Electron dense alteration of kidney basement membranes: A renal lesion specific of a systemic disease

Described here are the findings of a clinical, anatomic and chemical study of 40 patients having an original lesion of the basement membranes of the kidney.This lesion is characterized by an ultrastructural modification of the basement membrane substance which appears very dark (black) and homogeneous in electron micrographs. It affects the basement membranes of the glomerulus, Bowman's capsule and the renal tubules. Patients with this lesion all manifest the clinical course of a chronic nephritis and is almost invariably accompanied by proteinuria and microscopic hematuria. The disease evolves generally with intermittent episodes towards irreversible renal failure.Eight patients received kidney transplants. Study of these transplants has shown that the lesion recurs in the transplanted kidneys during the year following transplantation. Moreover, it is never found in kidneys transplanted into patients who did not have it in their own kidneys. This ultrastructural lesion can therefore be placed in the framework of a systemic disease whose etiology is not yet known. The study of these transplants also shows that the lesion can exist despite the absence of any detectable clinical or biologic signs and be well tolerated for periods which now exceed 4 years for three patients.     

Comparing and combining light dose fractionation and iron chelation to enhance experimental photodynamic therapy with aminolevulinic acid

BACKGROUND AND OBJECTIVES: Enhancement of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has been demonstrated experimentally using light dose fractionation or CP94 iron chelation. This study extends this research. STUDY DESIGN/MATERIALS AND METHODS: In normal rat colon, CP94 administration and light dose fractionation were independently and concurrently employed to enhance ALA-PDT. In colonic rat tumors, the most successful enhancement regimes were employed separately. RESULTS: Independent use of light dose fractionation and iron chelation produced similar results in normal colon (2.4- and 2.9-fold more necrosis than controls, respectively). Using both techniques simultaneously produced fivefold enhancement. In the colonic tumors, light dose fractionation and iron chelation (using different parameters) produced two and five times the volume of necrosis, respectively. CONCLUSIONS: Both techniques significantly enhanced ALA-PDT in the normal and neoplastic tissues investigated and produced similar levels of enhancement when comparable parameters were employed. Concurrent use of light dose fractionation and iron chelation in normal colon produced considerably more enhancement than either technique could achieve independently.     

手术机器人在人工全膝关节置换术中的应用及研究进展

目的总结手术机器人在人工全膝关节置换术（total knee arthroplasty，TKA）中的应用及研究进展。方法查阅国内外相关文献，分析手术机器人辅助 TKA（robotic-arm assisted TKA，RATKA）的优势及不足。结果TKA 术中准确重建下肢力线和旋转对线、精确截骨和植入假体对于提高疗效及延长假体寿命至关重要。传统 TKA 由于术者操作因素存在截骨偏差等问题，而 RATKA 在一定程度上解决了上述问题，能辅助精确截骨及植入假体、能更好地保护膝关节周围软组织。RATKA 术后患者满意度高，且术者学习曲线较短、提高了手术效率，但也存在手术耗时延长、并发症增加、医疗成本提高等不足。结论初步临床应用研究显示 RATKA 疗效满意，但与传统 TKA 相比其确切优势尚待大样本随机对照研究和长期随访来验证。     

Non‐steroidal mineralocorticoid receptor antagonism for the treatment of cardiovascular and renal disease

Pharmaceutical antagonism of the mineralocorticoid receptor (MR) can protect against organ damage caused by elevated aldosterone levels in patients experiencing heart failure (HF), chronic kidney disease (CKD), primary aldosteronism, and hypertension. While traditional steroid‐based MR antagonists effectively reduce mortality rates and extend patient survival, their broad application has been limited by significant side effects, most notably hyperkalaemia. Recently, finerenone (BAY 94‐8862) has emerged as a next‐generation non‐steroidal dihydropyridine‐based MR antagonist designed to minimize off‐target effects while maintaining potent efficacy. In this review, the outcomes of finerenone therapy in several diseases associated with MR activity are explored. The (pre‐) clinical efficacy of finerenone is compared with that of traditional steroid‐based MR antagonists. Finally, recent and ongoing clinical trials using finerenone to treat chronic HF, CKD, and diabetic nephropathy are discussed. Taken together, pre‐clinical and clinical evidence suggests that finerenone may achieve equivalent organ‐protective effects with reduced levels of electrolyte disturbance compared with traditional steroid‐based MR antagonists. This supports further clinical development of finerenone for the treatment of cardiovascular and renal disease.     

