Volume 129 · Issue 06 · 2016

Angiopoietin-2 (Ang-2) plays a crucial role in hypoxia-induced angiogenesis and is expressed only in sites of vascular remodeling. Ang-2 expression can be regulated by hypoxia inducible factors and other regulators with exposure to hypoxia. The objective of this study was to investigate the influence of percutaneous coronary intervention (PCI) on serum Ang-2 concentrations, and analyze the correlation between serum Ang-2 and the severity of coronary artery stenosis in patients with coronary heart disease (CHD).

Sixty-four patients with CHD were selected as the study group, each undergone PCI. Thirty-two healthy subjects were selected as the control group. Pre-PCI and post-PCI serum Ang-2 were measured by enzyme-linked immunosorbent assay. The severity of coronary artery stenosis was evaluated using angiographic Gensini scores, and the coronary collateral vessels were scored according to Rentrop’s classification.

Concentrations of pre-PCI serum Ang-2 in the study group were significantly higher than those in the control group (4625.06 ± 1838.06 vs. 1945.74 ± 1588.17 pg/ml, P < 0.01); however, concentrations of post-PCI serum Ang-2 were significantly lower than those of pre-PCI (3042.63 ± 1845.33 pg/ml vs. 4625.06 ± 1838.06 pg/ml, P < 0.01). Concentrations of pre-PCI serum Ang-2 were significantly correlated with Gensini scores (r = 0.488, P < 0.01); however, the decrease in serum Ang-2 after PCI was not correlated with Gensini scores, coronary collateral vessel grading, or left ventricular ejection fraction.

Serum Ang-2 concentrations significantly increased in patients with CHD, and PCI treatment significantly decreased these concentrations. Serum Ang-2 concentrations, but not the decrease in serum Ang-2 concentrations, were significantly correlated with the severity of coronary artery stenosis. These results suggested that Ang-2 may be a biomarker of myocardial ischemia and vessel remodeling.

Population-based cancer registry collects the data on cancer incidence and mortality deaths from covered population to describe and survey the epidemics in certain areas. The aim of this study was to estimate the cancer incidence and mortality in Wuwei, Gansu province, Northwestern China from 2003 to 2012. The goal is to better understand cancer distribution and long-term development of cancer prevention and treatment in Wuwei.

Data were collected from the Wuwei Cancer Registry between 2003 and 2012. In this registry, data from 46 cancer report centers were included in this analysis. Incidence/mortality rates, age-specific incidence/mortality rates, age-standardized incidence/mortality rates, and cumulative incidence/mortality rates were calculated. Totally, 9,836,740 person-years (5,110,342 for males and 4,726,398 for females) had been monitored over this time period. The gender ratio of male/female was 1.08:1. The number of new cancer cases and related deaths was 24,705 and 17,287 from 2003 to 2012, respectively.

The proportion of morphological verification was 74.43%. The incidence of cases identified through death certification only was 1.21%, and the mortality to incidence ratio was 0.70. The average crude incidence was 251.15/100,000 persons (310.61 and 186.87 for males and females per 100,000 persons, respectively). The age-standardized rates by Chinese standard population (ASR-China) and by world standard population (ASR-world) were 207.76 and 245.42 per 100,000 persons, respectively. The crude cancer mortality was 175.74/100,000 persons (228.34 and 118.86 for males and females per 100,000 persons). ASR for China and the world was 149.57 and 175.13/100,000 persons, respectively. The most common cancers and leading causes of cancer-related deaths in Wuwei were as follows: cancers of stomach, esophagus, liver, lung, colorectum, breast, cervix, lymphoma, blood (leukemia), brain, and central nervous system. In Wuwei, during 2003 and 2012, cancer incidence and mortality rates increased by 1.32% and 1.31%/year, respectively. During this time, colorectum cancer incidence and mortality rates increased by 2.69% and 7.54%/year, respectively, in Wuwei. The incidence and mortality of other gastric, esophageal, liver, and lung cancers also all increased.

The results of this study report a more accurate cancer burden among the population of Wuwei, China. Active research of cancers etiology and effective prevention should be established to reduce the incidence and mortality associated with cancers.

Both lower urinary tract dysfunction and urinary symptoms are prevalent in patients with multiple sclerosis (MS). Although the significance of identifying and treating urinary symptoms in MS is currently well-known, there is no information about the real prevalence and therapeutic effect of urinary symptoms in patients with MS. The purpose of this study was to analyze the major symptoms and urodynamic abnormalities, and observe the therapeutic effect in different MS characteristics.

