荟萃分析：超声内镜引导下细针穿刺联合K-ras基因突变检测对胰腺实性肿块的诊断价值

背景：目前胰腺导管腺癌与胰腺炎性肿块的鉴别诊断仍存在较大困难。在超声内镜引导下细针穿刺的基础上,一些辅助技术加以应用,如K-ras基因突变检测。我们旨在通过对现有相关文献的分析回顾,评价超声内镜引导下细针穿刺联合K-ras基因突变检测对胰腺实性肿块的诊断价值。 方法：我们系统性回顾了国内外多个数据库的研究,采用固定效应模型和随机效应模型对其进行Meta分析。 结果：共8项研究（包括696例胰腺导管腺癌患者与138例胰腺炎性肿块患者）符合入选标准。结果表明,超声内镜引导下细针穿刺联合K-ras基因突变检测对胰腺导管腺癌与胰腺炎性肿块的诊断灵敏度、特异度、阳性及阴性似然比分别为 90%, 95%, 13.45 and 0.13。值得注意的是,在123例穿刺结果为阴性或不能作出诊断的患者中,其中59例患者发现K-ras基因突变,并最终确诊为胰腺导管腺癌 (48%, 59 / 123)。 结论：K-ras基因突变检测可提高超声内镜引导下细针穿刺对胰腺实性肿块的诊断价值,并且尤其适用于疑似胰腺导管腺癌而穿刺细胞学结果为阴性的患者。     

Influential factors and effect evaluation of the intra-operative puncture biopsy for pancreatic masses

Background  It is a challenge for the surgeons to accurately diagnose the pancreatic masses preoperatively, which decides the choice of surgical managements and subsequently results in different survivor outcomes, operative complications, and mortality rates. The purposes of this study were to evaluate the diagnostic role that intra-operative puncture biopsy may play in pancreatic masses and to explore the relevant factors influencing the diagnosis.

Methods A retrospective study was performed on 94 in-patients admitted to Peking University First Hospital for pancreatic masses during the period from June 1994 to December 2007. They all underwent intra-operative puncture biopsy during exploratory laparotomy. The sensitivity and specificity of intra-operative puncture biopsy were calculated and the relevant factors to the diagnosis of biopsy were selected for the statistical analysis.

Results The overall sensitivity, specificity, positive predictive value, and negative predictive value of intra-operative puncture biopsy were 76.0%, 94.7%, 98.3% and 50.0%, respectively. The analysis of bivariate correlations showed that the size of the pancreatic masses (P=0.000), the number of puncture biopsies (P=0.000), and the presence of pancreatic fibrosis (P=0.012) had statistic significance for the diagnosis. But the multivariate analysis identified the size of the pancreatic masses (P=0.004) and the number of puncture biopsies (P=0.000) as independent predictive factors for intra-operative puncture biopsy. In addition, as the number of puncture biopsies increased, the sensitivity and specificity of diagnosis was improved (P=0.000). The sensitivity and specificity of intra-operative puncture biopsy were found to be lower for the pancreatic masses less than 25 mm compared with the masses larger than 25 mm (P=0.000). It was noted, however, that even if the masses were less than 25 mm, the sensitivity and specificity could be improved significantly as the number of puncture biopsies reached 3 to 6 (P=0.007).

Conclusions Intra-operative puncture biopsy is simple and accurate for qualitatively differentiating various types of pancreatic masses. Three to 4 biopsies could significantly improve the diagnostic effect for pancreatic masses, even if the masses are less than 25 mm in size.

