NSE Levels Research Articles

Puerarin protects against sepsis-associated encephalopathy by inhibiting NLRP3/Caspase-1/GSDMD pyroptosis pathway and reducing blood-brain barrier damage

Puerarin (Pue), an isoflavone compound extracted from Pueraria, has been shown to inhibit inflammation and reduce cerebral edema. The neuroprotective effect of puerarin has attracted much attention in recent years. Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis that causes damage to the nervous system. This study aimed to investigate the effect of puerarin on SAE and elucidate the potential underlying mechanisms. A rat model of SAE was established by cecal ligation and puncture, and puerarin was injected intraperitoneally immediately after the operation. Puerarin was found to improve the survival rate and neurobehavioral score of SAE rats, alleviate symptoms, inhibit the level of brain injury markers NSE and S100β, and improve the pathological changes in rat brain tissue. Puerarin was also found to inhibit the level of factors related to the classical pathway of pyroptosis, such as NLRP3, Caspase-1, GSDMD, ASC, IL-1β, and IL-18. Puerarin also reduced the brain water content and penetration of Evan’s Blue dye in SAE rats, and reduced the expression of MMP-9. In the in vitro experiments, we further confirmed the inhibitory effect of puerarin on neuronal pyroptosis by establishing a pyroptosis model in HT22 cells. Our findings suggest that puerarin may improve SAE by inhibiting the classical pathway of NLRP3/Caspase-1/GSDMD-mediated pyroptosis and reducing blood-brain barrier damage, thus playing a role in brain protection. Our study may provide a novel therapeutic strategy for SAE.

A study to determine enzalutamide long term safety and efficacy for men with castration-resistant prostate cancer: A multicenter, prospective DELC study.

66 Background: In the PREVAIL study, enzalutamide was demonstrated to be effective in men with chemo-naïve metastatic castration-resistant prostate cancer (CRPC). In Japan, enzalutamide was introduced in 2014. Real-world evidence is needed for the long-term safety and efficacy of enzalutamide. The aim of this study was to evaluate the efficacy, safety and prognostic factors in CRPC treated with enzalutamide. Methods: This multicenter, prospective, observational study enrolled 163 Japanese CRPC patients between January 2016 and March 2019. Eligibility criteria were men with chemo-naïve CRPC, no prior treatment with novel androgen receptor signaling inhibitors, and an ECOG- Performance Status ≤ 2. The switching of bicalutamide and flutamide was eligible. Written consent for participation has been obtained from the patient. Enzalutamide 160 mg/day was administered once daily according to usual practice. Data were collected from medical records at baseline and every 3 months until march 2021. The primary endpoint was overall survival (OS), and factors associated with OS were examined. Cox proportional hazards model was used for statistics. The secondary endpoints were PSA response and safety. Results: At a median follow-up of 26.0 months, the median OS was 42.1 months and 24-month OS rate was 69%. Univariate analysis showed that time to CRPC, pretreatment serum PSA, baseline NSE, and baseline interleukin-6 (IL-6) levels were associated with OS. Multivariate analysis revealed that pretreatment serum PSA (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.30-4.10), baseline NSE (HR 2.97, 95%CI 1.24-7.11), and baseline IL-6 (HR 2.32 95%CI 1.32-4.09) were independent risk factors for OS. PSA decline more than 50% was 74% (n=120). Fatigue (30%, n=49), constipation (20%, n=32) and appetite loss (18%, n=29) were the most common adverse events (AEs). Dose reduction/drug discontinuation rates were 20% (n=33) due to AEs and 18% (n=29) due to patient request. Conclusions: The efficacy and safety of enzalutamide in Japanese real clinical practice were comparable to those reported in PREVAIL study. The present analysis also suggests that serum PSA, NSE and IL-6 levels are independent prognostic factors in CRPC patients. Clinical trial information: UMIN000019855 . [Table: see text]

Detection of Changes in CEA and ProGRP Levels in BALF of Patients with Peripheral Lung Cancer and the Relationship with CT Signs.

