含克力芝组合的HAART方案对HIV/HCV混合感染的疗效探讨

目的探讨含克力芝(LPV/r)组合的高效抗反转录病毒治疗(HAART)方案,对艾滋病病毒(HIV)、丙型肝炎病毒(HCV)混合感染治疗的效果。方法采用前瞻性研究方法,选择HIV/HCV混合感染患者43例,通过Spw-Pb网络数据平台随机分为研究组与对照组。研究组22例,采用以洛匹那韦/利托那韦(LPV/r)为基础的HAART治疗方案;对照组21例,采用以依非韦伦(EFV)为基础的HAART治疗方案。研究组与对照组检测基线CD4+T淋巴细胞计数、HIV病毒载量、丙氨酸转氨酶(ALT)、胆固醇(CHO)、甘油三酯(TG)等指标;治疗后48周分别检测上述指标,研究终点为48周。观察病毒学、免疫学、ALT、CHO、TG等指标的变化。结果 HAART治疗48周,研究组与对照组HIV-RNA阴转率比较差异无统计学意义(P>0.05)。研究组与对照组基线CD4+T淋巴细胞、ALT、CHO、TG比较差异无统计学意义(均P>0.05);HAART治疗48周,研究组CD4+T淋巴细胞计数增长明显高于对照组,差异有统计学意义(P<0.05);而研究组与对照组ALT、CHO、TG比较差异无统计学意义(均P>0.05)。结论含LPV/r组合的抗病毒方案对HIV/HCV混合感染治疗效果较优越,CD4+T淋巴细胞增长较明显,胆固醇、甘油三酯变化不大,建议HIV/HCV混合感染HAART治疗选择LPV/r方案为佳。     

Systematic Review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

BackgroundThe 2013 American College of Cardiology/American Heart Association guidelines for the treatment of blood cholesterol found little evidence to support the use of nonstatin lipid-modifying medications to reduce atherosclerotic cardiovascular disease (ASCVD) events. Since publication of these guidelines, multiple randomized controlled trials evaluating nonstatin lipid-modifying medications have been published.MethodsWe performed a systematic review to assess the magnitude of benefit and/or harm from additional lipid-modifying therapies compared with statins alone in individuals with known ASCVD or at high risk of ASCVD. We included data from randomized controlled trials with a sample size of >1,000 patients and designed for follow-up >1 year. We performed a comprehensive literature search and identified 10 randomized controlled trials for intensive review, including trials evaluating ezetimibe, niacin, cholesterol-ester transfer protein inhibitors, and PCSK9 inhibitors. The prespecified primary outcome for this review was a composite of fatal cardiovascular events, nonfatal myocardial infarction, and nonfatal stroke.ResultsThe cardiovascular benefit of nonstatin lipid-modifying therapies varied significantly according to the class of medication. There was evidence for reduced ASCVD morbidity with ezetimibe and 2 PSCK9 inhibitors. Reduced ASCVD mortality rate was reported for 1 PCSK9 inhibitor. The use of ezetimibe/simvastatin versus simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) reduced the primary outcome by 1.8% over 7 years (hazard ratio: 0.90; 95% CI: 0.84–0.96], 7-year number needed to treat: 56). The PSCK9 inhibitor evolocumab in the FOURIER study (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) decreased the primary outcome by 1.5% over 2.2 years (hazard ratio: 0.80; 95% CI: 0.73–0.88; 2.2=year number needed to treat: 67). In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab reduced the primary outcome by 1.6% over 2.8 years (hazard ratio: 0.86; 95% CI: 0.79–0.93; 2.8-year number needed to treat: 63). For ezetimibe and the PSCK9 inhibitors, rates of musculoskeletal, neurocognitive, gastrointestinal, or other adverse event risks did not differ between the treatment and control groups. For patients at high risk of ASCVD already on background statin therapy, there was minimal evidence for improved ASCVD risk or adverse events with cholesterol-ester transfer protein inhibitors. There was no evidence of benefit for the addition of niacin to statin therapy. Direct comparisons of the results of the 10 randomized controlled trials were limited by significant differences in sample size, duration of follow-up, and reported primary outcomes.ConclusionsIn a systematic review of the evidence for adding nonstatin lipid-modifying therapies to statins to reduce ASCVD risk, we found evidence of benefit for ezetimibe and PCSK9 inhibitors but not for niacin or cholesterol-ester transfer protein inhibitors.     

