The Role of the Orexin System in Craniocerebral Trauma-Induced Epilepsy in Mice.

BACKGROUND: Following traumatic brain injury (TBI), an imbalance arises in the central nervous system within the hippocampus region, resulting in the proliferation of mossy cell fibers, causing abnormal membrane discharge. Moreover, disruptions in cellular neurotransmitter secretion induce post-traumatic epilepsy. Extensive experimental and clinical data indicate that the orexin system plays a regulatory role in the hippocampal central nervous system, but the specific regulatory effects are unclear. Therefore, further experimental evaluation of its relevance is needed. OBJECTIVE: This study aims to investigate the effects of orexin receptor agonists (OXA) on the seizure threshold and intensity in controlled cortical impact (CCI) mice, and to understand the role of the orexin system in post-traumatic epilepsy (PTE). METHODS: Male C57BL/6 mice weighing 18-22 g were randomly divided into three groups: Sham, CCI, and CCI+OXA. The three groups of mice were sequentially constructed with models, implanted with electrodes, and established drug-delivery cannulas. After a 30-day recovery, the Sham and CCI groups were injected with physiological saline through the administration cannulas, while the CCI+OXA group was injected with OXA. Subsequently, all mice underwent electrical stimulation every 30 minutes for a total of 15 times. Epileptic susceptibility, duration, intensity, and cognitive changes were observed. Concurrently, the expression levels and changes of GABAergic neurons in the hippocampus of each group were examined by immunofluorescence. RESULTS: Injecting OXA into hippocampal CA1 reduces the threshold of post-traumatic seizures, prolongs the post-discharge duration, prolongs seizure duration, reduces cognitive ability, and exacerbates the loss of GABAergic neurons in the hippocampal region. CONCLUSIONS: Based on the results, we can find that injecting OXA antagonists into the CA1 region of the hippocampus can treat or prevent the occurrence and progression of post-traumatic epilepsy.

Characteristics and Neural Mechanisms of Sleep-Wake Disturbances After Traumatic Brain Injury.

Sleep-wake disturbances (SWDs) are one of the most common complaints following traumatic brain injury (TBI). The high prevalence and socioeconomic burden of SWDs post-TBI have only been recognized in the past decade. Common SWDs induced by TBI include excessive daytime sleepiness (EDS), hypersomnia, insomnia, obstructive sleep apnea (OSA), and circadian rhythm sleep disorders. Sleep disturbances can significantly compromise quality of life, strain interpersonal relationships, diminish work productivity, exacerbate other clinical conditions, and impede the rehabilitation process of TBI patients. Consequently, the prompt regulation and enhancement of sleep homeostasis in TBI patients is of paramount importance. Although studies have shown that abnormal neural network function, neuroendocrine changes, disturbance of sleep-wake regulators, and immune inflammatory responses related to brain structural damage induced by TBI are involved in the development of SWDs, the exact neuropathological mechanisms are still poorly understood. Therefore, we systematically review the current clinical and experimental studies on the characteristics and possible neural mechanisms of post-TBI SWDs. Elucidating the neural underpinnings of post-TBI SWDs holds the potential to diversify and enhance therapeutic approaches for these conditions. Such advancements could hasten the recuperation of TBI patients and ameliorate their overall quality of life. It is our aspiration that departments specializing in neurosurgery, rehabilitation, and neuropsychiatry will be able to recognize and address these conditions promptly, thereby facilitating the healing journey of affected individuals.

Neuroprotective Effects of Vinpocetine Against Ischemia-Reperfusion Injury Via Inhibiting NLRP3 Inflammasome Signaling Pathway.

