The blood-brain barrier （BBB） is a physical and biochemical barrier that precisely regulates brain homeostasis and plays a central role in controlling the transport of endogenous and exogenous drugs and related metabolites across the blood-brain interface. These functions of the BBB are mediated by its major components， including brain microvascular endothelial cells （BMECs）， tight junction protein complexes， and influx and efflux transporter proteins. One of the pathological features of ischemic stroke （IS） is BBB disruption， which plays an important role in the development of post-stroke brain injury and subsequent neurological dysfunction. Therefore， given the increasing incidence of IS， there is an urgent need to develop new therapeutic strategies to prevent BBB dysfunction and thereby protect injured brain tissue after IS. This study describes the pathological mechanisms by which BMEC injury after IS leads to BBB dysfunction and elucidates the association between BMECs and IS， including the regulation of apoptosis， autophagy， inflammatory responses， oxidative stress， neurotoxic effects， and cerebral edema. In addition， this article summarizes Chinese herbal medicines that may prevent and treat IS by targeting BMECs. These include monomeric compounds and single herbs such as flavonoids， glycosides， phenols， phthalides， terpenoids， and Styrax. Traditional Chinese medicine （TCM） compound formulas and preparations include oral formulations such as Buyang Huanwu decoction， Sailuotong， Naoxintong capsules， Dandeng Tongnao capsules， and Shexiang Tongxin dropping pills， as well as injectable preparations such as Tongluo Jiunao injection， Xingnaojing injection， Danshen polyphenolic acid for injection， Yiqi Fumai injection， and Shuxuetong injection. This study aims to explore the protective effects of TCM against IS through targeted regulation of BMEC function， providing new insights into the mechanisms of IS and endovascular therapeutic strategies.

OBJECTIVE: To explore the neuroprotective effect and underlying mechanism of Xingnao Kaiqiao acupuncture (acupuncture for regaining consciousness and opening orifices) in the rat models of cerebral ischemia-reperfusion injury (CIRI) based on the p53 protein (p53)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. METHODS: Of 102 male Wistar rats, 20 rats were randomly collected as a sham-operation group. Using a modified external carotid artery filament insertion method, CIRI models were prepared by occluding the middle cerebral artery in the rest rats. After modeling and excluding 1 non-successfully modeled rat and 1 dead one, the other modeled rats were randomized into a model group, an agonist group, an acupuncture group, and an acupuncture + agonist group, 20 rats in each one. Xingnao Kaiqiao acupuncture therapy was delivered in the rats of the acupuncture group and the acupuncture + agonist group. The acupoints included "Shuigou" (GV26), bilateral "Neiguan" (PC6), and "Sanyinjiao" (SP6) on the affected side. Electroacupuncture was attached to "Neiguan" (PC6) and "Sanyinjiao" (SP6) on the affected side, with dense-disperse wave, a frequency of 2 Hz/15 Hz and intensity of 1 mA. The intervention was delivered twice daily, 20 min each time and for 7 consecutive days. In the agonist group and acupuncture+agonist group, p53 agonist, COTI-2 was intraperitoneally injected (15 mg/kg), once daily for 7 consecutive days. Neurological deficit was evaluated using Zausinger's six-point scale. Cerebral infarction volume was quantified by triphenyl tetrazolium chloride (TTC) staining. Histopathological changes were observed using hematoxylin-eosin (HE) staining. Iron deposition was assessed by Prussian blue staining. Mitochondrial ultrastructure in the ischemic cortex was examined under transmission electron microscopy (TEM). Serum iron (Fe²⁺) was measured with chromometry. Malondialdehyde (MDA) and glutathione (GSH) levels in the ischemic hippocampus were determined using thiobarbituric acid and microplate assays, respectively. The mean fluorescence intensity of reactive oxygen species (ROS) in the ischemic cortex was analyzed by flow cytometry. The mRNA and protein expression of GPX4, SLC7A11, and p53 in the ischemic hippocampus were evaluated using quantitative real-time PCR (qRT-PCR) and