Need for social work education and practice in the prevention of HIV/AIDS: A case study of Pakistan

ABSTRACT

HIV/AIDS in Pakistan was first diagnosed in 1986. The National AIDS Control Program was formulated in 1987. Unfortunately, after spending 26 years on the prevention of HIV/AIDS, we are still missing a major professional field in this effort: there is no evidence of the social worker in the National Health Policy of 2001 and in the National HIV/AIDS Policy of 2007. The aim of this study is to present the history and analysis of AIDS policies, laws, and strategic framework of Pakistan and make suggestions in social work education and practice’s role in combating HIV/AIDS in the country.     

基于RIP1/RIP3/NLRP3信号通路探讨祛瘀生新方治疗溃疡性结肠炎小鼠的作用机制

目的:研究祛瘀生新方对溃疡性结肠炎(UC)小鼠的治疗效果以及对RIP1/RIP3/NLRP3信号通路的调节作用.方法:将36只小鼠随机分为实验组(祛瘀生新组)、模型组、阳性对照组(美莎拉嗪组)、空白组、中药拆方1组(生新组)、中药拆方2组(祛瘀组),6只/组,采用3.5％葡聚糖硫酸钠盐(DSS)溶液自由饮水法制备UC小...     

A refractory human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis patient with lymphoma-type adult T-cell leukemia/lymphoma: A case report and review of the literature

Rationale:Adult T-cell leukemia/lymphoma (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are caused by HTLV-1, but the coexistence of both disorders is rare. The estimated incidence is approximately 3%.Patient concerns:A 54-year-old man was unable to stand up because of spastic paraparesis 1 month after the onset. He developed lymphadenopathy in the left supraclavicular fossa 5 months after the onset. The spastic paraplegia and sensory symptoms below the thoracic spinal cord level worsened.Diagnoses:Both blood and cerebrospinal fluid (CSF) tests were positive for anti-HTLV-1 antibodies. The patient was diagnosed with rapidly progressive HAM/TSP. He was also diagnosed with lymphoma-type ATL by the biopsy specimen of the lymph node. CSF examination at the time of symptom exacerbation showed abnormal lymphocytes, suggesting central infiltration of the ATL in the central nervous system.Interventions:Methylprednisolone pulse therapy and oral prednisolone maintenance therapy were administered for rapidly progressive HAM/TSP. Intrathecal injection of methotrexate was administered for the suggested central infiltration of the ATL.Outcomes:Methylprednisolone pulse therapy and intrathecal injection of methotrexate did not improve the patient''s exacerbated symptoms. Five months later, clumsiness and mild muscle weakness of the fingers appeared, and magnetic resonance imaging showed swelling of the cervical spinal cord. Clonality analysis showed monoclonal proliferation only in the DNA of a lymph node lesion, but not in the CSF and peripheral blood cells.Lessons:This was a case of rapidly progressive HAM/TSP associated with lymphoma-type ATL that was refractory to steroids and chemotherapy. The pathogenesis was presumed to involve ATL cells in the brain and spinal cord because of the presence of abnormal lymphocytes in the CSF, but DNA analysis could not prove direct invasion. This case suggests that when we encounter cases with refractory HAM/TSP, it should be needed to suspect the presence of ATL in the background.     

18F-FDG PET/CT imaging for aggressive melanotic schwannoma of the L3 spinal root: A case report

Rationale:Melanotic schwannoma (MS) is an unusual variant of a nerve sheath neoplasm that accounts for less than 1% of all primary peripheral nerve sheath tumors. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) has unique value in detecting malignant MS lesions. To date, only 4 cases of MS with hepatic metastasis have been reported. Herein, we report the fifth case, which is the first reported patient with MS of Asian ethnicity with hepatic metastasis.Patient concerns:A 29-year-old woman with a 1-day history of backache was admitted to our hospital. PET/CT showed a paravertebral heterogeneous soft tissue mass along the spinal nerve at the L2-L3 level with strong FDG uptake, and a nodule with increased FDG uptake in the lateral lobe of the left liver.Diagnosis:A puncture biopsy of the L3 bony destruction and surrounding soft tissue mass was performed. The final diagnosis was spinal MS with hepatic metastasis.Interventions:The patient underwent 6 courses of systemic chemotherapy.Outcomes:The patient did not receive further treatment for half a year after the end of chemotherapy and recovered well.Lessons:Unlike conventional schwannomas, which are completely benign, MS has an unpredictable prognosis. It is thought to have low malignant potential, and the malignant type tends to metastasize. FDG PET/CT has a unique and important value in the differential diagnosis of benign and malignant lesions, in detecting occult metastases, monitoring the treatment response, and assessing the prognosis of MS.     

