Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma

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).

The value of non-contrast dual-layer spectral detector CT with multiple parameters in the diagnosis of acute pulmonary embolism / 中华放射学杂志

Objective:To explore the diagnostic value of virtual monoenergetic image (VMI) and electron density map (EDM) generated by non-contrast dual-layer spectral detector CT in acute pulmonary embolism(APE).Methods:The clinical and imaging data of 27 patients (41 lesions) who underwent CT pulmonary angiography (CTPA) using dual-layer spectral detector CT and were diagnosed with APE in the Third Affiliated Hospital of Sun Yat-sen University from October 2022 to May 2023 were retrospectively analyzed. All patients received a dual-layer spectral detector CT non-contrast scan. Based on the non-contrast scan data, conventional 120 kVp polyenergetic images (PI), virtual monoenergetic images (40, 70, 100 keV VMI), electron density maps (EDM), and effective atomic number maps (Z eff) were respectively reconstructed. Taking CTPA as the gold standard, the detection rate of APE in different reconstruction images of non-contrast scan were evaluated. The vascular lesion was used as the pulmonary embolism group and the corresponding position of the normal vessel at the same level of the diseased vessel as the control group, and the Wilcoxon rank-sum test was used to compare the differences of CT values on PI and 40, 70, and 100 keV VMI (CT PI, CT 40 keV, CT 70 keV, CT 100 keV) as well as the ED values on the EDM, and the Z eff value on the Z eff images between the 2 groups. Parameters with statistically significant differences were included in a multifactor logistic regression, resulting in the construction of a logistic regression model. Receiver operator characteristic curve and area under curve (AUC) were applied to evaluate the diagnostic efficiency of different spectral quantitative parameters and logistic regression model in identifying pulmonary embolism group from normal control group. Results:The detection rates of APE on PI, EDM, Z eff map, and EDM and Z eff map fusion images were 14.6% (6/41), 82.9% (34/41), 51.2% (21/41), and 97.6% (40/41), respectively. CT PI, ED, CT 40 keV, CT 70 keV and CT 100 keV in pulmonary embolism group were statistically higher than those in control group ( Z values were 1 009.00, 1 024.50, 1 038.00, 1 079.00 and 1 076.00, respectively, P<0.05). Finally, CT PI, CT 40 keV, and CT 100 keV were selected to construct the logistic regression model. The AUC, sensitivity, specificity, and accuracy of the logistic regression model for distinguishing the embolism group from the control group were 0.771, 0.769, 0.744, and 0.756, respectively. Conclusion:Non-contrast images of dual-layer spectral detector CT VMI and EDM have some clinical value in detecting and diagnosing APE.

Potential Role of Right Cerebellum in Post-stroke Aphasia: A Preliminary Study Based on Granger Causality Analysis / 中国康复理论与实践

Objective To explore the recovery mechanism of language network among post-stroke aphasic patients by investigating the difference of whole-brain amplitude of low frequency fluctuations (ALFF) and the Granger causality analysis (GCA) between the patients and the controls. Methods From May, 2019 to May, 2021, 19 patients with aphasia after left hemispheric stroke and 17 age- and sex- matched healthy controls finished functional magnetic resonance imaging scanning. All the patients assessed with Chinese version of Western Aphasia Battery (WAB). Restplus was used for fMRI data analysis. Regions with significant difference of ALFF between groups were chosen as regions of interests (ROI) for the following GCA analysis. Results ALFF in left inferior frontal gyrus triangle (LIFGtri) and left medial frontal gyrus (LMFG) were significantly lower in the patients than in the controls. Effective connectivity from LIFGtri to LMFG and from LMFG to the right cerebellar Crus I were significantly lower in the patients. Effective connectivity from right cerebellar Crus II to LIFGtri, from right cerebellar Crus I to LMFG were significantly greater in the patients. Conclusion Unidirectional negative regulatory pathway such as LIFGtri→LMFG might be injured in post-stroke aphasia, while, connectivities between right cerebellar Crus II→LIFGtri and right cerebellar Crus I →LMFG enhanced. Right cerebellum might be the potential target for the language recovery.