     

内镜超声引导下细针抽吸术对胰腺导管腺癌的预测及诊断价值

目的探讨预测胰腺导管腺癌（PDAC）鉴别于胰腺其他实性肿瘤病变的因素,评估内镜超声引导下细针抽吸术（EUSFNA） 对PDAC的诊断价值。方法回顾性分析2009年1月~2016年5月南方医科大学南方医院消化内窥镜中心因胰腺占位行 EUS-FNA检查的患者的临床资料,排除诊断不明、资料缺失、重复穿刺、囊性占位病变以及良性病变病例,将患者分为PDAC组 与non-PDAC组,比较两组的EUS-FNA穿刺阳性率,统计EUS-FNA对PDAC诊断的敏感度、特异度、阳性预测值、阴性预测值 和准确率,纳入PDAC组和non-PDAC组患者的人口特征、临床特征、实验室检查和超声内镜成像特征等相关因素进行单因素 和多因素非条件logistic回归分析。结果纳入75例胰腺实体肿瘤病变中,PDAC占72.0%,non-PDAC占28.0%。EUS-FNA诊 断PDAC的敏感度、特异度、阳性预测值、阴性预测值和准确率分别是77.8%、100.0%、100.0%、63.6%、84.0%。PDAC组与non- PDAC组的EUS-FNA穿刺阳性率差异无统计学意义（77.8% vs 76.2%,P>0.05）。多因素logistic分析显示腹痛（OR=5.163,95% CI：1.093~24.389,P=0.038）、病灶性状（OR=7.105,95%CI：1.440~35.043,P=0.016）、病灶大小（OR=0.926,95%CI：0.877~0.978, P=0.006）、病灶转移（OR=6.165,95%CI：1.332~28.533,P=0.020）是预测PDAC的独立影响因子。结论腹痛、病灶转移、病灶大 小和病灶性状的超声内镜成像特征可以可靠地预测PDAC,并且EUS-FNA对PDAC的诊断是具有较高的敏感度和特异度。     

Investigation of drugs responsible for perioperative anaphylactic reactions using cellular allergen stimulation test

Background Anaphylactic reactions during anesthesia and operation are common and life threatening.Follow-up investigation is necessary for avoiding potential re-exposure of the patients to the offending drugs.The purpose of this study was to assess cellular allergen stimulation test （CAST） as a diagnostic instrument in immunoglobulin E （IgE）-and non-lgE-mediated anaphylactic reactions.Methods This study included 25 patients who developed perioperative anaphylactic reactions and 10 subjects that tolerated anesthetics and other drugs during perioperative period from September 2009 to October 2013 in Peking Union Medical College Hospital.We performed skin tests and flow cytometric analysis of basophil activation-based CAST in all subjects.Results Of the 25 patients,17 had IgE-mediated anaphylactic reactions （causative agent identified by skin tests） and 8 had non-lgE-mediated anaphylactic reactions （negative skin tests）.CAST showed a sensitivity of 42.9％,specificity of 90％,and negative predictive value of 80.6％ for neuromuscular blocking agents.Conclusions CAST may be useful for the diagnosis of anaphylactic reactions during perioperative period.Our findings call for further investigation to increase the sensitivity of the test.     

Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration in intrapulmonary lesions

Background Endobronchial ultrasound-guided transbronchial needle aspiration （EBUS-TBNA） is considered to have high value in the staging of mediastinal lymph nodes in lung cancer. The current study was conducted to investigate the diagnostic value of EBUS-TBNA in intrapulmonary lesions located near the central airway. Methods From September 2009 to March 2013, 66 patients with pulmonary masses located close to the central airways suspected to be lung cancer were accessed by EBUS-TBNA. Conventional bronchoscopic biopsy before EBUS-TBNA was nondiagnostic in all cases. If EBUS-TBNA did not result in a formal pathological diagnosis of malignancy, patients were subsequently referred for a surgical procedure. ResuLts Among the 66 cases, 59 were confirmed as pulmonary malignancies by EBUS-TBNA, of which 48 cases were non-small cell lung cancer, nine were small cell lung cancer, and two were metastatic lung tumors. No evidence of malignancy was found by biopsy and histopathological examination in the other seven cases. Thoracoscopy or thoracotomy was subsequently undergone for them. Postoperative pathological examinations confirmed three cases of squamous cell carcinoma of the lung, one case of lymphoma, two cases of sclerosing hemangioma, and one case of pulmonary tuberculoma. The definitive diagnosis rate of EBUS-TBNA for intrapulmonary lesions near the central airway was 89.4%. The sensitivity, specificity, and accuracy of EBUS-TBNA in distinguishing benign from malignant intrapulmonary lesions were 93.7%, 100.0%, and 93.9%, respectively. The positive and negative predictive values were 100.0% and 42.9%, respectively. The EBUS-TBNA procedures were well-tolerated by all patients. No associated complications were observed. Conclusions For intrapulmonary lesions near the central airway highly suspected of cancer, EBUS-TBNA has satisfactory diagnostic value. However, the negative predictive value of this technique is low, so negative results obtained by EBUSTBNA should be confirmed by other methods.     