Association of IL-10 -819C/T, -592A/C polymorphisms with the risk of preeclampsia: An updated meta-analysis

Objective:The purpose of our study was to investigate whether IL-10 -819C/T, -592A/C polymorphisms were associated with preeclampsia (PE) susceptibility.Methods:A comprehensive and systematic literature search was performed through online databases, including Web of Science, PubMed, EMBASE, and Chinese databases. Then eligible literatures were included according to inclusion criteria and exclusion criteria. Statistical data analysis was performed using Stata 10.0 software. Odds ratios (OR) and 95% confidence interval were applied to evaluated the association between IL-10 -819C/T, -592A/C polymorphisms and PE susceptibility.Results:According to inclusion and exclusion criteria, 9 case-control studies, including 1423 cases and 2031 controls, were included in this meta-analysis. Our meta-analysis revealed that no association was found between IL-10 -819C/T, -592A/C polymorphisms and the risk of PE in our study.Conclusion:Our meta-analysis suggested that IL-10 -819C/T and -592A/C polymorphisms had no association with PE susceptibility, but had a significant association with PE susceptibility in Asian and Caucasian.     

A simple procedure for estimation of the spatial QRS/T angle from the standard 12-lead electrocardiogram

The spatial QRS/T angle has been identified as a strong predictor of adverse cardiac events. Mean QRS and T amplitudes from X, Y, and Z leads generated by a matrix transformation method are often used to calculate the QRS/T angle (QRS/T_matrix). Many investigators find this procedure cumbersome. We used electrocardiographic data files of 14 881 men and women aged 45 to 65 years from the Atherosclerosis in Communities study to derive a simple formula for estimated spatial QRS/T angle (QRS/T_simple). QRS/T_simple is calculated as the inverse cosine between the mean QRS and T vectors, which are approximated by 3 QRS_net and T_net amplitudes for each vector. QRS/T_simple explained 79% of the variance of QRS/T_matrix (r = 0.89)_. Using sex-specific thresholds, QRS/T_simple detected abnormally wide QRS/T_matrix values with a sensitivity of 91% and specificity of 88%. It is concluded that this simple method may provide a satisfactory substitute for QRS/T from the matrix transformation method.     

Interventional Therapy Versus Medical Therapy for Secundum Atrial Septal Defect: A Systematic Review (Part 2) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

Secundum atrial septal defect (ASD) is the most common adult congenital heart defect and can present with wide variation in clinical findings. With the intention of preventing morbidity and mortality associated with late presentation of ASD, consensus guidelines have recommended surgical or percutaneous ASD closure in adults with right heart enlargement, with or without symptoms. The aim of the present analysis was to determine if the protective effect of secundum ASD closure in adults could be qualified by pooling data from published studies.A systematic review and meta-analysis were performed by using EMBASE, MEDLINE (through PubMed), and the Cochrane Library databases to assess the effect of secundum ASD percutaneous or surgical closure in unoperated adults ≥18 years of age. Data were pooled across studies with the DerSimonian-Laird random-effects model or a Bayesian meta-analysis model. Between-study heterogeneity was assessed with Cochran’s Q test. Bias assessment was performed with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar’s test and Egger’s test.A total of 11 nonrandomized studies met the inclusion criteria, contributing 603 patients. Pooled analysis showed a protective effect of ASD closure on New York Heart Association functional class and on right ventricular systolic pressure, volumes, and dimensions. Two additional studies comprising 652 patients were reviewed separately for mortality outcome and primary outcome of interest because they did not meet the inclusion criteria. Those studies showed that ASD closure was associated with a weak protective effect on adjusted mortality rate but no significant impact on atrial arrhythmias in patients >50 years of age. Across all studies, there was significant heterogeneity between studies for nearly all clinical outcomes. The overall body of evidence was limited to observational cohort studies, the limitations of which make for low-strength evidence. Even within the parameters of the included studies, quality of evidence was further diminished by the lack of well-defined clinical outcomes.In conclusion, pooled data analysis on the impact of secundum ASD closure in adults was notably limited because of the lack of randomized controlled trials in patients with only secundum ASD. The few cohort studies in this population demonstrated improvement in functional status and right ventricular size and function as shown by echocardiogram. However, our findings suggest that at the time of this publication, insufficient data are available to determine the impact of ASD repair on mortality rate in adults.     

