Objective:To investigate the role and molecular mechanism of death receptor 5 (DR5) in early brain injury (EBI) after subarachnoid hemorrhage (SAH), as well as the neuroprotective effect of soluble DR5 (sDR5) on SAH.Methods:Experiment 1: SD rats were randomly divided into sham-operated group ( n=6) and SAH group (SAH model was established by carotid artery puncture, n=30), and the SAH group was further subdivided into post-SAH (6 h) group, post-SAH (12 h) group, post-SAH (24 h) group, post-SAH (48 h) group and post-SAH (72 h) group ( n=6); Western blotting was used to detect the expressions of tumor necrosis factor (TNF)-α and DR5; immunofluorescent DR5 and neuronal nuclear antigen (NeuN) double staining was used to evaluate the DR5 expression in neurons. Experiment 2: SD rats were randomly divided into sham-operated group, SAH group, Trail group (injected Trail agonist dordaviprone), and Trail+sDR5 group (injected dordaviprone+sDR5, n=6); at the 24 th h of successfully constructed SAH model, the caspase family protein levels were detected by Western blotting, and Tunel staining and immunofluorescent DR5 and Caspase-3 double staining were performed. Experiment 3: SD rats were divided into sham-operated group, SAH group, Trail group and Trail+sDR5 group ( n=6); long-term motor functions, by modified Gracia score, forelimb placement experiment, rotarod test and misstep experiment, were evaluated 5, 7 and 12 d after successfully constructed SAH model; and long-term learning and memory functions were detected by water maze experiment 14, 16, 18, 20 and 21 d after successfully constructed SAH model. Results:(1) Result of Experiment 1: the expressions of TNF-α and DR5 in sham-operated group, post-SAH (6 h) group, post-SAH (12 h) group, post-SAH (24 h) group, post-SAH (48 h) group and post-SAH (72 h) group were statistically different ( F=837.992, P<0.001; F=503.942, P<0.001), and these expressions peaked 24 h after SAH; immunofluorescent DR5 and NeuN double staining showed that DR5 was located in neurons after SAH. (2) Result of Experiment 2: compared with the SAH group and Trail group, the Trail+sDR5 group had significantly decreased levels of activated caspase-8, tBid and activated caspase-3, significantly decreased numbers of Tunel positive cells and DR5 and activated caspase-3 co-marked positive cells ( P<0.05). (3) Result of Experiment 3: compared with the SAH group and Trail group, the Trail+sDR5 group had significantly increased Garcia scores, decreased failure rate in forelimb placement experiment, prolonged duration of stick rotation, and decreased foot fault rate ( P<0.05), suggesting that sDR5 could improve the long-term motor function deficit after SAH; water maze experiment showed that 21 d after SAH, compared with the SAH group and Trail group, Trail+sDR5 group had significantly increased proportion of escape time in the original platform quadrat in total escape time and increased proportion of movement path in the original platform quadrat in total movement path after platform removal ( P<0.05), suggesting that sDR5 could improve long-term learning and memory impairment after SAH. Conclusion:The sDR5 can inhibit DR5-Trail-mediated neuronal apoptosis and improve long-term neurological functional deficits after SAH.

Objective:To analyze the prevalence and distribution characteristics of diffuse idiopathic skeletal hyperostosis (DISH) in hospitalized patients with thoracic ossification of the ligamentum flavum (TOLF).Methods:The clinical records of 132 consecutive TOLF patients from January 2018 to June 2019 were retrospectively studied. DISH was identified by the preoperative X-ray and CT and its prevalence was calculated. The prevalence of patients with different genders, different age groups and different ossification types was compared. The segmental distribution of DISH and the distribution in the upper (T 1-T 4), middle (T 5-T 8), and lower thoracic spine (T 9-T 12) were analyzed. Ossification degree of DISH was evaluated based on the Meta scoring system. The demographic characteristics (age, gender, BMI, etc.) were compared between DISH and non-DISH group. Results:Forty-nine patients was diagnosed as DISH with the prevalence of 37.1% in all included cases. The prevalence was about twice as high in male (46.3%) than in female (23.1%) ( χ2=8.806, P=0.003). The prevalence in the age groups of <40, 40-49, 50-59, 60-69 and ≥70 years was 20.0%, 28.0%, 34.4%, 44.0%, and 66.7%, respectively. The prevalence in long-segment TOLF patients (45.1%) was significantly higher than that in short-segment TOLF patients (24.0%) ( χ2=5.937, P=0.015). DISH most frequently affected T 8,9 levels (91.8%). The total number and mean number of ossified segments were 365 and 7.4, respectively. Ossification lesions in the upper, middle, lower thoracic spine accounted for 26.03%, 40.54%, and 33.15%, respectively. Grade I, grade II, and grade III ossification accounted for 21.4%, 28.5% and 50.1%, respectively. The mean age of the DISH group was older than the non-DISH group ( t=2.024, P=0.045). The proportion of male patients in the DISH group was significantly higher than that in the non-DISH group ( χ2=8.806, P=0.003). The average height and weight in the DISH group were significantly greater than those in the non-DISH group ( t=2.564, P=0.012; t=2.191, P=0.030), whereas no significant differences in BMI and constituent ratio of concurrent diabetes, cardiac disease, hypertension between two groups were observed. Conclusion:The prevalence of DISH in patients with TOLF is 37.1%. Male, elderly and long-segment TOLF patients are associated with higher prevalence. DISH frequently occurs in the middle and lower thoracic spine, and T 8,9 is the common affected segment. Ossification lesions may develop with age. Demographic characteristics of DISH group differ, to some extent, from those of non-DISH group.