Western blotting, respectively. RESULTS: Compared with the sham-operated group, the model group exhibited the decrease in neurological deficit score (P<0.01), and the increase in cerebral infarction volume percentage (P<0.01). The changes of brain tissue were presented in extensive cellular necrosis, pyknotic and deeply-stained nuclei, and vacuolar degeneration. The iron deposition was elevated in cortex and hippocampus (P<0.01), mitochondrial membrane density increased, the cristae was broken or reduced, and the outer membrane ruptured. The levels of Fe²⁺ and MDA, as well as the mean flourscence intensity of ROS were elevated (P<0.01) and the level of GSH was reduced (P<0.01). The mRNA and protein expression of GPX4 and SLC7A11 was reduced (P<0.01), while that of p53 rose (P<0.01). When compared with the model group, in the agonist group, the neurological deficit score was reduced (P<0.05), the percentage of infarction volume was higher (P<0.01), the histopathological damage was further exacerbated, and the percentage of iron deposition increased in the cortex and hippocampus (P<0.01). The mitochondrial quantity decreased, the membrane density increased, the mitochondrial cristae were broken or reduced, and the outer membrane was ruptured. The levels of Fe²⁺ and MDA, as well as the mean flourscence intensity of ROS were higher (P<0.01, P<0.05) and the level of GSH was reduced (P<0.05). The mRNA and protein expression of GPX4 and SLC7A11 decreased (P<0.01, P<0.05), while that of p53 was elevated (P<0.01). Besides, in comparison with the model group, the neurological deficit score was higher in the acupuncture group and the acupuncture + agonist group (P<0.01, P<0.05), the percentage of cerebral infarction volume was lower in the acupuncture group (P<0.01), the pathological damage of brain tissue was alleviated in the acupuncture group and the acupuncture + agonist group, and the percentage of iron depositiondecreased in the cortex and hippocampus (P<0.01). The mitochondrial structure was relatively clear, the mitochondrial cristae were fractured or reduced mildly in the acupuncture group and the acupuncture + agonist group. The levels of Fe²⁺ and MDA, as well as the mean flourscence intensity of ROS were lower (P<0.01) and the level of GSH was higher (P<0.01) in the acupuncture group. The mean fluorescence intensity of ROS were dropped (P<0.01) in the acupuncture + agonist group. The mRNA expression of GPX4 and SLC7A11 was elevated (P<0.01) and that of p53 was reduced (P<0.01, P<0.05) in either the acupuncture group or the acupuncture + agonist group; the protein expression of GPX4 and SLC7A11 rose (P<0.05, P<0.01) and that of p53 was dropped (P<0.01) in the acupuncture group; and the protein expression of p53 was also lower in the acupuncture + agonist group (P<0.05). When compared with the agonist group, in the acupuncture + agonist group, neurological deficit score increased (P<0.01), the percentage of cerebral infarction volume decreased (P<0.01), the pathological brain tissue damage was reduced, the percentage of iron deposition in cortex and hippocampus decreased (P<0.01), the mitochondrial structure was relatively clear and the cristae broken or reduced slightly; the levels of Fe²⁺ and MDA, as well as the mean fluorescence intensity of ROS were dropped (P<0.01), while the level of GSH increased (P<0.05); the mRNA and protein expression of GPX4 and SLC7411 was elevated (P<0.01, P<0.05), and that of p53 reduced (P<0.01). In comparison with the acupuncture + agonist group, in the acupuncture group, the neurological deficit score increased (P<0.05), the percentage of cerebral infarction volume decreased (P<0.05), the pathological brain tissue damage was alleviated, the percentage of iron deposition in cortex and hippocampus decreased (P<0.01), the mitochondrial structure was normal in tendency; the levels of Fe²⁺ and MDA, as well as the mean fluorescence intensity of ROS were reduced (P<0.05), while the level of GSH rose (P<0.01); the mRNA and protein expression of GPX4 and SLC7411 was elevated (P<0.01, P<0.05), and that of p53 reduced (P<0.01, P<0.05). CONCLUSION Xingnao Kaiqiao acupuncture can alleviate neurological damage in CIRI rats, which is obtained probably by inhibiting ferroptosis through p53/SLC7A11/GPX4 pathway.
