Apatinib combined with temozolomide in diffuse midline glioma: a novel and effective therapy.

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.

[The Effects of Social Support and Health Literacy on Depression among Rural Patients with Hypertension].

OBJECTIVE: To explore the effects of social support and health literacy on depression among hypertensive patients in rural areas and to provide reference for improving depression in hypertensive patients. METHODS: A multi-stage stratified sampling method was used to select 549 hypertensive patients in a rural area of Chengdu city for a questionnaire survey. Structural equation model was used to analyze the effects of social support and health literacy on depression in hypertensive patients. RESULTS: Social support ( ß=-0.116, 95% CI: (-0.198)-(-0.132)) and health literacy ( ß=-0.209, 95% CI: (-0.289)-(-0.132)) had a direct negative effect on depression, and social support had a direct positive effect on health literacy ( ß=0.146, 95% CI: 0.064-0.229). Health literacy was a mediator between social support and depression ( ß=-0.030, 95% CI: (-0.054)-(-0.013)). The gender, employment status and per capita annual income of the patients affected the incidence of depression ( P<0.05). CONCLUSIONS: Social support and health literacy are important predictors of depression among hypertensive patients. We should construct a good social support network, strengthen the publicity of health knowledge, and improve social support and health literacy to alleviate the depression in hypertensive patients. At the same time, more attention should be paid to women, people with low per capita annual income and working hypertensive patients.

Combining therapy with recombinant human endostatin and cytotoxic agents for recurrent disseminated glioblastoma: a retrospective study.

BACKGROUND: The optimal chemotherapeutics of recurrent disseminated glioblastoma has yet to be determined. We analyzed the efficacy and safety of recombinant human endostatin (rh-ES) combined with temozolomide and irinotecan in patients with recurrent disseminated glioblastoma. METHODS: We retrospectively reviewed 30 adult patients with recurrent disseminated glioblastoma treated with this combination chemotherapy at Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University of China from November 2009 to August 2018. Temozolomide was given orally at 200 mg/m2 daily for 5 days and rh-ES was administrated 15 mg/d daily for 14 days of each 28-day treatment cycle. Irinotecan was given intravenously every 2 weeks on a 28-day cycle at 340 mg/m2 or 125 mg/m2 depending on antiepileptic drugs. Primary endpoint was progression-free survival (PFS) at 6 months (6 m-PFS). RESULTS: The 6 m-PFS was 23.3%. The median PFS was 3.2 months. The overall survival rate (OS) at 12 months was 28.6%. The median OS was 6.9 months. Six out of 30 (20%) patients demonstrated partial radiographic response and 11 (36.7%) remained stable. The PFS of the 6 patients who got partial response was 5.8, 6.3, 6.9, 13.6, 15.8 and 16.6 months, respectively, and the median time interval of first response was 4 (range, 2.0-6.6) months. The most common adverse events were hematologic toxicities and gastrointestinal effects. The Grade ≥ 3 adverse event was hematologic toxicities. The adverse events were manageable. CONCLUSIONS: Rh-ES, in combination with cytotoxic drugs, was an alternative effective regimen with manageable toxicities in treatment of recurrent disseminated glioblastoma.

Effects of the portage early education program on Chinese children with global developmental delay.

Children with global developmental delay (GDD) were trained with the Portage Guide to Early Education (PGEE) program.In the treatment group, the PGEE program was performed on children with GDD (45 cases) through a combination of family and hospital interventions, in a 1-to-1 ratio. The Gesell Infant Development Scale (GESELL) developmental quotient (DQ) and social adaptability were measured before and 6 months after PGEE implementation in the treatment group. These parameters were also evaluated in a control group (30 cases) during an initial visit and 6 months later.Before the PGEE intervention, no significant differences were observed between the general characteristics of children in the control and treatment groups. Six months after the PGEE intervention, the DQ values of the children with GDD in the treatment group (64.7 ±â€Š9.5) were significantly higher than those before treatment (54.6 ±â€Š9.3) and those of the control group (58.3 ±â€Š10.2) (P < .05). The PGEE intervention significantly increased the DQ values on 5 aspects, including gross motor, fine motor, adaptability, language, and personal social activity abilities, and the scores on the Infants-Junior Middle School Students' Social-Life Abilities Scales (SM scales), as compared with the control group (P < .05).The PGEE program improves the DQ, social adaptability, and prognosis of children with GDD.

