microRNA-466在宫颈癌及宫颈上皮内瘤变中的表达及其意义

目的:分析微RNA-466(microRNA-466,miR-466)在宫颈癌、宫颈上皮内瘤变(CIN)及正常宫颈的表达情况及其与临床病理之间的关系.方法:采用茎环RT-qPCR分析23例宫颈癌、47例CIN,以及13例正常宫颈组织中miR-466的表达,并分析其表达与宫颈癌常见的临床病理特征间的关系.结果:茎环RT-PCR方法能特异检测miR-466;荧光定量PCR分析示miR-466在宫颈癌中的表达低于CIN及正常宫颈组织(P＜0.05);正常宫颈与CIN之间比较差异无统计学意义(P＞0.05);miR-466的表达与年龄、肿块大小、大体类型及组织分化程度差异无统计学意义(P＞0.05);miRNA-466与预测的HPV特异性miRNA同源性分析提示,miR-466与HPV16、18的长控制区(LCR)序列高度同源;生物信息学分析提示,miR-466可调控多种靶基因.结论:miR-466在宫颈癌、CIN及正常宫颈中表达存在明显差异,其在正常宫颈及CIN中相对表达量明显高于宫颈癌;miR-466的异常表达,可能与HPV的LCR区高度同源性相关;miR-466可能调控多种靶分子,参与宫颈癌发生发展过程.     

Efficacy and safety of non-vitamin K antagonist oral anticoagulants in patients (≥80 years of age) with atrial fibrillation: systematic review and meta-analysis

Findings of prior studies about the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in patients (≥80 years of age) with atrial fibrillation (AF) are controversial. So we performed a meta-analysis to evaluate the efficacy and safety of NOACs versus vitamin K antagonists (VKAs) in patients (≥80 years of age) with AF. A systematic review of PubMed, Cochrane, Embase, Web of Science and Chinese BioMedical databases was conducted until 1 October 2022. Studies reporting the effects and safety of NOACs versus warfarin in patients (≥80 years of age) with AF were included. Two authors independently performed study selection and data extraction. Discrepancies were resolved by consensus or through an independent third reviewer. Data were synthesised according to the Preferred Reporting Items for Systematic Reviews guidelines. We identified 15 studies providing data of 70 446 participants (≥80 years of age) suffering from AF. According to the meta-analysis (odds ratio (OR) (95% confidence interval, CI)), NOACs conferred better efficacy profile than VKAs in stroke and systemic embolism (0.8 (0.73–0.88)) and all-cause mortality (0.61 (0.57–0.65)). Otherwise, NOACs conferred a better safety profile than VKAs in major bleeding (0.76 (0.70–0.83)) and intracranial haemorrhage (ICH; 0.57 (0.47–0.68)). In conclusion, for patients (≥80 years of age) with AF, the risks of stroke and systemic embolism, all-cause mortality, were lower in NOACs compared to warfarin. The risks of major bleeding and ICH were also lower in NOACs compared to warfarin. NOACs showed better efficacy and safety than warfarin.     

Twenty‐first century palliative care: a tale of four nations

Hospice and palliative care development, in terms of availability and services, occur to varying degrees in the developing world. In this paper, the evolution of palliative care practices in four developing nations (Nigeria, Georgia, Ethiopia and Tanzania) is described. By highlighting common problems as well as the unique individual perspectives of each country's practice, this paper aims at increasing global awareness of palliative care in the developing world. While the call for palliative care to become a fundamental human right is sustained, it is also hoped that this article will stimulate a global discussion on the best possible way to encourage the establishment and growth of palliative care services in other developing countries where hitherto it has not been in existence, with policymakers and healthcare professionals taking the lead through the institution of sound national policies to promote and provide palliative care to all citizenry.     

The anti-tumoral drug enzastaurin inhibits natural killer cell cytotoxicity via activation of glycogen synthase kinase-3β

Enzastaurin is a selective protein kinase Cβ inhibitor which is shown to have direct antitumor effect as well as suppress glycogen synthase kinase-3β (GSK-3β) phosphorylation (resulting in its activation) in both tumor tissues and peripheral blood mononuclear cells (PBMC). It is currently used in phase II trials for the treatment of colon cancer, refractory glioblastoma and diffuse large B cell lymphoma. In this study, the direct effect of enzastaurin on effector function of human natural killer (NK) cells was investigated. The results obtained showed that enzastaurin suppressed both natural and antibody-dependent cellular cytotoxicity (ADCC) of NK cells against different tumor targets. This inhibition was associated with a specific down-regulation of surface expression of NK cell activating receptor NKG2D and CD16 involved in natural cytotoxicity and ADCC respectively, as well as the inhibition of perforin release. Analysis of signal transduction revealed that enzastaurin activated GSK-3β by inhibition of GSK-3β phosphorylation. Treatment of NK cells with GSK-3β-specific inhibitor TDZD-8 prevented enzastaurin-induced inhibition of NK cell cytotoxicity. Apart from the known antitumor and antiangiogenic effects, these results demonstrate that enzastaurin suppresses NK cell activity and may therefore interfere with NK cell-mediated tumor control in enzastaurin-treated cancer patients.     

