Irgm1 knockout indirectly inhibits regeneration after skeletal muscle injury in mice

Immunity-related GTPase family M1 protein (lRGM1) plays an important role in host resistance to infection, immune inflammation, and tumors, and it is expressed in various tissues and cells, including the central nervous system, cardiovascular system, bone marrow-derived cells, glioma, and melanoma. However, the effect of IRGM1 in the muscles has not been reported to date. In this study, Irgm1^−/− mice were used to evaluate the effect of lrgm1 on regeneration after skeletal muscle injury. The tibialis anterior muscle in Irgm1^−/− mice was poorly repaired after BaCl₂-induced injury, whereas lrgm1 knockout itself had no significant effect on the differentiation of myoblasts. However, the microenvironment of Irgm1^−/− mice with a high interferon-gamma level inhibited the differentiation of myoblasts in vivo. These results suggest that lrgm1 knockout indirectly inhibits skeletal muscle regeneration after injury, providing new insights into the biological function of IRGM1.     

Germline variant burden in multidrug resistance transporters is a therapy-specific predictor of survival in breast cancer patients

Multidrug resistance due to facilitated drug efflux mediated by ATP-binding cassette (ABC) transporters is a main cause for failure of cancer therapy. Genetic polymorphisms in ABC genes affect the disposition of chemotherapeutics and constitute important biomarkers for therapeutic response and toxicity. Here we correlated germline variability in ABC transporters with disease-specific survival (DSS) in 960 breast cancer (BRCA), 314 clear cell renal cell carcinoma and 325 hepatocellular carcinoma patients. We find that variant burden in ABCC1 is a strong predictor of DSS in BRCA patients, whereas candidate polymorphisms are not associated with DSS. This association is highly drug-specific for subgroups treated with the MRP1 substrates cyclophosphamide (log-rank p = 0.0011) and doxorubicin (log-rank p = 0.0088) independent of age and tumor stage, whereas no association was found in individuals treated with tamoxifen (log-rank p = 0.13). Structural mapping of significant variants revealed multiple variants at residues involved in protein stability, cofactor stabilization or substrate binding. Our results demonstrate that BRCA patients with high variant burden in ABCC1 are less prone to respond appropriately to pharmacological therapy with MRP1 substrates, thus incentivizing the consideration of genomic germline data for precision cancer medicine.     

原发性肝淀粉样变1例报告并文献回顾

目的:报道1例原发性肝淀粉样变病例，提高该病的认识水平，减少误诊误治。方法:分析我院2015年03月诊治并经病理学确诊的肝淀粉样变1例，并结合国内外文献，对本病的临床表现、诊断、治疗及预后进行讨论分析。结果:患者临床表现为右上腹隐痛、腹胀、肝大；既往:1年前因脾破裂于我院肝胆外科行脾切除术；术后病理:（脾）内有较多出血，有血肿形成，周围脾白髓萎缩，红髓间质有玻璃样变性，符合陈旧性脾破裂伴血肿形成。肝功提示:碱性磷酸酶明显升高，白蛋白减低，球蛋白升高，肝脏CT示肝脏体积明显增大，肝脏实质强化不均匀，胆囊结石。肝穿刺组织病理活检:肝细胞索变性坏死，有炎细胞浸润，肝索内肝细胞间有粉染无结构物质，免疫组化染色结果:CD34(-)、刚果红染色(+)。结论:对肝淀粉样变缺乏诊治经验是该病误诊的原因之一，以腹痛、肝大为主要临床表现极易误诊为脂肪肝，肝硬化及原发性肝癌。当临床上遇到肝脏肿大明显伴碱性磷酸酶明显升高且与其他肝功生化指标变化不平行时，尤其合并多器官受累表现者，须警惕肝淀粉样变的可能，确诊的惟一方法是肝穿刺行组织病理检查，但应注意出血等并发症。     

活血利水法在骨伤科疾病中的应用

基于骨伤疾病瘀血内阻的重要病机和现代医家"治血重治水"的学术观点,探索概括了活血利水法在骨伤疾病中的应用现状,结合现代医学的认识,全方位分析了活血利水法的优势和缺点。活血利水法可应用于骨折、筋伤等骨伤科大部分疾病及骨伤科疾病的围手术期,能改善肢体肿胀,促进伤口愈合,便于患者早期功能康复,但目前的临床应用尚缺乏统一的规范和标准,且处方不良反应尚未完全阐明。     

谭新华从肝肾论治男科疾病临证经验

谭新华教授采用温肾补肝、益肾疏肝、填精消癥、养肾柔肝、补肾泻肝之法治疗男性不育症、勃起功能障碍、前列腺增生症、精索静脉曲张、慢性前列腺炎等男科疾病临床疗效显著。本文结合典型案例对谭教授从肝肾论治男科疾病经验进行总结。     

