BACKGROUND:Shujin Jiannao Prescription is an empirical formula for the treatment of cerebral palsy in Dongzhimen Hospital,Beijing University of Chinese Medicine,with clear clinical efficacy,but the specific mechanism needs to be elucidated. OBJECTIVE:To explore the possible mechanism of Shujin Jiannao Prescription in treating cerebral palsy. METHODS:Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into a normal group(n=12)and a model group(n=52).An animal model was established by the Rice-Vannucci method.After successful modeling,52 model rats were randomly divided into control model group(n=12),minocycline group,and the low-,medium-,and high-dose groups of the Shujin Jiannao Prescription(n=10 per group).Rats in the minocycline group were given 40 mg/kg·d minocycline by gavage;rats in the low-,medium,and high-dose groups were given 4,8,and 16 g/kg·d Shujin Jiannao Prescription granules by gavage,respectively;and rats in the normal group and control model group were given an equal dose of normal saline by gavage.Medication in each group was given once a day for 1 week.The rats in each group were evaluated behaviorally using suspension test,abnormal involuntary movement score,and Bederson score.The pathological changes of the cerebral cortex were observed by hematoxylin-eosin staining.The levels of tumor necrosis factor α,interleukin 1β,and interleukin 10 in the cerebral cortex were determined using ELISA.The positive expressions of Janus kinase 2(JAK2),phosphorylated Janus kinase 2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3)in the cerebral cortex were detected using immunohistochemistry.The protein expression levels of JAK2,p-JAK2,and p-STAT3 were detected using western blot. RESULTS AND CONCLUSION:Compared with the normal group,the suspension test score and involuntary movement score were decreased in the control model group(P＜0.01 or P＜0.05).The pathological results showed structural disruption of nerve cells,formation of large numbers of vacuoles,cell swelling,and increased intercellular space in the control model group.In addition,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were significantly increased(P＜0.01),the expression of interleukin 10 was decreased(P＜0.05),and the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly increased(P＜0.01)in the control model group compared with the normal group.Compared with the model group,minocycline and Shujin Jiannao Prescription at each dose could improve the behavioral indexes of rats(P＜0.01 or P＜0.05)and ischemic-hypoxic pathological changes were attenuated,with only a small amount of necrotic nerve cells and a few vacuoles,and reduced intercellular space.Moreover,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were decreased in each drug group compared with the control model group(P＜0.05),while the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly decreased(P＜0.01).The most obvious improvement was observed in the high-dose Shujin Jiannao Prescription group.To conclude,Shujin Jiannao Prescription can inhibit inflammation in the cerebral cortex of rats with hypoxic-ischemic brain injury.The mechanism may be related to the regulation of the JAK2/STAT3 signaling pathway.

Headache has high incidence and disability rates.The burden of headache in China has become an in-creasingly serious social problem.However,the diagnostic level of headache disorders varies among physicians due to the complexity of etiological classification.In order to help clinicians effectively improve the accuracy of clinical diagnosis,the Chinese People's Liberation Army(PLA)General Hospital led the development of the Clinical Decision Support Sys-tem(CDSS)for headache,and CDSS 2.0 has already been able to achieve a satisfactory diagnostic accuracy rate for head-ache.The Chinese PLA General Hospital has initiated the headache prevention and control base and system construction project in China.The application of CDSS to assist teaching in headache specialist training practice is an important means of headache specialist training.With the help of the CDSS system,neurologists are trained in headache specialty.Through the learning function of the CDSS,physicians can better understand the path of headache inquiry,improve the ability to identify secondary headache,be familiar with the ICHD-3 diagnostic criteria,learn standard headache cases,and improve the ability to employ standard treatment.In this paper,we will comprehensively discuss the role of the CDSS in the training of headache specialists and provide a summary and reflection,in order to provide a reference for the further development and improvement of headache specialist training in China.