Objective:To explore ways and methods for public mental health intervention during the COVID-19 epidemic.Methods:A comprehensive literature review was conducted. Mental healthcare publicity materials posted by over 100 Chinese hospitals in multiple media (till February 24, 2020) were also systematically collected and analyzed.Results:Firstly, anxiety and fear were the most common mental health problems among people during the epidemic. Secondly, to achieve better outcomes, mental health intervention should be provided according to the type of service clients. Thirdly, new media can facilitate the transmission of mental healthcare knowledge, but the limitation is that it can not approach older adults who have limited access to new media. It is therefore essential to strengthen the mental health knowledge transmission to older adults.Conclusions:Mental health intervention is effective when it is provided according to the type of service clients during the COVID-19 epidemic.

OBJECTIVE: To establish a digital subtraction angiography (DSA) information management and image analysis system to realize scientific management of DSA image information and efficient processing of image data. METHODS: Based on Java Web under Windows 7 environment, a dynamic Browser/Server mode system was constructed by JSP and Servlet on the network. Eclipse and MySQL were used as development tool and database development platform. Tomcat network information service was used as application server. Matlab codes were embedded to analyze DSA image. RESULTS: The system consists of five modules:image information management, image processing, image analysis, advanced retrieval and clinical data management. It may complete such process as storing, deleting, saving, analyzing of DSA image and basic information of patients. CONCLUSIONS The main interface of the system is user-friendly and easy to operate. The system will be helpful to the clinical, teaching and scientific research work related to DSA.
Angiography, Digital Subtraction ; statistics & numerical data ; Databases, Factual ; Humans ; Indonesia ; Information Management ; Internet ; Software ; User-Computer Interface

With the rapid development of biotechnology, therapeutic peptide has been a hot area in the central nervous system drugs due to its features of easy to design and target specificity. However, therapeutic peptide is difficult to cross the blood brain barrier into the central nervous system and target cells, coupled with its in vivo instability, which seriously restricts its application in central nervous system diseases. This review focuses on the progress of therapeutic peptides across the blood brain barrier targeting the central nervous system, compares and analyses the methods of increasing therapeutic peptides penetration, specificity and stability in combination with other molecules, in order to provide help for the development of central nervous system drugs.

