Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective:To observe the effects of intervention based on self-regulation mode on illness perception, medical coping styles and quality of life of patients with psoriasis.Methods:Eighty patients with psoriasis from February 2018 to August 2019 in Qinhuangdao First Hospital were selected and divided into two groups by random digits table method, 40 patients in each group. The control group was given routine intervention, and the experimental group was given intervention based on self-regulation mode. The Illness Perception Questionnaire-Revised (IPQ-R) scores, Medical Coping Modes Questionnaire (MCMQ) scores, dermatologylifequalityindex (DLQI) scores and compliance of the two groups were compared before and after intervention.Results:There was no significant difference in the score of IPQ-R, MCMQ, DLQI before intervention between the two groups( P>0.05). After intervention, scores of symptoms, disease perception and causes of the disease in IPQ-R were (7.24±0.75), (162.34±20.35), (76.23±8.65) points in the experimental group and (6.08±0.72), (123.26±18.57), (52.79±7.84) points in the control group, there were significant differences between the two groups ( t values were 7.057, 8.972, 12.699, P<0.01). In the MCMQ, facing score,avoidance score and yielding score were (25.67±2.83), (12.26±1.84), (9.12±1.24) points in the experimental group, (21.76±3.89), (14.35±2.48), (10.45±1.68) points in the control group, there were significant differences between the two groups ( t values were 5.141, -4.280, -4.028, P<0.01). The DLQI scores of experimental group were significantly higher than those of control group ( t values were 2.648-8.244, P<0.05 or 0.01), and compliance of experimental group (97.5%, 39/40) was significantly better than control group (80.00%, 32/40) with statistically significant( Z value was 40.000, P<0.01). Conclusions:Intervention based on self-regulation mode can effectively reduce negative emotions of patients with psoriasis, increase their illness perception and compliance, improve their medical coping styles, self-management ability and quality of life, with positive application value.

Objective To estimate the influence of curcumin on psoriasis-like lesions and proliferating cell nuclear antigen (PCNA) expression in guinea pigs,so as to investigate the therapeutic effect and mechanism of curcumin in psoriasis.Methods A model of psoriasis-like skin inflammation was established by applying propranolol 5％ cream (4 times a day for 3 weeks) to the dorsal skin of ears of 30 guinea pigs,which were then equally classified into 5 groups:model group receiving no treatment,observation group receiving no treatment but observation for 2 weeks,model control group treated with intragastric 25％ polyethylene glycol solution (1 rnl once a day) for 2 weeks,low-dose and high-dose curcumin groups treated with intragastric curcumin solution at 20 and 40 mg/kg per day respectively once a day for 2 weeks.Six guinea pigs receiving neither induction by propranolol nor treatment by curcumin or polyethylene glycol solution served as the normal control group.Skin specimens were harvested from the ears of guinea pigs in the normal control group after three weeks of breeding,in the model group immediately after the establishment of psoriasis-like model,in the observation group after 2 weeks of observation,and in the other 3 groups after 2 weeks of treatment.Subsequently,haematoxylin-eosin (HE) staining was conducted to observe histopathologic changes,and immunohistochemical assay to detect the expression of proliferating cell nuclear antigen (PCNA).Results Gross observation of the skin revealed that curcumin attenuated psoriasis-like skin manifestations in guinea pigs.There were significant differences in histopathologic scores (F=296.14,P＜ 0.01) and PCNA expression rate among the 6 groups (F =108.49,P ＜ 0.01).Least significant difference (LSD) test showed that both histopathologic scores and PCNA expression rate were significantly higher in the model group than in the normal control group (6.42 ± 0.49 vs.0.92 ± 0.20,63.17％ ± 5.47％ vs.20.83％ ± 2.99％,both P ＜ 0.01).After 2 weeks of treatment,both low-dose and high-dose curcumin groups showed significantly lower histopathologic scores (4.25 ± 0.27 and 1.75 ± 0.42 vs.6.42 ± 0.49,both P＜ 0.01) and PCNA expression rate (43.50％ ± 2.90％ and 25.50％ ± 3.74％ vs.63.17％ ± 5.47％,both P ＜ 0.01) compared with the model group.Conclusion Curcumin can attenuate pathological manifestations of psoriasis-like lesions,and downregulate PCNA expression in guinea pigs.

