Investigation of the effects of high cervical spinal cord electrical stimulation on improving neurological dysfunction and its potential mechanism in rats with traumatic brain injury.

To explore the effects of high cervical spinal cord electrical stimulation (cSCS) on the recovery of neurological function and its possible mechanism in rats with traumatic brain injury (TBI). 72 rats were randomly divided into: (1) a sham group; (2) a traumatic brain injury (TBI) group; (3) a TBI+cSCS group; (4) a LY294002+TBI+cSCS group. The degree of neurological dysfunction was evaluated by modified Neurological severity score (mNSS). The pathological changes of the brain tissue in the injured area were observed by HE staining, and the apoptosis of neuron cells were observed by TUNEL staining. The expressions of BDNF and VEGFmRNA were detected by polymerase chain reaction (PCR), and the expressions of p-AKT, AKT, Bcl-2, Bax and caspase-3 proteins were detected by western blot. Compared with that of the TBI and LY294002+TBI+cSCS groups, the mNSS of the TBI+cSCS group were significantly lower on day 3 and 7 ( P <0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the apoptosis of neuron cells in the TBI+cSCS group decreased significantly ( P < 0.05). Compared with the TBI and LY294002+TBI+cSCS group, the expression of Bcl-2 protein increased and the expressions of Bax and Caspase-3 proteins decreased in the TBI+cSCS group ( P < 0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the intensity of p-Akt/Akt in the TBI+cSCS group increased ( P < 0.05). We found that cSCS had a protective effect on neuron cells after craniocerebral injury and could improve neurological dysfunction in rats, the mechanism of which might be that cSCS made the PI3K/Akt pathway more active after TBI.

Hyperbaric oxygen via mediating SIRT1-induced deacetylation of HMGB1 improved cReperfusion inj/reperfusion injury.

Ischemic stroke leads to severe neurological dysfunction in adults. Hyperbaric oxygen (HBO) induces tolerance to cReperfusion inj/reperfusion (I/R) injury. Therefore, our aims were to investigate whether SIRT1 participates in regulatingin the neuro-protective effect of HBO in a cerebral I/R model and its mechanism. Mice N2a cells were used to construct an oxygen deprivation/reperfusion (OGD/R) model to simulate in vitro brain I/R injury and to evaluate the role of HBO in OGD/R stimulated cells. Cell proliferation was detected using MTT, and apoptosis was determined by flow cytometry. ELISA was used to measure the concentration of TNF-α, IL-1ß and IL-6 related inflammatory factors. RT-qPCR and western blot assays were performed to test the expression of SIRT1. Immunoprecipitation was used to detect acetylation of HMGB1. Expression of SIRT1 was obviously reduced after OGD/R treatment in N2a cells, while SIRT1 was obviously enhanced in HBO treated cells. Moreover, knockdown of SIRT1 induced neuro-inflammation damage in cells and HBO effectively improved the inflammatory response in OGD/R treated cells by affecting SIRT1 levels. Furthermore, HBO induced the deacetylation of HMGB1 via regulating SIRT1. Interestingly, HBO via regulating the SIRT1-induced HMGB1 deacetylation and suppressing MMP-9 improved ischemic brain injury. HBO regulated ischemic brain injury via regulation of SIRT1-induced HMGB1 deacetylation, making it a potential treatment for ischemic brain injury treatment.

Identify specific gene pairs for subarachnoid hemorrhage based on wavelet analysis and genetic algorithm.

Subarachnoid hemorrhage (SAH) is a fatal stroke caused by bleeding in the brain. SAH can be caused by a ruptured aneurysm or head injury. One-third of patients will survive and recover. One-third will survive with disability; one-third will die. The focus of treatment is to stop bleeding, restore normal blood flow, and prevent vasospasm. Treatment for SAH varies, depending on the bleeding's underlying cause and the extent of damage to the brain. Treatment may include lifesaving measures, symptom relief, repair of the bleeding vessel, and complication prevention. However, the useful diagnostic biomarkers of SAH are still limited due to the instability of gene marker expression. To overcome this limitation, we developed a new protocol pairing genes and screened significant gene pairs based on the feature selection algorithm. A classifier was constructed with the selected gene pairs and achieved a high performance.

Adjuvant treatment with Angong Niuhuang pills in treating traumatic brain damage: a meta-analysis of randomized controlled trials.