To investigate the relationship between the detection of changes in the levels of carcinoembryonic antigen (CEA) and progastrin-releasing peptide (ProGRP) in bronchoalveolar lavage fluid (BALF) and CT signs in patients with peripheral lung cancer. Retrospective analysis of 108 patients with perihilar lung cancer who attended our hospital from January 2019 to January 2022, 54 cases were randomly selected as the observation group and 50 cases as the control group. Patients in both groups received CT examination and BALF test at the same time to observe and compare the differences in serum levels, the relationship between CT signs and serum indices, and the diagnostic value of peripheral lung cancer between the two groups. The serum levels of ProGrp, CEA, CA211, and NSE in the observation group were significantly higher than those in the control group, and the difference was statistically significant (P < 0.05). The morphology, density, mass enhancement pattern, bronchial morphology, obstructive signs, and lymph node fusion of CT signs were compared between the observation group and the control group, indicating that CT signs were more helpful for the localization, diagnosis, and staging of lung cancer. The results of ROC curve analysis showed that the AUC value of low-dose CT combined with serum ProGrp, CEA, CA211, and NSE was 0.892, sensitivity was 96.21%, and specificity of 90.05%, which were significantly higher than those of the single tests, respectively. The positive likelihood ratio was 84.41% and the negative likelihood ratio was 87.11%. The combination of CT signs and serum tumour markers helps to improve the detection rate, sensitivity, and specificity of lung cancer, which has a high diagnostic rate for lung cancer and may provide evidence for the early diagnosis of lung cancer.

Novel blood-based biomarker candidates in screening for colorectal cancer.

244 Background: Colorectal cancer (CRC) is the third most common cancer worldwide motivating national screening strategies utilizing fecal immunochemical tests (FIT). Blood-based biomarkers could be an alternative method to increase compliance in population-based screening programs for early detection of CRC. We aimed to identify new blood-based biomarkers that could be potential candidates for use in colorectal cancer screening. Methods: In a nested cohort study of 1967 FIT positive participants of the Danish CRC screening program serum levels of GDF-15, hepsin, IL-8, keratin1-10, L1CAM, MIA, monocyte MCP-1, NSE and OPG were measured using the Luminex xMAP immunoassay platform. Main outcomes were CRC vs non-CRC and CRC, high-risk adenomas (HRA) or medium-risk adenomas (MRA) vs low-risk adenomas (LRA) or clean colorectum. Odds ratios for associations between biomarker expressions and outcomes were calculated using logistic regression models and visualized by area under the receiver operating characteristic (ROC) curve (AUC). Analyses were made on the Luminex biomarkers alone and with addition of clinical and demographic information. Results: FIT-induced colonoscopies detected 240 CRCs and 625 HRA or MRA. Multivariate analyses using all biomarkers and age found hepsin, IL-8 and OPG significantly (p&lt;0.001) associated in relation to the main outcome (CRC vs non-CRC) with odds ratios of 0.74 [0.59-0.92], 2.59 [2.12-3.15] and 0.90 [0.82-0.99], respectively. The full model using all biomarkers and age presented an AUC of 0.73 [0.70-0.77]. Conclusions: Changed serum levels of nine novel biomarkers seem to be potential predictors for early detection of CRC, especially hepsin, IL-8 and OPG. [Table: see text]

Malvidin alleviates mitochondrial dysfunction and ROS accumulation through activating AMPK-α/UCP2 axis, thereby resisting inflammation and apoptosis in SAE mice.

This study aimed to explore the protective roles of malvidin in life-threatened sepsis-associated encephalopathy (SAE) and illustrate the underlying mechanism. SAE mice models were developed and treated with malvidin for subsequently protective effects evaluation. Malvidin restored neurobehavioral retardation, declined serum S100β and NSE levels, sustained cerebrum morphological structure, improved blood-brain barrier integrity with elevated tight junction proteins, and decreased evans blue leakage, and finally protect SAE mice from brain injury. Mechanistically, malvidin prevented cerebrum from mitochondrial dysfunction with enhanced JC-1 aggregates and ATP levels, and ROS accumulation with decreased lipid peroxidation and increased antioxidant enzymes. UCP2 protein levels were found to be decreased after LPS stimulation in the cerebrum and BV-2 cells, and malvidin recovered its levels in a ROS dependent manner. In vivo inhibition of UCP2 with genipin or in vitro interference with siRNA UCP2 both disrupted the mitochondrial membrane potential, decreased ATP levels and intensified DCF signals, being a key target for malvidin. Moreover, dorsomorphin block assays verified that malvidin upregulated UCP2 expression through phosphorylating AMPK in SAE models. Also, malvidin alleviated SAE progression through inhibition of ROS-dependent NLRP3 inflammasome activation mediated serum pro-inflammatory cytokines secretion and mitochondrial pathway mediated apoptosis with weakened apoptosis body formation and tunel positive signals, and decreased Bax, cytochrome C, caspase-3 and increased Bcl-2 protein levels. Overall, this study illustrated that malvidin targeted AMPK-α/UCP2 axis to restore LPS-induced mitochondrial dysfunction and alleviate ROS accumulation, which further inhibits NLRP3 inflammasome activation and mitochondrial apoptosis in a ROS dependent way, and ultimately protected SAE mice, providing a reference for the targeted development of SAE prophylactic approach.