Influential factors and effect evaluation of the intra-operative puncture biopsy for pancreatic masses

Background  Polyunsaturated omega-3 fatty acids may beneficially influence healing processes and patient outcomes. The aim of this research was to study the clinical efficacy of fish oil enriched total parenteral nutrition in elderly patients after colorectal cancer surgery.

Methods  Fifty-seven elderly patients with colorectal cancer were enrolled in this prospective, randomized, double-blind, controlled clinical trial. All patients received isocaloric and isonitrogenous total parenteral nutrition by continuous infusion (20–24 hours per day) for seven days after surgery. The control group (n=28) received 1.2 g/kg soybean oil per day, whereas the treatment group (n=29) received 0.2 g/kg fish oil and 1.0 g/kg soybean oil per day. Blood samples were taken pre-operatively, and at days one and eight after the operation. The plasma levels of CD4, CD8, CD4/CD8, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were measured. Clinical outcomes were then analysed.

Results  Patient characteristics were comparable between the two groups. At day eight post-surgery, IL-6, TNF-α and CD8 titres were lower in the treatment group when compared to the control group; these results reached statistical significance. In the treatment group, there were fewer infectious complications and incidences of systemic inflammatory response syndrome (SIRS), and shorter lengths of hospital stay were observed. The total cost of medical care was comparable for the two groups. No serious adverse events occurred in either group.

Conclusions  Fish oil 0.2 g/kg per day administrated to elderly patients after colorectal surgery was safe and may shorten the length of hospital stay and improve clinical outcomes.

     

Krüppel-like factor 8 is a potential prognostic factor for pancreatic cancer

Background Pancreatic cancer is a lethal disease that is often diagnosed at an advanced stage.There is a lack of information to predict the prognosis of pancreatic cancer.Krüppel-like factor （KLF） 8 has been found to be deregulated in multiple cancers,and its high expression was correlated with poor prognosis.However,so far,no information was reported about the expression of KLF8 in pancreatic cancer.In the present study,we investigated,possibly for the first time,the expression of KLF8 in pancreatic cancer samples and analyzed its correlation with clinical parameters and overall survival （OS） rate.Methods We used immunohistochemical staining to detect KLF8 in 68 samples from patients who underwent surgery and its correlation with the clinicopathological characteristics.We used Kaplan-Meier curve to analyze the relationship between KLF8 expression and the OS time.Univariate analysis was performed in addition to multivariate hazard models with clinicopathological features to assess KLF8 as an independent prognostic factor.Results KLF8 was present in the cytoplasm of pancreatic cancer cells and 52.9％ of the 68 cases had positive expression.KLF8 expression was not associated with sex,age,tumor location,lymph node stage,and metastasis stage,but was associated with tumor stage （P=0.04）.Kaplan-Meier method demonstrated that patients with negative expression of KLF8 had a better prognosis.In univariate and multivariate models,KLF8 was a significant predictor of OS in pancreatic cancer.Conclusion Our results revealed that KLF8 may be a potential prognostic factor for pancreatic cancer.     

Clinical manifestation of the SRSF2 gene mutation in Chinese patients with chronic myelomonocytic leukemia

BackgroundSpliceosome mutations have been recently identified and associated with hematological malignancies. SRSF2, one of components of the splicing machinery, has a high mutation frequency during chronic myelomonocytic leukemia, according to previous reports. However, the relevance of this finding in Chinese populations remains unknown.

MethodsWe recruited 50 Chinese patients with chronic myelomonocytic leukemia to analyze the state of SRSF2 and to assess the corresponding clinical features by polymerase chain reaction followed by direct sequencing.