BACKGROUND: The Angong Niuhuang pill (ANP) has been widely used in the adjuvant treatment of patients with traumatic brain injury (TBI). However, the efficacy and adverse reactions of this drug are controversial. In this study, it was aimed to evaluate the effectiveness and safety of ANP on patients with TBI by a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, Embase, Cochrane Library, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wangfang databases were systematically searched from their establishment until June 2020. RCTs of ANP treating TBI were enrolled. Odds risk (OR) was used to assess the total effective rate and safety and mean difference (MD) and 95% confidence interval (CI) were used to assess the quantitative data. Tthe included literature's quality was evaluated by RevMan 5.3. The sensitivity and publication bias was evaluated by Stata 16.0. RESULTS: Twelve studies were identified in this systematic review, including 1,568 participants. The metaanalysis results suggested that ANP combined with routine treatment obviously improved the postoperative GCS [MD =1.97, 95% CI (1.22, 2.72), P<0.01] and GOS [OR =2.28, 95% CI (1.60, 3.22), P<0.01] of patients with TBI. ANP also increased Mg2+ concentration and decreased pulmonary infection. In addition, ANP significantly reduced NSE, gastrointestinal bleeding, and liver and kidney function damage. CONCLUSIONS: Based on limited evidence, ANP adjuvant therapy may have a clinical benefit in improving the prognosis of patients with TBI and reducing the associated complications. At the same time, more studies with larger sample sizes and high quality are required to determine the safety and effectiveness of ANP adjuvant therapy.

Regulatory effects of microRNA­184 on osteosarcoma via the Wnt/ß­catenin signaling pathway.

The present study aimed to investigate the role of microRNA (miRNA/miR)­184 in osteosarcoma growth, development and metastasis, and the effects of miRNA­184 on the proliferation, invasion and metastasis of osteosarcoma cells and associated mechanisms. In vitro, miR­184 was transfected into U­2OS cells and 143B cells. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to detect the expression of miR­184. MTT was utilized to detect cell proliferation. A Transwell assay was applied to detect cell invasiveness. In vivo, an osteosarcoma tibial orthotopic metastatic tumor model was established, and western blotting and RT­qPCR were used to detect the expression of Wnt and ß­catenin. Following the overexpression of miR­184, the proliferation and cell invasion ability were significantly increased in U­2OS and 143B cells. Following inhibition of miR­184, cell proliferation and cell invasion ability were significantly decreased. In nude mice, tumor volume significantly increased following overexpression of miR­184, and Wnt and phosphorylated ß­catenin levels were significantly increased. Following miR­184 inhibition, tumor volume was significantly decreased, and Wnt and phosphorylated ß­catenin levels were significantly decreased. The results of the present study indicated that the Wnt/ß­catenin signaling pathway serves a key function in the mechanism of osteosarcoma. Inhibition of miRNA­184 may reduce tumor volume of osteosarcoma via regulation of the Wnt/ß­catenin signaling pathway and may provide a novel strategy for the future diagnosis and treatment of osteosarcoma.

Clinical application of computed tomography-guided (125)I seed interstitial implantation for head and neck cancer patients with unmanageable cervical lymph node metastases.

BACKGROUND: To assess clinical application of computed tomography (CT)-guided (125)I seed implantation for patients who cannot endure or unwillingly receive repeated surgery, chemotherapy, or radiotherapy for unmanageable cervical lymph node metastases in head and neck cancer (HNC). METHODS: Thirty-one consecutive patients received CT-guided (125)I seed implantation between February 2010 and December 2013. To evaluate the clinical efficiency, karnofsky performance score (KPS), numeric rating scale (NRS), and tumor volume at 3-, and 6-month post-implantation were compared with pre-implantation, along with local control rate (LCR), overall survival rate (OSR), and complications at 3, 6 months, 1, and 2 years. RESULTS: The tumor volume was obviously decreased at 3-, and 6-month post-implantation (21.23 ± 8.83 versus 9.19 ± 7.52 cm(2); 21.23 ± 8.83 versus 6.42 ± 9.79 cm(2); P < 0.05) compared with pre-implantation. The NRS was statistically reduced (3.06 ± 1.06 versus 7.77 ± 0.92; 2.39 ± 1.15 versus 7.77 ± 0.92; P < 0.05), while KPS was significantly improved (83.18 ± 5.97 versus 73.60 ± 7.90; 82.86 ± 5.43 versus 73.60 ± 7.90; P < 0.05) postoperatively at 3 and 6 months, respectively. The LCR at 3, 6 months, 1, and 2 years was 96.30, 83.87, 64.51, and 45.16%, respectively. The OSR was 100, 100, 67.74, and 45.16%, respectively. Three cases experienced grade I and two had grade II acute radiation toxicity. CONCLUSIONS: CT-guided seed implantation may be feasible and safe for HNC patients whose neck nodes are not manageable by routine strategies with fewer complications, higher LCR, and significant pain relief.