Results of a multicenter observational program to evaluate the effectiveness of complex therapy of patients with chronic cerebrovascular pathology with cognitive impairment with Cortexin and Neuromexol (CORNELia study)

To evaluate the effectiveness of complex therapy with Cortexin and Neuromexol in patients with chronic cerebral ischemia (CCI) and cognitive impairment (CI). We examined 801 patients with CCI on the background of arterial hypertension and atherosclerosis with confirmed CI: 329 (41.1%) men and 472 (58.9%) women aged 30 to 80 years (mean age 64±10 years), who were examined. Cortexin and Neuromexol. Examination - Mini-Mental State Examination (MMSE) scale, hour-long drawing test (HDT) and severity of depressive states (Brief Geriatric Depression Scale, Mini Geriatric Depression Scal, MGDS). In 30 patients receiving Cortexin and Neuromexol (main group, MG) and 30 patients in the comparison group (CG), biomarkers of ischemic brain damage (NSE, antibodies to NR2, VEGFA) were determined. The examination was carried out before the start of treatment and after 30 days. During therapy with Cortexin and Neuromexol, characteristic signs of a decrease in the severity of CI were noted (p<0.05). A positive correlation was revealed between the performance indicators of the MMSE and TFC tests, both before and after treatment (r=0.5 and r=0.6, respectively; p<0.05). A positive effect of therapy on the emotional background of patients was noted, in particular, a decrease in the severity of depressive symptoms on the MGDS scale. During therapy, a 2-fold decrease in the NSE level (p<0.05) was detected in the MG, which indicates a decrease in the structural and functional parameters of biomembrane neurons in the brain. The concentration of antibodies to NR2 decreased compared to the baseline level in both groups (p<0.05), and VEGFA decreased only in the MG (p<0.05). The results of the study allow us to recommend the complex prescription of Cortexin 10 mg/day for 10 days and Neuromexol tablets 125 mg (375-750 mg/day) for 30 days for chronic CVD. Complex therapy with Cortexin and Neuromexol is effective and safe in patients with CCI and CI.

Research on the Correlation between NSE Level and Activities of Daily Living in Parkinson’s Disease

Research on the Correlation between NSE Level and Activities of Daily Living in Parkinson’s Disease

Changes in lung cancer-related serum tumor markers in patients with chronic kidney disease and determination of upper reference limit.

To investigate the changes in lung cancer-related serum tumor markers in patients with chronic kidney disease (CKD) and determine the upper reference limit for patients with different stages. Included inpatients diagnosed with CKD who did not receive dialysis temporarily in our hospital from March to September 2020. Changes in serum CA125, HE4, CYFRA21-1, SCCA, NSE and ProGRP in CKD patients were analyzed. The non-parametric method was used to estimate the upper reference limit of the above indicators in patients with CKD stages 2-5. The serum levels of HE4, CYFRA21-1, SCCA, and ProGRP in the CKD group were significantly higher than those in the healthy control group; CA125 and NSE levels were not statistically different. The false positives of SCC, CYFRA21-1, ProGRP, and HE4 increased significantly with the CKD stage. Still, NSE and CA125 did not show a significant increasing trend. Both HE4 and ProGRP have independent upper reference limits from CKD2 to CKD5 stage, namely 220.8 pmol/l and 101.4 pg/ml in the CKD2 stage, 496.7 pmol/l and 168.63 pg/ml in CKD3 stage, 4592.4 pmol/l and 272.8 pmol/l for CKD4 stage, CKD5 stage was 4778.2 pmol/l and 491.6 pmol/l. This study preliminarily determined the upper reference limits of Lung cancer-related tumor markers in patients with different CKD stages and provided laboratory support for the rational use and interpretation of Lung cancer-related tumor markers in special populations.