Potential Role of Right Cerebellum in Post-stroke Aphasia: A Preliminary Study Based on Granger Causality Analysis / 中国康复理论与实践

Objective To explore the recovery mechanism of language network among post-stroke aphasic patients by investigating the difference of whole-brain amplitude of low frequency fluctuations (ALFF) and the Granger causality analysis (GCA) between the patients and the controls. Methods From May, 2019 to May, 2021, 19 patients with aphasia after left hemispheric stroke and 17 age- and sex- matched healthy controls finished functional magnetic resonance imaging scanning. All the patients assessed with Chinese version of Western Aphasia Battery (WAB). Restplus was used for fMRI data analysis. Regions with significant difference of ALFF between groups were chosen as regions of interests (ROI) for the following GCA analysis. Results ALFF in left inferior frontal gyrus triangle (LIFGtri) and left medial frontal gyrus (LMFG) were significantly lower in the patients than in the controls. Effective connectivity from LIFGtri to LMFG and from LMFG to the right cerebellar Crus I were significantly lower in the patients. Effective connectivity from right cerebellar Crus II to LIFGtri, from right cerebellar Crus I to LMFG were significantly greater in the patients. Conclusion Unidirectional negative regulatory pathway such as LIFGtri→LMFG might be injured in post-stroke aphasia, while, connectivities between right cerebellar Crus II→LIFGtri and right cerebellar Crus I →LMFG enhanced. Right cerebellum might be the potential target for the language recovery.

Medical image software in anatomical measurements and precision craniotomy via suboccipital retrosigmoid sinus approach / 中华神经医学杂志

Objective:To evaluate the application of a medical image software (RadiAnt) in anatomical measurements and precision craniotomy via suboccipital retrosigmoid sinus approach.Methods:A total of 43 inpatients who underwent craniocerebral CT venography (CTV) in our hospital from June 2020 to June 2021 were selected for the study; the CTV data of 35 patients was used to measure the spatial relations between transverse sigmoid sinus junction (TSSJ) and asterion; the preoperative planning in suboccipital retrosigmoid sinus craniotomy with the software was performed in the left 8 patients. Craniotomy time (subjected to exposure of venous sinus margin), venous sinus injury and incidence of complications within 2 weeks of craniotomy in these 8 patients were recorded.Results:(1) Anatomic measurement: for the left side, TSSJ was located at (0.89±0.33) cm lateral and (0.63±0.46) cm inferior to the asterion, and their direct distance was (1.15±0.42) cm; TSSJ was located at (0.76±0.49) cm interior and (1.97±0.52) cm superior to the starting point of the mastoid notch, and their direct distance was (2.18±0.49) cm; about 29% asterion were located superior to the transverse sinus, 37% were located on the surface of the transverse sinus, and 34% were located inferior to the transverse sinus. For the right side, TSSJ was located at (0.88±0.39) cm lateral and (0.64±0.43) cm inferior to the asterion, and their direct distance was (1.12±0.54) cm; TSSJ was located at (0.74±0.40) cm interior and (1.93±0.45) cm superior to the starting point of the mastoid notch, and their direct distance was (2.16±0.43) cm; about 26% asterion were located superior to the transverse sinus, 40% were located on the surface of the transverse sinus, and 34% were located inferior to the transverse sinus. (2) Preoperative planning and surgeries: in these 8 patients, the key-hole was located at (0.96±0.49) cm lateral and (0.53±0.18) cm inferior to the asterion, and (0.46±0.35) cm interior and (1.76±0.47) superior to the starting point of mastoid notch. The interior of sigmoid sinus was located (0.13±0.51) cm interior and (0.21±0.46) cm superior to the starting point of mastoid notch. The inferior of the transverse sinus was located (2.17±0.45) cm interior and (0.53±0.35) cm inferior to the asterion. An accurate localization of the real position of TSSJ, inferior of transverse sinus and interior of sigmoid sinus was performed in all 8 surgical patients. The distance between the margin of the bone window and the interior of sigmoid sinus was (3.5±1.0) mm, and the craniotomy time was (25.7±4.1) min; no sinus injury was noted. Post-operative CT showed good reposition of the bone flaps and less bone defect. There was no cerebrospinal fluid leakage or subcutaneous effusion during the 2 weeks of follow-up.Conclusion:Anatomical measurements and preoperative planning can be quickly finished with low cost with Radiant ?, which provides an efficient and safe method for accurate craniotomy via suboccipital retrosigmoid approach.

