Successful Treatment for BK Virus Nephropathy by Leflunomide in a Kidney Transplant Patient: A Case Report

IntroductionThe immunosuppressant agents in kidney transplantation (KT) may lead to various complications such as opportunistic infections and malignancies. BK virus associated nephropathy is a significant complication following KT, and it can result in graft failure. BK virus causes tubulointerstitial nephritis, ureter stenosis, and even graft failure in KT recipients with impaired immune system. We described a 63-year-old woman, who was a hepatitis C carrier and on dialysis for 22 years before KT, who received cadaveric-donor KT 2 years previously. She reported decreasing urine output and general weakness. The serum creatinine level was slightly increased from 2.94 to 4.38 mg/dL.MethodsImmunosuppressant medications including prednisolone, everolimus, cyclosporin, and mycophenolate sodium were continued as maintenance therapy post KT. Kidney biopsy was performed due to deterioration of graft function.ResultsThe kidney biopsy showed consistent results with early-stage polyomavirus nephropathy, characterized by focal viral cytopathic changes with positive immunohistochemical signals and mesangial proliferative glomerulonephritis, immune-complex-mediated (Fig 1 and Fig 2). Negative C4d staining at peritubular capillary was reported. The dosage of mycophenolate sodium was tapered from 720 to 360 mg daily and that of everolimus increased from 0.5 to 1.0 mg daily due to BK viral infection with BK nephropathy. The serum creatinine level was 2.75 mg/dL after treatment.ConclusionEarly detection of BK nephropathy and decreasing immunosuppressant agents are the mainstay of treatment. Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy. We presented that the use of leflunomide in such situation is in a timely manner.     

从“肾毒”论治慢性肾脏病＊

慢性肾脏病是一种以肾脏功能的损伤为主要表现，并可累及全身多脏器的慢性进展性疾病。中医辨证治疗本病在延缓病情、改善预后等方面具有显著的优势。通过中医理论研究及临床经验总结，笔者提出从“肾毒”论治慢性肾脏病，认为其不仅是本病的致病因素，更是重要的病理产物，是本病发生发展、迁延难愈的关键。在治疗上提出以“益肾元、解肾毒”为大法，并根据不同兼夹辨证施治，采用药对，长治缓图。以“肾毒”立论拟定的经验方苏茵解毒方，在临床治疗和实验研究上均显示出明显的效果，并已制备成院内制剂临床使用，在疗效及经济效益方面均具有显著的优势。     

RNA sequencing screening of differentially expressed genes after spinal cord injury

In the search for a therapeutic schedule for spinal cord injury, it is necessary to understand key genes and their corresponding regulatory networks involved in the spinal cord injury process. However, ad hoc selection and analysis of one or two genes cannot fully reveal the complex molecular biological mechanisms of spinal cord injury. The emergence of second-generation sequencing technology(RNA sequencing) has provided a better method. In this study, RNA sequencing technology was used to analyze differentially expressed genes at different time points after spinal cord injury in rat models established by contusion of the eighth thoracic segment. The numbers of genes that changed significantly were 944, 1362 and 1421 at 1, 4 and 7 days after spinal cord injury respectively. After gene ontology analysis and temporal expression analysis of the differentially expressed genes, C5ar1, Socs3 and CCL6 genes were then selected and identified by real-time polymerase chain reaction and western blot assay. The mRNA expression trends of C5ar1, Socs3 and CCL6 genes were consistent with the RNA sequencing results. Further verification and analysis of C5ar1 indicate that the level of protein expression of C5ar1 was consistent with its nucleic acid level after spinal cord injury. C5ar1 was mainly expressed in neurons and astrocytes. Finally, the gene Itgb2,which may be related to C5ar1, was found by Chilibot database and literature search. Immunofluorescence histochemical results showed that the expression of Itgb2 was highly consistent with that of C5ar1. Itgb2 was expressed in astrocytes. RNA sequencing technology can screen differentially expressed genes at different time points after spinal cord injury. Through analysis and verification, genes strongly associated with spinal cord injury can be screened. This can provide experimental data for further determining the molecular mechanism of spinal cord injury, and also provide possible targets for the treatment of spinal cord injury. This study was approved ethically by the Laboratory Animal Ethics Committee of Jiangsu Province, China(approval No. 2018-0306-001) on March 6, 2018.     