Objective To explore the protective effect of erythropoietin(EPO) administrated by intranasal on cerebral ischemia reperfusion in rats with acute cerebral infarction reperfusion.Methods Total of 100 SD rats were divided into model control group,sham operation group,intraperitoneal administration group ([PEPO group),nasal saline group (INNS group) group,and nasal drug delivery group (INEPO group) with 20 in each group.The middle cerebral artery occlusion model of rat was established by thread embolism method and the NSS method was used to evaluate the neural behavior of rats.The expression of EPO in peripheral blood,cerebrospinal fluid and brain regions of rats were detected by Elisa.The vascular endothelial growth factor(VEGF) in brain was detected by immunofluorescence and then the density of newborn blood vessels in the brain was measured.Results Fifteen days after the operation,the NSS score of INEPO group(3.80± 1.61) was significantly lower than that of IPEPO group (11.53±2.11),and the difference was statistically significant(P＜0.01).And the levels of EPO in blood,cerebrospinal fluid and different brain regions of rats in INEPO group were higher than that of INNS group(all P＜0.01).Compared with IPE-PO group,the level of EPO cerebrospinal fluid and different brain regions of rats in INEPO group increased obviously,the difference was statistically significant (all P＜0.01),and the EPO concentration of the olfactory bulb was the most obvious (INEPO group:(1 456.90 ± 128.22) pg/ml,IPEPO group:(426.11 ± 36.68)pg/ml,P＜0.01).Seventy-two hours after operation,the expression of CD31 in ischemic penumbra of rats of model control group (18.21 ± 3.45),INNS group (18.54 ± 2.58),IPEPO group (27.01 ± 2.13) and INEPO group(35.52±2.79)was increased compared with sham operation group (5.14± 1.28),and the difference was statistically significant (all P＜0.05).The expression of CD31 in IPEPO group and INEPO group was significantly higher than that in INNS group (P＜0.05).In INEPO group,the expression of CD31 increased significantly compared with that of IPEPO group (P＜0.05).Conclusion Nasal administration of EPO can effectively improve the neurological function of rats with ischemia-reperfusion,and increase the expression of CD31 in the brain tissue of rats.The effect of nasal administration is better than that of intraperitoneal administration.

Objective To investigate the protective effect and its mechanism of metabotropic glutamate receptor 1 ( mGluR1) negative allosteric modulator JNJ16259685 on neuron after subarachnoid hemorrhage (SAH) in rats. Methods Ninety SPF-grade SD male rats were selected. They were randomly divided into 3 groups:sham operation group (n=18),SAH+placebo group (n=36),and SAH+JNJ16259685(JNJ) group (n=36). A SAH model was induced by intravascular puncture. SAH +placebo group received intraperitoneal injection of aseptic water containing 5% dimethyl sulfoxide (DMSO) at 2,24 and 48 h after operation. The SAH+JNJ group was intraperitoneally injected with 1 mg/kg JNJ16259685 ( dissolved in sterile water in 5% DMSO). Garcia scoring criteria were used to assess neurological deficits at 72 h after SAH. Dry and wet weight method was used to detect brain edema. Evans Blue method was used to assess blood-brain barrier permeability. A calcium assay kit was used to detect the mitochondrial calcium ion concentration. Immunofluorescence staining was used to observe neuronal apoptosis. GraphPad 7. 0 software was used to conduct one-way analysis of variance in all indicators among the 3 groups. Results Compared with the sham operation group,the Garcia score (11. 0 ± 0. 4) decreased in the SAH+placebo group. The water content in left and right hemispheres was 80. 5 ± 0. 1% and 80. 3 ± 0. 2% respectively,the Evans blue dye extravasation (2. 8 ± 0. 2),basal cortical mitochondrial calcium ion concentration (2. 5 ± 0. 3),and neuronal apoptosis in basal cortex and hippocampus CA1 region (the number of active caspase-3/NeuN positive cells was 300 ±30/mm2and 20 ± 2/mm respectively) increased (all P<0. 05);and the Garcia score (13. 0 ± 0. 5) was significantly higher in the SAH+JNJ group than in the SAH+placebo group. Water content in left and right hemispheres was 79. 8 ± 0. 2% and 79. 3 ± 0. 1% respectively,Evans blue dye extravasation (1. 8 ±0. 2),basal cortex mitochondrial calcium ion concentration (1. 7 ± 0. 1),basal cortex and the number of neuronal apoptosis in hippocampal CA1 region (the number of active caspase-3/NeuN positive cells were 180 ± 10/mm2,12 ±2/mm) reduced compared with the SAH+placebo group (all P<0. 05). Conclusion After SAH,JNJ16259685 relieves cerebral edema and reduces blood-brain barrier permeability,inhibits the increase of cortical mitochondrial calcium ion concentration,and reduces neuronal apoptosis,thereby exerting neuroprotective effects.

