Volume 129 · Issue 10 · 2016

Warfarin is the most common oral anticoagulant to decrease the stroke risk associated with atrial fibrillation (AF). There are very few prospective studies that have explored whether warfarin has an association with damage on renal function in Chinese patients with nonvalvular AF (NVAF). The aim of this study was to evaluate the effects of warfarin on renal function and study the factors associated with kidney dysfunction in Chinese adult NVAF patients without dialysis therapy.

From January 2011 to December 2013, a total of 951 NVAF patients from 18 hospitals were enrolled. The estimated glomerular filtration rate (eGFR) was calculated from baseline and follow-up serum creatinine levels. Kaplan–Meier survival curves compared the survival of a ≥25% decline in eGFR (hereafter, endpoint), while Cox models estimated hazard ratios (HRs) and 95% confidence intervals for this event after adjustment for age, gender, and selected potential risk factors for renal dysfunction. Cox regression analysis of the various clinical potential variables was performed to identify the predictors of a ≥25% decline in eGFR.

After a 58-month follow-up, 951 NVAF patients were divided by observation into warfarin (n = 655) and no anticoagulation groups (n = 296) and 120 (12.6%) patients experienced renal endpoint. Kaplan–Meier survival curves showed that the survival period was not different in the two groups (χ² = 0.178, log-rank P = 0.67), but patients with systolic blood pressure (SBP) <140 mmHg have significant difference with patients with SBP ≥140 mmHg (χ² = 4.903, log-rank P = 0.03). Multivariate Cox regression analysis revealed baseline eGFR and SBP as independent predictors of the endpoint, with HRs of 1.00, and 1.02, respectively.

In patients with NVAF, eGFR and SBP are associated with the deterioration of kidney function while Warfarin is not the risk factor of the ≥25% decline in eGFR.

Chinese Clinical Trial Registry (No. ChiCTR-OCH-13003729); http://www.chictr.org.cn/showproj .aspx?proj = 5831.

Survivin is an oncoprotein silenced in normal mature tissues but reactivated in serous ovarian cancer (SOC). Although transcriptional activation is assumed for its overexpression, the long 3’-untranslated region (3’-UTR) in survivin gene, which contains many alternate polyadenylation (APA) sites, implies a propensity for posttranscriptional control and therefore was the aim of our study.

The abundance of the coding region, the proximal and the distal region of survivin mRNA 3’-UTR, was evaluated by real-time polymerase chain reaction (PCR) in SOC samples, cell lines, and normal fallopian tube (NFT) tissues. The APA sites were confirmed by rapid amplification of cDNA 3’ ends and DNA sequencing. Real-time PCR were used to screen survivin-targeting microRNAs (miRNAs) that were inversely correlated with survivin. The expression of an inversely correlated miRNA was restored by pre-miRNA transfection or induction with a genotoxic agent to test its inhibitory effect on survivin overexpression.

Varying degrees of APA were observed in SOC by comparing the abundance of the proximal and the distal region of survivin 3’-UTR, and changes of 3’-UTR correlated significantly with survivin expression (r = 0.708, P < 0.01). The main APA sites are proved at 1197 and 1673 of survivin 3’-UTR by DNA sequencing. Higher level of 3’-UTR proximal region than coding region was observed in NFT, as well as in SOC and cell lines. Among the survivin-targeting miRNAs, only a few highly expressed miRNAs were inversely correlated with survivin levels, and they mainly targeted the distal part of the 3’-UTR. However, in ovarian cancer cells, restoration of an inversely correlated miRNA (miR-34c) showed little effect on survivin expression.

In NFT tissues, survivin is not transcriptionally silenced but regulate posttranscriptionally. In SOC, aberrant APA leads to the shortening of survivin 3’-UTR which enables it to escape the negative regulation of miRNAs and is responsible for survivin up-regulation.

Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD), and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients.

This was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years, range 17–30 years) and 135 healthy controls after matching for gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone, ACTH, and cortisol and biochemical tests.