基于代谢组学探讨艾灸关元穴对老年大鼠肾能量代谢的影响＊

目的 通过UHPLC-Q-TOF-MS代谢组学探讨艾灸关元穴对老年大鼠肾代谢物的影响，进而为艾灸关元穴的作用机制提供参考。方法 将8月龄SD雄性大鼠设为成年对照组（8只），21月龄SD雄性大鼠随机分为老年对照组（8只）、老年金匮肾气丸组（7只）、老年艾灸组（8只）。老年金匮肾气丸组每日按体重给药，老年艾灸组每日艾灸关元穴15 min，均每周5天。实验持续13周后检测大鼠肾组织线粒体呼吸耗氧速率、琥珀酸脱氢酶（SDH）活性以及血清肾功能指标，观察肾脏病理变化，结合UHPLC-Q-TOF-MS技术对大鼠的肾组织进行代谢轮廓分析，筛选代谢差异物并进行鉴定。结果 与老年对照组比较，老年艾灸组大鼠肾线粒体的呼吸耗氧速率和SDH酶的活力显著提高（P<0.01）。代谢组学结果显示，肾组织中筛选出13个共同差异化合物，分别是丁酸十二烷基酯、亚油酰胺、5-甲基四氢叶酸、PC（16∶0/22∶5（7Z，10Z，13Z，16Z，19Z））、6，8-二羟基嘌呤、1，2，3-丙烷三羧酸、3-（4-甲氧基苯基）-2-氧代丙酸、吲哚-3-乙酰甘氨酸、亚麻油酸、9，10-环氧十八烷酸、二十二碳五烯酸（22n-6）、牛磺胆酸、LysoPS （18∶0/0∶0）。结论 艾灸关元穴可通过调控老年大鼠的牛磺酸和亚牛磺酸代谢、α-亚麻酸代谢、亚油酸代谢、甘油磷脂代谢来调节肾的能量代谢。     

Review of clinical characteristics,immune responses and regulatory mechanisms of hepatitis E-associated liver failure

Hepatitis E virus (HEV) is the most common cause of acute liver failure (LF) and one of the most common factors causing acute injury in acute-on-chronic LF (ACLF). When HEV-related LF occurs, a series of changes take place in both the intrahepatic environment and extrahepatic microenvironment. The changed types and distribution of immune cells (infiltrating macrophages and increased lymphocytes) in liver tissue, as well the increased proinflammatory cytokines and chemokines in the blood, indicate that the occurrence and progression of HEV-related LF are closely related to immune imbalance. The clinical features and immune reaction in the body during HEV-related acute LF (ALF) and ACLF are complicated. This review highlights recent progress in elucidating the clinical manifestations of HEV-associated ALF and ACLF and discusses the corresponding systemic immune changes and possible regulatory mechanisms.     

经鼻高流量氧气湿化治疗老年慢性阻塞性肺疾病急性加重合并呼吸衰竭的可行性研究

ObjectiveTo investigate the feasibility of transnasal heated humidified high flow nasal cannula oxygen therapy (HFNC) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with respiratory failure in elderly patients. MethodsA total of 176 elderly patients with AECOPD complicated with respiratory failure who were hospitalized at Peking University Shougang Hospital from December 2016 to January 2022 were enrolled, including 82 patients in an HFNC group and 94 patients in an NPPV group. After treatment, pulse oxygen saturation (SPO₂), arterial partial pressure of carbon dioxide (PaCO₂), oxygenation index (OI), respiratory rate (RR), heart rate (HR), mean arterial pressure (MAP), comfort score, discharge rate, rate of endotracheal intubation, rate of transfer to intensive care unit (ICU), and mortality were compared between the two groups. The independent sample t-test was used for comparison between the two groups. Statistical data are expressed in percentage or number of cases and the χ² test was used for their comparisons. ResultsThe SPO₂ values at 30 min, 1 h, and 6 h were significantly higher in the HFNC group than in the NPPV group (t=-2.049,-2.618, and -3.314, P=0.043, 0.010, and 0.001, respectively). SPO₂ before discharge was significantly lower than that of the NPPV group (t=2.162, P=0.033), but OI at each time point and before discharge had no statistical significance (P＞0.05). MAP at 6 h was significantly higher in the HFNC group than in the NPPV group (t=-2.209, P=0.029), but within the normal range. HRs at 2 h and 3 h in the HFNC group were significantly higher than those of the NPPV group (t=-2.199 and -2.336, P=0.030 and 0.021, respectively). There were no significant differences in RR, HR, or MAP between the two groups at other time points and before discharge (P＞0.05). There was no significant difference in PaCO2 between the two groups (P＞0.05). Comfort score in the HFNC group was significantly higher than that of the NPPV group (t=-46.807, P＜0.001). There were no significant differences in discharge rate, ICU transfer rate, endotracheal intubation rate, and mortality between the two groups (P＞0.05). ConclusionHFNC is as effective as NPPV in treating elderly patients with AECOPD complicated with type Ⅰ or mild type Ⅱ respiratory failure, and HFNC is more comfortable than NPPV.     

