2018年 · 第131卷第22期

出版日期 2018-11-20电子版￥0.00元

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Editorial

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慢性肾脏病大数据研究

Xiao-Xi Zeng, Jing Liu, Liang Ma, Ping Fu

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245275

摘要

Original Article

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基于低温机灌注变量的肾移植延迟移植物功能预测评分模型

Chen-Guang Ding, Yang Li, Xiao-Hui Tian, Xiao-Jun Hu, Pu-Xun Tian, Xiao-Ming Ding, He-Li Xiang, Jin Zheng, Wu-Jun Xue

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245278

摘要

Background: Hypothermic machine perfusion (HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function (DGF) by HMP parameters is still controversial. Therefore, we used a readily available HMP variable to design a scoring model that can identify the highest risk of DGF and provide the guidance and advice for organ allocation and DCD kidney assessment. Methods: From September 1, 2012 to August 31, 2016, 366 qualified kidneys were randomly assigned to the development and validation cohorts in a 2:1 distribution. The HMP variables of the development cohort served as candidate univariate predictors for DGF. The independent predictors of DGF were identified by multivariate logistic regression analysis with a P < 0.05. According to the odds ratios (ORs) value, each HMP variable was assigned a weighted integer, and the sum of the integers indicated the total risk score for each kidney. The validation cohort was used to verify the accuracy and reliability of the scoring model. Results: HMP duration (OR = 1.165, 95% confidence interval [CI]: 1.008–1.360, P = 0.043), resistance (OR = 2.190, 95% CI: 1.032–10.20, P < 0.001), and flow rate (OR = 0.931, 95% CI: 0.894–0.967, P = 0.011) were the independent predictors of identified DGF. The HMP predictive score ranged from 0 to 14, and there was a clear increase in the incidence of DGF, from the low predictive score group to the very high predictive score group. We formed four increasingly serious risk categories (scores 0–3, 4–7, 8–11, and 12–14) according to the frequency associated with the different risk scores of DGF. The HMP predictive score indicates good discriminative power with a c-statistic of 0.706 in the validation cohort, and it had significantly better prediction value for DGF compared to both terminal flow (P = 0.012) and resistance (P = 0.006). Conclusion: The HMP predictive score is a good noninvasive tool for assessing the quality of DCD kidneys, and it is potentially useful for physicians in making optimal decisions about the organs donated.

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二肽基肽酶-4抑制剂联合血管紧张素受体阻滞剂对2型糖尿病肾病患者的肾脏保护作用

Dan-Dan Qiu, Jing Liu, Jing-Song Shi, Yu An, Yong-Chun Ge, Min-Lin Zhou, Song Jiang

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245277

摘要

Background: Treatment with the dipeptidyl peptidase-4 inhibitors (DPP4i) and angiotensin receptor blockers (ARBs) in patients with type 2 diabetic nephropathy (DN) has not been well characterized. This study aimed to assess the renoprotection of this combined treatment in DN patients. Methods: A total of 159 type 2 DN patients from 2013 to 2015 were enrolled retrospectively from a prospective DN cohort at the National Clinical Research Center of Kidney Diseases, Jinling Hospital (China). Fifty-seven patients received DPP4i and ARB treatment, and 102 patients were treated with ARBs alone. All patients were followed up for at least 12 months. Statistical analyses were performed using Stata version 12.0. Results: There were no significant differences at baseline for age, sex, body mass index, duration of diabetes, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR) between the two groups. Antihypertensive and antidiabetic medication use was similar in each group except calcium channel antagonists (P = 0.032). No significant changes in FBG and HbA1c were observed in the two groups after treatment. The eGFR decreased slower in the DPP4i + ARB group than in the ARB group at 12 months (∆12 months: -2.48 ± 13.86 vs. -6.81 ± 12.52 ml·min–1·1.73m–2, P = 0.044). In addition, proteinuria was decreased further in the DPP4i + ARB group than in the ARB group after 24 months of treatment (∆24 months: -0.18 [-1.00, 0.17] vs. 0.32 [-0.35, 0.88], P = 0.031). There were 36 patients with an eGFR decrease of more than 30% over 24 months. After adjusting for FBG, HbA1c, and other risk factors, DPP4i + ARB treatment was still associated with a reduced incidence of an eGFR decrease of 20% or 30%. Conclusions: The combined treatment of DPP4i and ARBs is superior to ARBs alone, as evidenced by the greater proteinuria reduction and lower eGFR decline. In addition, the renoprotection of DPP4i combined with ARBs was independent of glycemic control.

