Volume 131 · Issue 22 · 2018

慢性肾脏病(CKD)是一种主要的非传染性疾病，其全球患病率估计为8-16%：它极大地导致过早死亡和残疾调整生命年的损失。^[1,2]病因、进展机制和组织病理学表现的多样性给CKD的早期诊断和有效干预带来了挑战。^[3]此外，CKD是卫生资源的主要消耗：2015年，CKD和终末期肾病（ESRD）花费医疗保险（美国）超过980亿美元。^[4]由于慢性肾病的日益流行，中国也面临着巨大的经济负担。

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.

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.

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).

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.

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.

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.

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%.

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.

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.

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.

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.

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.

Vascular resistance and flow rate during hypothermic machine perfusion (HMP) of kidneys is correlated with graft function. We aimed to determine the effects of increasing HMP pressure versus maintaining the initial pressure on kidney transplantation outcomes.

We retrospectively reviewed the data of 76 primary transplantation patients who received HMP-preserved kidneys from 48 donors after cardiac death between September 1, 2013, and August 31, 2015. HMP pressure was increased from 30 to 40 mmHg (1 mmHg = 0.133 kPa) in kidneys with poor flow and/or vascular resistance (increased pressure [IP] group; 36 patients); otherwise, the initial pressure was maintained (constant pressure group; 40 patients). Finally, the clinical characteristics and transplantation outcomes in both groups were assessed.

Delayed graft function (DGF) incidence, 1-year allograft, patient survival, kidney function recovery time, and serum creatinine level on day 30 were similar in both groups, with improved flow and resistance in the IP group. Among patients with DGF, kidney function recovery time and DGF duration were ameliorated in the IP group. Multivariate logistic regression analysis revealed that donor hypertension (odds ratio [OR]: 1.43, 95% confidence interval [CI]: 1.02–2.06, P = 0.035), donor terminal serum creatinine (OR: 1.27, 95% CI: 1.06–1.62, P = 0.023), warm ischemic time (OR: 3.45, 95% CI: 1.97–6.37, P = 0.002), and terminal resistance (OR: 3.12, 95% CI: 1.76–6.09, P = 0.012) were independent predictors of DGF. Cox proportional hazards analysis showed that terminal resistance (hazard ratio: 2.06, 95% CI: 1.32–5.16, P = 0.032) significantly affected graft survival.

Increased HMP pressure improves graft perfusion but does not affect DGF incidence or 1-year graft survival.

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.

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.

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.

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.

NCT00856544 and NCT00413699.

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).

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.

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.

CYP3A4*1G polymorphism associated with the analgesic efficacy of intraoperative fentanyl in the patients undergoing hysteroscopy under general anesthesia.

The patterns of nonadherence to antiplatelet regimen in stented patients (PARIS) thrombotic risk score are a novel score for predicting the risk of coronary thrombotic events (CTEs) after percutaneous coronary intervention (PCI) with drug-eluting stents. However, the prognostic value of this score has not been fully evaluated in non-Euro-American PCI populations.

We performed a prospective, observational study of 10,724 patients who underwent PCI in Fuwai hospital, China and evaluated the PARIS thrombotic risk score’s predictive value of CTEs in the PCI population. The area under the receiver operating characteristic curve (AUROC) was used to assess the predictive value of the PARIS score for CTE.

Among 9782 patients without in-hospital events, a total of 95 CTEs occurred during the 2-year follow-up. The PARIS score was significantly higher in patients with CTEs (3.38 ± 2.04) compared with patients without events (2.53 ± 1.70, P < 0.001). According to the risk stratification of the PARIS thrombotic score, the risk of CTEs in the high-risk group was 3.14 times higher than that in the low-risk group (hazard ratio [HR], 3.14; 95% confidence interval [CI], 1.92–5.13; P < 0.001). However, the risk of CTEs in the intermediate-risk and low-risk groups was not significant (HR, 1.39; 95% CI, [0.86–2.24]; P = 0.184). The PARIS score showed prognostic value in evaluating CTEs in the overall population (AUROC, 0.621; 95% CI, 0.561–0.681), the acute coronary syndrome (ACS) population (AUROC, 0.617; 95% CI, 0.534–0.700; P = 0.003), and the non-ACS population (AUROC, 0.647; 95% CI, 0.558–0.736; P = 0.001).

In a real-world Chinese population, the PARIS thrombotic risk score shows a modest prognostic value for CTEs in patients after PCI. This score also has a predictive value for CTEs in the ACS and non-ACS subgroup populations.