Higher basal serum ACTH levels (8.25 ± 3.78 pmol/L vs. 6.97 ± 2.81 pmol/L) and lower cortisol levels (366.70 ± 142.48 nmol/L vs. 452.82 ± 141.53 nmol/L) were observed in male IHH patients than healthy subjects (all P < 0.05). IHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD (34.9% vs. 4.4%) than the controls (all P < 0.05). Basal serum ACTH (9.91 ± 4.98 pmol/L vs. 7.60 ± 2.96 pmol/L) and dehydroepiandrosterone sulfate (2123.7 ± 925.8 µg/L vs. 1417.1 ± 498.4 µg/L) levels were significantly higher in IHH patients with NAFLD than those without NAFLD (all P < 0.05). We also found that basal serum ACTH levels were positively correlated with NAFLD (r = 0.289, P < 0.05) and triglyceride levels (r = 0.268, P < 0.05) in male IHH patients. Furthermore, NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis.

The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

Previously, we reported that dual-specificity phosphatase 1 (DUSP1) was differentially expressed in endometrioid adenocarcinoma (EEA). However, the role of DUSP1 in EEA progression and the relationship between DUSP1 and medroxyprogesterone (MPA) are still unclear.

The expression of DUSP1 in EEA specimens was detected by immunohistochemical analysis. The effect of DUSP1 on cell proliferation was analyzed by Cell Counting Kit 8 and colony formation assay, and cell migration was analyzed by transwell assay. MPA-induced DUSP1 expression in EEA cells was measured by Western blot.

DUSP1 expression was deficient in advanced International Federation of Gynecology and Obstetrics stage, high-grade and myometrial invasive EEA. In EEA cell lines (Hec1A, Hec1B, RL952, and Ishikawa), the DUSP1 expression was substantially higher in Ishikawa cells than in other cell lines (P < 0.05). Knockdown of DUSP1 promoted Ishikawa cells proliferation, migration, and activation of mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/Erk) pathway. MPA-induced DUSP1 expression and inhibited MAPK/Erk pathway in Ishikawa cells.

Our data suggest that DUSP1 deficiency promotes EEA progression via MAPK/Erk pathway, which may be reversed by MPA, suggesting that DUSP1 may serve as a potential therapeutic target for the treatment of EEA.

Vulvovaginal candidiasis (VVC) was a common infection associated with lifelong harassment of woman’s social and sexual life. The purpose of this study was to describe the species distribution and in vitro antifungal susceptibility of Candida species (Candida spp.) isolated from patients with VVC over 8 years.

Species which isolated from patients with VVC in Peking University First Hospital were identified using chromogenic culture media. Susceptibility to common antifungal agents was determined using agar diffusion method based on CLSI M44-A2 document. SPSS software (version 14.0, Inc., Chicago, IL, USA) was used for statistical analysis, involving statistical description and Chi-square test.

The most common strains were Candida (C.) albicans, 80.5% (n = 1775) followed by C. glabrata, 18.1% (n = 400). Nystatin exhibited excellent activity against all species (<4% resistant [R]). Resistance to azole drugs varied among different species. C. albicans: clotrimazole (3.1% R) < fluconazole (16.6% R) < itraconazole (51.5% R) < miconazole (54.0% R); C. glabrata: miconazole (25.6% R) < clotrimazole (50.5% R) < itraconazole (61.9% R) < fluconazole (73.3% R); Candida krusei: clotrimazole (0 R) < fluconazole (57.7% R) < miconazole (73.1% R) < itraconazole (83.3% R). The susceptibility of fluconazole was noticeably decreasing among all species in the study period.

Nystatin was the optimal choice for the treatment of VVC at present. The species distribution and in vitro antifungal susceptibility of Candida spp. isolated from patients with VVC had changed over time.

Recent studies have suggested an association between elevated pelvic incidence (PI) and the development of lumbar spondylolysis. However, there is still lack of investigation for Han Chinese people concerning the normal range of spinopelvic parameters and relationship between abnormal sagittal parameters and lumbar diseases. The objective of the study was to investigate sagittal lumbosacral parameters of adult lumbar spondylolysis patients in Han Chinese population.