ObjectiveTo explore the mechanism of Tangbikang granules （TBK） against diabetic peripheral neuropathy （DPN） based on network pharmacology and in-vivo experiment. MethodThe active components in medicinals of TBK and their target genes were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The active components of the medicinals which are not included in TCMSP were searched from previous research. After the analysis of drug-likeness by SwissADME， the target genes of them were predicted with SwissTargetPrediction. DPN-related target genes were retrieved from GeneCards. The common targets of the disease and the prescription were the hub genes of TBK against DPN， which were uploaded to Metascape for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. High-sugar and high-fat diet and low-dose streptozotocin （STZ， ip） were employed to induce diabetes in rats， and then the model rats were respectively treated with low-dose （0.625 g·kg^-1）， medium-dose （1.25 g·kg^-1）， and high-dose （2.5 g·kg^-1） TBK for 12 weeks. Sensory nerve conduction velocity （SNCV） was evaluated. After hematoxylin and eosin （HE） staining， the sciatic nerve was observed under light microscope to examine the nerve damage. Real-time PCR was performed to detect the gene expression of adenosine monophosphate-activated protein kinase （AMPK） pathway-related targets in rat sciatic nerve， and Western blot to measure the protein expression of AMPK and phosphorylated （p）-AMPK in rat sciatic nerve. ResultThe main active components of TBK， such as quercetin， kaempferol， β-sitosterol， leech pteridine A， stigmasterol， and baicalein were screened out， mainly acting on interleukin-6 （IL-6）， tumor necrosis factor （TNF）， protein kinase B （Akt）， JUN， and HSP90AA1 and signaling pathways such as AMPK， nuclear factor-κB （NF-κB）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）. Molecular docking results showed that β-sitosterol and stigmasterol had high binding affinity with IL-6， TNF， JUN， and HSP90AA1. As for the animal experiment， compared with the normal group， model group had low SNCV of sciatic nerve （P<0.01）， disordered and loose myelinated nerve fibers with axonotmesis and demyelinization， low mRNA expression of AMPKα， AMPKβ， peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）， Sirtuin 3 （SirT3）， mitochondrial transcription factor A （TFAM）， and low p-AMPK/AMPK ratio in sciatic nerve （P<0.05， P<0.01）. Compared with the model group， TBK of the three doses raised the SNCV （P<0.01）， restored nerve morphology and nerve compactness， and increased the mRNA expression of AMPKα， AMPKβ， PGC-1α， SirT3， and TFAM （P<0.05， P<0.01）. The ratio of p-AMPK/AMPK in the high-dose and medium-dose TBK groups was higher than that in the model group （P<0.01）， while the protein expression in the low-dose TBK group was insignificantly different from that in the model group. ConclusionTBK exerts therapeutic effect on DPN through multiple pathways and targets. The mechanism is that it activates and regulates AMPK/PGC-1α/SirT3 signaling， which lays a basis for further study of TBK in the treatment of DPN.

Objective:To explore the value of the Pfirrmann grading standard for disc degeneration in the quantification of heterotopic ossification (HO) after artificial cervical disc replacement (ACDR).Methods:Data of 120 patients who underwent ACDR from January 2009 to December 2016 were retrospectively analyzed. There were 88 males and 32 females with an average age of 43.86±8.69 (range, 27-67) years old. There were 100 single-level replacements (9 Hybrid cases) and 20 double-level replacements (3 Hybrid cases). The occurrence of HO was observed by lateral radiographs of the cervical spine. The HO severity was assessed using the McAfee rating system. Degeneration degrees of cervical intervertebral discs were evaluated by the Pfirrmann grading standard based on the preoperative cervical MRI. The weighted Kappa test was used to analyze the consistency of evaluations between different observers of the Pfirrmann scoring system and the McAfee grading system. Pfirrmann scores for preoperative disc degeneration in the HO and non-HO groups were compared using the t-test. The chi-square test was used to analyze the effect of the Pfirrmann score on the incidence of postoperative segmental HO. The correlation between Pfirrmann score and McAfee grade, as well as postoperative ROM of HO group were analyzed by the Spearman rank-sum test. Quantitative indicators for risks of HO after ACDR surgery were proposed based on the incidence of segment HO in different Pfirrmann score groups. Results:One hundred and twenty patients were followed up for an average of 74.08±28.05 (range, 31-125) months. Based on statistics of cases 2 years after surgery, the overall HO incidence was 31.67% (38/120). The HO incidence was 27% (27/100) and 55% (11/20) for single-level and double-level replacements, respectively. There were 46 replacement segments in the HO group and 94 replacement segments in the non-HO group. The Pfirrmann score of HO group (3.17±1.08) was 25.80% significantly higher than that of the non-HO group (2.52±0.98) ( t=3.46, P=0.01). The incidence of HO in the replacement segment increased significantly with the preoperative Pfirrmann score ( χ2=12.44, P=0.01). The Pfirrmann score of the intervertebral disc in the HO group had a significant positive correlation with the McAfee grade ( R=0.54, P=0.01) and a significant negative correlation with the ROM ( R=-0.75, P=0.01). At 2 years after the operation, when the Pfirrmann score of the intervertebral disc was less than 3, the incidence of HO in the replacement segment was 20.55%(15/73); when the Pfirrmann score was equal to 3, the incidence of HO was 38.46% (10/26); when the Pfirrmann score was greater than 3, HO incidence was 51.22% (21/41). Conclusion:The Pfirrmann score of cervical disc degeneration was significantly related to the incidence of HO, McAfee grade, and ROM in the postoperative replacement segment. The Pfirrmann score of cervical disc degeneration can be used as a quantitativeindicator of HO risk in ACDR.