Purpose To investigate the relevance between the expression of miR-339-5p and the clinicopathological characteristics in diffuse large B-cell lymphoma (DLBCL). Methods The level of miR-339-5p expression was detected in 123 cases of diffuse large B-cell lymphoma tissues and 20 cases of reactive lymphoid hyperplasia tissues by chromogenic in situ hybridization ( CISH) technique. The expression of Ki-67 and BCL-6 protein was examined in diffuse large B-cell lymphoma tissues by immunohistochemical technique (IHC) (EnVision two-steps), and the correlation between the expression of miR-339-5p and BCL-6 and the clinicopathological param-eters was also analyzed. Results The positive rates of miR-339-5p were 39. 8% (49/123) in DLBCL tissues, which was significantly lower than that in RH tissues (90%, 18/20). The positive rates of miR-339-5p were 31. 0% (22/71) for germinal center B-cell-like (ABC type) DLBCL, which was significantly lower than that in activated B-cell-like (GCB type) DLBCL (27/52, 51. 9%). The low-er expression of miR-339-5p in DLBCL was correlated with late Ann Arbor staging and high-risk group of international prognostic index (P<0. 05). The survival rates of miR-339-5p negative patients of ABC type and GCB type of DLBCL were significantly lower than that of the positive patients (P<0. 01). The levels of miR-339-5p expression in DLBCL were negatively correlated with the levels of BCL-6 expression in DLBCL (P<0. 01). Conclusion The low expression of miR-339-5p might be relatived with the progression and poor prognosis of DLBCL.

Objective To explore the best treatment program for neurogenic dysphagia (ND) by observing the efficacy of three different rehabilitation programs.Methods Eighty-two dysphagic patients were randomly divi-ded into a swallowing training group (which received mouth,facial,and tongue function training along with cold sti-mulation of the pharynx,Mendelson's swallowing training,and swallowing behavior coordination training) and a group which received neuromuscular electrical stimulation (NMES) only.Low-frequency NMES was applied at the location of the swallowing obstacle using a biphase square wave 700ms long at 30-80 Hz with a current intensity of 0-15 mA.There was also a combined treatments group which received swallowing behavior therapy combined with NMES.All three groups were treated for 30 min daily for 20 days.Videofluoroscopy (VFSS) was conducted before and after treatment to assess swallowing function.Results After 20 days of treatment,swallowing function had improved in all three groups.The effectiveness rate was 73% in the swallowing training group,83% in the NMES group and 94% in the combined treatment group.The average VFSS score in the combined therapy group was significantly higher than that of either the swallowing training or NMES group.Conclusions NMES combined with swallowing behavior the-rapy can greatly improve swallowing function in patients with neurogenic dysphagia,especially those with pseudosupranuclear paralysis.

Objective To investigate the expression of COX-2,MMP-2 and TIMP-2 ,the pathological fea-tures ,and their relationship in breast cancer. Methods The expressions of COX-2 ,MMP-2 and TIMP-2 were deter-mined by S-P immunohistochemical method on tissue chips,which containing 127 cases of breast carcinoma. Results The positive rates of COX-2,MMP-2 and TIMP-2 protein were 81.1 (103/127)% ,96.9(123/127)% and 60.6 (77/127) % respectively;The expression of COX-2 was positively related to auxiliary lymph node metastasis and TNM staging (P<0.01 and P<0.05, respectively), and inversely related to PR expression (P<0.05). Further-more,the expression of COX-2 was positively correlated with MMP-2 (r=0. 290 ,P<0.01). Conclusions The ex-pression of COX-2 might be closely related to the invasion and metastasis of breast cancer and has a close relation-ship with MMP-2. The levels of MMP-2 might be partly regulated by COX-2.