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辅酶Q的新突变₁₀单加氧酶6引起局灶节段性肾小球硬化患者足细胞损伤

Cheng-Cheng Song, Quan Hong, Xiao-Dong Geng, Xu Wang, Shu-Qiang Wang, Shao-Yuan Cui, Man-Di Guo, Ou Li, Guang-Yan Cai, Xiang-Mei Chen 等

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245158

摘要

Background: Focal segmental glomerulosclerosis (FSGS) is a kidney disease that is commonly associated with proteinuria and the progressive loss of renal function, which is characterized by podocyte injury and the depletion and collapse of glomerular capillary segments. The pathogenesis of FSGS has not been completely elucidated; however, recent advances in molecular genetics have provided increasing evidence that podocyte structural and functional disruption is central to FSGS pathogenesis. Here, we identified a patient with FSGS and aimed to characterize the pathogenic gene and verify its mechanism. Methods: Using next-generation sequencing and Sanger sequencing, we screened the causative gene that was linked to FSGS in this study. The patient’s total blood RNA was extracted to validate the messenger RNA (mRNA) expression of coenzyme Q10 monooxygenase 6 (COQ6) and validated it by immunohistochemistry. COQ6 knockdown in podocytes was performed in vitro with small interfering RNA, and then, F-actin was determined using immunofluorescence staining. Cell apoptosis was evaluated by flow cytometry, the expression of active caspase-3 was determined by Western blot, and mitochondrial function was detected by MitoSOX. Results: Using whole-exome sequencing and Sanger sequencing, we screened a new causative gene, COQ6, NM_182480: exon1: c.G41A: p.W14X. The mRNA expression of COQ6 in the proband showed decreased. Moreover, the expression of COQ6, which was validated by immunohistochemistry, also had the same change in the proband. Finally, we focused on the COQ6 gene to clarify the mechanism of podocyte injury. Flow cytometry showed significantly increased in apoptotic podocytes, and Western blotting showed increases in active caspase-3 in si-COQ6 podocytes. Meanwhile, reactive oxygen species (ROS) levels were increased and F-actin immunofluorescence was irregularly distributed in the si-COQ6 group. Conclusions: This study reported a possible mechanism for FSGS and suggested that a new mutation in COQ6, which could cause respiratory chain defect, increase the generation of ROS, destroy the podocyte cytoskeleton, and induce apoptosis. It provides basic theoretical basis for the screening of FSGS in the future.

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适度提高低温机灌注压对心源性死亡肾移植术后供体的有益作用

Chen-Guang Ding, Pu-Xun Tian, Xiao-Ming Ding, He-Li Xiang, Yang Li, Xiao-Hui Tian, Feng Han, Qian-Hui Tai, Qian-Long Liu, Jin Zheng 等

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245274

摘要

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托法替尼在中国类风湿关节炎患者中的疗效和安全性

Zhan-Guo Li, Yi Liu, Hu-Ji Xu, Zhi-Wei Chen, Chun-De Bao, Jie-Ruo Gu, Dong-Bao Zhao, Yuan An, Lie-Ju Hwang, Lisy Wang 等

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245157

摘要

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies. Methods: ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout. Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population. Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population. Clinical Trial Identifier: NCT00856544 and NCT00413699.

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中国宫腔镜患者镇痛伤害感受指数评价CYP3A4*1G多态性对芬太尼镇痛的影响

Qi Yan, Yi Su, Lan Gao, Nan Ding, Hong-Ying Zhang, Wen E, Yue Wang, Yi Feng, Hai-Yan An

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.243934

摘要

Background: The clinical efficacy of fentanyl for pain control differs greatly across individuals. The purpose of this study was to investigate the impact of CYP3A4*1G polymorphism including wild-type homozygote (CYP3A4*1/*1, GG), mutant heterozygote (CYP3A4*1/*1G, GA), and mutant homozygote (CYP3A4*1G/*1G, AA) on fentanyl analgesia in Chinese patients undergoing hysteroscopy by the assessment of analgesia nociception index (ANI). Methods: A total of 200 gynecologic patients scheduled for elective hysteroscopy under general anesthesia at Peking University People’s Hospital from May to December in 2017 were enrolled in this study. Venous blood was withdrawn for genotyping of CYP3A4*1G before operation. Fentanyl 1 µg/kg was administered preoperatively followed by target-controlled infusion of propofol for induction and maintenance. Intraoperative analgesic efficacy of fentanyl was assessed by ANI monitoring at T0 (entering room), T1 (cervical dilation), T2 (start of cervical aspiration), and T3 (end of cervical aspiration) time points. The duration of propofol infusion and total dosage of propofol were recorded as well. Results: The patients were divided into three groups according to CYP3A4*1G polymorphism, including 143 in GG group, 47 in GA group, and 10 in AA group. There was no significant difference in clinical demographics among three groups. The frequency of CYP3A4*1G variant alleles accounted for 16.8% and the distribution of variant alleles was consistent with Hardy–Weinberg equilibrium. Using a multilevel model, ANI values at T1 (63.81 ± 19.61), T2 (63.63 ± 17.82), and T3 (65.68 ± 17.79) were significantly lower than that at T0 (77.16 ± 12.93) in the study population (F = 23.50, P < 0.001), suggesting that higher levels of pain at T1, T2, and T3 than T0. Patients with GG genotype showed significantly lower ANI than those with GA or AA genotypes during hysteroscopy under the same dose of fentanyl. Conclusion: CYP3A4*1G polymorphism associated with the analgesic efficacy of intraoperative fentanyl in the patients undergoing hysteroscopy under general anesthesia.

