monoxide poisoning (DEACMP). METHODS: The medical records of 20 patients with DEACMP were retrospectively reviewed. All the patients received hyperbaric oxygen treatment and other treatments as necessary. RESULTS: The patients had diverse clinical manifestations, including memory deficits, personality changes, cognitive or executive function deficits, mood disorders, Parkinsonism, dystonia or other motor impairments, and akinetic mutism. MRI revealed lesions in the bilateral cerebral white matter and/or basal ganglia. Except for the pathologically confirmed DEACMP, epileptic seizure, hemiplegia, and vegetative state, the remaining symptoms had been improved, especially the cognitive impairment, which had been decreased from 95% to 25% and psychiatric symptoms also decreased from 95% to 55% at the 6-month follow-up. CONCLUSIONS: The prognosis of patients with DEACMP was poor, and they had a relatively severe disability. The early use of hyperbaric oxygen is of great significance to improve clinical efficacy and get a better prognosis.

Imaging findings of cerebral fat embolism syndrome: a case report.

Cerebral fat embolism (CFE) syndrome is relatively rare in clinical practice. Currently, there is no uniform standard of magnetic resonance imaging for the diagnosis of the disease. In this report, we present head computed tomography and magnetic resonance images (T2-weighted images, fluid-attenuated inversion recovery images, diffusion-weighted images, and susceptibility-weighted images) in a case of CFE. This report explains the imaging characteristics of CFE and improves the clinician's understanding of this disease and its etiology.

Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFßR2/phosph-SMAD3 axis.

BACKGROUND: Circular RNAs (circRNAs) represent a class of non-coding RNAs (ncRNAs) which are widely expressed in mammals and tissue-specific, of which some could act as critical regulators in the atherogenesis of cerebrovascular disease. However, the underlying mechanisms by which circRNA regulates the ectopic phenotype of endothelial cells (ECs) in atherosclerosis remain largely elusive. METHODS: CCK-8, transwell, wound healing and Matrigel assays were used to assess cell viability, migration and tube formation. QRT-qPCR and Immunoblotting were used to examine targeted gene expression in different groups. The binding sites of miR-370-3p (miR-370) with TGFßR2 or hsa_circ_0003204 (circ_0003204) were predicted using a series of bioinformatic tools, and validated using dual luciferase assay and RNA immunoprecipitation (RIP) assay. The localization of circ_0003204 and miR-370 in ECs were investigated by fluorescence in situ hybridization (FISH). Gene function and pathways were enriched through Metascape and gene set enrichment analysis (GSEA). The association of circ_0003204 and miR-370 in extracellular vesicles (EVs) with clinical characteristics of patients were investigated using multiple statistical analysis. RESULTS: Circ_0003204, mainly located in the cytoplasm of human aorta endothelial cells (HAECs), was upregulated in the ox-LDL-induced HAECs. Functionally, the ectopic expression of circ_0003204 inhibited proliferation, migration and tube formation of HAECs exposed to ox-LDL. Mechanically, circ_0003204 could promote protein expression of TGFßR2 and its downstream phosph-SMAD3 through sponging miR-370, and miR-370 targeted the 3' untranslated region (UTR) of TGFßR2. Furthermore, the expression of circ_0003204 in plasma EVs was upregulated in the patients with cerebral atherosclerosis, and represented a potential biomarker for diangnosis and prognosis of cerebrovascular atherogenesis. CONCLUSIONS: Circ_0003204 could act as a novel stimulator for ectopic endothelial inactivation in atherosclerosis and a potential biomarker for cerebral atherosclerosis.

Low free triiodothyronineis predicts worsen neurological outcome of patients with acute ischemic stroke: a retrospective study with bioinformatics analysis.

BACKGROUD: Patients with acute ischemic stroke (AIS) often experience low serum free triiodothyronine (FT3), but the association of low FT3 with stroke severity, subtype and prognosis has not yet been thoroughly studied, and the molecular events underlying these clinical observation were also unclear. METHODS: We retrospectively collected 221 cases of AIS and 182 non-AIS cases with detailed clinical data from our department. FT3 concentrations were measured on admission to predict functional outcome within 3 months using multivariable models adjusted for other risk factors. Receiver operating characteristic (ROC) curves were calculated to define the best cutoff value of FT3 of stroke severity, subtypes and neurological outcome. Gene set enrichment, pathway mapping and network analyses of deferentially expressed genes (DEGs) were performed. RESULTS: FT3 was significantly decreased in AIS patients with National Institutes of Health Stroke Scale (NIHSS) > 3 and 3-months modified Rankin Scale (mRS) > 2. The cut-off value of FT3 for NIHSS on admission was 4.30 pmol/L. Also, FT3 level was significantly lower in large artery atherosclerosis (LAA) group and cardioembolism (CE) group than that in small vessel occlusion (SVO). FT3 value served as an independent predictor for neurological outcomes for which the cut-off value of FT3 was 4.38 pmol/l. Gene ontology (GO) analysis showed that the biological function of DEGs was mainly enriched in multicellur organism, neuron differentiation and cellular response to hypoxia. The cellular components were involved in extracelluar region, exosome and matrix, and the molecular functions were transcriptional activator activity, DNA binding and nuclear hormone receptor binding. Signal pathways analysis was indicative of neuroactive ligand-receptor interaction, thyroid hormone signaling pathway, and protein digestion and absorption these DEGs were involved in. Six related gene were identified as hubs from the protein-protein interaction (PPI) networks. Three modules were selected from PPI, of which MMP4, ADRA2C and EIF3E were recognized as the seed genes. CONCLUSIONS: Low FT3 value on admission was associated with stroke severity, subtype and prognosis. In addition, DEGs identified from bioinformatics analysis are likely to be candidates for elucidating clinical outcomes with low FT3, and provide us with therapeutic targets for improving stroke prognosis.