A model combined machine learning with imaging omics characteristics in differentiating anaplastic glioma from glioblastoma / 中华神经医学杂志

Objective:To construct and validate a prediction model combined machine learning with imaging omics characteristics in differentiating anaplastic glioma from glioblastoma.Methods:Imaging data of 241 patients with anaplastic glioma or glioblastoma, confirmed by pathology in our hospital from August 2005 to August 2012, were retrospectively collected. These patients were divided into a training group ( n=140) and a verification group ( n=101) according to random number table method. MRIcron software was used to delineate tumor boundaries of patients from the training group on preoperative T1 enhanced MR imaging. The regions of interest (ROIs) were outlined on preoperative T1 enhanced MR imaging, and the radiomic features were extracted from ROIs by Matlab software. Least absolute shrinkage and selection operator (LASSO) regression model was used to screen the features, and then, the selected features were used to construct the prediction model by support vector machine (SVM) classifier. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of the model. Results:In these 241 patients, 101 were with anaplastic glioma and 140 were with glioblastoma confirmed by pathology. In the training group and validation group, there was statistical difference in age between patients with anaplastic glioma and glioblastoma ( P<0.05); there was no significant difference in gender distribution, tumor location, and percentages of tumor necrosis or edema between patients with anaplastic glioma and glioblastoma ( P>0.05). Totally, 431 radiomic features were extracted; 11 radiomic features were screened by LASSO regression model and the prediction model was established. The AUC of ROC curve was 0.942 and 0.875, respectively, in the training group and validation group. Conclusion:The prediction model combined machine learning and imaging omics characteristics can effectively discriminate anaplastic glioma from glioblastoma.

Progress and analysis on the development of 2019-nCoV vaccine / 生物医学工程学杂志

As the COVID-19 pandemic is intensifying globally, more and more people are pinning their hopes on the development of vaccines. At present, there are many research teams who have adopted different vaccine technology routes to develop 2019-nCoV vaccines. This article reviews and analyzes the current development and research status of 2019-nCoV vaccines in different routes, and explores their possible development in the future.

Retinol dehydrogenase 10 promotes metastasis of glioma cells via the transforming growth factor-β/SMAD signaling pathway / 中华医学杂志(英文版)

BACKGROUND@#Glioma is the most common primary malignant tumor in the central nervous system. Because of the resistance of glioma to chemoradiotherapy and its aggressive growth, the survival rate of patients with glioma has not improved. This study aimed to disclose the effect of retinol dehydrogenase 10 (RDH10) on the migration and invasion of glioma cells, and to explore the potential mechanism.@*METHODS@#Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of RDH10 in healthy glial cells and glioma cells. Human glioma cell strains, U87 and U251, were infected with negative control or RDH10-interfering lentiviruses. RT-PCR and Western blotting were performed to determine the knockdown efficiency. Scratch and transwell assays were used to assess cell migration and invasion after RDH10 knockdown. Finally, changes in transforming growth factor-β (TGF-β)/SMAD signaling pathway-related expression were examined by Western blotting. Differences between groups were analyzed by one-way analysis of variance.@*RESULTS@#RDH10 was highly expressed in glioma cells. Compared with the control group, RDH10 knockdown significantly reduced RDH10 messenger RNA and protein expression levels in U87 and U251 glioma cells (U87: 1.00 ± 0.08 vs. 0.22 ± 0.02, t = 16.55, P < 0.001; U251: 1.00 ± 0.17 vs. 0.39 ± 0.01, t = 6.30, P < 0.001). The scratch assay indicated that compared with the control group, RDH10 knockdown significantly inhibited the migration of glioma cells (U87: 1.00% ± 0.04% vs. 2.00% ± 0.25%, t = 6.08, P < 0.01; U251: 1.00% ± 0.11% vs. 2.48% ± 0.31%, t = 5.79, P < 0.01). Furthermore, RDH10 knockdown significantly inhibited the invasive capacity of glioma cells (U87: 97.30 ± 7.01 vs. 13.70 ± 0.58, t = 20.36, P < 0.001; U251: 96.20 ± 7.10 vs. 18.30 ± 2.08, t = 18.51, P < 0.001). Finally, Western blotting demonstrated that compared with the control group, downregulation of RDH10 significantly inhibited TGF-β expression, phosphorylated SMAD2, and phosphorylated SMAD3 (TGF-β: 1.00 ± 0.10 vs. 0.53 ± 0.06, t = 7.05, P < 0.01; phosphorylated SMAD2: 1.00 ± 0.20 vs. 0.42 ± 0.17, t = 4.01, P < 0.01; phosphorylated SMAD3: 1.00 ± 0.18 vs. 0.41 ± 0.12, t = 4.12, P < 0.01).@*CONCLUSION@#RDH10 knockdown might inhibit metastasis of glioma cells via the TGF-β/SMAD signaling pathway.