Human wharton-jelly mesenchymal stromal cells reversed apoptosis and prevented multi-organ damage in a newborn model of experimental asphyxia

In this study, the effect of applying wharton jelly mesenchymal stromal cells (WJ-MSC) isolated from the human umbilical cord tissue on the neonatal mouse model caused experimental asphyxia in mice was investigated. WJ-MSC surface markers (CD44, CD90, CD105) were characterised by immunofluorescence staining, and pluripotency genes (Nanog, Oct-4, Sox-2) were characterised by qPCR. Blood, prefrontal cortex, cerebellum, hippocampus, lung, heart, kidney, and liver tissues were analysed twenty days after subcutaneously administered WJ-MSC. WJ-MSC administration significantly decreased serum TNF-α, NSE, GFAP, and IL-6 levels in the asphyxia mice. It was determined that WJ-MSC application in tissues accelerated cell regeneration and decreased oxidative stress. In conclusion, this study showed that multiorgan damage in asphyxia could be prevented by applying WJ-MSC at an early stage. Therefore, WJ-MSC application in infants with neonatal asphyxia in the clinic may be an innovative method in the future.

Abstract 106: Neurological Effects Of Methylene Blue In A Porcine Model Of Cardiac Arrest

Purpose To investigate the neuroprotective effects of methylene blue (MB) in a clinically relevant porcine model of cardiac arrest. Method: 40 anaesthetized pigs were subjected to myocardial infarction and seven minutes of untreated cardiac arrest. Animals were randomized into three groups: one group received saline only (control), one group received 2 mg/kg MB and saline (MB+saline), and one group received two doses of 2 mg/kg MB (MB+MB). The first intervention was given after the 3rd rhythm analysis, while the second dose was administered one hour after achieving return of spontaneous circulation (ROSC). The main investigator was blinded during resuscitation and the first hour after ROSC. Animals underwent intensive care and observation for 6 hours. Neurological outcomes were evaluated by cerebral microdialysis and serum-neuron specific enolase (NSE). Normality was assessed by qq-plot and histograms. Pointwise data were analyzed using Kruskal-Wallis test as data did not assume normal distribution. Data are presented as medians and 25 th and 75 th percentiles. A value of p&lt;0.05 was considered statistically significant. Results: The proportion of animals achieving ROSC was similar across groups: 11/13 (85%) in the control group, 10/13 (77%) in the MB+saline group, and 12/14 (86%) in the MB+MB group (p=0.81). Cerebral lactate and pyruvate levels increased after ROSC in all groups. Lactate/pyruvate ratios were comparable between groups two hours after ROSC (control: 25 (22;31); MB+saline: 24 (22;36); MB+MB: 23 (20;28); p=0.43). Cerebral glycerol levels initially increased in all groups with the highest levels at two hours after ROSC (control: 454 μmol/L (319;507); MB+saline 351 μmol/L (241;420); MB+MB 347 μmol/L (256;478); p=0.35). Glycerol levels decreased over time with no difference 6 hours after ROSC (control: 210 μmol/L (138;293); MB+saline (146 μmol/L (61;156); MB+MB: 105 μmol/L (63;159); p=0.07). Serum-NSE levels 6 hours after ROSC were not different between groups (control: 0.9 μg/L (0.7;1.5); MB+saline 1.5 μg/L (1.0;2.0); MB+MB: 1.0 μg/L (0.7;1.2); p=0.13). Conclusion Contrary to previous publications the current porcine trial did not observe any neuroprotective effects of MB when evaluated by cerebral microdialysis and NSE levels.

Association of Image-Defined Risk Factors with Clinical, Biological Features and Outcome in Neuroblastoma.