Objective To develop a kind of tissue microarray (TMA) for the teaching of pathological experiment. Methods A series of human normal tissues from heart, lung, liver, stomach, intestine, etc as well as their matched disease tissues were collected and made into TMA parraffin blocks by tissue chip instrument. After section, the slides were stained by hematoxylin-eosin staining and covered by the coverslips which were marked with serial columns and rows. Results All the specimens were arranged in good order on TMA paraffin block and the slides were stained clearly. And the location of each specimen was marked distinctively on TMA slides. Conclusions Compared with classical tissue slides, the TMA slides for the teaching of pathological experiment have many advantages such as good compare, easy memorizing, low expend and simple making. Take together, the TMA for teaching might have a good perspective for application in the future.

Objective To study features and significance of clinical stages and types of severe acute respiratory syndrome (SARS). Methods The clinical features of 330 patients with SARS were analyzed by SPSS 11.0 and SDAS software packages, and the standard for classification of clinical stages and types of SARS were studied. Results The disease course of SARS could be divided into four stages, namely, incubation stage, initial stage, climax stage and convalescence stage. The period of incubation stage was 1~12 (5.70?2.45) days. The initial stage was the pathoformic phase during 1 st~10 th (3.98?2.48) days after the onset. The fever was the first symptom and there were usually no catarrhal symptoms. Meanwhile, no abnormality was found in the chest X-ray examination. The climax stage included 3 sequential phases of pulmonary inflammatory exudation, pulmonary tissue consolidation and ARDS or multi-organ failure. In the phase of pulmonary inflammatory exudation, there were serious cough, mild shortness of breath and hypoxemia. Furthermore, chest X-ray examination showed that there was exaggeration of lung markings, haziness or patchy opacity. In the phase of pulmonary tissue consolidation, type I respiratory failure was usually seen in the patients. Shortness of breath and hypoxemia became more serious. Chest X-ray examination showed that the area of consolidation continued to enlarge to include the entire lung. The convalescence stage usually appeared 3 weeks after the onset and lasted for 5～56 (24.37?8.81) days. This stage could further be divided into phase I (complete recovery) and phase II (possible existence of pulmonary fibrosis). SARS could be clinically classified into mild type (ordinary type), severe type and extremely severe type (fulminant type) with a mortality of zero, 5.76% and 61.54%, respectively. There were very great differences in clinical features in three types of SARS. Conclusions SARS could be divided into the incubation stage, initial stage, climax stage and convalescence stage. The climax stage included 3 phases, i.e. pulmonary inflammatory exudation, pulmonary tissue consolidation, and ARDS or MOF. The convalescence stage could be divided into phase I (complete recovery) and phase II (possible existence of pulmonary fibrosis). SARS could be classified as mild type, severe type and extremely severe type.

Objective To analyze the clinical features of severe acute respiratory syndrome(SARS) in order to look for premonitory signs of deterioration of patients suffering from SARS. Methods Three hundred and thirty patients with SARS referred to the Chinese Disease Center(CDC) in Beijing were studied retrospectively by SPASS and SDAS software. The data reviewed included clinical manifestations, laboratory findings, and X-ray pictures. Results The prognosis of mild SARS was good with a cure ratio of 100%. Chest radiography revealed opacity or small subtle opacity in lung periphery in 53.1%, there were no signs of acute lung injury in 67.2%, and the opacity disappeared rapidly. In patients with severe SARS, the disease course was longer(41.3?5.6day), the duration of high fever was longer (8.66?3.22day), with the highest temperature reaching 39.04?0.71℃. The duration of respiratory insufficiency was also longer(8.80?4.56day), and 71.8% of them manifested acute lung injury, involving a large area of the lung, with central lesions in 21.8% or mixed in 50%. The opacity was denser, and it took a longer period to resolve. The levels of LDH, HBDH, ESR and CK-MB were high, with HBDH/LDH ratio ranged from 0.8 to 1.0. The mortality was high(14.54%). Logistic regression analysis showed that the premonitory mode of deterioration of the disease was P y=1=? s /(1+? s)(S=-10.598+0.102A+0.592B+0.077C+0.494D), with sensitivity of 86.67%, and specificity 80%, and it was correlated with age, duration of respiratory insufficiency, ESR, and duration of high temperature. Conclusions The premonitory mode of deterioration of SARS is a new, simple, low-cost, biomathematically and pathophysiogically based index. It allows the prediction of deterioration and severity of SARS.