Ischemic stroke is one of the main causes of serious disability and death worldwide. NLRP3 inflammasome is an intracellular pattern recognition receptor composed of polyprotein complex, which participates in mediating a series of inflammatory responses and is considered as a potential target for the treatment of ischemic stroke. Vinpocetine, a derivative of vincamine, has been widely used in the prevention and treatment of ischemic stroke. However, the therapeutic mechanism of vinpocetine is not clear, and its effect on NLRP3 inflammasome remains to be determined. In this study, we used the mouse model of transient middle cerebral artery occlusion (tMCAO) to simulate the occurrence of ischemic stroke. Different doses of vinpocetine (5, 10, 15 mg/kg/d) were injected intraperitoneally for 3 days after ischemia-reperfusion in mice. The effects of different doses of vinpocetine on the degree of ischemia-reperfusion injury in mice were observed by TTC staining and modified neurological severity score scale, and the optimal dose was determined. Then, based on this optimal dose, we observed the effects of vinpocetine on apoptosis, microglial proliferation and NLRP3 inflammasome. In addition, we compared the effects of vinpocetine and MCC950 (a specific inhibitor of NLRP3 inflammasome) on NLRP3 inflammasome. Our results show that vinpocetine can effectively reduce the infarct volume and promote the recovery of behavioral function in stroke mice, and the maximal beneficial effects were observed at the dose of 10 mg/kg/d. Vinpocetine can effectively inhibit the apoptosis of peri-infarct neurons, promote the expression of Bcl-2, inhibit the expression of Bax and Cleaved Caspase-3, and reduce the proliferation of peri-infarct microglia. In addition, vinpocetine, like MCC950, can reduce the expression of NLRP3 inflammasome. Therefore, vinpocetine can effectively alleviate the ischemia-reperfusion injury in mice, and the inhibition of NLRP3 inflammasome may be an important therapeutic mechanism of vinpocetine.

Leukocyte as an Independent Predictor of Lower-Extremity Deep Venous Thrombosis in Elderly Patients With Primary Intracerebral Hemorrhage.

Objective: Due to the interaction of leukocytes with platelets and coagulation factors, they may in turn play a role in hemostasis or the formation of thrombi. This study aimed to investigate the association of leukocytosis on admission with an increased risk of acute lower-extremity deep venous thrombosis (LEDVT) in elderly patients with primary intracerebral hemorrhage (ICH). Methods: This was a single-center, retrospective observational study of consecutive patients observed with spontaneous ICH aged 60 years or above at Lanzhou University Second Hospital from January 2017 to September 2021. Clinical data and demographic information were collected and analyzed. Univariate and multivariate analyses were conducted to identify independent risk factors of acute LEDVT. One-to-one matching was implemented to balance important patient characteristics by the groups' propensity score matching (PSM) analysis. Results: A total of 371 elderly patients with primary ICH fulfilled requirements for inclusion and exclusion, of whom 33 (8.89%) experienced LEDVT. Leukocyte counts were statistically higher in the LEDVT group compared to the non-LEDVT group [12.89 (8.80-14.61) × 109 cells/L vs. 8.31 (6.60-10.75) × 109 cells /L, p < 0.001]. Multivariate logistic regression models adjusted for several potential confounding factors were performed, and leukocytes were consistently a significant independent predictor of LEDVT. The optimal cut-off value of leukocyte counts calculated from the receiver operating characteristic (ROC) curve to predict LEDVT was 10.22 × 109 cells /L (area under the curve:0.714, 95%CI 0.665-0.759; the sensitivity was 72.73%; the specificity was 71.01%) in elderly patients with primary ICH. After one-to-one PSM, compared to the matched non-LEDVT group, the matched LEDVT group had significantly higher leukocyte counts [11.98 (8.40-13.94) × 109 cells/L vs. 6.12 (4.68-12.00) × 109 cells/L, p = 0.003]. After PSM, the ROC curve was plotted for leukocytes as a predictor of LEDVT, with an AUC of 0.722 (95%CI 0.593-0.828, p = 0.001; the sensitivity was 87.10%, and the specificity was 61.29%). Elevated leukocytes remained independently significant as predictors of LEDVT in elderly patients with primary ICH. Conclusion: Leukocyte at admission is an independent risk factor of LEDVT in elderly patients with primary ICH.

Ki20227 aggravates apoptosis, inflammatory response, and oxidative stress after focal cerebral ischemia injury.