[Treatment of metastatic thoracolumbar tumors by percutaneous vertebroplasty combined with interstitial implantation of ¹²5I seeds].

OBJECTIVE: To explore the value of percutaneous vertebroplasty combined with interstitial implantation of ¹²5I seeds in the treatment of metastatic thoracolumbar tumors. METHODS: Based on the CT images before ¹²5I seed implantation, a computer-based treatment planning system (TPS) was used to determine the optimal seed distribution. Under CT guidance and local anaesthesia, ¹²5I seeds were implanted into 22 osseous metastatic lesions in 18 patients. Based on the CT images after the implantation, quality check was carried out with TPS. DSA (digital subtraction angiography)-guided vertebroplasty was performed under local anaesthesia, and bone cement was injected into the vertebrae through pedicle of vertebral arch. RESULTS: All the 18 patients received percutaneous vertebroplasty combined with interstitial implantation of ¹²5I seeds. Every vertebra was injected with 2-6 ml bone cement, average 3.5 ml, and was injected with ¹²5I seeds 16-34 pills, average 26 pills. At 2-months follow-up, their numerical rating scale (NRS) pain scores were 7.12 ± 1.48 before and 2.26 ± 1.07 after treatment, with a significant difference (P < 0.05). CONCLUSIONS: Percutaneous vertebroplasty combined with interstitial implantation of ¹²5I seeds is a minimally invasive procedure with small wound and minor complications, and no need of external radiation therapy. It is effective in the alleviation of pain in metastatic thoracolumbar tumor patients, restrains the tumor growth, and improves the quality of life. It is a promising minimally invasive method in the treatment of metastatic thoracolumbar tumors.

Novel and recurrent mutations in the EXT1 and EXT2 genes in Chinese kindreds with multiple osteochondromas.

Multiple osteochondromas (MO) is an autosomal dominant hereditary disorder caused by heterozygous germline mutations in the exostonsin-1 (EXT1) or exostosin-2 (EXT2) genes. In this study, we screened mutations in the EXT1/EXT2 genes in four Chinese MO kindreds by direct sequencing. Three point mutations were detected, including a nonsense mutation in the EXT2 gene (c.544C > T) and two splice site mutations in the EXT1 and EXT2 genes, respectively (EXT1: c.1883 + 1G > A and EXT2: c.1173 + 1G > T). Although splice site mutations constitute at least 10% of all mutations that cause MO, there has been limited research on their pathogenic effect on RNA processing due to poor availability of patient RNA samples. In this study, ex vivo and in vivo splicing assays were used to investigate the effect of EXT1 and EXT2 mutations on aberrant splicing at the mRNA level. Our results indicate that identified splice site mutations can cause either cryptic splice site usage or exon skipping.

Early hyperbaric oxygen therapy inhibits aquaporin 4 and adrenocorticotropic hormone expression in the pituitary gland of rabbits with blast-induced craniocerebral injury.

In the present study, rabbits were treated with hyperbaric oxygen for 1 hour after detonator-blast- induced craniocerebral injury. Immunohistochemistry showed significantly reduced aquaporin 4 expression and adrenocorticotropic hormone expression in the pituitary gland of rabbits with craniocerebral injury. Aquaporin 4 expression was positively correlated with adrenocorticotropic hormone expression. These findings indicate that early hyperbaric oxygen therapy may suppress adrenocorticotropic hormone secretion by inhibiting aquaporin 4 expression.

Apoptosis-related protein expression in rabbits with blast brain injury following early hyperbaric oxygen therapy.

We treated detonator-explosion-induced craniocerebral injury in rabbits with hyperbaric oxygen 1-24 hours post-injury. Expression of the apoptosis-regulating protein cytochrome c, the pro-apoptotic protein Bax and the apoptosis marker caspase-3 in the tissues surrounding the area of injury was significantly reduced, while that of the anti-apoptotic protein Bcl-2 was significantly increased. Our findings indicate that the curative effects of early hyperbaric oxygen on cortical cell apoptosis is associated with suppression of cytochrome c release from mitochondria. This mechanism underlies the observed reduction in Bax expression and upregulation of Bcl-2 expression.