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.

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.

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.

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.

The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R). This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation of NLRP3 inflammasome.

A mouse model of ORG was established by high-fat diet feeding. The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079). The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3, ASC, and caspase-1, as well as the podocyte-associated molecules including nephrin, podocin, and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Western blot analysis, respectively.

The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo, which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules. Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression of podocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro, and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.

P2X7R could trigger the activation of NLRP3 inflammasome, and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.

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.

Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and arranged to harvest EMPs in two parts: the first part consisted of EMP^control and EMP^hypoxia and the second part included EMP^vehicle, EMP^{NC mimic}, and EMP^{miR-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.

Compared with EMP^control- and EMP^hypoxia-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 EMP^hypoxia 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 EMP^{miR-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 EMP^hypoxia and EMP^{miR-19b mimic} .

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.

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.

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.

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).

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.

编者按：在中国，轻度病变肾病（MLN）、局灶节段性肾小球硬化（FSGS）、膜性肾病（MN）和IgA肾病（IgAN）等病理类型是慢性肾脏病（CKD）患者的常见类型。^[1]对于识别特殊的CKD病理类型，超声引导下经皮肾活检是肾脏科医生的重要诊断工具。临床上，部分患者会出现活检后并发症，如肾出血引起肉眼血尿、肾周血肿引起腰痛或腹痛，或轻度发热等。此外，一些CKD患者由于临床禁忌症而不可行进行肾活检。本文提出了一种通过临床指标的统计概率来评价或预测CKD病理类型的系统方法。该方法基于CKD患者的基本性质、临床特征和实验室结果的频率差异。本研究旨在从非创伤性统计学角度建立一种识别CKD病理类型的替代方法。

编者：局灶节段性肾小球硬化（FSGS）是终末期肾病的主要原因之一。^[1,2]然而，由于生理病理机制尚不清楚，没有理想的干预措施可以防止FSGS的进展。阿霉素(ADR)诱导的FSGS是一种公认的模拟人FSGS的模型。ADR是一种常见的与肾毒性相关的化疗药物，通过触发氧自由基和抗氧化酶之间的失衡而导致肾损伤；^[3,4,5]然而，ADR诱导的FSGS的确切机制尚不完全清楚。代谢组学分析被认为有希望通过评估细胞过程的终产物并在生物信息学平台中提供所有代谢物的无偏鉴定和定量来监测治疗反应、做出诊断和跟踪疾病的发病机制。^[6]在本研究中，我们旨在使用超高效液相色谱-质谱（UPLC-MS/MS）数据收集技术研究ADR诱导的FSGS模型的血清代谢组学变异。在这里，我们描述了在我们实验室使用BALB/c小鼠生成FSGS模型的方法。通过蛋白尿增加、血清肌酐（SCR）升高和体重减轻评估ADR诱导的FSGS的临床特征。在ADR给药后4周收获血清和器官，以评估肾功能、肾脏病理变化以及血清代谢组学变异。

致编者：足细胞性折叠性肾小球病（PIG）于2008年作为一种新的疾病实体被提出，^[1]由于与之相关的肾小球罕见的病理变化，引起了人们的极大关注。猪的特征是增厚的肾小球基底膜（GBM）的特异性变化，包括微球、微管结构和足细胞折叠。然而，猪的临床特征和发病机制仍不清楚。为了阐明这种肾小球病的特征，有必要从报告的病例中积累更多的信息。在此，我们报告了一例肾小球病，显示足细胞折叠与原发性干燥综合征(pSS)和桥本甲状腺炎相关。

致编者：慢性肾脏疾病-骨矿物质紊乱（CKD-MBD）在血液透析（HD）患者中普遍存在。它增加了心血管发病率和死亡率的风险，特别是血管钙化。^[1]因此，有效控制CKD-MBD生化指标异常至关重要。国际指南已提供了CKD-MBD的措施，但来自发展中国家的相关研究有限，尤其是在中国。^[2]

致编者：干燥综合征（SS）是一种多系统慢性自身免疫性疾病，主要影响泪腺和唾液腺，导致眼部和口腔干燥。SS以大量自身抗体为特征，涉及多个系统，包括淋巴系统、血液、肺、肾、肝、肌肉和关节。晚期并发症包括间质性肺纤维化、周围神经病变、气管支气管干燥、失明、关节痛、口腔念珠菌病和淋巴瘤。SS的主要组织病理学特征是外分泌腺的淋巴细胞浸润，导致腺泡细胞死亡，可能通过凋亡。^[1]SS的确切病因和发病机制尚不清楚。