Sacubitril/Valsartan: The Newest Addition to the Toolbox for Guideline-Directed Medical Therapy of Heart Failure

Sacubitril/valsartan combines a neprilysin inhibitor with an angiotensin receptor blocker. As an inhibitor of neprilysin, an enzyme that degrades biologically active natriuretic peptides, this first-in-class therapy increases levels of circulating natriuretic peptides, resulting in natriuretic, diuretic, and vasodilatory effects. In patients with chronic New York Heart Association class II-IV heart failure with reduced ejection fraction, the PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduced the primary endpoint of cardiovascular mortality and heart failure hospitalization, compared with enalapril. The rate of all-cause mortality was also significantly reduced. Subsequently, the American College of Cardiology/American Heart Association/Heart Failure Society of America recently updated guideline recommendations for Stage C patients with heart failure with reduced ejection fraction to recommend angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril/valsartan in conjunction with other evidence-based therapies to reduce morbidity and mortality. Several analyses have suggested the cost-effectiveness of this new therapy. To ensure tolerability, initiating the lower dosage form of sacubitril/valsartan is warranted in patients with severe renal impairment, moderate hepatic impairment, and low blood pressure, and close monitoring is warranted in such patients. A 36-hour washout period is recommended when switching patients from an angiotensin-converting enzyme inhibitor to sacubitril/valsartan. Similarly, sacubitril/valsartan is contraindicated in patients receiving concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and those with a history of angioedema.     

Apremilast in the Treatment of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Pilot Study

Objective: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a disease with an uncertain cause and limited effective treatments. Apremilast (Celgene Corporation, Summit, NJ, USA) is a selective phosphodiesterase type 4 (PDE4) inhibitor that modulates the immune system. An open‐label, one‐arm, pilot study was conducted to explore its potential for improving CP/CPPS symptoms. Methods: Males ≥ 18 years of age were treated with 20 mg oral apremilast twice daily for up to 12 weeks. Outcomes were measured with Global Response Assessment (GRA), pain visual analog scale (VAS), Chronic Prostatitis Symptom Index (CPSI), Pittsburgh Sleep Quality Index (PSQI), SF‐12 mental (MCS) and physical (PCS) health‐related quality of life subscales, and voiding diaries. Repeated measures and paired t‐tests evaluated changes from baseline to end of treatment, and at a final visit 4 weeks off the drug. Results: Seventeen men (94% Caucasian; mean age 48.2 ± 10 years) were treated (mean 115.8 ± 56.1 doses). Mean VAS (3.4 ± 2.0 vs 1.8 ± 1.7; P = 0.0011), PSQI (9.4 ± 4.4 vs 7.4 ± 4.2; P = 0.037) and CPSI (26.1 ± 5.0 vs 17.2 ± 8.3; P = 0.0016) scores improved from baseline to end of treatment. Incontinence episodes per day improved slightly (P = 0.042). When only those completing at least 8 weeks of treatment were examined (n = 9), significant changes in CPSI, VAS, and PSQI were still observed. At the final visit, 8/9 (88.9%) men also reported some improvement in pain related to sex. Side‐effects were generally mild and well tolerated. Conclusion: These results suggest that apremilast may improve CP/CPPS symptoms with only mild side‐effects. However, placebo controlled studies are necessary to determine efficacy.     

