Ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma: CARTITUDE‐1 (phase 2) Japanese cohort

Chimeric antigen receptor (CAR) T cells targeting B‐cell maturation antigen have shown positive responses in patients with multiple myeloma (MM). The phase 2 portion of the CARTITUDE‐1 study of ciltacabtagene autoleucel (cilta‐cel) included a cohort of Japanese patients with relapsed/refractory MM. Following a conditioning regimen of cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²), patients received a single cilta‐cel infusion at a target dose of 0.75 × 10⁶ (range, 0.5–1.0 × 10⁶CAR‐positive viable T cells/kg). The primary endpoint was overall response rate (ORR; defined as partial response or better) by International Myeloma Working Group criteria. A key secondary endpoint was the rate of very good partial response (VGPR) or better (defined as VGPR, complete response, stringent complete response). This first analysis was performed at 6 months after the last patient received cilta‐cel. Thirteen patients underwent apheresis, nine of whom received cilta‐cel infusion. Eight patients who received cilta‐cel at the target dose responded, yielding an ORR of 100%. Seven of eight (87.5%) patients achieved a VGPR or better. One additional patient who received a below‐target dose of cilta‐cel also achieved a best response of VGPR. MRD negativity (10⁻⁵ threshold) was achieved in all six evaluable patients. Eight of nine (88.9%) patients who received cilta‐cel infusion experienced a grade 3 or 4 adverse event, and eight (88.9%) patients experienced cytokine release syndrome (all grade 1 or 2). No CAR‐T cell neurotoxicity was reported. A positive benefit/risk profile for cilta‐cel was established for heavily pretreated Japanese patients with relapsed or refractory MM.     

视神经周围炎的研究进展

视神经周围炎(OPN)是指涉及视神经鞘膜的一系列病理性炎症.OPN的经典三联征包括单侧视神经病变伴随疼痛和/或视盘水肿,此病症与其它视神经病变相似,导致诊断延迟和治疗欠佳.2016年1月,我们对发表于Medline和Ovid数据库的关键词为“视神经周围炎”的各种语言的文献进行了检索,共查找到60篇文献,发表于1956-2015年.两位作者(Tai ELM和Tevaraj JMP)分别对论文摘要进行了独立筛选,并筛选出相关文章.本次综述,我们强调OPN的特点,特别是OPN和视神经炎之间的临床差异.虽然大多数OPN的病例是特发性的,但仍需进行调查以排除特异性感染和继发性OPN的炎症原因.MRI是非常重要的检查方法,由于OPN视神经周围炎症的影像学诊断.糖皮质激素治疗可使症状与体征迅速好转,长期口服糖皮质激素并慢速递减可以降低复发的风险.     

Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): Acute and subchronic toxicity studies

Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days.     

Antioxidant and hepatoprotective effects of Orthosiphon stamineus Benth. standardized extract

Orthosiphon stamineus (OS), Benth. (Lamiaceae) is widely used in Malaysia for treatments of various kidney and liver ailments. In the experiment, DPPH* radicals scavenging, Fe(3+)-induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus (SEOS) were determined. The results indicated that SEOS exhibited antioxidant, lipid peroxidation inhibition and free radical scavenging activities. The hepatoprotective activity of the SEOS was studied using CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring liver function tests through the measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Furthermore, hepatic tissues were also subjected to histopathological studies. Pretreatment of SEOS (125, 250, 500 and 1000 mg/kg p.o.) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of serum ALT and AST activities. The results of the present study indicated that the hepatoprotective effect of Orthosiphon stamineus might be ascribable to its antioxidant and free radical scavenging property.     

Paraaortic sentinel lymph node detection in intermediate and high-risk endometrial cancer by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR)

ObjectiveWe aimed to evaluate the accuracy of sentinel lymph node (SLN) mapping with transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) to detect lymph node (LN) metastases, in patients with intermediate and high-risk endometrial cancer (EC), focusing on its performance to detect paraaortic involvement.MethodsProspective study including women with preoperative intermediate or high-risk EC, according to ESMO-ESGO-ESTRO consensus, who underwent SLN mapping using the TUMIR approach. SLNs were preoperatively localized by planar and single photon emission computed tomography/computed tomography images, and intraoperatively by gamma-probe. Immediately after SLN excision, all women underwent systematic pelvic and paraaortic lymphadenectomy by laparoscopy.ResultsThe study included 102 patients. The intraoperative SLN detection rate was 79.4% (81/102). Pelvic and paraaortic drainage was observed in 92.6% (75/81) and 45.7% (37/81) women, respectively, being exclusively paraaortic in 7.4% (6/81). After systematic lymphadenectomy, LN metastases were identified in 19.6% (20/102) patients, with 45.0% (9/20) showing paraaortic involvement, which was exclusive in 15.0% (3/20). The overall sensitivity and negative predictive value (NPV) of SLNs by the TUMIR approach to detect lymphatic involvement were 87.5% and 97.0%, respectively; and 83.3% and 96.9%, for paraaortic metastases. After applying the MSKCC SLN mapping algorithm, the sensitivity and NPV were 93.8% and 98.5%, respectively.ConclusionThe TUMIR method provides valuable information of endometrial drainage in patients at higher risk of paraaortic LN involvement. The TUMIR approach showed a detection rate of paraaortic SLNs greater than 45% and a high sensitivity and NPV for paraaortic metastases in women with intermediate and high-risk EC.     