ResultsTen of 50 patients (20%) harbored SRSF2 mutations, including five P95R, two 95H, and three P95L point mutations. The patient group was older than the wild type group (P <0.01). No significant statistical differences were observed with regard to the other clinical characteristics (sex, peripheral blood count, serum lactate dehydrogenase, karyotype, World Health Organization classification, etc.) between these two groups. Two of the patients showed an early evolution to acute myeloid leukemia.

ConclusionsSRSF2 mutations are frequent in chronic myelomonocytic leukemia patients, but show a relatively lower incidence in Chinese patients. Moreover, the mutation can be related to old age and an unfavorable prognosis. Our results provide valuable insights for the development of a diagnostic marker, or for the identification of a therapeutic target for chronic myelomonocytic leukemia.

     

Diagnostic value of endometrial thickness determined by transvaginal sonography in infertile women with endometrial polyps

Background  Endometrial polyps (EPs) occur in approximately 34.9% of infertile women. Transvaginal sonography (TVS) is a routine, non-invasive component of fertility evaluation. Most ultrasonographic studies of EPs have focused on abnormal uterine bleeding; few have assessed EPs in infertile women. Furthermore, no studies have explored endometrial thickness and its correlation with EPs in infertile women. This study aimed to assess transvaginal sonographic assessment of endometrial thickness and its value in diagnosis and prediction of EPs in infertile women.

Methods  A retrospective study on 314 infertile women was conducted from June to December 2010. After TVS, endometrial biopsies were obtained by hysteroscopy. Pathologically confirmed EPs were taken as the gold standard.

Results  Based on recognized criteria, TVS had a sensitivity of 37.04%, specificity of 98.71%, positive predictive value of 90.91%, negative predictive value of 81.85%, and accuracy of 82.80% for diagnosing EPs. Mean endometrial thickness was significantly different in patients with and without EPs (P=0.0001). In women in the mid and late-proliferative phase, the endometrial thickness was significantly greater in those with EPs than in those without them (P=0.0001 and 0.024). Receiver operating characteristic analysis showed that endometrial thickness had a sensitivity of 85.2% and specificity of 38% in the diagnosis of EPs, the area under the curve being 0.64. In the mid-proliferative phase, sensitivity was up to 90.9%, the area under the curve being 0.70.

Conclusions  TVS is poor at detecting EPs in infertile women; however, transvaginal sonographic measurement of endometrial thickness is helpful. It is suggested that the diagnostic value of TVS for EPs in infertile women could be improved by adding the measurement of endometrial thickness to the variables that are routinely assessed.

     

Allergic diseases, immunoglobulin E, and autoimmune pancreatitis: a retrospective study of 22 patients

Background Autoimmune pancreatitis （ALP） is a chronic inflammatory disease of pancreas.We evaluated the clinical manifestations,imaging,and histological presentations of AlP in Chinese patients,and investigated the roles of immunoglobulin E （IgE） and allergic diseases in the diagnosis and pathogenesis of AIP.Methods The clinical records of 22 patients diagnosed with AlP were reviewed and analyzed.All patients with AlP fulfilled the 2006 revised diagnostic criteria proposed by Japan Pancreas Society or the Korean Criteria for AIP.Results Half （11/22） of AlP patients had allergic diseases.Twenty-one patients had elevated serum IgE levels,and 14 patients had IgE levels more than 3 times that of normal.There were no significant differences between the patients with higher or lower IgE,with or without allergic disease,in clinical features,laboratory tests,diffuse or focal lesions,or the choice of treatment methods; however,more complaints of body weight loss were observed in patients with higher IgE levels.Patients with higher IgE levels and with allergic diseases were more likely to have onset in March,April,May,August,September,or October.IgE levels decreased after therapy,but increased again during recurrence.Increased number of mast cells was found in the pancreatic tissue in AIP.Conclusions IgE maybe a useful marker for monitoring therapeutic response and recurrence of AlP.Allergic processes may play an important role in the pathogenesis of AIP.     