We enrolled 126 patients with urological dysfunction who were recruited between July 2008 and January 2015 in Beijing Tian Tan Hospital, Capital Medical University and conducted overactive bladder system score (OABSS), urodynamic investigation, and expanded disability status scale (EDSS). Changes of urinary symptoms and urodynamic parameters were investigated.

Urgency was the predominant urinary symptom, and detrusor overactivity was the major bladder dysfunction. There was a positive correlation between EDSS and OABSS. Clinically isolated syndrome (CIS) had lowest EDSS and OABSS. CIS exhibited significant improvements in OABSS, maximum urinary flow rate (Qmax), and bladder volume at the first desire to voiding and maximum bladder volume after the treatment (P < 0.05). Relapsing–remitting MS showed significant improvements in the OABSS, Qmax, and bladder volume at the first desire to voiding, maximum bladder volume and bladder compliance after the treatment (P < 0.05). Progressive MS exhibited significant increase in the bladder volume at the first desire to voiding, the detrusor pressure at maximum flow rate (PdetQmax), and bladder compliance after the treatment (P < 0.05).

Urodynamic parameters examined are important in providing an accurate diagnosis, guiding management decisions of MS. Early and effective treatment may improve the bladder function and the quality of life at the early stages of MS.

Obstructive sleep apnea (OSA) is a common sleep disorder and is characterized by airway collapse at multiple levels of upper airway. The effectiveness of nasal surgery has been discussed in several studies and shows a promising growing interest. In this study, we intended to evaluate the effects of nasal surgery on the upper airway dimensions in patients with OSA using three-dimensional (3D) reconstruction of cone-beam computed tomography (CT).

Twelve patients with moderate to severe OSA who underwent nasal surgery were included in this study. All patients were diagnosed with OSA using polysomnography (PSG) in multi sleep health centers associated with Massachusetts General Hospital, Massachusetts Eye and Ear Infirmary and the Partners Health Care from May 31, 2011 to December 14, 2013. The effect of nasal surgery was evaluated by the examination of PSG, subjective complains, and 3D reconstructed CT scan. Cross-sectional area was measured in eleven coronal levels, and nasal cavity volume was evaluated from anterior nasal spine to posterior nasal spine. The thickness of soft tissue in oral pharynx region was also measured.

Five out of the 12 patients were successfully treated by nasal surgery, with more than 50% drop of apnea–hypopnea index. All the 12 patients showed significant increase of cross-sectional area and volume postoperatively. The thickness of soft tissue in oral pharynx region revealed significant decrease postoperatively, which decreased from 19.14 ± 2.40 cm² and 6.11 ± 1.76 cm² to 17.13 ± 1.91 cm² and 5.22 ± 1.20 cm².

Nasal surgery improved OSA severity as measured by PSG, subjective complaints, and 3D reconstructed CT scan. 3D assessment of upper airway can play an important role in the evaluation of treatment outcome.

Ankylosing spondylitis (AS) is the most common rheumatic condition that is slowly progressive and predominantly affects adolescents. Pathological bone formation associated with AS is an important cause of disability. The aim of the study was to investigate the possible involvement of the genes related to endochondral ossification and ectopia ossification in genetic susceptibility to AS in a Chinese Han population.

Sixty-eight single nucleotide polymorphisms (SNPs) from 13 genes were genotyped in discovery cohorts including 300 AS patients and 180 healthy controls. The rs10019009 in dentin matrix protein 1 (DMP1) gene shown as association with AS after multiple testing corrections in discovery cohorts was replicated in a validation independent cohort of 620 AS patients and 683 healthy controls. The rs10019009 was assessed with bioinformatics including phylogenetic context, F-SNP and FastSNP functional predictions, secondary structure prediction, and molecular modeling. We performed a functional analysis of rs10019009 via reverse transcription-polymerase chain reaction, alkaline phosphatase (ALP) activity in human osteosarcoma U₂OS cells.

Interestingly, the SNP rs10019009 was associated with AS in both the discovery cohort (P = 0.0012) and validation cohort (P = 0.0349), as well as overall (P = 0.0004) in genetic case–control association analysis. After a multivariate logistic regression analysis, the effect of this genetic variant was observed to be independent of linkage disequilibrium. Via bioinformatics analysis, it was found that the amino acid change of the rs10019009 led to changes of SNP function, secondary structure, tertiary conformation, and splice mode. Finally, functional analysis of rs10019009 in U₂OS cells demonstrated that the risk T allele of the rs10019009 increased enzymatic activity of ALP, compared to that of the nonrisk allele (P = 0.0080).