Identification of key genes and pathways in discoid lupus skin via bioinformatics analysis

Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus; however, the molecular mechanisms underlying DLE remain unknown. Therefore, we aimed to identify key differentially expressed genes (DEGs) in discoid lupus skin and investigate their potential pathways.To identify candidate genes involved in the occurrence and development of the disease, we downloaded the microarray datasets {"type":"entrez-geo","attrs":{"text":"GSE52471","term_id":"52471"}}GSE52471 and {"type":"entrez-geo","attrs":{"text":"GSE72535","term_id":"72535"}}GSE72535 from the Gene Expression Database (GEO). DEGs between discoid lupus skin and normal controls were selected using the GEO2R tool and Venn diagram software (http://bioinformatics.psb.ugent.be/webtools/Venn/). The Database for Annotation, Visualization, and Integrated Discovery (DAVID), Enrichr, and Cytoscape ClueGo were used to analyze the Kyoto Encyclopedia of Gene and Genome pathways and gene ontology. Protein-protein interactions (PPIs) of these DEGs were further assessed using the Search Tool for the Retrieval Interacting Genes version 10.0.Seventy three DEGs were co-expressed in both datasets. DEGs were predominantly upregulated in receptor signaling pathways of the immune response. In the PPI network, 69 upregulated genes were selected. Furthermore, 4 genes (CXCL10, ISG15, IFIH1, and IRF7) were found to be significantly upregulated in the RIG-I-like receptor signaling pathway, from analysis of Enrichr and Cytoscape ClueGo.The results of this study may provide new insights into the potential molecular mechanisms of DLE. However, further experimentation is required to confirm these findings.     

玻璃体切割联合内界膜剥除治疗糖尿病性黄斑水肿

评估玻璃体切割联合内界膜剥除对糖尿病性黄斑水肿（DME）的疗效。方法：回顾性病例对照研究。2014年6月至2017年1月间因糖尿病视网膜病变合并玻璃体积血或增殖病变于温州医科大学附属眼视光医院杭州院区行玻璃体切割手术治疗，且术前或术中经光学相干断层扫描（OCT）检查确诊合并DME的患者31例（33眼）纳入研究。16例（18眼）术中联合内界膜剥除作为剥膜组，15例（15眼）仅接受玻璃体切割手术治疗者作为对照组。所有手术均由同一医师主刀完成。术后1、3个月随访时复查OCT，对比观察黄斑中心厚度（CMT）和视力的术后变化情况。随访中CMT和最佳矫正视力（BCVA）比较采用重复测量方差分析，组间CMT和BCVA比较采用独立样本t检验。结果：手术前，手术后1、3个月2组间比较LogMAR视力总体差异有统计学意义（F=15.93，P<0.001）。术后 1个月时剥膜组BCVA高于对照组（t=2.55，P=0.02），但术后3个月时2组间差异无统计学意义（t=0.82， P=0.42）。手术前，手术后1、3个月CMT总体差异无统计学意义（F=2.85，P=0.065）。术后1、3个月时，剥膜组的CMT均低于对照组，2组间差异均有统计学意义（t=2.24，P=0.03；t=3.79，P=0.001）。术后1个月时，剥膜组有效（与术前比CMT减少20%以上）、无效（变化不超过20%）及恶化（增厚超过 20%）的例数分别为8、6、4例，术后3个月时则分别为11、5、2例，与对照组相比，术后1个月时组间差异无统计学意义（Z=-1.687，P=0.092），术后3个月时剥膜组DME改善有效比例明显高于对照组，组间差异有统计学意义（Z=-2.177，P=0.029）。结论：对于非牵拉性DME，内界膜剥除有助于术后早期DME消退。