Animals ; Reperfusion Injury/metabolism* ; Male ; Acupuncture Therapy ; Rats ; Tumor Suppressor Protein p53/genetics* ; Brain Ischemia/metabolism* ; Rats, Wistar ; Signal Transduction ; Humans ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Disease Models, Animal ; Acupuncture Points ; Amino Acid Transport System y+/genetics*

Objective To investigate the clinical effect of anterior controllable antedisplacement and fusion (ACAF) for the treatment of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine.Methods The data of 45 cases with cervical posterior longitudinal ligament ossification treated by ACAF from March 2017 to October 2017 were retrospectively analyzed,including 25 males and 20 females,age 45-68 years,average 57.5 years.There were 18 cases involving C3 vertebral body,30 cases involving C4 vertebral body,40 cases involving C5 vertebral body,34 cases involving C6 vertebral body,and 7 cases involving C7 vertebral body.The function of the neural function was evaluated by the Japanese Orthopaedic Association (JOA) scoring system at preoperation and latest follow-up.The curvature of the cervical spine was measured on the lateral X-ray film of the cervical spine,the maximum occupying ratio of the spinal canal was measured on the cross section of the CT scan,and compression of the cervical spinal cord was evaluated by the cervical MRI.Results Patients were followed up for 3 to 6 months (average,3.9 months).The improvement of neurological function was obtained in all the patients.The JOA score improvement rate at the latest follow-up was 71.3％±9.6％.The cervical lordosis was improved from preoperative 4.5°±3.8° to 10.3°±4.8° at the latest follow-up.The canal stenosis ratio was decreased from preoperative 54.3％±8.2％ to 12.5％±5.3％ at the latest follow-up.MRI showed that the cervical spinal cord was adequately decompressed in situ.No specific complications were identified that were associated with this technique.Conclusion The present study elaborates the surgical tips and demonstrates the satisfactory outcome of ACAF for the treatment of OPLL.This novel technique has the potential to serve as an alternative surgical technique for the treatment of cervical OPLL.

Objective To determine the application value of quantitative detection of DNA in cervical lesion screening.Methods Retrospective analysis of 82 518 cases of cervical lesions was carried out.The sensitivity,specificity,positive predictive value (PPV),and negative predictive value (NPV) of DNA quantification and ThinPrep cytology test (TCT) for the diagnosis of cervical lesions were compared with the results of biopsy.The accuracy of the two methods was evaluated by applying the receiver operating characteristic curve.Results The sensitivity of DNA quantification,TCT,and combined diagnosis was 77.37％,70.97％,and 90.24％,respectively,and the specificity was 65.59％,70.42％,and 45.06％,respectively.The sensitivity of cell DNA quantitative analysis was higher but the specificity was lower than that of TCT,while the sensitivity of combined diagnosis was the highest.In DNA quantitative analysis of patients with and without atypical squamous cells of undetermined significance (ASCUS),the positive rates of pathology were 42.71％ and 12.5％,respectively.The misdiagnosis rate of cell DNA quantitative analysis for screening cervical adenocarcinoma (39.13％) was higher than that for screening cervical squamous cell carcinoma (15.11％).In a cytologic smear,the misdiagnosis rate of cells ＜ 5 000 (57.83％) was much higher than that of cells ＞ 5 000 (22.63％).However,a combined diagnosis with TCT could reduce the misdiagnosis rate from 20.19％ to 13.38％.Conclusion Cell DNA quantification is more sensitive than TCT,but the specificity of cell DNA analysis is lower than that of TCT,and the screening rate for cervical adenocarcinoma is high.Quantitative DNA analysis combined with TCT can significantly improve the screening sensitivity.