These results suggested that the DMP1 gene seems to be involved in genetic predisposition to AS, which may contribute to the ectopic mineralization or ossification in AS. In addition, DMP1 gene may be a promising intervention target for AS in the future.

Diffusion-weighted imaging (DWI) with the intravoxel incoherent motion (IVIM) model has shown promising results for providing both diffusion and perfusion information in cervical cancer; however, its use to predict and monitor the efficacy of neoadjuvant chemotherapy (NACT) in cervical cancer is relatively rare. The study aimed to evaluate the use of DWI with IVIM and monoexponential models to predict and monitor the efficacy of NACT in cervical cancer.

Forty-two patients with primary cervical cancer underwent magnetic resonance exams at 3 time points (pre-NACT, 3 weeks after the first NACT cycle, and 3 weeks after the second NACT cycle). The response to treatment was determined according to the response evaluation criteria in solid tumors 3 weeks after the second NACT treatment, and the subjects were classified as two groups: responders and nonresponders groups. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion-related pseudo-diffusion coefficient (D*), and perfusion fraction (f) values were determined. The differences in IVIM-derived variables and ADC between the different groups at the different time points were calculated using an independent samples t-test.

The D and ADC values were all significantly higher for the responders than for the nonresponders at all 3 time points, but no significant differences were observed in the D* and f values. An analysis of the receiver operating characteristic (ROC) curves indicated that a D value threshold <0.93 × 10⁻³ mm²/s and an ADC threshold <1.11 × 10⁻³ mm²/s could differentiate responders from nonresponders at pre-NACT time point, yielding area under the curve (AUC) of which were 0.771 and 0.806, respectively. The ROC indicated that the AUCs of D and ADC at the 3 weeks after the first NACT cycle and 3 weeks after the second NACT cycle were 0.823, 0.763, and 0.787, 0.794, respectively. The AUC values of D and ADC at these 3 time points were not significantly different (P = 0.641, 0.512, and 0.547, respectively).

D and ADC values may be useful for predicting and monitoring the efficacy of NACT in cervical cancer. An IVIM model may be equal to monoexponential model in predicting and monitoring the efficacy of NACT in cervical cancer.

Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome that is typically caused by a deletion of the distal portion of the short arm of chromosome 4. However, there are few reports about the features of Chinese WHS patients. This study aimed to characterize the clinical and molecular cytogenetic features of Chinese WHS patients using the combination of multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (array CGH).

Clinical information was collected from ten patients with WHS. Genomic DNA was extracted from the peripheral blood of the patients. The deletions were analyzed by MLPA and array CGH.

All patients exhibited the core clinical symptoms of WHS, including severe growth delay, a Greek warrior helmet facial appearance, differing degrees of intellectual disability, and epilepsy or electroencephalogram anomalies. The 4p deletions ranged from 2.62 Mb to 17.25 Mb in size and included LETM1, WHSC1, and FGFR3.

The combined use of MLPA and array CGH is an effective and specific means to diagnose WHS and allows for the precise identification of the breakpoints and sizes of deletions. The deletion of genes in the WHS candidate region is closely correlated with the core WHS phenotype.

Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD). Moreover, the exactly topological organization of networks underlying MDD remains unclear. This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients.

The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls. The brain fractional anisotropy-weighted structural networks were constructed, and the global network and regional nodal metrics of the networks were explored by the complex network theory.

Compared with the healthy controls, the brain structural network of MDD patients showed an intact small-world topology, but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found. Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions.

All these resulted in a less optimal topological organization of networks underlying MDD patients, including an impaired capability of local information processing, reduced centrality of some brain regions and limited capacity to integrate information across different regions. Thus, these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network.

Schizophrenia (SCZ) is a severe, debilitating, and complex psychiatric disorder with multiple causative factors. An increasing number of studies have determined that rare variations play an important role in its etiology. A somatic mutation is a rare form of genetic variation that occurs at an early stage of embryonic development and is thought to contribute substantially to the development of SCZ. The aim of the study was to explore the novel pathogenic somatic single nucleotide variations (SNVs) and somatic insertions and deletions (indels) of SCZ.