Impact of vitamin D supplementation on the outcome of tuberculosis treatment: a systematic review and meta-analysis of randomized controlled trials

Background Vitamin D supplementation is believed to be beneficial in the treatment of patients with tuberculosis （TB）,however,results from clinical trials have been inconclusive.Methods We performed a systematic literature search across MEDLINE,EMBASE,the Cochrane Central Register of Controlled Trials,Springer,EBSCO,ProQuest,HighWire Press,and Web of Science,published as of December 2013.We individually inspected citations and extracted data independently.We estimated pooled risk ratios （RR） and 95％ confidence intervals （CI） using random-effect models.We also assessed risk of bias using the Jadad scale and the quality of the evidence using GRADE.We included all randomized controlled trials comparing vitamin D with or without standard TB therapy or placebo.Results A total of five studies were analyzed in our meta analysis covering 841 newly-diagnosed TB cases.Patients receiving vitamin D supplementation had a 39％ reduced risk of sputum smear or culture positive after six weeks of antiTB treatment than those in the control group,although this is not statistically significant （pooled RR 0.61,95％ CI 0.24 to 1.56,P=0.30）.Apart from an increased serum vitamin D level in the supplement group after eight weeks of treatment there was no evidence of any additional adverse effects related to vitamin D.Conclusions The meta analysis results indicate that vitamin D supplementation does not seem to have any beneficial effect in the treatment of TB.Future rigorous randomized controlled trials are needed to explore whether the supplementation of vitamin D could shorten treatment duration and to confirm whether the polymorphisms of vitamin D receptor have any potentially beneficial effect.     

Structural and evolutionary characteristics of pyruvate phosphate dikinase in Giardia lamblia and other amitochondriate protozoa

Background Pyruvate phosphate dikinase （PPDK） reversibly catalyzes the interconversion of phosphoenolpyruvate （PEP） and pyruvic acid,leading to catabolism and adenosine triphosphate （ATP） synthesis or gluconeogenesis and ATP consumption.Molecular modeling of PPDKs from divergent organisms demonstrates that the orientation of the phosphorylatable histidine residue within the central domain of PPDK determines whether this enzyme promotes catabolism or gluconeogenesis.The goal of this study was to determine whether PDDK from Giardia underwent adaptive evolution in order to produce more energy under anaerobic conditions.Methods A total of 123 PPDK sequences from protozoans,proteobacteria,plants,and algae were selected,based upon sequence similarities to Giardia lamblia PPDK and Zea mays PPDK.Three-dimensional （3-D） models were generated for PPDKs from divergent organisms and were used to compare the orientation of the phosphorylatable histidine residue within the central domain of PPDKs.These PPDKs were compared using a maximum-likelihood tree.Results For PPDK from Giardia,as well as from other anaerobic protozoans,the central domain tilted toward the N-terminal nucleotide-binding domain,indicating that this enzyme catalyzed ATP synthesis.Furthermore,the orientation of this central domain was determined by interactions between the N-and C-terminal domains.Phylogenetic analysis of the N-and C-terminal sequences of PPDKs from different species suggested that PPDK has likely undergone adaptive evolution in response to differences in environmental and metabolic conditions.Conclusion These results suggested that PPDK in anaerobic organisms is functionally adapted to generate energy more efficiently in an anaerobic environment.     

Screening of pathogenic genes in Chinese patients with arrhythmogenic right ventricular cardiomyopathy

Background Arrhythmogenic right ventricular cardiomyopathy （ARVC） is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes. Methods A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C. Results Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in nondesmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them （one of each gene） appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers. Conclusions Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Nondesmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.     

Differentiation of neuromyelitis optica from multiple sclerosis in a cohort from the mainland of China