Objective To explore the diagnostic value of MR elastography and diffusion?weighted imaging in patients with liver fibrosis in the context of chronic hepatitis B. Methods Twenty?four patients with chronic hepatitis B, whose course of liver disease was more than 6 months and hepatitis B surface antigen was positive, were prospectively enrolled in the First Affiliated Hospital of Soochow University from July to December 2017. All of the patients underwent abdominal transient elastography (TE), routine MRI, magnetic resonance elastography (MRE) and DWI examination, TE and MRI were performed within one week. TE liver stiffness was measured, the MRE liver stiffness and ADC value were measured on MR imagings. All patients were divided into three groups: mild and non fibrosis (F0 to 1), significant fibrosis(F2 to 3) and cirrhosis (F4), according to the recommended standard of FibroTouch. Correlation between TE liver stiffness, MRE liver stiffness and ADC values were identified by using Spearman correlation test. The difference of the MRE liver stiffness and ADC value among the three groups was tested using independent sample t test. The overall predictive ability of MRE and DWI in assessment of liver fibrosis and cirrhosis was analyzed by constructing ROC curve. Results TE and MRI were successfully performed in all subjects, and the image quality was good. The MRE liver stiffness in mild and non fibrosis, significant fibrosis and cirrhosis was (2.32±0.31),(3.43±1.05),(4.77±0.68) kPa with statistically significant difference(F=61.690, P<0.01). The ADC values in three groups were (1.31 ± 0.14)×10-3, (1.23 ± 0.15)×10-3,(1.22±0.12)×10-3mm2/s without significant difference(F=1.074,P=0.360). The TE liver stiffness in three groups was (5.61±1.05),(9.56±0.57),(17.25±3.55)kPa, respectively, there was significant correlation between the MRE liver stiffness and the TE liver stiffness(t=0.858, P<0.01), but no significant correlation between the TE liver stiffness and the ADC value was found (r=-0.326,P=0.120). The area under ROC of MRE liver stiffness in diagnosing liver fibrosis grade (≥F2 and F4) was 0.96 and 1.00 respectively, while the AUC of ADC value was less than 0.70, which were 0.67 and 0.62 respectively. Conclusion MRE is a non?invasive promising tool for assessing liver fibrosis with chronic hepatitis B, while DWI has limited role.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a primary headache syndrome with an unclear pathogenesis. However, there is increasing evidence in the literature for secondary SUNCT being attributable to certain known lesions. We explored the possible neurobiological mechanism underlying SUNCT based on all reported cases of secondary SUNCT for which detailed information is available. Here we report a case of neuromyelitis optica spectrum disorders that had typical symptoms of SUNCT that might have been attributable to involvement of the spinal nucleus of the trigeminal nerve. We also review cases of secondary SUNCT reported in the English-language literature and analyze them for demographic characteristics, clinical features, response to treatment, and imaging findings. The literature review shows that secondary SUNCT can derive from a neoplasm, vascular disease, trauma, infection, inflammation, or congenital malformation. The pons with involvement of the trigeminal root entry zone was the most commonly affected region for inducing secondary SUNCT. In conclusion, the neurobiology of secondary SUNCT includes structures such as the nucleus and the trigeminal nerve with its branches, suggesting that some cases of primary SUNCT have underlying mechanisms that are related to existing focal damage that cannot be visualized.
Headache Disorders ; Headache* ; Inflammation ; Neurobiology ; Neuromyelitis Optica ; Pons ; Tears* ; Trigeminal Nerve ; Vascular Neoplasms