Controlled clinical trial with the combination therapy with metformin, thiazolidinediones, glucagon-like peptide 1 analog in patients with type 2 diabetes and metabolic syndrome / 中华内分泌代谢杂志

Objective The aim of this study was to compare the efficacy and safety of metformin/thiazolidinediones (TZDs) / glucagon-like peptide 1 (GLP-1) analogs (triple therapy) with conventional glucose-lowering therapy ( conventional therapy ) for patients with type 2 diabetes and metabolic syndrome. Methods A prospective randomized-controlled 26-week study was carried out. A total of 82 patients with type 2 diabetes and metabolic syndrome were randomized to receive either triple therapy protocal or just conventional therapy, altogether with 41 cases in each group. Results HbA1C value was significantly reduced in triple therapy group versus the conventional therapy group [(2.23 ± 1.75)％ vs (1.48 ± 1.59)％, P<0.05]. Values of body mass index, waist circumference, and visceral fat area were significantly reduced in triple therapy group as compared to those of conventionaltherapygroup[(2.50±1.81vs0.92±1.82)kg/m2,(6.75±4.92vs1.66±3.25)cm,(24.10±19.10vs 10.02±20.10)cm2, all P<0.01, respectively]. Control rates of HbA1C and fasting plasma glucose for triple therapy were higher than those for conventional therapy ( both P<0. 05 ) . No hypoglycemia occurred in triple therapy group. Subjects receiving triple therapy experienced more frequent gastrointestinal side effects than those in conventional therapy group ( 18. 87％ vs 3. 92％, P<0. 05 ) . The most common side event was mild nausea ( 90％) . Conclusion Combination therapy with metformin/TZDs/GLP-1 analogs had statistically significant advantages in the control of body weight, waist circumference, and visceral fat area in addition to the control of blood glucose over conventional glucose-lowering therapy in our patient cohort, it seems to be an optimized therapeutic regimen for patients with type 2 diabete and metabolic syndrome.

Retinol dehydrogenase 10 promotes metastasis of glioma cells via the transforming growth factor-β/SMAD signaling pathway / 中华医学杂志(英文版)

Background@#Glioma is the most common primary malignant tumor in the central nervous system. Because of the resistance of glioma to chemoradiotherapy and its aggressive growth, the survival rate of patients with glioma has not improved. This study aimed to disclose the effect of retinol dehydrogenase 10 (RDH10) on the migration and invasion of glioma cells, and to explore the potential mechanism.@*Methods@#Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of RDH10 in healthy glial cells and glioma cells. Human glioma cell strains, U87 and U251, were infected with negative control or RDH10-interfering lentiviruses. RT-PCR and Western blotting were performed to determine the knockdown efficiency. Scratch and transwell assays were used to assess cell migration and invasion after RDH10 knockdown. Finally, changes in transforming growth factor-β (TGF-β)/SMAD signaling pathway-related expression were examined by Western blotting. Differences between groups were analyzed by one-way analysis of variance.@*Results@#RDH10 was highly expressed in glioma cells. Compared with the control group, RDH10 knockdown significantly reduced RDH10 messenger RNA and protein expression levels in U87 and U251 glioma cells (U87: 1.00 ± 0.08 vs. 0.22 ± 0.02, t= 16.55, P < 0.001; U251: 1.00 ± 0.17 vs. 0.39 ± 0.01, t= 6.30, P < 0.001). The scratch assay indicated that compared with the control group, RDH10 knockdown significantly inhibited the migration of glioma cells (U87: 1.00% ± 0.04% vs. 2.00% ± 0.25%, t= 6.08, P < 0.01; U251: 1.00% ± 0.11% vs. 2.48% ± 0.31%, t= 5.79, P < 0.01). Furthermore, RDH10 knockdown significantly inhibited the invasive capacity of glioma cells (U87: 97.30 ± 7.01 vs. 13.70 ± 0.58, t = 20.36, P < 0.001; U251: 96.20 ± 7.10 vs. 18.30 ± 2.08, t = 18.51, P < 0.001). Finally, Western blotting demonstrated that compared with the control group, downregulation of RDH10 significantly inhibited TGF-β expression, phosphorylated SMAD2, and phosphorylated SMAD3 (TGF-β: 1.00 ± 0.10 vs. 0.53 ± 0.06, t= 7.05, P < 0.01; phosphorylated SMAD2: 1.00 ± 0.20 vs. 0.42 ± 0.17, t= 4.01, P < 0.01; phosphorylated SMAD3: 1.00 ± 0.18 vs. 0.41 ± 0.12, t= 4.12, P < 0.01).@*Conclusion@#RDH10 knockdown might inhibit metastasis of glioma cells via the TGF-β/SMAD signaling pathway.