致编者：中国医生经常谈到中药的特性和治疗功效的结合。他们认为，中药的性质和疗效应该被视为一个“有机整体”。“基于治疗功效的使用”可能导致省略CMM的特性。它也不能满足“鉴别诊断和治疗”的要求，从而限制了使用CMM的灵活性。CMM的四性、五味、经络、疗效与脏腑证候相对应，表明了中医的“整体”观念。^[1]目前，已经进行了许多研究来挖掘CMM的特性和治疗效果之间的关联规则。一些研究人员挖掘文本数据，以确定CMM的特性和治疗效果之间的相关性。虽然获得了一些结果，但结果存在局限性，并且所获得的关联规则是否显著仍未确定。本文基于策略模式，设计并开发了一个挖掘CMM属性与疗效之间关联规则的系统。策略模式定义了一系列算法，封装了每一个算法，并使它们可以互换。这种模式使得能够根据用户的选择来实现或交换不同的算法。^[2]因此，我们可以根据数据集的特征选择合适的算法。充分利用策略模式选择合适的挖掘算法，使关联挖掘过程人性化、智能化、快速化。

编者按：Dieulafoy病的特征是在粘膜下层内运行的异常大口径的迂曲动脉，易溃烂出血。这种血管异常通常发生在胃肠道。累及呼吸系统的情况很少见。支气管Dieulafoy病引起的大咯血是一种危及生命的疾病。在紧急情况下需要立即有效的治疗以提高生存率。在此，我们报告一例支气管血管异常并表现为复发性大咯血的患者。患者签署了知情同意书。

致小编：20岁未婚男青年，因定期体检意外发现心脏增大，住院治疗1周。他的父母和两个姐妹在心电图（ECG）和超声心动图（Echo）检查中没有异常发现。他有一个叔叔在47岁时不明原因猝死。患者无药物滥用、吸烟、大量饮酒或非法药物使用史。血液检查显示脑钠肽前体升高（2292 pg/ml，正常范围：<125 pg/ml）、肌酸激酶-肌肉/脑质量（10.3 ng/ml，正常范围：0.3-4.0 ng/ml）、丙氨酸转氨酶（194 U/L，正常范围：9-50 U/L）和天冬氨酸转氨酶（271 U/L，正常范围：15-40 U/L），而其他血液检查结果均在正常范围内。12导联体表心电图显示房性心律伴2：1房室传导阻滞（AVB）和B型Wolff-Parkinson-White综合征（WPW），心室率为43次/分钟，左心室（LV）肥厚伴劳损，室间传导阻滞。约1周前在另一家医院进行了心电图检查，也显示房性心律和B型WPW，但当时心室率为72次/分钟（A：V=1：1）。回声显示心脏增大（左心房[LA]47 mm，右心房[RA]43 mm，LV 61 mm × 68 mm × 86 mm，右心室[RV]33 mm），室间隔和LV壁弥漫性增厚达18 mm，运动减少，LV射血分数低（LVEF 40%），二尖瓣和三尖瓣轻度反流。X线显示左心室增大，心胸比值为0.64。

致小编：痉挛是中风后常见的运动障碍。在中风后1至6周内，大约40%的中风患者在受影响的一侧发生痉挛。在这里，我们报告了一名中风痉挛患者，使用配对脉冲经颅磁刺激来探索肉毒杆菌毒素注射后痉挛状态释放的中枢机制。

编者按：H7N9感染后，宿主淋巴细胞免疫起到抗病毒作用。^[1]此外，低频率的T细胞与疾病严重程度相关。^[2]在此，我们介绍了一名H7N9感染患者，其患有危及生命的淋巴细胞减少症（仅0.06 × 10⁹/L在外周血中），这是我们以前几乎从未见过的。我们还测量了血液和支气管肺泡灌洗液（BALF）中T细胞亚群的比例。

对可能代表线粒体的细胞内结构的首次观察发表于19世纪40年代。线粒体（复数线粒体）是由线粒体外膜(OMM)、膜间空间、线粒体内膜和基质空间组成的双膜结合生物体，^[1]其普遍存在于除成熟红细胞以外的所有哺乳动物真核细胞中。线粒体的主要功能是代谢体内的糖脂；此外，它还服务于许多其他生理功能，如信号传导、细胞分化和细胞死亡，以及维持对细胞周期和细胞生长的控制。^[2]