腺病毒介导的人视网膜母细胞瘤94基因对人食管癌细胞辐射增敏作用的研究

目的 探讨重组腺病毒人视网膜母细胞瘤94基因(Ad-Rb94)对γ射线杀伤人食管癌 EC109细胞的增敏作用。方法 将Ad-Rb94体外转染后的EC109细胞,按数字随机表法,分为空白对照组、Ad-LacZ对照组、Ad-Rb94组、照射组和Ad-Rb94联合照射组,观察EC109的细胞的抑制率、细胞周期和Rb蛋白的表达。结果 Ad-Rb94组、照射组和Ad-Rb94联合照射组对EC109细胞生长均具有抑制作用,Ad-Rb94联合照射组的抑制效应最强,明显高于Ad-Rb94组和照射组(F=23.31,P<0.05)。Ad-Rb94联合照射组EC109细胞出现明显的G₂期阻滞,G₂期细胞所占比例达50%。Ad-Rb94联合照射组表达Rb蛋白的细胞明显增加,阳性率达71%,较Ad-Rb94组和照射组差异有统计学意义(χ²=8.31和6.73,P<0.05)。结论 Rb94基因联合照射能明显提高对人食管癌细胞的辐射增敏性。     

益生菌联合应用行为分析法治疗儿童孤独症谱系障碍的前瞻性随机对照研究

目的探讨益生菌联合应用行为分析法（applied behavior analysis，ABA）治疗儿童孤独症谱系障碍（autism spectrum disorder，ASD）的疗效。方法选取2019年5月至2020年12月在江苏大学附属医院就诊的ASD患儿41例，随机分为观察组（n=21）和对照组（n=20）。观察组给予口服益生菌联合ABA干预，对照组仅给予ABA干预，比较两组的疗效。在干预前、干预后3个月分别依据孤独症治疗评估量表（autism treatment evaluation checklist，ATEC）对两组患儿行为症状的严重程度进行评分，并分别留取患儿的粪便标本，基于16s rRNA高通量测序分析两组患儿的肠道菌群差异。结果干预前，观察组与对照组ATEC评分差异无统计学意义（P>0.05）；干预后3个月，观察组与对照组ATEC评分均较干预前明显下降，且观察组ATEC评分低于对照组（P<0.05）。干预前，观察组与对照组肠道菌群构成情况无明显差异；干预后3个月，观察组与对照组肠道菌群构成情况存在明显差异。观察组双歧杆菌属、乳杆菌属、粪杆菌属、瘤胃菌属、普雷沃菌属、布劳特菌属的相对丰度明显高于对照组（P<0.05），志贺氏菌属、梭状菌属的相对丰度明显低于对照组（P<0.05）。结论益生菌可能通过调节肠道菌群微生态进一步改善传统ABA治疗儿童ASD的疗效。     

Sensitivity of the denaturing gradient gel electrophoresis technique in detection of known mutations and novel Asian mutations in the CFTR gene

More than 500 mutations have been identified in the CFTR gene, making it an excellent system for testing mutation scanning techniques. To assess the sensitivity of denaturing gradient gel electrophoresis (DGGE), we collected a representative group of 202 CFTR mutations. All mutations analyzed were detected by scanning methods other than the DGGE approach evaluated in this study. DGGE analysis was performed on 24 of the 27 exons and their flanking splice site sequences. After optimization, 201 of the 202 control samples produced an altered migration pattern in the region in which an alteration occurred. The remaining sample was sequenced and found not to have the reported mutation. The ability of DGGE to identify novel mutations was evaluated in three Asian CF patients with four unknown CF alleles. Three novel Asian mutations were detected—K166E, L568X, and 3121-2 A→G (in homozygosity)—accounting for all CF alleles. These results indicate that an optimized DGGE scanning strategy is highly sensitive and specific and can detect 100% of mutations. Hum Mutat 9:136–147, l997. © 1997 Wiley-Liss, Inc.     

间变性淋巴瘤激酶抑制剂不良反应管理西南专家建议（2021年版）

间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）融合基因作为肿瘤驱动基因，对非小细胞肺癌（non-small cell lung cancer, NSCLC）的发生和发展至关重要，而靶向ALK融合基因已成为ALK阳性NSCLC患者的主要治疗手段。第一、二代ALK抑制剂（ALK inhibitor, ALKi）克唑替尼、塞瑞替尼、阿来替尼、恩沙替尼已在中国上市并广泛应用。然而，针对ALKi不良反应尚无统一的管理指导规范，在一定程度上降低甚至限制了ALKi的临床使用及患者获益。本文由四川省肿瘤学会肺癌专业委员会及四川省肿瘤性疾病医疗质量控制中心牵头，针对国内已经获批上市的ALKi，参考国内外临床研究和相关文献，并结合专家实践经验，总结出《ALKi不良反应管理专家建议（2021年版）》，以期为临床提供切实可行的ALKi不良反应的管理策略。