A total of 52 adult patients with symptomatic lumbar spondylolysis treated in the General Hospital of Armed Police Force (Beijing, China) were identified as the spondylolysis group. All the 52 patients were divided into two subgroups, Subgroup A: 36 patients with simple lumbar spondylolysis, and Subgroup B: 16 patients with lumbar spondylolysis accompanying with mild lumbar spondylolisthesis (slip percentage <30%). Altogether 207 healthy adults were chosen as the control group. All patients and the control group took lumbosacral lateral radiographs. Seven sagittal lumbosacral parameters, including PI, pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), L5 incidence, L5 slope, and sacral table angle (STA), were measured in the lateral radiographs. All the parameters aforementioned were compared between the two subgroups and between the spondylolysis group and the control group with independent-sample t-test.

There were no statistically significant differences of all seven sagittal lumbosacral parameters between Subgroup A and Subgroup B. PI, PT, SS, and LL were higher (P < 0.05) in the spondylolysis group than those in the control group, but STA was lower (P < 0.001) in the spondylolysis group.

Current study results suggest that increased PI and decreased STA may play important roles in the pathology of lumbar spondylolysis in Han Chinese population.

Tuberculosis (TB) remains a major global public health challenge. Articular TB is an important form of extrapulmonary tuberculosis, and its diagnosis is difficult because of the low sensitivity of traditional methods. The aim of this study was to analyze the diagnostic value of T-SPOT.TB on synovial fluid for the diagnosis of articular TB.

Patients with suspected articular TB were enrolled consecutively between August 2011 and December 2015. T-SPOT.TB was performed on both synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs). The final diagnosis of articular TB was independent of the T-SPOT.TB result. The diagnostic sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB on SFMCs and PBMCs were analyzed.

Twenty patients with suspected articular TB were enrolled. Six were diagnosed with articular TB, and 14 patients were diagnosed with other diseases. Sensitivity and specificity were 83% and 86% for T-SPOT.TB on SFMCs, and 67% and 69% for T-SPOT.TB on PBMCs, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of T-SPOT.TB on SFMCs were 71% and 92%, respectively. The PPV and NPV were 50% and 82% for T-SPOT.TB on PBMCs.

Sensitivity, specificity, and NPV of T-SPOT.TB on SFMCs appeared higher than that on PBMCs, indicating that T-SPOT. TB on SFMCs might be a rapid and accurate diagnostic test for articular TB.

A study has identified several novel susceptibility variants of the mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) gene for type 2 diabetes mellitus (T2DM) within the German population. Among the variants, five single nucleotide polymorphisms (SNPs) of MAP4K4 (rs1003376, rs11674694, rs2236935, rs2236936, and rs6543087) showed significant association with T2DM or diabetes-related quantitative traits. We aimed to evaluate whether common SNPs in the MAP4K4 gene were associated with T2DM in the Chinese population.

Five candidate SNPs were genotyped in 996 patients newly diagnosed with T2DM and in 976 control subjects, using the SNPscan^™ method. All subjects were recruited from the Second Affiliated Hospital, Harbin Medical University from October 2010 to September 2013. We evaluated the T2DM risk conferred by individual SNPs and haplotypes using logistic analysis, and the association between the five SNPs and metabolic traits in the subgroups.

Of the five variants, SNP rs2236935T/C was significantly associated with T2DM in this study population (odds ratio = 1.293; 95% confidence interval: 1.034–1.619, P = 0.025). In addition, among the controls, rs1003376 was significantly associated with an increased body mass index (P = 0.045) and homeostatic model assessment-insulin resistance (P = 0.037).

MAP4K4 gene is associated with T2DM in a Chinese Han population, and MAP4K4 gene variants may contribute to the risk toward the development of T2DM.

Disrupted Ca²⁺ homeostasis contributes to the development of colonic dysmotility in ulcerative colitis (UC), but the underlying mechanisms are unknown. This study aimed to examine the alteration of colonic smooth muscle (SM) Ca²⁺ signaling and Ca²⁺ handling proteins in a rat model of dextran sulfate sodium (DSS)-induced UC.

Male Sprague-Dawley rats were randomly divided into control (n = 18) and DSS (n = 17) groups. Acute colitis was induced by 5% DSS in the drinking water for 7 days. Contractility of colonic SM strips (controls, n = 8 and DSS, n = 7) was measured in an organ bath. Cytosolic resting Ca²⁺ levels (n = 3 in each group) and Ca²⁺ transients (n = 3 in each group) were measured in single colonic SM cells. Ca²⁺ handling protein expression was determined by Western blotting (n = 4 in each group). Differences between control and DSS groups were analyzed by a two-sample independent t-test.

