Capsaicin Reduces Cancer Stemness and Inhibits Metastasis by Downregulating SOX2 and EZH2 in Osteosarcoma.

Metastasis of osteosarcoma is an important adverse factor affecting patients' survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100[Formula: see text][Formula: see text]M, 24[Formula: see text]h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment's inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin's dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or disease-free survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2. Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness.

Elevated intraspinal pressure in traumatic spinal cord injury is a promising therapeutic target.

The currently recommended management for acute traumatic spinal cord injury aims to reduce the incidence of secondary injury and promote functional recovery. Elevated intraspinal pressure (ISP) likely plays an important role in the processes involved in secondary spinal cord injury, and should not be overlooked. However, the factors and detailed time course contributing to elevated ISP and its impact on pathophysiology after traumatic spinal cord injury have not been reviewed in the literature. Here, we review the etiology and progression of elevated ISP, as well as potential therapeutic measures that target elevated ISP. Elevated ISP is a time-dependent process that is mainly caused by hemorrhage, edema, and blood-spinal cord barrier destruction and peaks at 3 days after traumatic spinal cord injury. Duraplasty and hypertonic saline may be promising treatments for reducing ISP within this time window. Other potential treatments such as decompression, spinal cord incision, hemostasis, and methylprednisolone treatment require further validation.

Combined the GABA-A and GABA-B receptor agonists attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism.

Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. In this study, we employed prenatally exposed to valproic acid (VPA) to establish a validated ASD mouse model and found impaired inhibitory gamma-aminobutyric acid (GABAergic) neurotransmission through a presynaptic mechanism in these model mice, which was accompanied with decreased GABA release and GABA-A and GABA-B receptor subunits expression. And acute administration of individual GABA-A or GABA-B receptor agonists partially reversed autistic-like behaviors in the model mice. Furthermore, acute administration of the combined GABA-A and GABA-B receptor agonists palliated sociability deficits, anxiety and repetitive behaviors in the animal model of autistic-like behaviors, demonstrating the therapeutic potential of above cocktail in the treatment of ASD.

[Effect of early electroacupuncture intervention on conscious state of patients after traumatic brain injury surgery].

OBJECTIVE: To evaluate recovering consciousness effect of electroacupuncture (EA) on patients after traumatic brain injury (TBI) surgery. METHODS: A total of 100 patients with traumatic coma were randomly divided into an observation group and a control group, 50 cases in each group. The control group was mainly treated with awakening drugs and neurotrophic drugs; on the basis of treatment in the control group, the observation group was treated with EA at Neiguan (PC 6) and Shuigou (GV 26) with disperse-dense wave, 2 Hz/100 Hz in frequency, 0.1-5 mA in intensity. After 30 min of EA, the needles were stayed 60 min. The treatment was performed once a day for 14 consecutive days. The changes in Glasgow coma score (GCS) was observed in the two groups before treatment and after 7, 14 days of treatment; and the two groups were followed up for 3 months after treatment to evaluate the Glasgow outcome scale (GOS) and Barthel index (BI) scores. RESULTS: After 7, 14 days of treatment, the GCS scores of the two groups were higher than those before treatment (P<0.05), and the increase degree in the observation group was significantly larger than that in the control group (P<0.05). At 3 months of follow-up, the GOS and BI scores of the observation group were better than those of the control group (P<0.05). CONCLUSION: Early electroacupuncture intervention can effectively promote the recovery of consciousness after traumatic brain injury surgery, and has a curative long-term effect.

A mysterious risk factor for bone cement leakage into the spinal canal through the Batson vein during percutaneous kyphoplasty: a case control study.