FK506 Attenuated Pilocarpine-Induced Epilepsy by Reducing Inflammation in Rats.

Background: The status epilepticus (SE) is accompanied by a local inflammatory response and many oxygen free radicals. FK506 is an effective immunosuppressive agent with neuroprotective and neurotrophic effects, however, whether it can inhibit the inflammatory response and attenuate epilepsy remains unclear. Objective: This study aims to clarify the effect of FK506 on inflammatory response in rats with epilepsy. Methods: A total of 180 rats were randomly and equally divided into the control group, epilepsy group, and FK506 group. The rat SE model in the epilepsy group and FK506 group was induced by lithium chloride combined with pilocarpine. In the FK506 group, FK506 was given before the injection of pilocarpine. The control group was given the same volume of saline. Then the effect of FK506 on epilepsy in rats and the changes of inflammatory factors and free radicals in hippocampus were examined using hematoxylin and eosin (HE) staining, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. Results: FK506 ameliorated the course of pilocarpine-induced epilepsy and the neuronal loss in the rat hippocampus after SE. FK506 reduced the increased content of nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) in the hippocampus after SE. Besides, FK506 also significantly reduced the levels of factors involved in inflammatory response such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), and Protein Kinase C δ (PKCδ) that rise after epilepsy. Conclusion: FK506 ameliorated the course of pilocarpine-induced epilepsy, significantly reduced free radical content, and inhibited the expression of inflammatory factors, which provided a theoretical basis for the application of FK506 in the treatment of epilepsy.

The Association Between the Incidence Risk of Peripheral Neuropathy and PD-1/PD-L1 Inhibitors in the Treatment for Solid Tumor Patients: A Systematic Review and Meta-Analysis.

Purpose: We conducted this study to determine the relationship between PD-1/PD-L1 inhibitors and the incidence risk of peripheral neuropathy in patients with solid tumors. Method: The process of the meta-analysis was performed by us according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Incidence of all-grade and grade 3-5 treatment-related peripheral neuropathy in patients with solid tumors were taken into account. Results: After screening and eligibility assessment, a total of 17 clinical trials involving 10,500 patients were selected for the final meta-analysis. The incidence risk of peripheral neuropathy for all grade was significantly lower in the PD-1/PD-L1 inhibitor group than that of the control group, either monotherapy (OR = 0.08, 95%CI:[0.03, 0.19]) or chemotherapy (OR = 0.05, 95%CI:[0.03, 0.11]). Similar incidence trend could also be seen for the incidence risk of grade 3-5 peripheral neuropathy. When PD-1/PD-L1 inhibitors were used in combination with chemotherapy, the incidence risk of peripheral neuropathy was higher than in the control chemotherapy group, whether it was all-grade (OR = 1.22, 95%CI:[1.00, 1.49]) or grade 3-5 degree (OR = 1.74, 95%CI:[1.03, 2.92]). Conclusion: Compared with chemotherapy, incidence risk of peripheral neuropathy related to PD-1/PD-L1 inhibitor was significantly lower than that of the chemotherapy group, while PD-1/PD-L1 inhibitor increased the incidence risk of peripheral neuropathy when it was combined with chemotherapy.

Assessment of cerebral infarction after transient cerebral ischemic attack by ABCD2 score combined with the position of intracranial vascular stenosis.

This study aims to investigate the value of the ABCD score combined with the position of the offending vessel stenosis in predicting the risk of transient ischemic attack (TIA) to develop into cerebral infarction.The ABCD score and head magnetic resonance imaging + magnetic resonance angiography (MRA) results of 192 patients with TIA were retrospectively analyzed. With the 7th day as the endpoint time, these patients were divided into 3 groups, according to ABCD scores: low-risk group (n = 105), moderate-risk group (n = 60), and high-risk group (n = 27). Blood vessels were screened using head MRA results, and patients were accordingly divided into 2 groups: proximal vascular stenosis group (n = 71) and nonproximal vascular stenosis group (n = 171). Then, the association of the position of the intracranial vascular stenosis and ABCD score with short-term prognosis was analyzed.Based on the ABCD score, the incidence of cerebral infarction after 1 week was significantly higher in the high-risk group (85.7%) than in the moderate-risk group (16.7%) and low-risk group (1.9%), and the differences were statistically significant (P < .05). When the ABCD score was ≥4 points, the incidence of cerebral infarction after 1 week was significantly higher in the proximal vascular stenosis group (59.1%) than in the nonproximal vascular stenosis group (30.8%), and the difference was statistically significant (P < .05). When the ABCD score was <4 points, the incidence of cerebral infarction after 1 week in the proximal stenosis group (2%) was not significantly different from that in the nonproximal stenosis group (1.9%, P > .05).The ABCD score combined with proximal offending vessel stenosis can improve the short-term prediction of cerebral infarction in patients with TIA.