The survival of microglia depends on the colony-stimulating factor-1 receptor (CSF1R) signaling pathway under physiological conditions. Ki20227 is a highly selective CSF1R inhibitor that has been shown to change the morphology of microglia. However, the effects of Ki20227 on the progression of ischemic stroke are unclear. In this study, male C57BL/6 mouse models of focal cerebral ischemic injury were established through the occlusion of the middle cerebral artery and then administered 3 mg/g Ki20227 for 3 successive days. The results revealed that the number of ionized calcium-binding adaptor molecule 1/bromodeoxyuridine double positive cells in the infarct tissue was reduced, the degree of edema was increased, neurological deficits were aggravated, infarct volume was increased, and the number of peri-infarct Nissl bodies was reduced. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in the peri-infarct tissue was increased. The expression levels of Bax and Cleaved caspase-3 were up-regulated. Bcl-2 expression was downregulated. The expression levels of inflammatory factors and oxidative stress-associated factors were increased. These findings suggested that Ki20227 blocked microglial proliferation and aggravated the pathological progression of ischemia/reperfusion injury in a transient middle cerebral artery occlusion model. This study was approved by the Animal Ethics Committee of Lanzhou University Second Hospital (approval No. D2020-68) on March 6, 2020.

CCNB2 is a novel prognostic factor and a potential therapeutic target in low-grade glioma.

BACKGROUND: Cyclin B2 (CCNB2) is an important component of the cyclin pathway and plays a key role in the occurrence and development of cancer. However, the correlation between prognosis of low-grade glioma (LGG), CCNB2, and tumor infiltrating lymphocytes is not clear. METHODS: The expression of CCNB2 in LGG was queried in Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and TIMER databases. The relationships between CCNB2 and the clinicopathological features of LGG were analyzed using the Chinese Glioma Genome Atlas (CGGA) database. The relationship between CCNB2 expression and overall survival (OS) was evaluated by GEPIA2. The correlation between CCNB2 and LGG immune infiltration was analyzed by the TIMER database. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect CCNB2 expression. RESULTS: The expression of CCNB2 differed across different tumor tissues, but was higher in LGG than in normal tissues. LGG patients with high expression of CCNB2 have poorer prognosis. The expression of CCNB2 was correlated with age, WHO grade, IDH mutational status, 1p/19q codeletion status, and other clinicopathological features. The expression of CCNB2 in LGG was positively correlated with the infiltration level of B cells, dendritic cells, and macrophages. qRT-PCR results revealed that the expression of CCNB2 in LGG tissues was higher than normal tissues and higher expression of CCNB2 was associated with worse prognosis. CONCLUSION: CCNB2 may be used as a potential biomarker to determine the prognosis of LGG and is also related to immune infiltration.

The Influence of Interpersonal Behaviors and Population Density on Grip Strength of Elderly People: An Analysis of the Direct vs. Indirect Effects via Social Participation.

The impact of social participation (SP) on the health of the elderly has been widely recognized, and urban-rural differences in social participation have attracted attention. However, few studies discussed the impact of social participation on specific health indicators and the further subdivision of urban-rural differences. This research aims to use the dimensions of interpersonal behaviors and population density rather than simple urban-rural distinctions to justify community differences and compare these differences' direct and indirect effects on grip strength. This study used 15,871 respondents aged over 50 years from the China Health and Retirement Longitudinal Study (CHARLS). An SEM (Structural Equation Modeling) analysis was used to explore the joint effect of interpersonal behavior and population density on social participation and the consequent impact on changes in grip strength and compare the differences among different genders, ages, wealth levels, and family relationships. The results indicated that community differences characterized by interpersonal behavior and population density have direct effects on grip strength and indirect effects on it through social participation. The conclusion is that the frequency of social activities, such as mah-jong and dancing in the Metropolitan Fringe and county-level cities is higher than that in Metropolitan centers. The high frequency of these activities has a positive and indirect impact on grip strength, and community differences have a more significant impact on women's social participation than men. However, the direct effect of community differences as defined by interpersonal communication and population density on grip strength is greater than the indirect effect of other factors through social participation.

Analysis of High-Risk Factors Associated with the Progression of Subaneurysmal Aorta to Abdominal Aortic Aneurysm in Rural Area in China.