Long-Term Remission of Recurrent Brainstem Pilocytic Astrocytoma with Neuraxis Dissemination Using Recombinant Human Endostatin After Failure of Vincristine and Carboplatin.

BACKGROUND: There is no standard salvage treatment for recurrent and/or unresectable brainstem low-grade gliomas after failure from carboplatin and vincristine chemotherapy. Recombinant human endostatin (rh-ES), a mild inhibitor of angiogenesis, has been used for treating lung cancer. But so far as we know, there is no experience for brainstem gliomas. CASE DESCRIPTION: The authors present a pediatric case of recurrent brainstem pilocytic astrocytoma with neuraxis dissemination who experienced tumor progression with carboplatin and vincristine chemotherapy but then had a dramatic and long-term remission for at least 29 months after combined treatment of rh-ES with carboplatin and vincristine. CONCLUSION: This case suggests that the addition of rh-ES to carboplatin and vincristine regimens may be synergistic and results in a long-term remission in patients with brainstem low-grade gliomas, even if the tumor is widely spread in the central nervous system.

Bifurcations in a low-order nonlinear model of tropical Pacific sea surface temperatures derived from observational data.

Aiming at tackling the difficulty in exactly constituting the sea surface temperature (SST) dynamical model, the paper introduces the dynamical system reconstruction idea and establishes the nonlinear dynamical model of SST field based on 1963-2010 monthly average Hadley SST data. Time coefficients series after empirical orthogonal functions decomposition are taken as the dynamical model variables and Genetic Algorithms is used to optimize and retrieve the model parameters. The stability of the equilibrium in the reconstructed model is analyzed and dynamical actions such as bifurcation and mutation are discussed. Also the activity configuration and aberrance mechanism of the SST field are developed upon the actual activity characteristics of the SST field in the Tropical Pacific Ocean in that year. Results reveal that the bifurcation action of the SST field system from one stable high-value equilibrium to another stable low-value equilibrium accords with the La Niña process while the mutation action of the SST field system from two stable equilibriums to another stable equilibrium accords with the El Niño process.

[Effect of lamellar keratoplasty time on the production of serum specific antibody in corneal alkali burns].

OBJECTIVE: To observe the production of serum specific anti-denatured corneal antibody and the effects of lamellar keratoplasty on changes of corneal histopathology in different stages after alkali burns. METHODS: 20 male New Zealand rabbits, with alkali burns in right eye were randomly divided into 5 groups including: burned group; 2 early lamellar keratoplasty group (operation at 3 or 7 days post alkali burns respectively); 2 middle and later lamellar keratoplasty groups (operation at 2 or 5 weeks after alkali burns respectively). The level of serum specific antibody in each group was detected by ELISA and the corneal structure was evaluated by light and electron microscopy in different stages after alkali burns. RESULTS: The anti-denatured corneal antibody was induced after corneal alkali burns. The level of antibody significantly increased at 2th week post, peaking burn at 5 or 6th week, then decreasing. More antibodies were detected when contralateral eye was burn at 8 week post first burn. However, only slight increasing antibody was detected in early lamellar keratoplasty group. Furthermore, no significant changes of antibody production were observed in middle and later lamellar keratoplasty group. The light and electron microscopic analysis showed that, the corneal epithelium recovered better, the fibre of corneal stroma arranged better, inflammatory cells infiltrated less and neovascularization formed less in lamellar keratoplasty groups comparing to the burned group. The early lamellar keratoplasty groups recovered better than in middle and later lamellar keratoplasty groups. CONCLUSION: Early lamellar keratoplasty after corneal alkali burns can significantly decrease the immune response. Histopathological data also indicate that early lamellar keratoplasty can improve the tissue regeneration and recovery, prevent topical inflammatory reaction, and abate corneal neovascularization. This study suggests that early lamellar keratoplasty is more effective than the conservative treatment.