Neuroblastoma (NB) is the most common pediatric extracranial solid tumor and the most common cancer encountered in children younger than 12 months of age. Localized tumors have a good prognosis, but some cases undergo treatment failure and recurrence. The aim of the study was to analyze the link between the neuroblastoma risk factors and the prognosis for patients diagnosed with NB. All patients admitted to the department of Pediatric Surgery, "Grigore Alexandrescu" Clinical Emergency Hospital for Children, between 1 January 2010 and 1 July 2022 were included in this analysis when diagnosed with neuroblastoma. Thirty-one patients with NB were admitted to the surgical department, 20 boys and 11 girls. We observed an association between large tumors and positive imaging-defined risk factor (IDRF) status; The Fisher test showed an association between the tumor's diameter when bigger than 8 cm and a positive IDRF status, with p &lt; 0.001. We supposed that positive IDRF status at diagnosis may be linked to other prognostic factors. We discovered that an NSE value over 300 was associated with IDRF status (p &lt; 0.001, phi = 0.692) and death. This study confirms the impact of IDRF status at diagnosis as it can be clearly correlated with other risk factors, such as a high level of NSE, MYCN amplification status, large tumor size, incomplete tumor resection, and an unfavorable outcome.

Drug Therapy of Cognitive Dysfunction in Minimally Invasive Surgery during Anesthesia with Sevoflurane

The objective: To conduct a comparative assessment of efficacy of Cytoflavin and Cellex for management of cognitive disorders after videolaparoscopic cholecystectomy performed under general inhalation anesthesia with sevoflurane.Results. In three representative groups (n = 30) of patients, markers of inflammation (CRP and IL-6), levels of brain-specific proteins (S-100 and NSE) were studied. Neuropsychological testing were performed by using the MoCA test, frontal dysfunction test battery (FAB) by two stages (stage I ‒ on the eve of the operation, stage II ‒ on the 7th day of the postoperative period). In patients of Group I (n = 30), disorders of higher mental functions of the early postoperative period persisted, which served as the basis for finding ways to eliminate and manage the identified disorders. For this purpose, Cytoflavin was used in Group II (n = 30), and Cellex was used in Group III (n = 30).Comparative characteristics of the level of brain-specific proteins revealed a statistically significant decrease at stage I in Groups II and III versus Group I. The lowest level of both NSE (by 1.45 μg/l, p = 0.041) and S-100 (by 10.1 ng/l, p = 0.044) was observed in Group III versus Group II. In addition, at the second stage of the study, the greatest severity of the inflammatory response was noted in Groups II and III of patients compared to Group I and this degree of severity could be potentiated by the ongoing drug therapy. If in Group I, disorders of higher mental functions persisted on the 7th day of the postoperative period, then as a result of the ongoing drug therapy in Groups II and III, it was possible to achieve significantly better results of neuropsychological testing.Conclusion. Administration of drug therapy contributed to the improvement of higher mental function eliminating cognitive deficit in the early postoperative period.

Clinic and diagnosis of encephalopathy of critical conditions in children with infectious diseases

Purpose: to assess the functional state of the brain in critically ill encephalopathy in children with infectious diseases.Materials and methods: 75 patients aged from 1 month to 17 years 11 months with infectious diseases, who were in the intensive care unit of the clinic, were examined, divided into two groups: the main group and the comparison group. Exclusion criteria: patients with cerebral palsy, organic lesions of the central nervous system, neuroinfections and epilepsy. Conducted daily clinical and neurological examination; study of the level of neurospecific proteins (NSE, protein S100) in blood serum; electroencephalography; study of evoked potentials of various modalities; ultrasound examination of the optic nerves, neuroimaging.Results: All patients had general infectious manifestations, the development of sepsis syndrome, cerebral systemic disorders with impaired consciousness, as well as convulsive syndrome. In the acute period of the disease in the main group, NSE values in 87.5% of children were within the upper limit of normal, S100 protein levels were many times higher than those in the comparison group. In dynamics, all patients showed an increase in the level of NSE, which correlated with persistent neurological symptoms in the form of irritability, weakness, and cognitive decline. In the comparison group, an increase in NSE occurred in 53% of children, an increase in S100 - in 83%. By the time of discharge, 47% of patients had an increase NSE and S100 protein. Visual evoked potentials in 84% of the children of the main group in the acute period, had a decrease the amplitude of the N2-P2 cortical response was revealed without significant dynamics in the future, which was accompanied by pronounced clinical manifestations, which made it possible to substantiate the expediency of dispensary observation of children who underwent a critical condition against the background of severe infectious pathology.Conclusion: in infectious diseases in children that are not accompanied by inflammatory processes in the nervous system, but proceed with the development of a critical condition, there is a neuropsychiatric deficit in the outcomes, which necessitates follow-up follow-up of such patients in the future.