Average tension and amplitude of spontaneous contractions of colonic muscle strips were significantly enhanced in DSS-treated rats compared with controls (1.25 ± 0.08 g vs. 0.96 ± 0.05 g, P = 0.007; and 2.67 ± 0.62 g vs. 0.52 ± 0.10 g, P = 0.013). Average tensions of carbachol-evoked contractions were much weaker in the DSS group (1.08 ± 0.10 g vs. 1.80 ± 0.19 g, P = 0.006). Spontaneous Ca²⁺ transients were observed in more SM cells from DSS-treated rats (15/30 cells) than from controls (5/36 cells). Peak caffeine-induced intracellular Ca²⁺ release was lower in SM cells of DSS-treated rats than controls (0.413 ± 0.046 vs. 0.548 ± 0.041, P = 0.033). Finally, several Ca²⁺ handling proteins in colonic SM were altered by DSS treatment, including sarcoplasmic reticulum calcium-transporting ATPase 2a downregulation and phospholamban and inositol 1,4,5-trisphosphate receptor 1 upregulation.

Impaired intracellular Ca²⁺ signaling of colonic SM, caused by alteration of Ca²⁺ handing proteins, contribute to colonic dysmotility in DSS-induced UC.

In the past decades, studies on infant anemia have mainly focused on rural areas of China. With the increasing heterogeneity of population in recent years, available information on infant anemia is inconclusive in large cities of China, especially with comparison between native residents and floating population. This population-based cross-sectional study was implemented to determine the anemic status of infants as well as the risk factors in a representative downtown area of Beijing.

As useful methods to build a predictive model, Chi-squared automatic interaction detection (CHAID) decision tree analysis and logistic regression analysis were introduced to explore risk factors of infant anemia. A total of 1091 infants aged 6–12 months together with their parents/caregivers living at Heping Avenue Subdistrict of Beijing were surveyed from January 1, 2013 to December 31, 2014.

The prevalence of anemia was 12.60% with a range of 3.47%–40.00% in different subgroup characteristics. The CHAID decision tree model has demonstrated multilevel interaction among risk factors through stepwise pathways to detect anemia. Besides the three predictors identified by logistic regression model including maternal anemia during pregnancy, exclusive breastfeeding in the first 6 months, and floating population, CHAID decision tree analysis also identified the fourth risk factor, the maternal educational level, with higher overall classification accuracy and larger area below the receiver operating characteristic curve.

The infant anemic status in metropolis is complex and should be carefully considered by the basic health care practitioners. CHAID decision tree analysis has demonstrated a better performance in hierarchical analysis of population with great heterogeneity. Risk factors identified by this study might be meaningful in the early detection and prompt treatment of infant anemia in large cities.

To review hot issues and future direction of renal tumor biopsy (RTB) technique.

The literature concerning or including RTB technique in English was collected from PubMed published from 1990 to 2015. Study Selection: We included all the relevant articles on RTB technique in English, with no limitation of study design.

Computed tomography and ultrasound were usually used for guiding RTB with respective advantages. Core biopsy is more preferred over fine needle aspiration because of superior accuracy. A minimum of two good-quality cores for a single renal tumor is generally accepted. The use of coaxial guide is recommended. For biopsy location, sampling different regions including central and peripheral biopsies are recommended.

In spite of some limitations, RTB technique is relatively mature to help optimize the treatment of renal tumors.