One Chinese family with a monozygotic (MZ) twin pair discordant for SCZ was included. Whole exome sequencing was performed in the co-twin and their parents. Rigorous filtering processes were conducted to prioritize pathogenic somatic variations, and all identified SNVs and indels were further confirmed by Sanger sequencing.

One somatic SNV and two somatic indels were identified after rigorous selection processes. However, none was validated by Sanger sequencing.

This study is not alone in the failure to identify pathogenic somatic variations in MZ twins, suggesting that exonic somatic variations are extremely rare. Further efforts are warranted to explore the potential genetic mechanism of SCZ.

Antimicrobial peptides, including cathelicidin LL-37, human beta defensin (HBD)-2, and HBD-3, are important elements of the innate immune response and involved in modulation of the adaptive immunity, and they also play an important role in cutaneous defense against Mycobacterium tuberculosis.

The fresh skin tissues and paraffin-embedded biopsy samples from three cutaneous tuberculosis, two tuberculids, and ten healthy individuals were collected. The expressions of LL-37, HBD-2, and HBD-3 mRNA in the lesions of three cutaneous tuberculosis and two tuberculids were detected by quantitative real-time polymerase chain reaction; the protein expressions were detected by immunohistochemistry and Western blotting methods.

The expressions of LL-37 mRNA and protein in the lesions of cutaneous tuberculosis and tuberculids were similar to that of normal skin. The expression of HBD-2 mRNA had an increasing trend in the lesions of cutaneous tuberculosis and tuberculids compared with that of normal skin; however, the expression of HBD-2 protein in the lesions of cutaneous tuberculosis had a decreasing trend compared with that of normal skin, and the expression of HBD-2 protein in the lesions of tuberculids was similar to that of normal skin. The expressions of HBD-3 mRNA and protein in lesions of cutaneous tuberculosis and tuberculids were similar to that of normal skin.

Our study indicated that the expression of HBD-2 and HBD-3 mRNA and protein in lesions of cutaneous tuberculosis may be not consistent with that of tuberculids. However, an inherent limitation of the present study was that the sample size was small, and the roles and regulation mechanisms of LL-37, HBD-2, and HBD-3 in cutaneous tuberculosis and tuberculids need to be further investigated.

The aim of this study was to assess the efficacy and safety of vinorelbine and cisplatin (NP chemotherapy) alone or in combination with Aidi injection for the treatment of advanced nonsmall cell lung cancer (NSCLC).

Pertinent publications were identified in PubMed, EMBASE, Cochrane Library, CNKI, CQVIP, and Wanfang databases, up to December 8, 2015. After quality assessment of all included randomized controlled trials evaluating Aidi injection combined with NP chemotherapy for the treatment of advanced NSCLC, a meta-analysis was performed by Review Manager 5.2 and STATA 12.0 for statistical analyses.

Twelve studies including 509 and 503 cases in the experimental and control groups, respectively, were finally analyzed. The meta-analysis revealed that when cisplatin dose ranging from 20 to 40 mg/m², combination of Aidi injection and NP chemotherapy was statistically different compared with NP chemotherapy alone in enhancing efficiency (relative risk [RR] = 1.24, 95% confidence interval [CI] [1.05–1.47], P = 0.010) and reducing the incidence of Grade II or above nausea and vomiting (RR = 0.49, 95% CI [0.30–0.80], P = 0.005). Meanwhile, with cisplatin ranging from 80 to 120 mg/m², no significant differences in efficiency (RR = 1.11, 95% CI [0.87–1.42], P = 0.390) and Grade II or above nausea and vomiting (RR = 0.88, 95% CI [0.71–1.10], P = 0.260) were obtained. In addition, Aidi injection combined with NP chemotherapy was superior to NP chemotherapy alone in improving the quality of life, alleviating Grade II or above leukopenia and thrombocytopenia.

Aidi injection combined with NP chemotherapy can enhance efficiency, improve the quality of life, and decrease adverse effects in patients with advanced NSCLC.

To review theories and technologies of big data mining and their application in clinical medicine.

Literatures published in English or Chinese regarding theories and technologies of big data mining and the concrete applications of data mining technology in clinical medicine were obtained from PubMed and Chinese Hospital Knowledge Database from 1975 to 2015. Study Selection: Original articles regarding big data mining theory/technology and big data mining’s application in the medical field were selected.