Objective To explore the effects of application calcitonin gene related peptide(CGRP) in cisterna magna on cerebral vasospasm after experimental subarachnoid hemorrhage (subarachnoid hemorrhage,SAH) in rat models.Methods 64 male Wistar rats were randomly divided into 4 groups.Group A was normal control group.After the subarachnoid hemorrhage models were established,group B,C,D were given normal saline,CGRP and adenovirus CGRP through cisterna magna respectively.White blood cells in cerebrospinal fluid were detected by automatic blood analyzer,CGRP activity was detected by enzyme linked immunosorbent assay,circulating endothelial cells were observed through laser scanning confocal microscope and parietal cortex regional cerebral blood flow were observed by laser doppler flowmeter.Basilar artery vasospasm and arterial blood gas analysis were detected by digital subtraction angiography and blood gas analyzer respectively.Results Before and after administration,there were no statistical differences in white blood cells and artery blood gas among the 4 groups (both P＞ 0.05).After administration 48 h,compared with group A,concentrations of CGRP in cerebrospinal fluid group B (0.006±0.002) did not increase (P＞0.05),but increased 200 times in Group C ((1.160±0.170) nmol/L,P＜0.05)and nearly 400 times in group D ((2.071±0.412) nmol/L,P＜0.05).Peripheral blood circulating endothelial cells count:after administration 48 h,group C((5.56±0.61) ind/0.9 μL) was less than in group B((9.94± 0.73) ind/0.9 μL).Group D((5.16±0.61) ind/0.9 μL) was less than group C(P＜0.01).Regional cerebral blood flow:after administration,compared with group B,cerebral blood flow of group C and group D increased,and the differences were both statistically significant (P＜0.01).Basilar artery diameter was detected after administration 12 h,group D ((1.000±0.025) mm) was 13％ bigger than group B ((0.670±0.028)mm,P＜0.05),3％ bigger than group C ((0.900±0.023) mm) (P＞0.05).Conclusion Cerebral vasospasm after SAH can be effectively improved by administration CGRP in cisterna magna.Adenovirus CGRP effect is better than CGRP.

Objective To explore the effect of protein kinase C inhibitor on the level of phosphralated extracellular regulated protein kinases in the spinal trigeminal nucleus of migraine model rats.Methods Healthy adult male SD rats were randomly divided into four groups:normal group (group C),sham operation group (group C),migraine model group(group M),and H-7group(H-7group),with 18 rats in each group.Dural blood flow and the extracellular discharge frequency in the spinal trigeminal nucleus was recorded.ERK1/2 phosphorylation was tested.Results (1) Dural blood flow:compared with group C((3.8± 1.0)％),the dural blood flow in M group ((78.0±4.2) ％)increased obviously(P＜0.01) ; compared with M group((78.0±4.2)％),the dural blood flow in H-7 group((-24.8±4.9) ％) decreased obviously(P＜0.01).(2) The percentage of extracellular discharge frequency change:two hours after treatment,the percentage of extracellula discharge frequency change in group M ((325.9 ±47.3)％)was higher than that in group C((107.3±16.4)％).The percentage of discharge frequency change in group H-7((136.0±26.5)％) was lower than that in group M((325.9±47.3)％).There was no significant difference in the percentage of discharge frequency change between group H-7((136.0±26.5) ％) and group C((107.3 ± 16.4)％).(2) ERK1/2 phosphorylation:the ERK1/2 phosphorylation in group M was higher than that in group C.The ERK1/2 phosphorylation in group H-7 was lower than than that in group C and group M.Conclusion ERK1/2 is a downstream PKC signal path and PKC may have indirect activation of ERK1/2.

Purpose To explore the relationship between expression of PCNA and COX-2 in the early laryngeal cancer with negative surgical margins and the local recurrence of tumor. Methods Totally 63 patients with early laryngeal cancer were enrolled in this stud-y, CO2 laser surgery was adopted as treatment, the expression of PCNA and COX-2 was detected in the resected tumor tissue and surgi-cal margins, and the survival and tumor recurrence were also observed. Results The positive rate of the expression of PCNA and COX-2 in the 63 patients with early laryngeal cancer tumor tissues were 73. 02% and 71. 43%, while that in the cutting edge were 33. 33% and 30. 16%, respectively. The expression of PCNA and COX-2 in tumor tissue and cutting edge were of all positive in 41 cases and 13 cases, and the positive rate was 65. 08% and 20. 63%, respectively. In the all followed-up patients, 17 cases were detected of local recurrence, the recurrence rate was 26. 98%, and the recurrence rate in the patients with PCNA positive was 71. 43%, while in the patients with COX-2 positive was 73. 68% (P<0. 05). The combined detection of PCNA and COX-2 positive recurrence rate was significantly higher than that of single positive (P<0. 05). Conclusion PCNA and COX-2 in the early laryngeal cancer with negative surgical margins are important biological markers for the evaluation of prognosis of laryngeal cancer patients, and to formulate the subse-quent treatment regimen. The combined detection of two proteins is more reliable for postoperative management.