BACKGROUND: Percutaneous kyphoplasty (PKP) can effectively treat osteoporotic vertebral compression fractures (OVCFs). Although satisfactory clinical outcomes can be achieved, bone cement leakage remains a primary complication of PKP. Previous studies have found many high risk factors for bone cement leakage into the spinal canal; however, less attention to the posterior wall morphologies of different vertebral bodies may be one reason for the leakage. Here, we investigated the effect of posterior vertebral wall morphology in OVCF patients on bone cement leakage into the spinal canal during PKP. METHODS: Ninety-eight OVCF patients with plain computed tomography (CT) scans and three-dimensional (3D) reconstruction images from T6 to L5 were enrolled. 3D-CT and multiplanar reconstructions (MPR) were used to measure the concave posterior vertebral wall depth (PVWCD) and the corresponding midsagittal diameter of the nonfractured vertebral body (VBSD), and the PVWCD/VBSD ratio was calculated. All subjects were divided into the thoracic or lumbar groups based on the location of the measured vertebrae to observe the value and differences in the PVWCD between both groups. The differences in PVWCD and PVWCD/VBSD between the thoracic and lumbar groups were compared. Three hundred fifty-seven patients (548 vertebrae) who underwent PKP within the same period were also divided into the thoracic and lumbar groups. The maximal sagittal diameter (BCSD), the area of the bone cement intrusion into the spinal canal (BCA), and the spinal canal encroachment rate (BCA/SCA × 100%) were measured to investigate the effect of the thoracic and lumbar posterior vertebral wall morphologies on bone cement leakage into the spinal canal through the Batson vein during PKP. RESULTS: The PVWCDs gradually deepened from T6 to T12 (mean, 4.6 mm); however, the values gradually became shallower from L1 to L5 (mean, 0.6 mm). The PVWCD/VBSD ratio was approximately 16% from T6 to T12 and significantly less at 3% from L1 to L5 (P < 0.05). The rate of bone cement leakage into the spinal canal through the Batson vein was 10.1% in the thoracic group and 3.7% in the lumbar group during PKP. In the thoracic group, the BCSD was 3.1 ± 0.5 mm, the BCA was 30.2 ± 3.8 mm2, and the BCA/SCA ratio was 17.2 ± 2.0%. In the lumbar group, the BCSD was 1.4 ± 0.3 mm, the BCA was 14.8 ± 2.2 mm2, and the BCA/SCA ratio was 7.4 ± 1.0%. The BCSD, BCA and BCA/SCA ratio were significantly higher in the thoracic group than in the lumbar group (P < 0.05). CONCLUSIONS: The PVWCD in the middle and lower thoracic vertebrae can help reduce bone cement leakage into the spinal canal by enabling avoiding bone cement distribution over the posterior 1/6 of the vertebral body during PKP. The effect of the difference between the thoracic and lumbar posterior vertebral wall morphology on bone cement leakage into the spinal canal through the Batson vein in OVCF patients during PKP is one reason that the rate of bone cement leakage into the thoracic spinal canal is significantly higher than that into the lumbar spinal canal.

Risk Factors for Recurrence of Chronic Subdural Hematoma: A Single Center Experience.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a common form of intracranial hemorrhage with a substantial recurrence rate. We aimed to investigate the predictive factors for the postsurgical recurrence of CSDH. METHODS: We retrospectively reviewed the medical records of patients with CSDH who underwent surgery in West China Hospital between January 2012 and June 2018. Univariate and multivariate analyses were performed to identify the relationships between recurrence of CSDH and factors such as age, sex, history of injury, Markwalder grading, computed tomography findings, surgical methods, and outcomes. RESULTS: A total of 328 patients (281 men and 47 women) aged 22-93 years (mean age, 65.14 ± 13.76 years) were included. Computed tomography findings at admission showed mixed density hematoma in 136 patients, isodensity hematoma in 140, high-density hematoma in 34, and low-density hematoma in 18. The mortality and recurrence rate were 0.30% (1 of 328) and 2.44% (8 of 328), respectively. Six months postoperatively, 327 patients had Markwalder grade 0. Hematoma recurred in 8 patients of which 7 were mixed density hematoma and 1 was isodensity hematoma. Six patients who underwent craniotomy had thickened inner neomembrane that was resected. Univariate and multivariate analyses found mixed density hematoma to be an independent risk factor for the recurrence of CSDH. CONCLUSIONS: Burr hole craniostomy with irrigation and closed-system drainage is effective for the surgical treatment of CSDH. Mixed density hematoma is an independent predictor for the recurrence of CSDH. Presence of thick inner neomembrane might be the primary cause of CSDH recurrence.

Prospective randomized evaluation of therapeutic decompressive craniectomy in severe traumatic brain injury with mass lesions (PRECIS): study protocol for a controlled trial.

BACKGROUND: For cases of severe traumatic brain injury, during primary operation, neurosurgeons usually face a dilemma of whether or not to remove the bone flap after mass lesion evacuation. Decompressive craniectomy, which involves expansion of fixed cranial cavity, is used to treat intra-operative brain swelling and post-operative malignant intracranial hypertension. However, due to indefinite indication, the decision to perform this procedure heavily relies on personal experiences. In addition, decompressive craniectomy is associated with various complications, and the procedure lacks strong evidence of better outcomes. In the present study, we designed a prospective, randomized, controlled trial to clarify the effect of decompressive craniectomy in severe traumatic brain injury patients with mass lesions. METHODS: PRECIS is a prospective, randomized, assessor-blind, single center clinical trial. In this trial, 336 patients with traumatic mass lesions will be randomly allocated to a therapeutic decompressive craniectomy group or a prophylactic decompressive craniectomy group. In the therapeutic decompressive craniectomy group, the bone flap will be removed or replaced depending on the emergence of brain swelling. In the prophylactic decompressive craniectomy group, the bone flap will be removed after mass lesion evacuation. A stepwise management of intracranial pressure will be provided according to the Brain Trauma Foundation guidelines. Salvage decompressive craniectomy will be performed for craniotomy patients once there is evidence of imaging deterioration and post-operative malignant intracranial hypertension. Participants will be assessed at 1, 6 and 12 months after randomization. The primary endpoint is favorable outcome according to the Extended Glasgow Outcome Score (5-8) at 12 months. The secondary endpoints include quality of life measured by EQ-5D, mortality, complications, intracranial pressure and cerebral perfusion pressure control and incidence of salvage craniectomy in craniotomy patients at each investigation time point. DISCUSSION: This study will provide evidence to optimize primary decompressive craniectomy application and assess outcomes and risks for mass lesions in severe traumatic brain injury. TRIAL REGISTRATION: ISRCTN20139421.