This review characterized the basic theories and technologies of big data mining including fuzzy theory, rough set theory, cloud theory, Dempster–Shafer theory, artificial neural network, genetic algorithm, inductive learning theory, Bayesian network, decision tree, pattern recognition, high-performance computing, and statistical analysis. The application of big data mining in clinical medicine was analyzed in the fields of disease risk assessment, clinical decision support, prediction of disease development, guidance of rational use of drugs, medical management, and evidence-based medicine.

Big data mining has the potential to play an important role in clinical medicine.

蟑螂洛福单胞菌(L.blattarum）是一种多鞭毛原生动物，寄生在白蚁和蟑螂的肠道内，属于Lophomonas亚序，乳腺炎命令。支气管肺100余例L.blattarum自1993年以来就有感染的报道。然而，我们在电镜下从6例肺部疾病患者的支气管肺泡灌洗液(BALF)中鉴定出可移动细胞，最终发现这些细胞实际上是支气管纤毛上皮细胞，与报道的基本相同L.blattarum在光学显微镜下的形态学文献中。^[1]通过仔细的文献综述，我们发现所有报道的L.blattarum感染只是通过光学显微镜下的形态学而不是电子显微镜、分离和培养或分子程序来诊断；这些文献中显示的图像均与支气管纤毛上皮细胞的显微特征相符。没有确凿的证据可以考虑L.blattarum迄今为止作为呼吸道感染的病原体。因此，我们认为支气管肺L.blattarum感染可能被误诊了。在这里，我们总结了关于当前的证据不足L.blattarum感染及其与纤毛上皮细胞的差异，以提高临床鉴别能力，避免今后的误诊。

葡萄膜黑色素瘤是成人最常见的原发性眼部恶性肿瘤，年发病率为6-7例/百万人。^[1,2,3]脉络膜是最常见的受累部位，发生在90%以上的患者中。^[3]我们对1997年至2011年铜仁眼科中心的葡萄膜黑色素瘤进行了回顾性研究。共记录了682例葡萄膜黑色素瘤。其中局部切除手术176例（25.8%）。术后大部分存活，恢复良好。然而，3例脉络膜黑色素瘤患者术后不久发生了危及生命的急性肺栓塞（APE）并发症。到目前为止，据我们所知，很少有脉络膜黑色素瘤术后严重并发症的报道。

促性腺激素释放激素激动剂（GnRH-a）是治疗子宫内膜异位症最常用的疗法之一。但遗憾的是，至今没有文献认识到GnRH-a可能与血栓形成有关。下面的病例正是关于使用GnRH-a后发生的血栓栓塞，因为雌二醇（E2）在注射后短时间内达到峰值。

“不能插管，不能通气”的情况虽然罕见，但却是麻醉医生的噩梦。困难气道定义为困难的面罩或声门上气道（SGA）通气、困难的SGA放置、喉镜检查、气管插管或插管失败。我们介绍了三例困难气道及其气道管理。

致编者：我们怀着极大的兴趣阅读了陈先生的原创文章等人。^[1]发表在《中华医学杂志》上，比较了汉族和黎族创伤后应激障碍（PTSD）患者的血清细胞因子浓度。作者发现，与正常对照组相比，PTSD患者的细胞因子白细胞介素（IL）-2、IL-6、IL-8和肿瘤坏死因子（TNF）-α的血清浓度显著更高，并且细胞因子浓度因种族而异。

致编者：2015年11月12日，一位63岁女性因头痛、呕吐2周病史转诊至当地医院。她描述她的头痛是全身性的，没有畏光或任何其他视觉异常。她在病程中没有发烧。入院后2天进行脑脊液(CSF)检查，显示白细胞(WBC)计数为3.8 × 10⁷细胞/L，颅内压30 cmH₂O（1厘米/小时₂O=0.098 kPa），生化正常，无隐球菌头颅磁共振成像显示正常的实质图像，磁共振静脉造影(MRV)显示静脉窦发育不良，可能提示左侧横窦血栓形成[图1a].其他实验室研究平淡无奇。然而，她的视力和听力在入院3周内下降。

编者按：慢性阻塞性肺疾病（COPD）是一种常见的可预防和可治疗的疾病，其特征是由于气道和肺部异常炎症对有害颗粒或气体的持续和进行性气流限制。异物吸入很少诱发COPD加重。在本报告中，我们描述了一名因异物吸入导致COPD急性加重的男性患者。