Controlled clinical trial with the combination therapy with metformin, thiazolidinediones, glucagon-like peptide 1 analog in patients with type 2 diabetes and metabolic syndrome / 中华内分泌代谢杂志

Objective@#The aim of this study was to compare the efficacy and safety of metformin/thiazolidinediones (TZDs) / glucagon-like peptide 1 (GLP-1) analogs (triple therapy) with conventional glucose-lowering therapy(conventional therapy) for patients with type 2 diabetes and metabolic syndrome.@*Methods@#A prospective randomized-controlled 26-week study was carried out. A total of 82 patients with type 2 diabetes and metabolic syndrome were randomized to receive either triple therapy protocal or just conventional therapy, altogether with 41 cases in each group.@*Results@#HbA1C value was significantly reduced in triple therapy group versus the conventional therapy group [(2.23±1.75)% vs (1.48±1.59)%, P<0.05]. Values of body mass index, waist circumference, and visceral fat area were significantly reduced in triple therapy group as compared to those of conventional therapy group [(2.50±1.81 vs 0.92±1.82)kg/m2, (6.75±4.92 vs 1.66±3.25)cm, (24.10±19.10 vs 10.02±20.10)cm2, all P<0.01, respectively]. Control rates of HbA1C and fasting plasma glucose for triple therapy were higher than those for conventional therapy (both P<0.05). No hypoglycemia occurred in triple therapy group. Subjects receiving triple therapy experienced more frequent gastrointestinal side effects than those in conventional therapy group (18.87% vs 3.92%, P<0.05). The most common side event was mild nausea (90%).@*Conclusion@#Combination therapy with metformin/TZDs/GLP-1 analogs had statistically significant advantages in the control of body weight, waist circumference, and visceral fat area in addition to the control of blood glucose over conventional glucose-lowering therapy in our patient cohort, it seems to be an optimized therapeutic regimen for patients with type 2 diabete and metabolic syndrome.

In Vivo Assessment of Neurodegeneration in Type C Niemann-Pick Disease by IDEAL-IQ

OBJECTIVE: To noninvasively assess the neurodegenerative changes in the brain of patients with Niemann-Pick type C (NPC) disease by measuring the lesion tissue with the iterative decomposition of water and fat with echo asymmetry and least square estimation-iron quantification (IDEAL-IQ). MATERIALS AND METHODS: Routine brain MRI, IDEAL-IQ and 1H-proton magnetic resonance spectroscopy (1H-MRS, served as control) were performed on 12 patients with type C Niemann-Pick disease (4 males and 8 females; age range, 15–61 years; mean age, 36 years) and 20 healthy subjects (10 males and 10 females; age range, 20–65 years; mean age, 38 years). The regions with lesion and the normal appearing regions (NARs) of patients were measured and analyzed based on the fat/water signal intensity on IDEAL-IQ and the lipid peak on 1H-MRS. RESULTS: Niemann-Pick type C patients showed a higher fat/water signal intensity ratio with IDEAL-IQ on T2 hyperintensity lesions and NARs (3.7–4.9%, p < 0.05 and 1.8–3.0%, p < 0.05, respectively), as compared to healthy controls (HCs) (1.2–2.3%). After treatment, the fat/water signal intensity ratio decreased (2.2–3.4%), but remained higher than in the HCs (p < 0.05). The results of the 1H-MRS measurements showed increased lipid peaks in the same lesion regions, and the micro-lipid storage disorder of NARs in NPC patients was detectable by IDEAL-IQ instead of 1H-MRS. CONCLUSION: The findings of this study suggested that IDEAL-IQ may be useful as a noninvasive and objective method in the evaluation of patients with NPC; additionally, IDEAL-IQ can be used to quantitatively measure the brain parenchymal adipose content and monitor patient follow-up after treatment of NPC.

Changes in topological properties of brain structural network in patients with neuromyelitis optica spectrum disorder based on diffusion tensor imaging / 中华神经医学杂志

Objective To explore the topological properties of the brain structural network in patients with neuromyelitis optica spectrum disorder (NMOSD).Methods Diffusion tensor imaging was performed in 41 NMOSD patients (patient group) and 40 age-and sex-matched healthy volunteers (control group) who were admitted to the Department of Neurology,The Third Affiliated Hospital to Sun Yat-sen University from September 2014 to October 2017.The deterministic fiber tracking techniques were used to construct the white matter structural weighted network.Topological properties of the brain structural network were then calculated based on complex graph theory analysis.The 2 groups were compared in terms of global and local parameters of the brain structural network using statistical methods.Results The brain structural networks in both groups exhibited small world properties.Compared with the control group,the global efficiency of the brain structural network in the patient group was significantly decreased and the shortest path length significantly increased (P=0.002,P=0.002,FDR correction).There were no statistically significant differences between the brain structural networks of the 2 groups in terms of clustering coefficient,the shortest path length on average,value of small world property,average clustering coefficient or local efficiency (P=0.780,P=0.496,P=0.279,P=0.269,P=0.050,FDR correction).Compared with the control group,the nodal efficiency of the brain structural network of the patient group was significantly decreased in the frontal lobe (bilateral precentral gyrus,middle frontal gyrus of the right orbital part,inferior frontal gyrus of the right opercular part,right rolandic operculum,bilateral median cingulate and paracingulate gyri),parietal lobe (right posterior cingulate gyrus,right superior parietal gyrus,left inferior parietal of angular gyri,right angle gyrus,and right precuneus),temporal lobe (bilateral hippocampus and right parahippocampal gyrus),occipital lobe (left cuneus,left superior occipital gyms,bilateral middle occipital gyrus,and left inferior occipital gyrus) and subcortical region (right caudate nucleus and right thalamus) (P＜0.05,FDR correction).Conclusion There is abnormal connection in brain structural network in NMOSD patients.

Effect of Repeated Transcranial Magnetic Stimulation on Reorganization of Aphasia after Stroke: A Study Based on Functional Magnetic Resonance Imaging / 中国康复理论与实践

Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the brain functional reorga-nization of aphasia after stroke, with functional magnetic resonance imaging (fMRI). Methods From January, 2017 to February, 2018, six eligible stroke patients with aphasia were recruited in experimental group, and nine age-gender matched healthy adults were recruited in healthy control group. Subjects in both groups received task-fMRI, and the experimental group was assessed with Chinese version of Western Aphasia Battery (WAB) examination before and after rTMS treatment. Four patients underwent rTMS at the right inferior frontal gyri pars triangularis marked by neuro-navigation-guided system, 1 Hz, five times per week for two weeks. The fMRI data were processed by SPM 12. The differences of brain activation and voxel changes be-tween two groups were compared. The fMRI data including the differences in brain activation, voxel volume and activation voxel indices (AVI) and WAB scores were analyzed before and after rTMS. Results The cerebral hemisphere activation in the experimental group was higher than that of the healthy control group, including the regions of interest (ROI) such as bilateral supplementary motor area and middle frontal gyrus, and the non-ROI (n-ROI) such as left praecuneus, left postcentral gyrus, right hippocampus, right paracingulate cor-tex, etc., while the activation reduced in the areas of left pars triangularis and n-ROI such as left calcarine fissure cortex, left gyrus lingualis, the right anterior cingulate and the paracingulate cortex. Cases 1 and 2 had shorter course of disease, smaller lesion volume, and activation increased in bilateral cerebral hemispheres before treat-ment. AVI showed that their hemispheric dominance was right, and activation reduced in bilateral cerebral hemi-sphere after treatment, but the high-efficiency language function area of ROI, such as the left pars triangularis, turned from inactive to active, and the hemispheric dominance lateralized from right to left, with the improve-ment of language function. For the case 3 and case 4, the disease courses were longer, the lesions sizes were larg-er, and both cerebral hemisphere activations were reduced before treatment. AVI showed that the hemispheric dominance of case 3 was right and was left in case 4. After treatment, bilateral cerebral hemispheres were activat-ed more than before, and the hemispheric dominance of language function was in the right hemisphere; the left middle frontal gyrus and right middle temporal gyrus were activated from no activation before treatment in case 3. The activation of the supplemental motor area on the right side was increased. In case 4, there was no activa-tion in ROI before treatment. After treatment, the bilateral supplementary motor area, right pars opercularis, and the right middle temporal gyrus were activated. Conclusion Low-frequency rTMS could improve the language function by optimizing bilateral cerebral hemisphere brain areas related with language function in patients with aphasia after stroke.

The prospect of chlorogenic acid in the treatment of glioma / 中国肿瘤临床

As a common primary intracranial tumor,malignant glioma accounts for 81% of all central nervous system malignancies.Af-ter standard treatment,such as surgery combined with external radiotherapy and chemotherapy,glioblastoma patients'survival is on-ly 14.4 months.Hence,the traditional treatment is difficult to meet patients'needs of survival and life quality.In recent years,chloro-genic acid(CGA),as plant extract polyphenols,has received widespread attention.Its antitumor properties,through its effects on the immune system,anti-oxidation properties,cell cycle regulation,and inhibition of tumor cell metastasis and invasion,have been exten-sively studied.This article will discuss the mechanisms involved in glioma treatment,synergism with other drugs,and metabolism in the human body,to provide a reference for the application of CGA in the treatment of the condition.

The effect of constraint-induced aphasia on language recovery and functional reorganization of the brain in Broca's aphasia after a stroke / 中华物理医学与康复杂志

Ohjective To explore the impact of constraint-induced aphasia therapy (CIAT) on language function and neural activity in patients with chronic Broca's aphasia.Methods Two chronic aphasics whose use of language was recovering after standard language therapy were selected to receive 1.5 h of CIAT twice daily for two weeks (30 hours in total).Before and after the CIAT they were tested using a block-designed picture-naming task,fMRIs were taken and their use of language was examined.Results The language function assessments showed relatively large improvements in the subjects' use of language after 4 weeks of conventional language training,but not much further change after 8 and 12 weeks.After the two weeks of CIAT,their language function improved further to a certain extent.fMRI showed increased activation in the left inferior frontal gyrus with or without enhanced activation in the left hemisphere,and reduced activation in the right inferior frontal gyrus.Conclusions Functional reorganization induced in the brain by CIAT was associated with up-regulation of the left inferior frontal gyrus or down-regulation of the right inferior frontal gyrus.Even the whole language network may have been modified.

Correlation between apparent diffusion coefficient values and histopathological grading of cerebral gliomas / 中华神经医学杂志

Objective To investigate the relationship between apparent diffusion coefficient (ADC) values and histopathological grading of cerebral gliomas.Methods A retrospective analysis was performed to investigate the clinical data of 76 patients with cerebral gliomas,admitted to our hospital from April 2013 to December 2016.According to Classification Criteria of Central Nervous System Tumors by WHO in 2016,these 76 patients were divided into low grade cerebral glioma group (grading Ⅰ-Ⅱ,n=21),moderate grade cerebral glioma group (grading Ⅲ,n=23) and high grade cerebral glioma group (grading Ⅳ,n=32).MR imaging,enhanced MR imaging and diffusion weighted imaging (3.0T,b value:1000 s/mm2) were performed to detect the ADC values.One-way ANOVA was used to compare ADC values between the 3 different histopathological groups.Spearman correlation analysis was used to analyze the correlation between histopathological grading of cerebral gliomas and ADC values.A receiver operating characteristic curve (ROC) analysis was performed to evaluate the diagnostic efficiency of ADC values.Results The ADC values of low grade,moderate grade and high grade cerebral gliomas were (1.37±0.26)×103 mm2/s,(0.97±0.11)×103 mm2/s,(0.75±0.13)×10-3 mm2/s,respectively;statistically significant differences were observed between each two groups (P＜0.05).There was a negative correlation between ADC values and histopathological grading of cerebral gliomas (r=-0.868,P=-0.000).ROC analysis showed that the optimal cutoff point of ADC values was 1.11 × 10.3 mm2/s in diagnosing low grade cerebral gliomas,enjoying sensitivity and specificity of differential diagnosis of 95.2％ and 96.4％;ROC curve showed that the optimal cutoffpoint of ADC values was 0.93×10-3 mm2/s in diagnosing high cerebral gliomas,enjoying sensitivity and specificity of differential diagnosis of 81.8％ and 93.7％.Conclusion ADC values are important for predicting histopathological grading of cerebral gliomas.