OBJECTIVE: To determine the risk factors associated with the progress of subaneurysmal aorta (SAA) to abdominal aortic aneurysm (AAA) and provide a reference for the prevention of AAA in rural areas. METHODS: A total of 747 SAA patients screened by the Health Management Center of the Second Hospital of Lanzhou University from January 2015 to January 2016 were recruited. The ratio of SAA progressing to AAA was observed through 5 years of follow-up. Logistic stepwise regression analysis was performed to analyze the high-risk factors. The relevant clinical prediction model score table (Nom) was made and the C-index and calibration chart were used to verify the prediction ability of the model. RESULTS: Of the 747 patients diagnosed with SAA, 260 developed to AAA, with an incidence of 34.8%. Univariate analysis showed that age (62-65 years old), abdominal aorta diameter greater than 2.7 cm, smoking after 30 years old, moderate to severe hypertension, and blood pressure variability were the important high-risk factors of SAA progressing to AAA. Logistic regression analysis showed that these factors were statistically significant. The nomogram of clinical prediction model score showed that when 50-60% of SAA developed to AAA, the score was 189-201 and the C-index was 0.883, verifying the moderate predictive ability of this model. CONCLUSION: Age, smoking habit, degree of hypertension, and control situation were high-risk factors associated with the progression of SAA to AAA. The control of the above high-risk factors was imperative for the prevention of AAA in rural areas without sufficient medical resources.

Pharmacological Targeting of CSF1R Inhibits Microglial Proliferation and Aggravates the Progression of Cerebral Ischemic Pathology.

Ischemic stroke can induce rapid activation of the microglia. It has been reported that the microglia's survival is dependent on colony-stimulating factor 1 receptor (CSF1R) signaling and that pharmacological inhibition of CSF1R leads to morphological changes in the microglia in the healthy brain. However, the impact of CSF1R inhibition on neuronal structures and motor ability after ischemia-reperfusion remains unclear. In this study, we investigated microglial de-ramification, proliferation, and activation after inhibition of CSF1R by a tyrosine kinase inhibitor (ki20227) in a mouse model of global cerebral ischemia induced by bilateral common carotid artery ligation (BCAL). In addition to microglial morphology, we evaluated the mRNA expression of cytokines, chemokines, and inflammatory receptors. Our results show that pharmacological inhibition of CSF1R in ischemic mice resulted in the blockade of microglial proliferation and a shift in microglial morphology reflected by excessive de-ramification and a more activated phenotype accompanied by an enhanced innate immune response. Furthermore, we show that pharmacological inhibition of CSF1R in ischemic mice resulted in the aggravation of neuronal degeneration and behavioral impairment. Intravital two-photon imaging revealed that although pharmacological inhibition of CSF1R did not affect the recovery of dendritic structures, it caused a significant increase in spine elimination during reperfusion in ischemic mice. These findings suggest that pharmacological inhibition of CSF1R induces a blockade of microglial proliferation and causes acute activation of the microglia accompanied by a severe inflammatory response. It aggravates neuronal degeneration, loss of dendritic spines, and behavioral deficits after transient global cerebral ischemia.

Lactic acid, neuron-specific enolase, and blood-brain barrier index after a severe traumatic brain injury: a prospective study.

OBJECTIVE: To explore the clinical significance of dynamic monitoring of cerebrospinal fluid (CSF) and serum Lactic acid（Lac), neuron-specific enolase (NSE), and the blood-brain barrier (BBB) index in evaluating the condition and prognosis after a severe traumatic brain injury (TBI). METHODS: A total of 52 severe TBI patients admitted to the Department of Neurosurgery within 24 hours after injury were dynamically monitored. CSF and serum samples were collected on the 1st, 3rd, and 7th day after a severe TBI to monitor the changes in Lac, NSE, and the BBB index. Intracranial pressure (ICP), Glasgow coma scale (GCS), and 6-month Glasgow outcome scale-extended (GOS-E) were tested. According to the results of GOS-E, the patients were divided into two groups (i.e. the poor prognosis group and good prognosis group). Statistical analysis was conducted to investigate the clinical significance of dynamic monitoring of CSF and serum Lac, NSE, and BBB index after a severe TBI. RESULTS: After a severe TBI, the levels of Lac, NSE, and BBB in CSF and serum were significantly higher than those in the normal range. Lac, NSE, and the BBB index did not correlate with ICP (except serum Lac) but had correlations with GCS and post-injury 6 months post-injury (except serum Lac). Moreover, the correlations between Lac, NSE, and BBB index were statistically significant (p < 0.05): CSF Lac and CSF NSE; CSF Lac and serum NSE; Lac and BBB index of CSF; Lac and BBB index of CSF; NSE and CSE of serum; CSF NSE and BBB index; and serum NSE and BBB index. Additionally, serum NSE is correlated with NSE in CSF (p < 0.05). CONCLUSION: After a severe TBI, dynamic monitoring of CSF and serum Lac, NSE, and BBB index has the potential to assess the condition, predict the prognosis, and have clinical significance.