Development of exploratory algorithms to aid in risk of malignancy prediction of indeterminate pulmonary nodules

Early detection of lung cancer allows for earlier stage treatment initiation and improved patient prognosis. This report focuses on utilization of combining patient demographic information with non-invasive biomarkers and their potential ability to predict risk of malignancy of nodules. A pilot study cohort of 141 subjects with IPNs (105 stage I cancer and 36 benign nodules) were collected by RUMC. The demographic variables of gender, age, sex, race, ethnicity, nodule size (mm), and smoking pack years, as well as the plasma levels of CA-125, SCC, CEA, HE4, ProGRP, NSE, Cyfra 21-1, hs-CRP, Ferritin, IgG, IgG1, IgG2, IgG3, IgG4, IgE, IgM, IgA, KFLC, and LFLC, were assessed for this cohort. Multivariable analyses of the previously aforementioned biomarkers and demographic variables yielded a reduced algorithm consisting of CA-125, total IgG, IgA, IgM, IgE, LFLC, nodule size, and smoking pack years with improved performance (AUC 0.82, 95 %CI 0.74–0.90) over the same analysis of the demographic variables (age, nodule size, and smoking pack years) alone (AUC 0.70, 95 %CI 0.61–0.78). This reduced algorithm of biomarkers and demographic variables may aid in assessing the risk of IPN malignancy which could be a useful stratification tool in early detection of lung cancer in high-risk subjects.

Effects of breviscapine on cerebral ischemia-reperfusion injury and intestinal flora imbalance by regulating the TLR4/MyD88/NF-κB signaling pathway in rats

Ethnopharmacological relevanceThe plant Erigeron breviscapus (Vant.) Hand.-Mazz.,a Chinese herbal medicine with multiple pharmacological effects and clinical applications, has been traditionally used in the treatment of paralysis caused by stroke and joint pain from rheumatism by the Yi minority people of Southwest China for generations.However, its mechanism involves many factors and has not been fully clarified. Aim of the studyTaking intestinal flora as the target, the protective effect of extract(breviscapine) of E. breviscapus on cerebral ischemia and its possible mechanism were discussed from the perspective of brain inflammatory pathway and intestinal CYP3A4, which depends on intestinal flora. Materials and methodsIn this study, we first verified the binding ability between major active ingredient of Erigeron breviscapus and the core target TLR4 protein by molecular docking using Vina software.We established a rat model of cerebral ischemia-reperfusion injury in vivo.The neurological function of rats was scored by Bederson score table, the cerebral infarction volume was detected by TTC staining, and the serum NSE level was detected by ELASA. 16S rRNA sequencing was used to detect the intestinal flora of rats in each group.The expression levels of cerebral TLR4/MyD88/NF-κB and CYP3A4 mRNA and protein in different intestinal segments were detected by qRT-PCR and Western blot. ResultsCompared with the model group, the neurological injury score, infarct volume and serum NSE concentration of breviscapine low, medium and high dose groups and nimodipine groups decreased significantly. Meanwhile, breviscapine could significantly reduce the expression level of the TLR4/MyD88/NF-κB in brain tissue and CYP3A4 in different intestinal segments of rats with cerebral ischemia-reperfusion injury. In addition, breviscapine also significantly ameliorated intestinal flora dysbiosis of rats with cerebral ischemia-reperfusion injury. ConclusionsBreviscapine can protect rats from cerebral ischemia-reperfusion injury by regulating intestinal flora, inhibiting brain TLR4/MyD88/NF-κB inflammatory pathway and intestinal CYP3A4 expression.

Predictors of Early Neurological Deterioration and Functional Outcome in Acute Ischemic Stroke: The Importance of Large Artery Disease, Hyperglycemia and Inflammatory Blood Biomarkers.

