Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion

Background

Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities.

Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.     

Application of neuroendoscopic surgical techniques in the assessment and treatment of cerebral ventricular infection

Cerebral ventricular infection(CVI) is one of the most dangerous complications in neurosurgery because of its high mortality and disability rates. Few studies have examined the application of neuroendoscopic surgical techniques(NESTs) to assess and treat CVI. This multicenter, retrospective study was conducted using clinical data of 32 patients with CVI who were assessed and treated by NESTs in China. The patients included 20 men and 12 women with a mean age of 42.97 years. NESTs were used to obliterate intraventricular debris and pus, fenestrate or incise the intraventricular compartment and reconstruct cerebrospinal fluid circulation, and remove artificial material. Intraventricular irrigation with antibiotic saline was applied after neuroendoscopic surgery(NES). Secondary hydrocephalus was treated by endoscopic third ventriculostomy or a ventriculoperitoneal shunt. Neuroendoscopic findings of CVI were used to classify patients into Grade I(n = 3), Grade II(n = 13), Grade III(n = 10), and Grade IV(n = 6) CVI. The three patients with grade I CVI underwent one NES,the 23 patients with grade II/III CVI underwent two NESs, and patients with grade IV CVI underwent two(n = 3) or three(n = 3) NESs.The imaging features and grades of neuroendoscopy results were positively related to the number of neurosurgical endoscopic procedures.Two patients died of multiple organ failure and the other 30 patients fully recovered. Among the 26 patients with secondary hydrocephalus,18 received ventriculoperitoneal shunt and 8 underwent endoscopic third ventriculostomy. There were no recurrences of CVI during the 6-to 76-month follow-up after NES. Application of NESTs is an innovative method to assess and treat CVI, and its neuroendoscopic classification provides an objective, comprehensive assessment of CVI. The study trial was approved by the Institutional Review Board of Beijing Shijitan Hospital, Capital Medical University, China.     

Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies

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张宁教授“固本泻浊法”治疗肾病综合征经验浅谈

肾病综合征是儿童和成人常见的肾脏疾病之一，激素治疗常不能达到满意的效果，并会出现多种不良反应。张宁教授运用中医治疗肾病综合征经验丰富，认为肾病综合征病性虚实夹杂，脾肾亏虚为本，肝失疏泄、湿热内阻、瘀血停滞为标。标实的病理因素由本虚引起及加重。治以“固本泻浊法”，健脾益肾，兼以调肝养血、清热化湿、活血化瘀，提高了临床疗效，减少了不良反应。     

伞骨草利尿抗炎活性及急性毒性研究＊

目的 研究伞骨草水提物的利尿和抗炎作用，以及利尿后对电解质平衡、糖代谢及肾脏功能的影响，并对伞骨草水提物安全性进行初步评价。方法 采用小鼠代谢笼法，检测盐水负荷小鼠在给药6 h后的排尿量，并分析小鼠尿液中离子浓度、血清中糖原、尿素氮和肌酐的变化；采用二甲苯致小鼠耳廓肿胀法，计算耳廓肿胀度及肿胀抑制率，角叉菜胶致大鼠足趾肿胀法，计算足趾肿胀率，小鼠急性毒性试验初步评价伞骨草水提物的安全性。结果 与对照组比较，伞骨草水提物能明显增加小鼠的排尿量，尿液中K⁺、Cl^-的浓度明显增加，高剂量组Na⁺、Ca²⁺浓度明显增加；伞骨草对小鼠血清中的糖原、尿素氮和肌酐均无明显影响；伞骨草中、高剂量对二甲苯所致小鼠耳廓肿胀和角叉菜胶所致大鼠足趾肿胀具有明显的抑制作用；伞骨草水提物24 h内小鼠单次灌胃给药急性毒性试验的LD₅₀为：12.33 g·kg^-1（相当于生药82.15 g·kg^-1），动物在4 h内出现毒性反应，主要表现为主要表现为腹泻、俯卧、竖毛、运动失调、死亡，腹泻至给药第2天恢复。结论 伞骨草水提物具有明显的利尿和抗炎作用，并且对机体的血糖水平和肾脏功能无明显影响。