BACKGROUND: Cervical intervertebral foramen stenosis induced by cervical spondylosis of nerve root type usual y requires surgical treatment. The ways mainly include anterior cervical discectomy and fusion and cervical posterior intervertebral foramen decompression. Which is the best way is stil inconclusive. With innovation, anterior cervical discectomy and fusion for cervical spondylosis of nerve root type has become the mainstream in the current treatment. OBJECTIVE: To study the relationship between curative effects and intervertebral foramen-associated parameter changes in patients with cervical spondylosis of nerve root type after anterior cervical discectomy and fusion. METHODS: From March 2011 to April 2013, 132 patients with cervical spondylosis of nerve root type were treated with anterior cervical discectomy and fusion in the Changzheng Hospital Affiliated to the Second Military Medical University. Neck pain and arm pain visual analogue score, neck disability index score and imaging changes were evaluated before and after treatment. RESULTS AND CONCLUSION: 132 patients were fol owed up for 25(4-28) months. Significant differences in neck pain visual analogue scale, anterior intervertebral disc height, posterior intervertebral disc height, intervertebral foramen height, anterior and posterior diameters of the intervertebral foramen, the area of the intervertebral foramen, and the Cobb angle of the fused segment were detected in al patients before and after treatment (P < 0.05). Posterior intervertebral disc height was positively correlated with intervertebral foramen area (r=0.427, P=0.000). The increased Cobb angle of the fused segment was negatively associated with the size of intervertebral foramen (r=-0.273, P=0.003). Intervertebral foramen area was negatively associated with arm pain visual analogue score (r=-0.502, P=0.000). These results indicated that anterior cervical discectomy and fusion with an interbody fusion cage can obviously enlarge intervertebral foramen in patients with cervical spondylosis of nerve root type, and obtain good curative effect. The size of the intervertebral foramen is negatively related to the axial pain. The reconstruction of the intervertebral disc height is necessary to expand the intervertebral foramen. However, the increase of the curvature fusion segments is not helping to expand the intervertebral foramen.

BACKGROUND:Intervertebral disc degeneration is one of the ancient and common clinical diseases. Its complex pathogenesis affected by various factors, such as environment and genes, is stil in debate. Because of the technical limitations, there is stil no deep understanding on the molecular mechanism of intervertebral disc degeneration. However, its molecular mechanism in recent years has made considerable development. OBJECTIVE: To summarize and discuss the molecular mechanism of intervertebral disc degeneration, thereby providing the basis for the effective treatment. METHODS: CNKI and Medline databases were retrieved by the first author using computer to search relevant articles published from 2005 to 2015. The key words were “intervertebral disc degeneration, molecular mechanism, environmental factors, genes, matrix, degradation enzyme,inflammatory factor, biological environment, treatment” in Chinese and English, respectively. Mechanisms of intervertebral disc degeneration, involving genes, cel senescence and apoptosis, degradation enzyme and substrate, inflammatory cytokines, were summarized to explore the pathogenesis and possible effective treatment of intervertebral disc degeneration. RESULTS AND CONCLUSION:Totaly 153 articles were initialy retrieved and finaly 52 articles were included in result analysis according to inclusive and exclusive criteria. Unique structure and biochemical properties of the intervertebral disc are easy to cause intervertebral disc degeneration. Traditionaly, environmental factors, such as occupation and smoking, are considered as the main factors inducing intervertebral disc degeneration; however, more and more studies have shown that genes have the most important influence on intervertebral disc degeneration. Declined extracelular matrix, increased degradation enzymes, and overexpression of inflammatory factors can al destroy the entire structure of intervertebral disc, and accelerate the process of intervertebral disc degeneration. Effective treatment for intervertebral disc degeneration can be formulated depending on the deep understanding on its molecular mechanisms. Although there is a further understanding on the molecular medium of intervertebral disc degeneration, the complex biochemical environment within the intervertebral disc is stil a great chalenge to the treatment of intervertebral disc degeneration.

OBJECTIVE: To determine the expression of vascular endothelial growth factor (VEGF) and their receptor in nasal inverted papillomas (NIP) and to clarify the function of VEGF in the occurrence of NIPs and the correlation with malignant phenotype. METHOD: VEGF and its receptor (flk-1), expression were examined by immunohistochemistry using LSAB method in sections of NIP from 48 patients and squamous carcinoma from 8 patients. RESULT: All the epithelium together with the adjacent vascular and stroma,expressed increased positive staining of VEGF and flk-1 with the degree of atypical hyperplasia in epithelium. The VEGF/flk-1 expression in epithelium was significantly stronger in severe atypical hyperplasia than that in mild atypical hyperplasia, and same in mild atypical hyperplasia than in NIPs (P<0.01). CONCLUSION VEGF/flk-1 participate in the growth of NIPs. The enhanced VEGF/flk-1 in the epithelium may be identified as one of the parameters in judging malignant transformation of NIPs.
Aged ; Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Nose Neoplasms ; genetics ; metabolism ; pathology ; Papilloma, Inverted ; genetics ; metabolism ; pathology ; Prognosis ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism