Objective To establish a stable implanted model of VX2 rabbit brain tumor, and to evaluate the pathological and imaging features and tumor angiogenesis. Methods Thirty New Zealand white rabbits were implanted with 100 ?l viable VX2 tumor cells (107/ml) through a hole 5 mm to the right of the sagittal suture and 5 mm posterior to the coronal suture bored by a dental drill. MRI was performed every ~2 days after 7 days of implantation to evaluate the growth of the tumor, and perfusion CT studies were performed in different days of tumor growth. After that the animals were sacrificed on days 14, 18, 22, 26, and 30 of tumor implantation. 2% Evans blue (2 ml/kg) was given intravenously in 16 of these animals ~1 hour prior to sacrifice to detect the breakdown of the blood-brain barrier (BBB). The specimens of the rabbit brains were examined pathologically and histologically. VEGF and MVD were evaluated in immunohistochemical examination. Results Of the 22 animals included into the study, the tumor grew in 20 animals, which could be seen clearly on MR imaging. Pathologic examination showed characteristics of squamous carcinoma. VEGF was expressed in all tumors with the mean rate of positive cells of (52.51?19.15)% (19.5%-92.9%). Mean MVD was (51.30?14.42)pice piece/microscope (25-81 pice piece/microscope). Using Pearson′s linear correlation analysis, positive correlation was found between tumor growth time and volume (r=0.791, P=0.000), between MVD and tumor growth time (r=0.875, P=0.000), and between MVD and tumor volume (r=0.901, P=0.000), respectively. Spearman′s rank correlation analysis showed positive correlation between VEGF grade and blue stain of the tumor (r_s=0.594, P=0.015). Conclusion A stable model of VX2 rabbit brain tumor has been established with the method of skull drilling. The method was simple and easy to use, with a high tumor growth rate and remarkable angiogenesis. The model is helpful for the pathological and radiological study of tumor angiogenesis.

Objective To compare the effect of clustered acupuncture of the scalp combined with constraint induced movement therapy (CIMT) with that of conventional acupuncture of the body points plus conventional rehabilitation intervention after cerebral infarction using blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI).Methods Thirty acute cerebral infarction patients with hemiplegia were equally divided into two groups at random.The test group received the clustered acupuncture of the scalp combined with CIMT,while the control group received the body point acupuncture plus conventional rehabilitation intervention.Before and after two weeks of treatment,blood oxygenation level-dependent functional magnetic resonance imaging at 3.0 T was performed during a passive digital opposition movement.The volume and intensity of the activated areas were compared.Fugl-Meyer assessment (FMA) was carried out as well.Results The most pronounced activation appeared in the contralateral somatosensory motor cortex for both groups.There was no significant difference in average FMA scores between the two groups before the treatment,but after the treatment the averages were significantly different.An increase in activated volume and intensity in the contralateral SMC was observed in both groups after the treatment,but the test group showed a much larger change in both activated volume and intensity.Conclusion The clustered acupuncture of the scalp combined with CIMT can achieve a more significant improvement in functional recovery after acute cerebral infarction than conventional acupuncture of the body points plus conventional rehabilitation intervention.Such combined therapy is worthy of application in clinical practice.

To investigate the relationship between severity of cerebrovascular atherosclerosis stenosis and that of coronary atherosclerosis stenosis.Methods Cerebral angiography and coronary angiography were performed in 34 patients who had coronary disease with cerebral ischemia.Patients were divided into 3 subgroups according to the degree ofstenosis on angiography,concomitant diseases,risk factors and biochemical data.Results The follow-up study showed that the incidence of cardiac and cerebrovascular death increased significantly in patients with moderate to severe stenosis of coronary and cerebral arteries;the severity of stenosis in the coronary artery parallels that in the solitary carotid artery,or dual carotid and vertebral arteries.Conclusions Patients with coronary and cerebral artery stenosis,especially those with multi-risk factors,such as hypertension,diabetes and cigarette smoking,should receive intensive treatment to reduce cardiac and cerebrovascular events.(J Geriatr Cardiol 2008;5:227-229)

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

Objective:To observe the effects of transcranial direct current stimulation (tDCS) on functional connectivity (FC) in language-related brain regions of patients with picture-naming dysfunction after cerebral infarction by using resting state functional magnetic resonance imaging(rs-fMRI).Methods:Twenty-eight patients with post-infarction picture-naming dysfunction were divided into an acute stage group( n=16) and a recovery stage group( n=12) according to the course of the disease, and 18 middle-aged and elderly volunteers were recruited as the normal control group.The anodic tDCS was applied on the posterior perisylvian region(PPR) of the left sylvian of the patients, 5 days a week for 2 weeks.Before and after the 2 weeks′ treatment, the rs-fMRI and Psycholinguistic Assessment of Chinese Aphasia (PACA)-picture-naming subscale were performed, and FC changes in language-related brain areas were observed. Results:After treatment, the PACA scores of patients in both acute and recovery stage groups were significantly improved after treatment( P<0.05). Compared with normal subjects, FC in multiple brain regions and particularly the Wernicke area was reduced in both cerebral hemispheres among the patient group. It was more severe in the dominant hemisphere.After the tDCS treatment, FC in both frontotemporal lobes and in the Wernicke area was significantly enhanced in both the acute and recovery groups. Further comparison showed that in the acute group FC in both temporo-occipital lobes was significantly enhanced after treatment. In the recovery group, the enhanced FC in the left temporal lobe before the treatment was significantly reduced after treatment. Conclusion:The fMRI technique can evaluate changes in brain connectivity in aphasia patients with picture-naming dysfunction after cerebral infarction accurately and non-invasively.tDCS may improve picture-naming function of stroke patients by enhancing the FC in bilateral language-related brain areas(concentrated in frontotemporal lobes) and Wernicke area.

Objective: To explore the correlations relating functional MRI (fMRI) and diffusion tensor imaging (DTI) parameters with pre-operative neurological status and post-operative outcomes for patients with cervical spondylotic myelopathy (CSM). Methods: Eighty-seven CSM patients treated with surgical decompression and 38 healthy counterparts were enrolled as the CSM and control groups respectively. DTI and fMRI of the cervical spine were performed while the subjects performed a finger-tapping task with their right hands before the operation and 6 months later. The control group was evaluated only when they were enrolled. All of the patients were given systematic rehabilitation treatment after the surgery. The Japanese Orthopaedic Association (JOA) scoring system for CSM was used to evaluate neurological status, and a JOA recovery rate <50% was defined as a poor recovery. Results: Compared with the healthy controls, the pre-operative patients showed significantly higher volume of activation (VOA) in the left precentral gyrus (PrCG), but that had decreased significantly 6 months after the surgery. Before the surgery, the patients′ fractional isotropy (FA) was significantly less than that of the controls, but it had increased significantly 6 months after the operation. There was no difference in VOA in the left postcentral gyrus (PoCG) between the CSM patients and the controls before the surgery. The VOA ratio (PrCG/PoCG), VOA-PrCG, VOA-PoCG and FA were significantly correlated with both the JOA scores and recovery rates. Receiver operating characteristic (ROC) curve analyses were performed for the predictive ability with respect to surgical outcomes. The largest area under the ROC curve was observed for the VOA ratio (0.805), followed by FA (0.740), and the VOA-PrCG (0.715). The fMRI and DTI showed better potential for predicting functional outcomes than with standard MRI parameters. Multivariate logistic regression revealed that the VOA ratio and FA were independently associated with poor outcomes. Conclusions fMRI and DTI parameters may be more valuable than conventional MRI results for neurological assessment and prognosis with CSM patients. They can also provide references for making up rehabilitation plans.

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10⁷/kg on day 0) and (4.0-6.8) ×10⁷/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.

In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/proteins is mainly limited in parenteral approach. Oral therapy which was hampered by harsh gastrointestinal environment and poorly penetrating epithelial barriers often results in low bioavailability (less than 1%-2%). Therefore, delivery systems that are rationally designed to overcome these challenges in gastrointestinal tract and ameliorate the oral bioavailability of therapeutic peptides/proteins are seriously promising. In this review, we summarized various multifunctional delivery systems, including lipid-based particles, polysaccharide-based particles, inorganic particles, and synthetic multifunctional particles that achieved effective oral delivery of therapeutic peptides/proteins.