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中国经皮冠状动脉介入治疗人群中支架置入患者抗血小板治疗不依从模式对血栓风险评分预测价值的验证：一项前瞻性观察研究

Xue-Yan Zhao, Jian-Xin Li, Xiao-Fang Tang, Jing-Jing Xu, Ying Song, Lin Jiang, Jue Chen, Lei Song, Li-Jian Gao, Zhan Gao 等

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245263

摘要

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13例中国Leigh综合征线粒体DNA突变患者的临床、神经影像学和病理学分析

Xiao-Lin Yu, Chuan-Zhu Yan, Kun-Qian Ji, Peng-Fei Lin, Xue-Bi Xu, Ting-Jun Dai, Wei Li, Yu-Ying Zhao

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245265

摘要

Background: Leigh syndrome (LS) is a rare disease caused by mitochondrial defects and has high phenotypic and genotypic heterogeneity. We analyzed the clinical symptoms, neuroimaging, muscular histopathology, and genotypes of 13 Chinese LS patients with mitochondrial DNA (mtDNA) mutations. Methods: Mutations in mtDNA were identified by targeted sequencing. The brain imaging features on magnetic resonance imaging (MRI) were analyzed. The levels of lactate in fasting blood and cerebrospinal fluid (CSF) were routinely tested. The levels of urinary organic acids, plasma amino acids, and acylcarnitines were examined with gas chromatography–mass spectrometry and tandem mass spectrometry. The histopathological traits of skeletal muscles were analyzed under microscope. Results: Among 13 patients, mutations of MT-NDs (n = 8) and MT-ATP6 (n = 4) genes were most common. Strabismus (8/13), muscle weakness (8/13), and ataxia (5/13) were also common, especially for the patients with late-onset age after 2 years old. However, respiratory distress was common in patients with early-onset age before 2 years old. The most frequently affected brain area in these patients was the brain stem (12/13), particularly the dorsal part of midbrain, followed by basal ganglia (6/13), thalamus (6/13), cerebellum (5/13), and supratentorial white matter (2/13). Besides, the elevated lactate levels in CSF (6/6) were more common than those in serum (7/13). However, the analysis of abnormal plasma amino acid and urinary organic acid showed limited results (0/3 and 1/4, respectively). Muscular histopathology showed mitochondrial myopathy in the three late-onset patients but not in the early-onset ones. Conclusions: Noninvasive genetic screening is recommended for mtDNA mutations in MT-NDs and MT-ATP6 genes in patients with ophthalmoplegia, muscle weakness, ataxia, and respiratory disorder. Furthermore, the lactate detection in CSF and the brain MRI scanning are suggested as the diagnosis methods for LS patients with mtDNA mutations.

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嘌呤能2 × 7受体通过激活核苷酸结合和寡聚结构域样受体蛋白3炎症小体参与肥胖相关肾小球病的足细胞损伤

Xiao-Xia Hou, Hong-Rui Dong, Li-Jun Sun, Min Yang, Hong Cheng, Yi-Pu Chen

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245270

摘要

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缺氧诱导的内皮微粒通过递送MicroRNA-19b对人脐静脉内皮细胞迁移和血管生成的影响

Hui-Zhu Liang, Su-Fang Li, Feng Zhang, Man-Yan Wu, Chang-Long Li, Jun-Xian Song, Chongyou Lee, Hong Chen