Objective To evaluate theclinical efficacy and safety of anterior cervical ossified posterior longitudinal ligament en bloc resection (ACOE),and analyze the advantages of ACOE compared to the traditionally anterior cervical surgery.Methods The clinical datawith more than one year follow-up of 96 patients suffered from cervical ossification of the posterior longitudinal ligament(OPLL) from April 2010 to March 2017 was retrospectively analyzed,including 57 males and 39 females,aged 32-69 years,average 54.6±8.7 years.There were 29 cases of nodular type (30.2％),48 cases of segmental type (50.0％),5 cases of continuous type(5.2％),and 14 cases of mixed type (14.6％).The neurological function assessments before and after operation were performed using the Japanese Orthopaedic Association (JOA) scoring system and the visual analogue scale (VAS) scoring system.The effect of ossified mass resection was observed by three-dimensional reconstruction CT scan.The spinal cord decompression was evaluated by MRI.The cervical curvature was compared before and after surgery by cervical lateral radiograph.The operation time,intraoperative blood loss,recovery rates of the JOA scores and complication rates of this group were compared with the cases of anterior cervical ossified posterior longitudinal ligament piecemeal resection (ACOP) reported by the recent literature to analyze the clinical efficacy,safety and advantages of ACOE.Results All the surgeries of 96 cases were successfully performed,including 57 cases (59.4％) with subtotal resectionof single vertebra,31 cases (32.3％) with subtotal resectionof doublevertebras,1 case (1.0％) with expanded intervertebral decompression,4 cases (4.2％) with "vertebra + semi-vertebra" subtotal resection,1 case (1.0％) with "semi-vertebra + vertebra + semi-vertebra" subtotal resection,2 cases with "double vertebras + semi-vertebra" subtotal resection (2.1％).Ninty-six cases were followed up for 12 to 78 months,with an average of 28.0±9.3 months.The preoperative JOA score with (11.38±2.80) scores was increased to 15.32± 1.62 scores at the last follow-up,and the recovery rate of JOA score was 74.63％±13.18％.The preoperative VAS score with 6.00±1.41 scores was reduced to 2.35±1.11 scores at the last follow-up.The cervical curvature increased from 10.4°±9.0° before surgery to 15.8°±8.1° at the last follow-up.CT showed that the ossified masses of the surgical segments were completely excised without residue;MRI showed that the compressionsof spinal cords and dural sacs were completely relieved,with nice morphology recovery.There was no neurological deterioration in this group.There were 6cases of cerebrospinal fluid leakage (CSFL),3 cases of C5 nerve palsy,1 case of Hornersyndrome,2 cases of dysphagia and hoarseness,1 case of titanium mesh subsidence with screw loosing.At the final followups,except one case of occasional throat foreign body sensation,the above complications were all remittedat different followup periods.Compared with the cases of ACOP reported by the recent meta-analysis,the operation time,the intraoperative blood loss,the complication rate of dysphagia with hoarseness and neurological deterioration were lower than those reported in the literature.The recovery rate of JOA scorewas higher than which reported in the literature.Conclusion ACOE is safe and effective for the treatment of cervical OPLL,which may be superior to traditional anterior cervical surgery in terms of surgical safe-ty,controllability of cerebrospinal fluid leakage and improvement of neurological function.