Effect of multi-parameter three-dimension arterial spin labeling in diagnosis of transient ischemic attack / 中华神经医学杂志

Objective To evaluate the application of multi-parameter three-dimension arterial spin labeling (3D-ASL) in observing the brain perfusion of patients with transient ischemic attack (TIA). Methods A total of 42 TIA patients, admitted to our hospital from July 2014 to March 2017, were included in this study. All subjects underwent conventional MRI, diffusion-weighted imaging (DWI), magnetic resonance angiography (MRA) and 3D-ASL scanning. Abnormal signals, and cerebral arterial stenosis or occlusion were observed under MRI, DWI and MRA; cerebral blood flow (CBF) map was drew after analyzing the 3D-ASL imaging, and abnormal reperfusion of ASL-CBF was qualitatively and quantitatively analyzed. The detection rate of abnormal reperfusion in TIA patients by 3D-ASL (PLD=1.5 s, PLD=2.5 s) and MRA were compared. Results Forty-two TIA patients showed no positive findings on conventional MRI and DWI maps, of which 18 patients showed different degrees of cerebral artery stenosis on MRA maps. Twenty-seven patients (PLD=1.5 s, 64.29％) and 21 (PLD=2.5 s, 50％) on ASL-CBF maps showed different sizes and degrees of abnormal hypoperfusion, and significant difference was found in detection rate of hypoperfusion by 3D-ASL (PLD=1.5 s and PLD=2.5 s, χ2=23.333, P=0.000). The detection rates of hypoperfusion by 3D-ASL (PLD=1.5 s and PLD=2.5 s) were 中华神经医学杂志2017年12月第16卷 第12期 Chin J Neuromed, December 2017, Vol.16, No.12 significantly higher than that by MRA (χ2=17.500, P=0.000; χ2=31.500, P=0.000). Conclusions The 3D-ASL can quantitatively analyze the degrees of perfusion of patients with TIA. 3D-ASL can comprehensively reflect the perfusion status in patients with TIA, and short PLD 3D-ASL is more sensitive than long PLD ASL in finding TIA, while long PLD 3D-ASL can reflect the perfusion status more truly.

Bilateral arm training and cortical reorganization in cerebral infarction: A functional MRI study / 中华物理医学与康复杂志

Objective To study the effect of bilateral arm training on cortical reorganization in cerebral infarction patients using blood oxygen level-dependent functional MRI (BOLD-fMRI).Methods Fourteen cerebral infarction subjects with moderate to severe upper limb impairment participated in this randomized and single-blinded training study.Subjects in the bilateral arm training group (n =7) practiced bilateral symmetrical or opposite activities,while the control group (n =7) performed conventional,mainly unilateral,arm training.Those in both groups received fMRI scans before and after the training with passive elbow movement as the task in the imaging.Results Both groups had significant improvements in their average scores on the Fugl-Meyer upper extremity assessment and in their modified Barthel index scores after the treatment,and there were no significant differences between the two groups.Brain activation had increased in both groups after the treatment,especially in the bilateral training group.After the treatment,the first motor area (M 1),the first somatosensory area and the supplementary motor area on both sides were activated in the bilateral training group.Moreover,for patients in the bilateral training group with injuries of moderate severity,the M1 of the opposite side tended to be activated,while for those more severely injured the same side had a tendency to be activated.Conclusion Convalescing subcortical infarction patients with moderate to severe upper limb impairment benefit from bilateral arm training in terms of motor activity and performing activities in daily life.It may be related to the normalization of inhibition between the hemispheres of the bilateral cerebral cortex and the reconnection of ipsilateral corticospinal pathways.

Correlation between multiple blood factors and severity of coronary atherosclerosis on 320 slice dynamic volume computed tomography / 实用放射学杂志

Objective To evaluate the clinical value of hs-CRP,Tbil and BUA in the diagnosis of coronary atherosclerosis on 320 slice dynamic volume computed tomography(320-DVCT).Methods 160 patients with stable angina pectoris were included.All patients underwent 320-DVCT coronary artery imaging and laboratory testing including plasma hs-CRP,Tbil and BUA.The plaques of coronary artery were classified as soft plaque,fibrous plaque and calcified plaque on CT values.The three indicators were used to confirm the ability of diagnosis on number of lesions,plaque character and the degree of stenosis.100 healthy persons served as the control group.Results With the concentration of hs-CRP,BUA increased and Tbil concentration decreased,the number and the stenosis degree of coronary lesions became increased,and easier to form a soft plaque.Conclusion The hs CRP,Tbil and BUA can offer the accurate diagnosis of lesions number,plaque character and stenosis degree of the coronary artery,which is showed on 320-DVCT.The hs-CRP,Tbil and BUA are conducive to the risk assessment of coronary atherosclerosis.