BackgroundEarly neurological deterioration (END) in acute ischemic stroke (AIS) can be associated with poor outcome. The aim of this study was to investigate the association between infarction subtypes, biomarkers and END, and to identify patients with risk of unfavorable functional outcome.Materials and MethodsThis prospective study enrolled 101 patients with AIS. Neurological status was evaluated according to NIHSS at acute onset, on days 2, 3, and 90. END was defined as ≥2-point increase of NIHSS within 72 hours. Functional outcome was assessed using NIHSS and the modified Rankin Scale (mRS) at day 90.ResultsEND was observed in 20, 8%. Patients with large artery disease had higher risk of developing END compared with patients with cardioembolism or small vessel disease (p <0.01). Significant higher blood glucose level and leukocytes were observed in the END group. Patients with END had higher scores of mRS at day 90 (p <0.01). Levels of NSE, IL-6, hsCRP and NT-proBNP were higher in the patients with unfavorable compared with favorable functional outcome.ConclusionLarge artery disease, high blood glucose and leukocytes levels are associated with END. Elevated levels of blood markers NSE, IL-6, HsCRP and NT-proBNP indicate poor functional outcome at 90 days after AIS. These patients must be identified and be offered treatment immediately in order to improve the functional outcome after AIS.

Effect of Hours of Exposure to Cement Dust on Cancers Markers on Cement Workers in Port Harcourt

The study was aimed at evaluating the effect of cement dust exposure on cement loaders in Port Harcourt. The study was a cross sectional study which used convenient sampling size of 100 healthy male cement workers recruited in one cement depot and eight cement loading sites in Port Harcourt using simple random technique. Subjects were classified into three groups based on daily hour cement exposure; group 1 (1-5 hrs), group 2 (6-10 hrs) and group 3 (&gt;10 hrs). Group 1 had 27 subjects, group 2 had 62 subjects and group 3 had 11 subjects. 4 ml of the venous blood was drawn into plain vacutainer bottles for the evaluation of Neuron specific Enolase, Vascular Endothelial Growth Factor A, and Total Antioxidant Status. ELISA method was used for the laboratory determination of VEGF-A and NSE while a colorimetric method was used for TAS estimation. Results showed TAS level among the classes was not significantly different (p=0.3304) and has the mean value of 2.02±0.40; 2.16±0.41 and 2.1 ±0.41 in groups 1, 2 and 3 respectively. VEGF-A level among the classes was not significantly different (p=0.7123) with mean value of 406.00 ±234.80; 439.60 ±369.40 and 361.00 ±171.00 in groups 1, 2 and 3 respectively. The mean value for NSE level among the groups (1, 2, and 3) were 3.78±1.49; 4.17±2.91 and 3.42±0.98 but there was no significantly difference (p=0.5551). This has shown that hourly exposure to cement dust among healthy cement workers does not have significant impact on cancer markers (VEGF-A, NSE and TAS). A higher timeframe assessment may provide a better picture of the effect of cement dust exposure since many diseases associated with cement dust exposure are chronic.

Different clinical characteristics and survival between surgically resected pure and combined small cell lung cancer.

BackgroundSmall cell lung cancer (SCLC) is the most malignant and common form of neuroendocrine lung cancer with pure (P‐SCLC) and combined subtypes (C‐SCLC). However, little is known about the differences between these two groups and in this study we aimed to provide a more comprehensive insight into SCLC.MethodsData from 580 postoperative patients with pathologically confirmed SCLC in Shanghai Chest Hospital from January 2010 to December 2020 were collected retrospectively. The clinical characteristics and prognosis were analyzed.ResultsA total of 357 P‐SCLC patients and 223 C‐SCLC patients were included. The results indicated that P‐SCLC appeared to have a higher proportion of being located in the middle lobe than C‐SCLC. The incidences of P‐SCLC in patients with visceral pleural invasion (VPI) and in stage II were higher than C‐SCLC, while C‐SCLC was more likely to be accompanied by higher incidences of epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) rearrangement, and higher levels of CEA, SCCA and CYFRA21‐1 than P‐SCLC. The most common were SCLC combined with large cell neuroendocrine components among 223 C‐SCLCs. Survival analysis confirmed a more favorable disease‐free survival (DFS) (p = 0.016) and overall survival (OS) (p = 0.024) in patients with P‐SCLCs compared with C‐SCLCs. Histological type, tumor location, pN stage, adjuvant chemotherapy, serum NSE and CA125 levels were independent risk factors for survival rate in SCLC. In addition, adjuvant chemotherapy was beneficial in improving stage I P‐SCLC and C‐SCLC DFS and OS rates, and similar results were not seen in adjuvant radiation therapy.ConclusionsPatients with C‐SCLC have a poorer prognosis than P‐SCLC patients. We determined that large cell neuroendocrine carcinoma was the most common additional component of C‐SCLC, and patients with this component appeared to have a longer DFS and OS than other combined components.