Objective To explore the association between PI3K polymorphisms in insulin signal transduction pathway and Alzheimer's disease (AD)risk.Methods There were three groups,including 112 cases for AD +T2D group,231 cases for only AD group,and 231 cases for healthy controls group.The polymorphisms in PI3K gene was sequenced by PCR and the concentration of PI3K in serum was tested by enzyme -linked immunosorbent assay (ELISA).Results Overall,there was significantly statistical difference in PI3K rs3730087 polymorphism among three groups (χ2 =20.99,P =0.000 3).The CC frequency of PI3K rs3730087 polymorphism in AD with T2D group and AD control group was significantly higher than that in the healthy control group.The PI3K protein level of differ-ent genotype was statistically significant (F =27.450,P <0.000 1).As for CC genotypes of PI3K rs3730087 poly-morphism,the PI3K protein level was statistically different among these three groups (F =8.096,P =0.000 6).Moreover,the PI3K protein level of the three groups was different (F =9.034,P =0.000 1),which in both AD group was lower as compared with healthy control group.Conclusion The study suggested that CC genotype of PI3K rs3730087 polymorphism in insulin signaling transduction pathway might be a risk factor for AD with T2D and it also affects the expression level of PI3K protein.However,the polymorphism is not shown to be exclusive in AD patients with T2D.

BACKGROUNDThe molecular and cellular origins of migraine headache are among the most complex problems in contemporary neurology. Up to now the pathogenesis of migraine still remains unclearly defined. The objective of this study was to explore new factors that may be related to the mechanism of migraine.

METHODSThe present study performed a comprehensive analysis of gene expression in the trigeminal nucleus caudalis induced by electrical stimulation of dura mater surrounding the superior sagittal sinus in conscious rats using microarray analysis followed by quantitative real-time reverse-transcribed polymerase chain reaction (qRT-PCR) verification. Student's two sample t-test was employed when two groups were compared. A P value <0.05 was considered to be statistically significant.

RESULTSComparing the placebo and the electrical stimulation groups, 40 genes were determined to be significantly differentially expressed. These significantly differentially expressed genes were involved in many pathways, including transporter activity, tryptophan metabolism, G protein signaling, kinase activity, actin binding, signal transducer activity, anion transport, protein folding, enzyme inhibitor activity, coenzyme metabolism, binding, ion transport, cell adhesion, metal ion transport, oxidoreductase activity, mitochondrion function, and others. Most of the genes were involved in more than 2 pathways. Of particular interest is the up-regulation of Phactr3 and Akap5 and the down-regulation of Kdr.

CONCLUSIONThese findings may provide important clues for a better understanding of the molecular mechanism of migraine.

Animals ; Dura Mater ; physiology ; Electric Stimulation ; Gene Expression ; physiology ; Male ; Microarray Analysis ; Migraine Disorders ; genetics ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Superior Sagittal Sinus ; physiology

Objective To investigate the species and drug resistance of pathogens causing bloodstream infections in hospitalized patients,and provide scientific evidence for antimicrobial use and control of healthcare-associated blood-stream infection.Methods From January 1 to December 31,2012,16 428 blood specimens were performed blood culture,pathogens were isolated and performed antimicrobial susceptibility testing.Results Of 16 428 blood speci-mens from 5 546 patients,384 (6.92%)were positive for blood culture,398 pathogenic isolates were detected,of which gram-positive bacteria,gram-negative bacteria,and fungi accounted for 23.62% (n=94),68.34% (n=272),and 8.04% (n=32)respectively,positive rate of blood culture were highest in 61-80 age group(8.26%), the top five departments of positive rate of blood culture were departments of burn,traditional Chinese medicine, cardiac intensive care unit,transplantation and traumatology;gram-positive cocci were highly susceptible to vanco-mycin,teicoplanin and linezolid,one Enterococcus faecium strain was found to be resistant to vancomycin;Among gram-negative bacilli,Enterobacteriaceae were highly susceptible to amikacin and carbapenems;drug resistance rates of Acinetobacterbaumannii and Pseudomonasaeruginosa to carbapenems was 70.97% and 35.90% respective-ly.Conclusion Gram-negative bacteria are the major pathogens causing bloodstream infection,positive rate of blood culture of elderly people is high.It is necessary to conduct regular surveillance on distribution and drug resistance of pathogens.