Clinicopathological features with outcomes of a series of conventional and proximal-type epithelioid sarcomas,diagnosed over a period of 10 years at a tertiary cancer hospital in India

Epithelioid sarcoma (ES) is an uncommon sarcoma. Lately, its variants, including proximal-type ES, have been recognized. The present study highlights clinicopathological features of 26 (65%) conventional and 14 (35%) cases of proximal-type ES. Thirty-eight percent of cases were seen in 21-30-year age group, including 77.5% cases in men. Extremities were the commonest sites in both the subtypes. Histologically, conventional-type ES displayed nodular tumor aggregates with necrosis, while proximal-type showed solid arrangement of large, "rhabdoid-like" cells. More cases (64.2%) of the proximal type were of grade 3. A range of differential diagnoses was considered. Most important immunohistochemical markers were vimentin, epithelial membrane antigen, cytokeratin, CD34, and desmin. Maximum (72.5%) cases were treated surgically. Recurrences and metastasis were observed more in the proximal type. The 7-year disease-free survival was 19.4% in the conventional and nil in the proximal subtype (p = 0.06). The overall survival rate was also lower in the proximal (31.3%) than conventional type (90.2%; p < 0.001). Other unfavorable parameters were deeper location, larger size, and higher tumor stage. This unusual sarcoma, with characteristic growth patterns, merits a proper histological evaluation, as it has many mimics. Proximal-type ES is rather a morphological subtype, associated with an aggressive course.     

Upper gastrointestinal endoscopy: a review of 10,000 cases

A total of 10,000 patients underwent upper gastrointestinal endosopy examination between August 1979 and October 1994 at Tikur Anbessa Hospital, Addis Ababa. The major indications were dyspepsia (59.4%), upper gastrointestinal bleeding (18%) and liver disease (10.8%). The other indications include dysphagia (2.2%), gastric outlet obstruction (2.1%), postoperative dyspeptic symptoms (1.9%), weight loss and/or anemia (1.4%), epigastric mass (0.6%) and odynophagia 0.2%. The mean age of the patients and their sex ratio was 36 years and 2:1, respectively. Twenty eight percent of the patients had normal findings. The commonest abnormal findings include duodenal ulcer (41%), esophageal varices (9%), acute gastritis (6%), duodenitis (3.4%), and reflux esophagitis (2.3%). Benign gastric ulcer was rare. The ratio of duodenal ulcer to gastric ulcer was 19.1%. Duodenal ulcer (45.6%), esophageal varices (15.6) and acute gastritis (5.7%) were found to be the commonest causes of upper gastrointestinal bleeding. The endoscopy or histology diagnosis of cancer in both the esophagus and stomach was 2.8% and 1.3%, respectively. The agreement between endoscopy and histology in the diagnosis of esophageal and gastric cancer was 80%. There was no major complication related to endoscopy or premeditation. Endoscopy is a fairly accurate and safe procedure and therefore should be available and applied widely for the diagnosis of upper gastrointestinal diseases in Ethiopia.     

Access to Revascularization Among Patients with Acute Myocardial Infarction in New York City—Impact of Hospital Resources

Timely revascularization can improve survival in patients with acute myocardial infarction. Identification of factors associated with increased use of revascularization in appropriate patients could improve outcomes. Using New York City hospital discharge records for 1988-1992 and 1998-2002, we determined revascularization rates for patients hospitalized with MI by neighborhood. Odds ratios for revascularization were estimated using a spatial model adjusting for neighborhood sociodemographic characteristics, while accounting for similarities in the rate of revascularization among geographically adjacent neighborhoods. Only 16 out of 112 New York City hospitals performed coronary revascularization. They were located in 14 of 41 neighborhoods. In general, patients living in neighborhoods with higher percentages of patients admitted to hospitals capable of revascularization service were more likely to be revascularized than those in neighborhoods with low percentages of patients admitted to hospitals with revascularization resources. This was true regardless of neighborhood availability of revascularization, after accounting for neighborhood socioeconomic characteristics and patients' clinical status. Revascularization rates in New York City increased from 1988-1992 to 1998-2002 in every neighborhood and as a whole from 103 to 326 per 1,000 hospitalized AMI patients. This increase was not explained by the addition of new revascularization services. Thus, in New York City, where only certain hospitals can perform revascularization, efficient delivery of patients to hospitals with these resources appears to increase the likelihood of revascularization performance among AMI patients without increasing the number of new hospitals capable of revascularization.     

The effect of omitted covariates on confidence interval and study power in binary outcome analysis: a simulation study

BACKGROUND/OBJECTIVES: The consequence of omitted but balanced covariates on odds ratio point estimation is well-known in the literature. When exposure or intervention has a non-null effect on disease outcome, omitted covariates lead to underestimation of the effect of exposure or intervention. However, the effect of omitted covariates on confidence interval and study power is unknown. STUDY DESIGN AND SETTING: A simulation study is carried out to assess the effect of omitted covariates on confidence interval and study power for a plausible range of scenarios. Coverage probability and study power are assessed systematically over a range of study size, type of omitted covariate and magnitude of effect. A real-life example using a randomised experiment on flies' sexuality is provided. RESULTS: When a balanced covariate is omitted, coverage probability was lowered by 2.9-80%. Likewise study power was reduced by as much as 58%. The impact becomes substantial when the covariate is continuous, has large variability and has a larger effect than the effect of exposure or intervention. The result from a real-life example concurs with the simulation finding. CONCLUSION: Omitting an important balanced covariate lowers both coverage probability and study power. This implies the need for thoughtful consideration of important covariates at the design as well as the analysis stages of a study.