最近，在单个冠状窦分支（多点左心室（LV）起搏的心脏再同步治疗（CRT）^™起搏[MPP]，St.Jude Medical，Inc.，Sylmar，CA，USA)已经商业化。具有MPP功能的CRT系统为医生进一步增强心力衰竭患者的CRT提供了一种新的策略。早期临床研究表明，与常规双心室(BiV)起搏相比，MPP对LV dP/dt提供了急性益处_马克斯,^[1]LV不同步，^[2]LV峰值径向应变，^[3]和LV电激活，^[4]并改善12个月时的CRT反应。^[5]在本报告中，我们介绍了两例中国MPP CRT病例，在各种MPP和常规BiV起搏配置下进行了急性血流动力学评估，证明MPP可以为患者提供进一步的益处。

临床上持续性房颤（AF）伴全身性栓塞并不少见。相比之下，阵发性AF导致栓塞的发生率远低于持续性AF。^[1]脑动脉是房颤引起栓塞最常见的部位，其次为肠系膜动脉、脾动脉、下肢动脉和肾动脉。然而，并发双侧肾动脉栓塞的发生在阵发性房颤患者中极为罕见。在我们收集的资料范围内，只有三宗类似的个案被呈报。^[2,3,4]

原发性中枢神经系统淋巴瘤（PCNSL）被定义为局限于脑、眼、脊髓或软脑膜的淋巴瘤。它约占所有脑肿瘤的3%，占所有非霍奇金淋巴瘤病例的2-3%。约20%的PCNSL患者在临床分期期间可检测到眼部受累，原发性玻璃体视网膜淋巴瘤是最常见的亚型。PCNSL的葡萄膜受累并不常见，据我们所知，PCNSL伴睫状体受累(CBL)尚未见报道。

横纹肌肉瘤（RMS）是一种累及横纹肌的恶性肿瘤，最常见于儿童年龄组。通常，患有RMS的儿童表现为持续性耳分泌物、耳息肉和听力损失，其类似于慢性中耳炎（COM）的症状。^[1,2]这种与COM的相似性通常会延迟诊断。RMS的组织学诊断总是一个挑战，因为有许多其他疾病表现出类似的特征，如耳息肉。^[3]我们讨论了一个不寻常的RMS病例，一个15个月大的女孩表现为急性中耳炎（AOM）和乳突脓肿。耳息肉活检证实了诊断。

Kearns-Sayre综合征（KSS）是一种极其罕见的线粒体肌病，以进行性眼外肌麻痹、双侧色素性视网膜病变和心脏传导异常为特征。此外，KSS患者可能出现近端肌无力、糖尿病、听力损失、小脑共济失调和脑脊液蛋白水平升高。^[1]

致编者：63岁男性，因人格改变和社交退缩于2015年03月03日转入神经内科。他似乎不愿意和家人说话，而他以前很善于社交，很关心家人。他表现出不寻常的行为，把衣服穿反了，冲动地吃东西。他白天也过度嗜睡。然而，患者本人并不知道这种行为。在当地医院怀疑他患有单纯疱疹性脑炎，然后静脉注射阿昔洛韦21天。患者的病情没有好转。

致编辑：皮肤镜检查是一种非侵入性且广泛使用的诊断皮肤病变的工具。它能够观察肉眼不可见的形态模式。^[1]鉴于皮肤病的多种临床特征和不常见的临床表现，有时可能会对患者进行不正确的诊断和随后的不当治疗，患者的卵泡开口充满角质化物质、卵泡堵塞、基底层坏死部分以及卵泡周围和真皮中层的炎性细胞浸润，这表明诊断为盘状红斑狼疮[图1c].该男子在接受羟氯喹200 mg/d（误配）全身治疗4个多月后痊愈。在这种模棱两可的情况下，皮肤镜检查可以是正确诊断疾病的重要工具。^[2]在本文中，我们报告了一例男性盘状红斑狼疮。盘状红斑狼疮表现不典型，经皮肤镜观察，后经组织病理学检查证实。

编者：迟发性肌张力障碍（TD）是一种特殊类型的继发性肌张力障碍，主要由长期应用多巴胺受体拮抗剂引起。^[1]深部脑刺激（DBS）已经成为治疗肌张力障碍的一种有前途的疗法。在这里，我们报告了丘脑底核（STN）刺激对一名TD患者12年随访后的长期影响。

致编者：异常右冠状动脉（RCA）罕见，通常起源于左瓦尔萨尔瓦窦。起源于左前降支（LAD）冠状动脉的异常RCA极为罕见。了解冠状动脉异常很重要，因为它们可能与潜在的严重心脏事件有关。因此，我们报告了一例罕见的左前降支中部（mLAD）异常起源的病例，该病例表现为RCA起源附近的急性心肌梗死，危及LAD和RCA。