The value of intraoperative intracranial pressure monitoring for predicting re-operation using salvage decompressive craniectomy after craniotomy in patients with traumatic mass lesions.

BACKGROUND: The risk factors of predicting the need for postoperative decompressive craniectomy due to intracranial hypertension after primary craniotomy remain unclear. This study aimed to investigate the value of intraoperative intracranial pressure (ICP) monitoring in predicting re-operation using salvage decompressive craniectomy (SDC). METHODS: From January 2008 to October 2014, we retrospectively reviewed 284 patients with severe traumatic brain injury (STBI) who underwent craniotomy for mass lesion evacuation without intraoperative brain swelling. Intraoperative ICP was documented at the time of initial craniotomy and then again after the dura was sutured. SDC was used when postoperative ICP was continually higher than 25 mmHg for 1 h without a downward trend. Univariate and multivariate analyses were applied to both initial demographic and radiographic features to identify risk factors of SDC requirement. RESULTS: Of 284, 41 (14.4%) patients who underwent SDC had a higher Initial ICP than those who didn't (38.1 ± 9.2 vs. 29.3 ± 8.1 mmHg, P < 0.001), but there was no difference in ICP after the dura was sutured. The factors which have significant effects on SDC are higher initial ICP [odds ratio (OR): 1.100, 95% confidence interval (CI): 1.052-1.151, P < 0.001], older age (OR: 1.039, 95% CI: 1.002-1.077, P = 0.039), combined lesions (OR: 3.329, 95% CI: 1.199-9.244, P = 0.021) and early hypotension (OR: 2.524, 95% CI: 1.107-5.756, P = 0.028). The area under the curve of multivariate regression model was 0.771. CONCLUSIONS: The incidence of re-operation using SDC after craniotomy was 14.4%. The independent risk factors of SDC requirement are initial ICP, age, early hypotension and combined lesions.

Decompressive craniectomy or not: intraoperative experience in 41 patients with severe traumatic brain injury.

OBJECTIVE: To present our experience in using decompressive craniectomy (DC) among severe traumatic brain injury (TBI) patients during operation and to discuss its indication. METHODS: From October 2008 to May 2009, 41 patients aged between 18 and 75 years with severe TBI were included in this study. They underwent DC or non-DC (NDC) according to their intraoperative findings. Postoperative intracranial pressure (ICP), complications, requiring second operation or not and outcomes were observed. RESULTS: Fifteen patients underwent DC and 26 patients did not. The average postoperative ICP of each patient was lower than 20 mm Hg. For patients received DC, 2 had seizures after operation and 1 developed cerebrocele in the follow-up period; only 1 NDC patient had post-traumatic seizures, but none of them had delayed haematoma, cerebrospinal fluid fistula, cerebrocele or infections. At the end of follow-up, 10 patients died, 6 had the GOS of 2, 2 of 3, 9 of 4 and 14 of 5. CONCLUSIONS: DC is necessary to manage fulminant intracranial hypertension or intraoperative brain swelling. If there was not brain swelling after removal of the haematoma and necrotized neural tissues, it is safe to replace skull flap. The intraoperative finding is an important factor to decide whether to perform DC or not.

Epidemiological features of 1 281 patients with head injuries arising from the 2008 Wenchuan earthquake.

OBJECTIVE: To analyze the epidemiological features of patients with head injuries in the 2008 Wenchuan earthquake. METHODS: Medical records of patients with head injuries who were admitted to 14 hospitals in Deyang, Mianyang and Chengdu cities after the earthquake were retrospectively analyzed. The patients'age, gender, cause of injury, diagnosis, and outcome were analyzed retrospectively. RESULTS: A total of 1 281 patients with 807 males and 474 females were included. According to Glasgow Coma Scale score at admission, 1 029 patients presented with mild injury, 161 moderate injury and 91 severe injury. The major cause of injuries (83%) was bruise by collapsed buildings. Open head injuries accounted for 60.8%. A total of 720 patients underwent surgical treatment. Good recovery was achieved in 1 056 patients, moderate disability in 106, severe disability in 71, coma in 29 and death in 19. CONCLUSIONS: In this series, male patients were more than female patients. The main cause of injury was hit by falling objects due to building collapse. Minor and open craniocerebral injuries were most common. The epidemiological features of head injuries in Wenchuan earthquake may be helpful to preparation for future rescue.

