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).

Statistical analysis of duration of each phase of Unity MR-linac in clinical application / 中华放射肿瘤学杂志

Objective:To analyze the duration of each phase of Unity MR-linac in clinical application, aiming to provide reference for clinical optimization of the process time.Methods:Clinical data of 55 patients treated with Unity MR-linac were retrospectively analyzed. All patients were divided into the adapt to position (ATP) and adapt to shape (ATS) groups according to the planning method. The duration of each phase in the treatment process, the name and the time of each sequence, the number of beams, segments and total monitor units (MUs) were recorded and compared between two groups. In addition, the set-up time was counted according to different treatment sites. The time of each sequence and set-up time were expressed as the median M (Q 1, Q 3), and the number of beams, segments and total MUs of each plan were described as the mean±SD. Results:42 patients underwent ATP with a total of 305 treatment sessions: setup time was 3(2, 5) min, MR scanning time was 5(4, 7) min, registration time was 3(3, 4) min, adaptive planning time was 8(4, 12) min, beam on time was 8(6, 11) min, and the total time was 30(25, 36) min. 13 patients received ATS with a total of 65 treatment sessions: setup time was 2(2, 3) min, MR scanning time was 7(5, 8) min, registration time was 4(3, 5) min, time of delineation of target and organs at risk was 12(9, 16) min, adaptive planning time was 11(10, 14) min, beam on time was 10(9, 11) min and the total time was 55(49, 61) min. The set-up time according to treatment sites was 4(2, 4) min in the head and neck, 2(2, 4) min in the chest, and 3(2, 5) min in the abdomen. The number of fields, segments and total MUs during ATP were 8.1±1.7, 49.9±31.2, 846.75±363.44 in the head and neck, 8.0±2.0, 60.7±13.3, 790.21±279.00 in the chest, and 9.7±2.0, 81.2±22.3, 2007.32±1053.81 in the abdomen, respectively. The number of fields, segments and total MUs during ATS in head and neck of one case were 13, 39, 993.07, and 9.5±1.5, 65.5±6.3, 2763.26±835.41 in the abdomen.Conclusions:MR-guided radiotherapy yields huge potential in clinical application. However, there is still much room for the improvement of shortening the process duration.

Clinical value of gallbladder-preserving cholelithotomy by natural orifice transumbilical endoscopic surgery / 中华消化内镜杂志

Objective@#To investigate the clinical value of gallbladder-preserving cholelithotomy by natural orifice transumbilical endoscopic surgery on patients with cholecystolithiasis.@*Methods@#A retrospective study was performed on data of 15 patients with cholecystolithiasis, who underwent gallbladder-preserving cholelithotomy by natural orifice transumbilical endoscopic surgery from April 2018 to July 2018. The operative data, including situation of operation, operative time, intraoperative hemorrhage, and postoperative complications were recorded.@*Results@#The procedure was performed successfully in all patients with a mean operative time of 108±12 min (ranged from 92-129 min). The intraoperative hemorrhage was 10-30 mL. Eight patients suffered from slight right upper abdominal pain, and 7 patients felt slight pain in umbilical a week after surgery. No fever, incision infection, umbilical hemia, peritonitis, and ascites were reported. The clear-liquid diet was recommended for one day after operation, and postoperative activity was allowed since the second day after operation. All patients were discharged on the fourth or fifth day, and all recovered to their normal life at one week after discharge. Follow-up showed that the scar was small and hidden in umbilical without visible incision after one month. Ultrasonic examination results showed that gallbladder contractile function worked perfectly in four patients and no gallbladder stone was found after three months.@*Conclusion@#Gallbladder-preserving cholelithotomy by natural orifice transumbilical endoscopic surgery is a safe and effective option for patients with cholecystolithiasis, provides excellent cosmetic outcomes, and can be appropriately carried out under the strict control of surgical indications.

Clinical value of gallbladder-preserving cholelithotomy by natural orifice transumbilical endoscopic surgery / 中华消化内镜杂志

Objective To investigate the clinical value of gallbladder-preserving cholelithotomy by natural orifice transumbilical endoscopic surgery on patients with cholecystolithiasis. Methods A retrospective study was performed on data of 15 patients with cholecystolithiasis,who underwent gallbladder-preserving cholelithotomy by natural orifice transumbilical endoscopic surgery from April 2018 to July 2018. The operative data,including situation of operation,operative time,intraoperative hemorrhage,and postoperative complications were recorded. Results The procedure was performed successfully in all patients with a mean operative time of 108±12 min (ranged from 92-129 min). The intraoperative hemorrhage was 10-30 mL. Eight patients suffered from slight right upper abdominal pain,and 7 patients felt slight pain in umbilical a week after surgery. No fever,incision infection,umbilical hemia,peritonitis,and ascites were reported. The clear-liquid diet was recommended for one day after operation,and postoperative activity was allowed since the second day after operation. All patients were discharged on the fourth or fifth day,and all recovered to their normal life at one week after discharge. Follow-up showed that the scar was small and hidden in umbilical without visible incision after one month. Ultrasonic examination results showed that gallbladder contractile function worked perfectly in four patients and no gallbladder stone was found after three months. Conclusion Gallbladder-preserving cholelithotomy by natural orifice transumbilical endoscopic surgery is a safe and effective option for patients with cholecystolithiasis,provides excellent cosmetic outcomes,and can be appropriately carried out under the strict control of surgical indications.

Efficient evaluation of standardized specific immunotherapy in personalized maintenance phase to patients of allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the efficacy of individualized subcutaneous immunotherapy (SCIT) in allergic rhinitis(AR) maintain phase.@*METHOD@#Compare nasal symptom scores (VAS) and special disease scale--nasal conjunctivitis quality of life questionnaire(RQLQ) score after 3 years treatment to evaluate the therapeutic effect of each group and the level of improving patients quality of life. Take patients' blood to detect the serum level of IL-10 by enzyme linked immunosorbent test (enzyme linked immunosorbent assay).@*RESULT@#After 3 years treatment, there was no difference of VAS between the conventional SCIT group and the individualized SCIT group. ELISA results showed that the level of IL-10 was significantly higher in the drug symptomatic treatment group than that in the healthy group, the levels of IL-10 were significantly lower in the conventional SCIT group and the individualized SCIT group than that in the healthy group, but there was no difference between the conventional SCIT and the individualized SCIT group.@*CONCLUSION@#After 3 years treatment, there was no difference between conventional and individualized SCIT groups. But the efficacy of the conventional and individualized SCIT groups were significantly better than that in the drug symptomatic treatment group.

The role of glucocorticoids in the treatment of chornic rhinosinusitis / 临床耳鼻咽喉头颈外科杂志

Glucocorticoids (GC) are increasingly being used to treat chronic rhinosinusitis, its efficacy and safety are the focus of attention. This article will be divided into chronic rhinosinusitis with nasal polyps and without nasal polyps two subtypes discussed nasal and oral glucocorticoids in the clinical therapeutic efficacy and medication safety.

Basal-like breast cancer / 国际肿瘤学杂志

Basal-like breast cancer (BLBC) is a basal cell phenotype and associated with different levels of expression in basal cell keratin and (or) myoepithelial markers in breast cancer,which has a unique genetic phenotype and morphological characteristics.BLBC is prevalent in young woman,and it is easy to relapse and metastasis. Additionally,most BLBC has expression loss of estrogen receptor and progesterone receptor and human epidermal growth factor receptor 2,which limits the targeted therapeutic options for these predominantly triple-negative breast cancers.