Background Although there were criteria for diagnosis of neuromyelitis optica （NMO） and multiple sclerosis （MS）,it is still difficult to differentiate NMO from MS,due to the overlapping clinical manifestations.Therefore it is necessary to characterize clinical features of NMO and MS patients in the mainland of China,to simplify the process of disease diagnosis,and to identify criteria for the differential diagnosis of NMO and MS.Methods A total of 138 Chinese Han patients from the mainland of China including 73 NMO,60 MS and 5 MS-like patients with positive NMO-IgG were included in the study.Clinical records were reviewed retrospectively and the results of clinical examination,laboratory experiments,magnetic resonance imaging （MRI） and evoked potentials （EPs） were compared between NMO and MS patients.In addition,the relationship between the NMO-IgG serologic status and clinical characteristics were analyzed.Results Compared with MS patients （1.3∶ 1.0）,more female prevalence was observed in NMO patients （4.2∶ 1.0; P=0.003）.There were also statistically significant differences in visual EPs,oligoclonal bands,brainstem lesions in MRI and longitudinally extensive spinal cord lesions （LESCLs） between NMO and MS patients.Brainstem lesions observed in brain MRI were found in 17.9% of MS patients,over 3.7 times higher than in NMO patients （4.8%,P=0.024）.When stratified NMO patients by NMO-IgG,LESCLs were found in 42.1% of NMO-IgG-negative NMO patients,over 3.5 times higher than in NMO-IgG-positive patients （11.9%,P=0.008）.Statistical difference was also observed in CD4＋/CD8＋ ratios between NMO-IgG-positive and-negative NMO patients.Conclusions Comprehensive analysis of MRI,laboratory and EPs data can facilitate differential diagnosis of MS and NMO.In addition,the combination of LESCLs and brain MRI findings failing to satisfy MRI criteria for MS is highly sensitive and specific for NMO.     

A scoring system for prediction of early recurrence after liver resection for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma

Background The management of Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is controversial due to the early recurrence after curative hepatectomy, and many variables were related to the prognosis. The purpose of this study was to predict the tumor recurrence in early postoperative period of the patients with BCLC stage B HCC.

Methods From January 2004 to January 2012, 104 patients with BCLC stage B HCC underwent hepatectomy. Clinicopathological factors and follow-up data were statistically analyzed to establish a predicting scoring system.

Results The overall survival rates for one, three, and five years were 69.2%, 52.7%, and 42.3%, and the disease-free survival rates for one, three, and five years were 52.9%, 47.3%, and 37.5%, respectively. The multiple factors analysis showed that the micro-vessel invasion, lymph nodes metastasis, multiple lesions, and the high expression of HMGB1 were independent factors (P <0.05). A scoring system was established to predict the early recurrence within one year after the surgery for BCLC stage B HCC, according to the analysis results with a specificity of 85.1% and a sensitivity of 80.3%.

Conclusion Variant clinicopathological factors were associated with early postoperative recurrence for BCLC stage B HCC and recurrence early after hepatectomy was more likely in patients with a higher score of the scoring system.

     

Blockade of the OX40/OX40L pathway and induction of PD-L1 synergistically protects mouse islet allografts from rejection

Background OX40/OX40 ligand （OX40/OX40L） and programmed death-1/programmed death ligand-1 （PD-1/PD-L1） co- stimulator/signals play important roles in T cell-induced immune responses. The aim of this study was to investigate the roles of OX40/OX40L and PD-1/PD-L1 costimulatory pathways in mouse islet allograft rejection. Methods Lentiviral vectors containing OX40L siRNA sequences and an adenovirus vector containing the PD-L1 gene were constructed. The streptozotocin-induced model of diabetes was established in C57BL/6 （H-2b） mice. Diabetic C57BL/6 mice were randomly allocated into five groups： group 1, untreated control; group 2, Ad-EGFP treatment; group 3, Ad-PD-L1 treatment; group 4, OX40L-RNAi-LV treatment; group 5, OX40L-RNAi-LV combined with Ad-PD-L1 treatment. Lentiviral vector and the adenovirus vector were injected, singly or combined, into the caudal vein one day before islet transplantation. The islets of DBA/2 （H-2d） mice were transplanted into the renal subcapsular space of the diabetic recipients. Recipient blood glucose and the survival time of the allografts were monitored. Antigen-specific mixed lymphocyte reaction was also evaluated.     