分期实施异体角膜缘干细胞移植与穿透性角膜移植术治疗严重化学伤

有1位于1996年实施右眼穿透性角膜移植术失败的双眼严重眼表化学伤的患者, 62岁,右眼视力手动,左眼视力光感。于2006-09-16/2007-02-07分别对右眼实施了异体角膜缘干细胞移植术和穿透性角膜移植术,经过术后5m的药物治疗观察,最终获得了右眼最佳矫正视力为6/30,角膜移植片透明,眼表得以重建,并未发现明显排斥迹象的良好效果。     

Synergistic effect of modified pore and heterojunction of MOF-derived α-Fe2O3/ZnO for superior photocatalytic degradation of methylene blue

Mesoporous heterojunction MOF-derived α-Fe₂O₃/ZnO composites were prepared by a simple calcination of α-Fe₂O₃/ZIF-8 as a sacrificial template. The optical properties confirm that coupling of both the modified pore and the n–n heterojunction effectively reduces the possibility of photoinduced charge carrier recombination under irradiation. The mesoporous Fe(25)ZnO with 25% loading of α-Fe₂O₃ exhibited the best performance in MB degradation, up to ∼100% after 150 minutes irradiation, higher than that of pristine ZnO and α-Fe₂O₃. Furthermore, after three cycles reusability, mesoporous Fe(25)ZnO still showed an excellent stability performance of up to 95.42% for degradation of MB. The proposed photocatalytic mechanism of mesoporous Fe(25)ZnO for the degradation of MB corresponds to the n–n heterojunction system. This study provides a valuable reference for preparing mesoporous MOF-derived metal oxides with an n–n heterojunction system to enhance MB photodegradation.

Mesoporous heterojunction MOF-derived α-Fe₂O₃/ZnO composites were prepared by a simple calcination of α-Fe₂O₃/ZIF-8 as a sacrificial template.     

Ternary Copper Tungsten Sulfide (Cu2WS4) Nanoparticles Obtained through a Solvothermal Approach: A Bi-Functional Electrocatalyst for the Hydrogen Evolution Reaction (HER) and Oxygen Evolution Reaction (OER)

In this work, Cu₂WS₄ nanoparticles have been synthesized via a solvothermal decomposition approach using a heterobimetallic single source precursor, WCu₂S₄(PPh₃)₃. The single source precursor, WCu₂S₄(PPh₃)₃, has been characterized using multinuclear NMR spectroscopy, while Cu₂WS₄ nanoparticles have been characterized by powder X-ray diffraction (PXRD) for which Rietveld refinement has been performed to authenticate the lattice structure of the decomposed product, Cu₂WS₄. Furthermore, FESEM and EDAX analyses have been performed to assess the morphology and composition of Cu₂WS₄. An electrochemical study in acidic as well as basic media suggested that Cu₂WS₄ nanoparticles possess efficient bifunctional activity towards electrochemical hydrogen as well as oxygen evolution reactions. Linear sweep voltammetry (LSV) performed in 0.5 N H₂SO₄ indicates an onset potential for the HER of 462 mV and a Tafel slope of 140 mV dec⁻¹. While LSV performed in 0.1 M KOH indicates an onset potential for the OER of 190 mV and a Tafel Slope of 117 mV dec⁻¹.     

In-Silico Monte Carlo Simulation Trials for Investigation of V2O5 Reinforcement Effect on Ternary Zinc Borate Glasses: Nuclear Radiation Shielding Dynamics

In the current study, promising glass composites based on vanadium pentoxide (V₂O₅)-doped zinc borate (ZnB) were investigated in terms of their nuclear-radiation-shielding dynamics. The mass and linear attenuation coefficient, half-value layer, mean free path, tenth-value layer, effective atomic number, exposure-buildup factor, and energy-absorption-buildup factor were deeply simulated by using MCNPX code, Phy-X PSD code, and WinXcom to study the validation of ZBV1, ZBV2, ZBV3, and ZBV4 based on (100−x)(0.6ZnO-0.4B₂O₃)(x)(V₂O₅) (x = 1, 2, 3, 4 mol%) samples against ionizing radiation. The results showed that attenuation competencies of the studied glasses slightly changed while increasing the V₂O₅ content from 1 mol% to 4 mol%. The domination of ZnO concentration in the composition compared to B₂O₃ makes ZnO substitution with V₂O₅ more dominant, leading to a decrease in density. Since density has a significant role in the attenuation of gamma rays, a negative effect was observed. It can be concluded that the aforementioned substitution can negatively affect the shielding competencies of studied glasses.