Bladder cancer hunting: A microfluidic paper-based analytical device.

Bladder cancer is the fourth most common cancer in men, and it is becoming a prevalent malignancy. Most of the regular clinical examinations are prompt evaluations with cystoscopy, renal function testing, which require high-precision instrument, well-trained operators, and high cost. In this study, a microfluidic paper-based analytical device (µPAD) was fabricated to detect nuclear matrix protein 22 (NMP22) and bladder cancer antigen (BTA) from the urine samples. Urine samples were collected from 11 bladder cancer patients and 10 well-beings as experiment and control groups, respectively, to verify the working efficiency of µPAD. A remarkable checkout efficiency of up to 90.91% was found from the results. Meanwhile, this method is feasible for home-based self-detection from urine samples within 10 min for the total process, which provides a new way for quick, economical, and convenient tumor diagnosis, prognosis evaluation, and drug response.

Bilateral Dysplastic Gangliocytoma with Concurrent Polyostotic Fibrous Dysplasia: A Case Report and Literature Review.

BACKGROUND: Dysplastic gangliocytoma is a sporadic cerebellar benign tumor with the characteristics of hamartoma and true tumor, also known as Lhermitte-Duclos disease (LDD). Bone fibrous dysplasia (FD) is a slowly progressive self-limited benign bone tissue disease. Cowden syndrome, an autosomal dominant genetic disorder caused by germline mutations in the PTEN gene, is considered to be closely related to dysplastic gangliocytoma. McCune-Albright syndrome is a disease characterized by café-au-lait skin macules, polyostotic FD, and precocious puberty. The etiologic mechanism of both conditions is not yet clear. We report a rare case of bilateral dysplastic gangliocytoma with concurrent polyostotic FD. CASE DESCRIPTION: We describe a 16-year-old boy with both LDD and FD. He presented for medical examination with headache and poor eyesight. Magnetic resonance imaging revealed proliferation of the skull and abnormal signals in the cerebellum, and supratentorial hydrocephalus. Subtotal resection of the cerebellar tumor was performed, and the diagnosis of LDD and FD was confirmed by histopathology. No other abnormal changes were found in systemic medical examination and no PTEN gene mutation was found in the genetic analysis; therefore, the diagnoses of Cowden syndrome and McCune-Albright syndrome were excluded. CONCLUSIONS: LDD and FD are 2 rare diseases, and the simultaneous occurrence of the 2 conditions has not been reported before, to our knowledge. Our report challenges the etiology of the 2 diseases and the relationship between them, hoping to provide a reference for the study of the 2 diseases.

The value of ultrasound for detecting hand fractures: A meta-analysis.

BACKGROUNDS: Hand fractures are the second most common upper-extremity fractures. The standard X-ray has shortcomings, such as exposure to radiation. Ultrasound has been reported as an alternative method of detecting hand fractures. In this study, we used meta-analysis to assess the diagnostic value of ultrasound for hand fractures. METHODS: Web of Science, PubMed, Embase, and Cochrane Library databases were searched for relative citations up to June 2019. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the summary receiver operating characteristic curve (AUC), and summary receiver operating characteristic (SROC) curve were estimated. RESULTS: Seven studies including 842 participants (845 examined hands) met our inclusion criteria. The pooled sensitivity, specificity, PLR, and NLR of ultrasound for detecting hand fractures were 91%, 96%, 20.66, and 0.09, respectively. The pooled DOR was 231.17, indicating a very powerful diagnostic ability of ultrasound. Meta-regression showed that there was no heterogeneity with respect to age, cut-off, the performer of the ultrasound, and the types of hand fractures. CONCLUSIONS: Our results showed that ultrasound had an excellent diagnostic value for hand fractures. In clinic, we proposed using ultrasound as a first-line and radiation-free modality in detecting hand fractures, including phalanx and metacarpal fractures.