RT-PCR检测外周血K-ras基因突变和CA-199、CA-50联合检测在胰腺癌诊断中的作用

目的：研究外周血K—ras基因突变和CA-199、CA-50联合检测在胰腺癌诊断中的作用。方法：选择同一时期住院的14例胰腺癌患者和16例非胰腺癌患者．同时应用反转录PCR检测外周血K—ras基因突变和CA-199、CA-50检测,统计分析检测结果。结果：外周血K-ras基因突变检测对胰腺癌诊断的敏感度和特异度分别为42．9％和93．8％,胰腺癌患者CA．199、CA一50二者检测结果差异无显著性．K—ras基因突变和CA-199联合检测系列试验诊断胰腺癌的敏感度和特异度分别为35．7％和93．8％．平行试验的敏感度和特异度分别为78．6％和62．5％。部分胰腺癌患者外周血K-ras基因的检测结果和CA—199、CA-50值与胰腺癌病期呈一定的相关性,结论：RT—PCR检测外周血K—ras基因突变和CA—199联合检测可以弥补单一检测的不足,部分结果与临床病期有一定相关．有助于胰腺癌的辅助诊断,但敏感度偏低,应用临床还需进一步研究。     

Rejection of insulin therapy among patients with type 2 diabetes in China: reasons and recommendations

Background Insulin injection therapy is one of the most effective treatments for type 2 diabetes meUitus （T2DM）. Many people with T2DM in western countries resist starting insulin therapy; whether the same is true in China is unknown. This survey-based study assessed acceptance and rejection of insulin therapy among individuals with T2DM in China and self- reported reasons for these therapy choices. It also examined what methods may be useful for increasing the rate of insulin acceptance. Methods A multi-center, cross-sectional survey was conducted between April and July 2010 to a convenience sample of inpatients and outpatients at 50 medical centers across 29 administrative divisions in China. Data were collected on sociodemographic and T2DM characteristics, therapy regime, and attitudes toward insulin therapy. Results A total of 6 043 patients were surveyed, and 5 961 complete questionnaires （98.6%） were used in the analysis. Just over half the respondents （3 460, 58.0%） reported negative attitudes to insulin therapy, including 2 508 of the 4 469 patients （56.1%） whose physicians had recommended it to them. Of the patients counseled to use insulin, 800 （17.9%） were unwilling to start therapy and cited the following reasons： inconvenience （64.3%）; concerns over addiction （24.6%）; pain （14.3%）; side effects （14.1%）; and high cost （13.6%）. Logistic regression suggested that respondents would be more willing to undertake insulin therapy if they had received diabetes education, had positive attitudes to the treatment, had higher glycosylated hemoglobin level, or had suffered diabetes for a longer period or with more complications. Conclusions Patients with T2DM in China are often resistant to insulin therapy if they have been diagnosed with the disease for a relatively short time or if the disease has been relatively mild. Educating patients on the benefits of insulin therapy, not only at the initial diagnosis with T2DM but also when insulin therapy becomes necessary, will l     

Progression of solitary and multifocal papillary thyroid carcinoma — a retrospective study of 368 patients

Background  Papillary thyroid carcinoma (PTC) represents one of the most frequent endocrine malignancies. Several factors have been found to be involved in determining the outcome of treatment for patients with PTC. Large tumor size, diagnosis at an early age, extra-thyroidal invasion, aggressive histological variants, and distant metastases are the most important determinants of a poor outcome. BRAF^V600E mutation has been found to be a major genetic alteration in PTC. This study aimed to evaluate progression in patients with multifocal and solitary PTC.

Methods  We performed a retrospective study to analyze 368 patients with PTC who underwent surgery, including 282 patients with solitary PTC and 86 patients with multifocal PTC. The status of BRAF^V600E mutation in all tumor foci from multifocal PTC was detected.

Results  Our study suggested that multifocal PTC was more related to lymph node metastasis and vascular invasion than solitary PTC. However, the distant metastasis rate and 10-year survival rate showed no difference between these two groups. The number of tumor foci did not affect progression of disease in multifocal PTC patients. Lymph node metastasis in multifocal PTC patients was associated with larger tumors, diagnosis at early stage, and extra-thyroidal invasion.

Conclusion  The status of BRAF^V600E mutation was more frequent in multifocal PTC patients with lymph node metastasis and diagnosis at later age.