Increased Serum NSE and S100B Indicate Neuronal and Glial Alterations in Subjects Under 71 Years With Mild Neurocognitive Disorder/Mild Cognitive Impairment.

BackgroundMild cognitive impairment (MCI) is considered a pre-stage of different dementia syndromes. Despite diagnostic criteria refined by DSM-5 and a new term for MCI – “mild neurocognitive disorder” (mild NCD) – this diagnosis is still based on clinical criteria.MethodsTo link mild NCD to the underlying pathophysiology we assessed the degree of white matter hyperintensities (WMH) in the brain and peripheral biomarkers for neuronal integrity (neuron-specific enolase, NSE), plasticity (brain-derived neurotrophic factor, BDNF), and glial function (S100B) in 158 community-dwelling subjects with mild NCD and 82 healthy controls. All participants (63–79 years old) were selected from the Leipzig-population-based study of adults (LIFE).ResultsSerum S100B levels were increased in mild NCD in comparison to controls (p = 0.007). Serum NSE levels were also increased but remained non-significant after Bonferroni-Holm correction (p = 0.04). Furthermore, age by group interaction was significant for S100B. In an age-stratified sub-analysis, NSE and S100B were higher in younger subjects with mild NCD below 71 years of age. Some effects were inconsistent after controlling for potentially confounding factors. The discriminatory power of the two biomarkers NSE and S100B was insufficient to establish a pathologic threshold for mild NCD. In subjects with mild NCD, WMH load correlated with serum NSE levels (r = 0.20, p = 0.01), independently of age.ConclusionOur findings might indicate the presence of neuronal (NSE) and glial (S100B) injury in mild NCD. Future studies need to investigate whether younger subjects with mild NCD with increased biomarker levels are at risk of developing major NCD.

Comparison of the somatic mutations between circulating tumor DNA and tissue DNA in Chinese patients with non-small cell lung cancer

Non-invasive liquid biopsies of circulating tumor DNA (ctDNA) is a rapidly growing field in the research of non-small cell lung cancer (NSCLC). In this study, factors affecting the concordance of mutations in paired plasma and tissue and the detection rate of ctDNA in real-world Chinese patients with NSCLC were identified. Peripheral blood and paired formalin-fixed paraffin-embedded tumor tissue samples from 125 NSCLC patients were collected and analyzed by sequencing 15 genes. Serological biomarkers were tested by immunoassay. The overall concordance between tumor and plasma samples and the detection rate of somatic mutations in ctDNA was 69.2% and 78.4%, respectively. The concordance and detection rate raised with clinical stage were stage I: 14.3%, 14.3%; stage II: 53.3%, 60.0%; stage III: 71.4%, 78.1%; stage IV: 74.1%, 85.2%. With increased tumor diameter, the concordance and detection rate raised from 33.33% to 71.64% and 33.33% to 80.8%, respectively. For patients with partial response, stable disease, progressive disease, and who were treatment-naïve, the concordance and detection rates were 0.0%, 62.7%, 75.2, 73.6%, and 16.7%, 61.9%, 83.3%, 86.5%, respectively. Serological markers: CEA, CA125, NSE, and CYFRA21-1 were significantly higher for patients with detectable somatic alterations in ctDNA than in those who were ctDNA negative (17.08 ng/mL vs. 3.95 ng/mL, 21.63 U/mL vs. 18.27 U/mL, 17.68 U/mL vs. 14.14 U/mL, and 6.55 U/mL vs. 3.81 U/mL, respectively). Advanced-stage, treatment naïve or poor therapy outcome, and large tumor size were associated with a high concordance and detection rate. Patients with detectable mutations in ctDNA had a higher level of carcinoembryonic antigen, CA125, NSE, and CYFRA21-1.