Cross-sectional study of craniocerebral trauma in a tertiary hospital after 2008 Sichuan earthquake: a brief report of 242 cases and experiences from West China Hospital.

BACKGROUND: We aim to analyze clinical features of patients with craniocerebral trauma after 2008 Sichuan earthquake in China. METHODS: Medical records of patients with craniocerebral trauma admitted to Department of Neurosurgery in West China Hospital within 30 days after earthquake were retrospectively analyzed. Demographic data, clinical diagnosis, treatment, and prognosis were reviewed. Patients' data from peripheral hospitals were also analyzed. RESULTS: Two hundred forty-two patients with craniocerebral injuries were included in the study. The male to female ratio was 1.3:1, and more than half of the patients were between 20 and 60 years. Majority of patients suffered from mild to moderate injuries (88.4%). Scalp wound was the leading type, followed by skull fractures and brain contusion and laceration. Fifty patients (20.7%) underwent craniotomy. Overall mortality was 5.4% (n = 13). In survivors, 186 patients had good outcome (Glasgow Outcome Scale score ≥4, 76.9%). Staphylococcus aureus (n = 74, 44.6%), Aerobacter cloacae (n = 37, 22.3%), and Staphylococcus epidermidis (n = 33, 19.9%) were most frequently isolated bacteria in wound smear. Over 85% (n=6) of patients with infectious wound (n=7) obtained delayed first stage healing. Mortality of patients in local hospitals ranged from 3.8% to 8.9%. CONCLUSIONS: Most patients admitted to tertiary hospitals are mildly or moderately injured. Cooperation among different departments is critical to shorten delay in emergency room. First stage wound healing or delayed first stage healing can be achieved in most patients after treatment. More than 76% of seismic injury patients in a tertiary medical center have good outcome.

The epidemiology and clinical management of craniocerebral injury caused by the Sichuan earthquake.

BACKGROUND: Earthquake is one of the most devastating natural disasters that threaten human lives. Worldwide more than 3 million deaths have been caused by earthquakes in recent 20 years. AIM: To analyze clinical features of head injuries after Sichuan earthquake. MATERIALS AND METHODS: From May 12 to June 12, 2008, Departments of Neurosurgery in major Hospitals in Sichuan Province admitted 1368 patients with head injuries caused by the Sichuan earthquake; the epidemiology, mechanism, severity, complications, treatments and outcome of head injury were retrospectively analyzed. RESULTS: Of the 1,368 patients, 755 were men and 613 women. Collapsing building was the most important cause of head injury. Most of the patients, 85% had mild to moderate head injury. The type of injury was open scalp injury in 65% of patients. About 47% of the head-injured patients were admitted within 72 h after earthquake. Skeletal bone fracture was the most common associated injury (9%). Only 98 patients received surgery. Glasgow Outcome Scale on discharge or transfer was: 5 in 1,121 (82%) patients, 4 in 173 (13%) patients, and 3 or less in 74 (5%) patients. Overall 33 (2%) patients died. CONCLUSIONS: The characteristics of Sichuan earthquake-related head injury are quite distinct. Early standardized treatment is important to have better outcomes.

Internal open brain injury or cranial burst fracture: report of 8 cases.

AIMS: We report a special type of skull fracture in children - internal open brain injury (IOBI). We summarize its clinical characteristics and propose a treatment strategy based on our experience. METHODS: Eight patients between 2 and 5 years old were identified to have IOBI. Preoperative computed tomography (CT) scanning was performed in each case and magnetic resonance imaging was conducted when available. All patients were treated surgically. The clinical data were retrospectively analyzed and each patient underwent follow-up CT scanning. RESULTS: IOBI has no special clinical manifestations other than scalp swelling, linear skull fracture and local brain contusion. Acute cerebral extrusion outside the calvaria and lacerated dura mater were seen during operation in each patient. Each patient's neurological status generally improved after surgery. No patient developed posttraumatic epilepsy during the 4- to 20-month follow-up period. CONCLUSIONS: IOBI is a type of head trauma in which dura mater is lacerated and the cerebrum is extruded outside the calvaria but the scalp remains intact. Craniotomy with evacuation of devitalized brain tissue and dural repair should be performed.