TACE 术前天冬氨酸氨基转移酶与淋巴细胞比值对原发性肝癌并门脉癌栓患者预后预测的价值

目的 探讨肝动脉化疗栓塞（transcatheter arterial chemoembolization，TACE）术前天冬氨酸氨基转移酶与淋巴细胞比值（aspartate aminotransferase to lymphocyte ratio index，ALRI）在原发性肝癌并门脉癌栓（primary liver cancer-portal vein tumor thrombosis，PLC-PVTT）患者预后预测中的价值。方法 选取2013年11月21日至2018年8月22日于广西医科大学附属肿瘤医院接受TACE治疗的175例PLC-PVTT患者为研究对象。采用时间依赖性ROC曲线确定ALRI的最佳临界值。采用Cox 回归模型分析总生存期（overall survival，OS）的独立预测因素，Kaplan-Meier法计算生存率。结果 ROC曲线显示，ALRI的最佳临界值为49.37，对应曲线下面积为0.71。Kaplan-Meier分析显示，ALRI>49.37的患者OS较ALRI≤49.37的患者短（P=0.003）。Cox 回归分析结果显示，ALRI>49.37、行1次以上TACE治疗、Child-Pugh分级B级、凝血酶原时间≥13 s是患者TACE术后OS的独立危险因素（均P＜0.05）。结论 TACE术前ALRI>49.37是PLC-PVTT患者OS的独立危险因素。     

Hepcidin – Potential biomarker of contrast-induced acute kidney injury in patients undergoing percutaneous coronary interventions

PurposeContrast-induced acute kidney injury (CI-AKI) is a common and potentially serious complication of percutaneous coronary interventions (PCI). In this study, we tested the hypothesis whether serum and urinary hepcidin could represent early biomarkers of CI-AKI in patients with normal serum creatinine undergoing PCI. In addition, we assessed serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, eGFR and serum creatinine in these patients.MethodsSerum and urinary hepcidin and NGAL, serum cystatin C, were evaluated before, and after 2, 4, 8, 24 and 48 h after PCI using commercially available kits. Serum creatinine was assessed before, 24 and 48 h after PCI.ResultsWe found a significant rise in serum hepcidin as early as after 4 and 8 h when compared to the baseline values. Serum NGAL increased after 2, 4 and 8 h, and in urinary NGAL after 4, 8 and 24 h after PCI. We found a significant fall in urinary hepcidin after 8 and 24 h after PCI. Serum cystatin C increased significantly 8 h after PCI, reaching peak 24 h after PCI and then decreased after 48 h. The prevalence of CI-AKI was 8%. Urine hepcidin was significantly lower 8 and 24 h after PCI in patients with CI-AKI, while serum and urine NGAL were significantly higher in patients with CI-AKI.ConclusionsOur findings suggest that serum hepcidin might be an early predictive biomarker of ruling out CI-AKI after PCI, thereby contributing to early patient risk stratification. However, our data needs to be validated in large cohorts with various stages of CKD.     

Heterologous fibrin sealant potentiates axonal regeneration after peripheral nerve injury with reduction in the number of suture points

The use of suture associated with heterologous fibrin sealant has been highlighted for reconstruction after peripheral nerve injury, having the advantage of being safe for clinical use. In this study we compared the use of this sealant associated with reduced number of stitches with conventional suture after ischiatic nerve injury. 36 Wistar rats were divided into 4 groups: Control (C), Denervated (D), ischiatic nerve neurotmesis (6 mm gap); Suture (S), epineural anastomosis after 7 days from neurotmesis, Suture + Fibrin Sealant (SFS), anastomosis with only one suture point associated with Fibrin Sealant. Catwalk, electromyography, ischiatic and tibial nerve, soleus muscle morphological and morphometric analyses were performed. The amplitude and latency values of the Suture and Suture + Fibrin Sealant groups were similar and indicative of nerve regeneration.The ischiatic nerve morphometric analysis in the Suture + Fibrin Sealant showed superior values related to axons and nerve fibers area and diameter when compared to Suture group. In the Suture and Suture + Fibrin Sealant groups, there was an increase in muscle weight and in fast fibers frequency, it was a decrease in the percentage of collagen compared to group Denervated and in the neuromuscular junctions, the synaptic boutons were reestablished.The results suggest a protective effect at the lesion site caused by the fibrin sealant use. The stitches reduction minimizes the trauma caused by the needle and it accelerates the surgical practice. So the heterologous fibrin sealant use in nerve reconstruction should be considered.     

Impaired self-awareness after traumatic brain injury: a systematic review. Part 1: Assessment,clinical aspects and recovery

BackgroundImpaired self-awareness (ISA) has frequently been found to be both frequent and deleterious in patients with moderate to severe traumatic brain injury (TBI).ObjectivesThe present paper is the first of a two-part systematic review of ISA after traumatic brain injury (TBI), focusing on assessment methods, clinical aspects and recovery.MethodsFollowing the PRISMA guidelines, 95 articles meeting the inclusion criteria were included.ResultsISA occurs in 30% to 50% of patients with moderate to severe TBI, although it tends to improve with time. There is no one single gold-standard measure of ISA. Self-proxy discrepancy scores, with scales such as the Patient Competency Rating Scale or the Awareness Questionnaire, or a structured interview such as the Self Awareness of Deficits Interview, are the most frequently used assessment methods, with adequate psychometric properties. Scores on these different scales correlate only moderately with each other, which suggests that they may address different aspects of self-awareness. ISA mainly concerns cognitive and behavioral problems rather than physical or sensory impairments and may concern different areas of functioning, such as anticipatory, emergent or meta-cognitive awareness.ConclusionISA is a complex and multifaceted issue that should be systematically assessed in rehabilitation settings using a range of relatively well-validated tools. The consequences and predictors of ISA after TBI will be addressed in a companion paper.