Metal/Graphene Composites: A Review on the Simulation of Fabrication and Study of Mechanical Properties

Although carbon materials, particularly graphene and carbon nanotubes, are widely used to reinforce metal matrix composites, understanding the fabrication process and connection between morphology and mechanical properties is still not understood well. This review discusses the relevant literature concerning the simulation of graphene/metal composites and their mechanical properties. This review demonstrates the promising role of simulation of composite fabrication and their properties. Further, results from the revised studies suggest that morphology and fabrication techniques play the most crucial roles in property improvements. The presented results can open up the way for developing new nanocomposites based on the combination of metal and graphene components. It is shown that computer simulation is a possible and practical way to understand the effect of the morphology of graphene reinforcement and strengthening mechanisms.     

LW/SO cell line: A tool for studying the phenotypical characterization and commitment of hematopoietic stem cells

We report our observations with the cell line LW/SO, which was recently derived from the bone marrow of a patient with acute myeloid leukemia. Based on the morphological and histochemical examination, the leukemic cells were classified primarily as FAB type M4. However, 2 years later, in relapse, the cells changed their morphology and were hence specified as FAB type M2 (slightly positive for acid phosphatase and Sudan black). The cells established have now been in culture for approximately 11 months and display nearly 100% CD4/5/7/15/25/71/120_a,b at varying densities. Some of them spontaneously and reversibly become either CD34 + /38-or CD34-/38 + , yet the majority of the cells remain negative for both. All attempts to separate the cells with a distinct phenotype by limiting dilution or sorting through a flow cytometer failed repeatedly. The subsets, enriched up to 98% (regardless of their primary immunophenotype CD34-/38-, CD34 + /38-, or CD34-/38+), soon displayed a phenotypical constellation similar to that before sorting. The ratio of CD34-to CD34+ seems to be influenced by the cell density: The greater the cell-to-cell contact, the lower the percentage of CD34-expressing cells. Some of the cells apparently differentiate into T-cell phenotype and acquire CD3 and T-cell receptor (TCR) α/ β molecules. While the quantity of CD34-expressing cells significantly increased in the presence of dexamethasone (10^-7 M), and some of them additionally acquired CD33 antigen, the percentage of CD3-positive cells was enhanced by adding 1% DMSO in medium. In contrast, cytokines such as IL-1, IL-2, IL-3, IL-4, IL-6, G-CSF, GM-CSF, or SCF (c-kit ligand) altered neither the proliferation capacity nor the phenotypical constellation of LW/SO cells (each tested alone). Although normal karyotype was obtained from the bone marrow cells, the LW/SO cells revealed a homogeneous chromosomal composition of 45, X,-X, der(9) inv(9) (pl2ql3) del(9) (p22?). These data suggested that LW/SO cells might be the leukemic counterpart of putative pre-CD34-positive progenitors. In order to substantiate this assumption, we analyzed the expression of other so-called T-cell markers on CD34+ cells from peripheral blood stem cell aphereses of five patients who later underwent high-dose chemotherapy and subsequent stem cell retransfusion. These data clearly revealed that a considerable amount of CD34+ hematopoietic progenitors co-express CD2/4/(5)/(7)/25 at an early stage of differentiation, and support the notion that CD34-negative LW/SO cells with the surface markers CD4/5/7/25 are probably phenotypical representatives of pluripotent stem cell. Hence, not all CD34-negative populations with so-called T-cell surface markers should be considered T-cells; some may constitute the ancestor of CD34 antigen-expressing progenitors.     

The role of estrogen receptor-beta gene +1730G/A polymorphisms in recurrent pregnancy loss: A protocol for systematic review and meta-analysis

Objective:To identify the role of estrogen receptor-beta (ER-β) gene +1730G/A (rs4986938) polymorphisms in recurrent pregnancy loss (RPL).Methods:All relevant case-control studies will be systematically searched in multiple databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Internet (CNKI), Wanfang and Cqvip. Both pooled odds rations (ORs) and 95% confidence intervals (CIs) will be used to assess the association between ER-β gene +1730G/A polymorphisms and RPL risk. The publication bias will be evaluated using Egger test.Results:ER-β gene +1730G/A variation may be associated with a higher risk of RPL in Caucasian population.Conclusions:The findings of this meta-analysis will provide high-quality evidence for the association between ER-β gene +1730G/A polymorphisms and RPL, facilitating clinical practice and further scientific studies.OSF registration number:10.17605/OSF.IO/EW9FB.