Traumatic bifrontoparietal extradural hematomas with detachment of superior sagittal sinus: a case report and review of the literature.

A 45-year-old man suffered bifrontoparietal extradural hematoma resulting from head injury, which cause superior sagittal sinus detachment from its subperiosteal loggia. We present the patient who was treated by early surgical evacuation of the hematoma with an excellent outcome and we also perform a review of the current literature.

Multiple myeloma with pathologically proven skull plasmacytoma after a mild head injury: Case report.

RATIONALE: MM is a malignant tumor originating from the plasma cells of the bone marrow. Central nervous system myelomatosis is very rare and may be a complication of MM. PATIENT CONCERNS: A 60-year-old man presented with a slowly growing soft mass at his right frontal scalp after a mild head injury 6 months ago. DIAGNOSES: Neuroradiological examinations revealed a solid intracranial-extracranial mass with an osteolytic lesion in the skull. Histopathological examination showed skull plasmacytoma, and postoperative examinations revealed multiple myeloma. INTERVENTIONS: The tumor was completely removed and the skull defect repaired with the titanium mesh. Then, chemotherapy was initiated after surgery with bortezomib and dexamethasone. OUTCOMES: The patient received eight chemotherapies within one year after surgery. LESSONS: Despite a history of head injury, a differential diagnosis should be kept in mind during the diagnosis of solid intracranial-extracranial masses, especially in the presence of osteolytic skull at the lesioned site.

Animal experimental studies using small intestine endoscope.

AIM: To assess the feasibility and safety of a novel enteroscope, negative-pressure suction endoscope in examining the small intestine of a porcine model. METHODS: In vitro experiments in small intestinal loops from 20 pigs and in vivo experiments in 20 living pigs were conducted. RESULTS: In in vitro experiments, a negative pressure of > 0.06 MPa was necessary for optimal visualization of the intestine, and this pressure did not cause gross or histological damage to the mucosa. For satisfactory examination of the small intestine in vivo, higher negative pressure (> 1.00 MPa) was required. Despite this higher pressure, the small intestine did not show any gross or microscopic damage in the suctioned areas. The average time of examination in the living animals was 60 ± 7.67 min. The animals did not experience any apparent ill effects from the procedure. CONCLUSION: Small intestine endoscope was safely performed within a reasonable time period and enabled complete visualization of the intestine in most cases.

Exogenous Neural Stem Cells Transplantation as a Potential Therapy for Photothrombotic Ischemia Stroke in Kunming Mice Model.

Stroke is considered as the second leading cause of death worldwide. The survivors of stroke experience different levels of impairment in brain function resulting in debilitating disabilities. Current therapies for stroke are primarily palliative and may be effective in only a small population of stroke patients. In this study, we explore the transplantation of exogenous neural stem cells (NSCs) as the potential therapy for the photothrombotic ischemia stroke in a Kunming mice model. After stroke, mice receiving NSC transplantation demonstrated a better recovery of brain function during the neurobehavioral tests. Histology analysis of the brain samples from NSC transplanted mice demonstrated a reduction of brain damage caused by stroke. Moreover, immunofluorescence assay for biomarkers in brain sections confirmed that transplanted NSCs indeed differentiated to neurons and astrocytes, consistent with the improved brain function after stroke. Taken together, our data suggested that exogenous NSC transplantation could be a promising therapy for stroke.

Neural stem cell transplantation promotes behavioral recovery in a photothrombosis stroke model.

Stem cell-based therapy provides a promising approach for treat stroke. Neural stem cells isolated from mice hippocampus possessing the capacity of differentiate into neurons and astrocytes both in vitro and vivo. Here, we investigated the capability of neural stem cell transplantation in photothrombosis stroke model. Nissl staining revealed that the cortical infarct significantly decreased by 16.32% (Vehicle: 27.93le: an mm(3), n=6, NSC: 23.37le: ai mm(3), n=6, P<0.05) in the NSC group compared with the vehicle. More over transplantation of neural stem cells significantly (P<0.01) improved neurological performance compared with vehicle. These results indicate that transplantation of neural stem cell is an effective therapy in ischemic stroke.