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245271

摘要

Background: Microparticles (MPs) are small extracellular plasma membrane particles shed by activated and apoptotic cells, which are involved in the development of atherosclerosis. Our previous study found that microRNA (miR)-19b encapsulated within endothelial MPs (EMPs) may contribute to the upregulation of circulating miR-19b in unstable angina patients. Hypoxia is involved in atherosclerosis as a critical pathological stimulus. However, it still remains unclear whether the increase of miR-19b levels in EMPs is related to hypoxia and if the effect of miR-19b - wrapped within EMPs - stimulates hypoxia on vascular endothelial cells. This study aimed to explore the changes of miR-19b in EMPs induced by hypoxia as well as their effects on endothelial cells. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and arranged to harvest EMPs in two parts: the first part consisted of EMPcontrol and EMPhypoxia and the second part included EMPvehicle, EMPNC mimic, and EMPmiR-19b mimic. Cell migration was detected by scratch migration and transwell chamber migration. Angiogenesis was assessed by tube formation assays. Furthermore, we predicted the target gene of miR-19b by bioinformatics analysis, and luciferase assay was used to verify the targeted gene of miR-19b. Data were analyzed by one-way analysis of variance. Student’s t-test was used when two groups were compared. Results: Compared with EMPcontrol- and EMPhypoxia-inhibited migration of cells by scratch migration assay (80.77 ± 1.10 vs. 28.37 ± 1.40, P < 0. 001) and transwell chamber migration assay (83.00 ± 3.46 vs. 235.00 ± 16.52, P < 0.01), the number of tube formations was markedly reduced by 70% in the EMPhypoxia group (P < 0.001) in vitro analysis of HUVECs. Meanwhile, a strong inhibition of migration and tube formation of HUVECs in the presence of miR-19b-enriched EMPmiR-19b mimic was observed. This effect might be due to the delivery of miR-19b in EMPs. Transforming growth factor-β2 (TGFβ2) was predicted to be one of the target genes of miR-19b, and we further confirmed that TGFβ2 was a direct target gene of miR-19b using the luciferase assay. The expression of TGFβ2 in HUVECs was inhibited by treatment with EMPhypoxia and EMPmiR-19b mimic . Conclusions: MiR-19b in EMPs induced by hypoxia could reduce endothelial cell migration and angiogenesis by downregulating TGFβ2 expression, which may have inhibited the progression of atherosclerosis.

Meta Analysis

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幽门螺杆菌感染与2型糖尿病患者蛋白尿的发生相关：一项系统综述和荟萃分析

Yan Shi, Jia-Yu Duan, Dong-Wei Liu, Ying-Jin Qiao, Qiu-Xia Han, Shao-Kang Pan, Li Tang, Guang-Yan Cai, Xiang-Mei Chen, Zhang-Suo Liu 等

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245269

摘要

Background: Type 2 diabetes (T2DM) patients are susceptible to Helicobacter pylori (HP), and it has been reported that the occurrence of proteinuria is associated with HP infection in T2DM patients; however, this view remains controversial. This meta-analysis aimed to explore the association between HP infection and the occurrence of proteinuria in T2DM patients. In addition, we hope to provide some recommendations to readers in clinical or related fields. Methods: Our meta-analysis was conducted with the methodology of the Cochrane Collaboration. Search strategies were formulated by relevant professionals. Case–control studies that compared the occurrence of proteinuria in T2DM patients with and without HP infection were involved in our meta-analysis. Relevant English or Chinese studies were searched on online databases before 2018, including PubMed, the Cochrane library, Medline, Google Scholar, the China National Infrastructure, and Wanfang database. The search strategies were "diabetic proteinuria, diabetic microalbuminuria, diabetic albuminuria, diabetic kidney disease, diabetic renal dysfunction, diabetic renal disease, diabetic nephropathy, diabetic complications, and diabetic mellitus, combined with HP." The quality of these involved articles was separately assessed by two investigators using the Newcastle–Ottawa Scale (NOS). Odds ratios (ORs) and associated 95% confidence intervals (CIs) were extracted and pooled using fixed-effects models. Results: Seven studies involving 1029 participants were included. The quality of these seven articles was all above five stars as assessed by NOS, and there was no significant publication bias in our meta-analysis. We found that T2DM patients with HP infection had a 2.00 times higher risk of the occurrence of proteinuria than patients without HP infection (OR: 2.00, 95% CI: 1.48–2.69). Conclusions: Our analysis showed that HP infection was associated with the occurrence of proteinuria in T2DM patients. HP radical surgery might be a therapeutic option for protecting kidney function in patients with T2DM.

Correspondence

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慢性肾脏病病理类型的统计预测

Mei-Fang Song, Zong-Wei Yi, Xue-Jing Zhu, Xue-Ling Qu, Chang Wang, Zai-Qi Zhang, Lin Sun, Fu-You Liu, Yuan Yang

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245273

摘要

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阿霉素诱导的局灶节段性肾小球硬化小鼠模型的血清代谢谱

Li Lyu, Cai-Li Wang, Zeng-Yan Li, Ying-Jin Shi, Yan-Hui Zhang, Yan Mi, Zhao Hu

中华医学杂志英文版2018年 131卷 22期

DOI: 10.4103/0366-6999.245266