Temporal Trends of Women Enrollment in Major Cardiovascular Randomized Clinical Trials

Background

Although it is known that women do not participate in trials as frequently as men, there are limited recent data examining how women recruitment has changed over time.

腰椎融合术前相邻节段存在退变因素对术后早期临床疗效的影响

目的探讨腰椎拟融合节段的相邻节段术前存在的椎管狭窄因素对术后早期临床疗效的影响。方法采用前瞻性对比研究，将 2015 年 7 月—2017 年 12 月收治的符合选择标准的 183 例 L₄～S₁ 腰椎管狭窄症患者，根据术前椎间盘退变情况及椎管狭窄情况判断的相邻节段退变（adjacent segment degeneration，ASD）状态不同分成两组，A 组 98 例（术前相邻节段无退变），B 组 85 例（术前相邻节段已退变）。两组患者性别、美国麻醉医师协会（ASA）分级、体质量指数（body mass index，BMI）、合并滑脱状态及术前腰、腿痛疼痛视觉模拟评分（VAS）、日本骨科协会（JOA）评分、Oswestry 功能障碍指数（ODI）等一般资料比较差异无统计学意义（P>0.05）；A 组患者年龄显著小于 B 组（t=−3.560，P=0.000）。记录并比较两组患者手术时间、术中出血量、住院时间、围术期并发症；末次随访时采用腰、腿痛 VAS 评分、JOA 评分、ODI 评分评价疗效。比较两组间末次随访时 ASD 发生情况，采用 logistic 回归分析影响患者术后出现 ASD 的独立危险因素。 结果两组患者手术时间、术中出血量及住院时间比较差异均无统计学意义（P>0.05）。A、B 组围术期并发症发生率分别为 13.3% 和 20.0%，比较差异无统计学意义（χ²=1.506，P=0.220）。两组患者均获随访，A、B 组随访时间分别为（24.9±8.8）个月和（24.8±7.8）个月，差异无统计学意义（t=0.050，P=0.960）。至末次随访时，两组患者均未出现相邻节段病变。两组患者末次随访时椎间盘 Pfirrmann 分级与术前比较差异均无统计学意义（P>0.05）；术前及末次随访时两组间 Pfirrmann 分级差异均有统计学意义（P<0.001）。至末次随访时 A、B 组分别有 21 例（21.4%）和 53 例（62.4%）出现 ASD，比较差异有统计学意义（χ²=31.652，P=0.000）；术后相邻节段椎管狭窄程度加重是术后发生 ASD 的主要原因。两组患者末次随访时各临床评分均较术前显著改善（P<0.05），末次随访时 A 组 JOA 评分显著高于 B 组（P<0.05）。B 组患者中术后出现 ASD 患者末次随访时的腰痛 VAS 评分、ODI 评分显著高于非 ASD 患者（P<0.05）。logistic 回归分析显示，术前相邻节段存在退变因素与 BMI 是影响患者术后出现 ASD 的独立危险因素（P<0.05）。 结论术前相邻节段存在退变因素，会显著影响患者术后早期临床疗效及增加术后出现 ASD 的风险，相邻节段椎管狭窄程度加重是术后早期 ASD 主要的病理类型。应根据术前相邻节段椎管的整体退变情况评估术前相邻节段的退变状态。     

Dietary fat intake and metabolic syndrome in adults: A systematic review

Background and aimsThe metabolic syndrome (MetS) is a cluster of coexisting cardiovascular risk factors. The role of specific dietary fats was reemphasized by dietary recommendations. This systematic review aims to assess evidence for the effect of dietary fat intake on MetS occurrence and reversion in adults.Methods and ResultsThe MEDLINE database was used to search the existing literature. We included observational studies that analyzed dietary fat intake in adults with MetS and clinical trials that compared the effects of different dietary fat diets on MetS and/or its components. Thirty articles were selected (14 observational and 16 clinical trials), and we included information of dietary fat and fatty acids as well as MetS, body mass index, cholesterol, hypertension, and diabetes in adults. SFA intake was found to be positively associated with MetS components. Most of the observational reviewed studies found beneficial associations between MUFA and PUFA (including n-3 and n-6 subtypes) intake and MetS components. Clinical trials also supported the benefits of MUFA- or PUFA-enriched diets (including low-fat diets) in reducing MetS.ConclusionsThe effects of dietary SFAs on MetS will be influenced by other specific nutrients. Replacement of SFA by MUFA and PUFA has been associated with a decrease in MetS. Dietary recommendations should emphasize on different qualities of fat intake, not only to reduce total fat intake, to obtain health benefits in adults.     

Sinonasal tract pathology: an updated review of select entities

The sinonasal tract is host to numerous benign and malignant entities that can pose diagnostic challenges to pathologists as a result of limited exposure in daily practice. This review concentrates on certain key characteristics of select entities with focus on differential diagnosis, novel subtypes and/or molecular distinction. The aim of this review is to summarize current knowledge and shed light on diagnostically challenging and emerging entities in sinonasal tract pathology.     

Suppression of puerarin on polymethylmethacrylate-induced lesion of peri-implant by inhibiting NF-κB activation in vitro and in vivo

Puerarin (PR), a natural isoflavone isolated from Chinese traditional plant pueraria lobata, has attracted considerable attention due to its important biological and pharmacological activities. However, its effects on lesion of peri-implant and related mechanism of action are still not clear, which require further investigation. In this study, we evaluated the effects of PR on polymethylmethacrylate (PMMA)-induced lesion of peri-implant in vitro and in vivo, and explored its possible mechanism of action. Our results indicated that PR could inhibit PMMA-induced osteoclastogenesis in RAW264.7 cells with a dose-dependent manner in vitro and effectively down-regulate mRNA and protein expressions of matrix metalloprotein 9 (MMP-9), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and receptor activator of nuclear factor (NF)-κB (RANK), primarily via the suppression of NF-κB signaling. Furthermore, we found that PMMA induction could directly cause the phosphorylation of IκB and significantly promote the nuclear translocation of p65 in RAW264.7 cells. In other words, PR was able to dose-dependently attenuate the PMMA-induced nuclear translocation of p65 in RAW264.7 cells. In vivo, PR was observed to attenuate PMMA-induced osteoclastogenesis, osteolysis, mRNA expressions of receptor activator of nuclear factor (NF)-κB ligand (RANKL) and RANK, as well as protein levels of MMP-9, TNF-α, IL-6, and p65 in a murine calvarial osteolysis model. These findings suggested that PR might be a potential therapeutic drug to lesion of peri-implant, and provided new insights for understanding its possible mechanism.     

膝关节骨软骨损伤评估及治疗方法

目的探讨膝关节骨软骨损伤评估、治疗方法以及疗效。方法2010 年 1 月—2016 年 1 月，收治 17 例膝关节骨软骨损伤患者。男 2 例，女 15 例；年龄 15～33 岁，平均 19.3 岁。致伤原因：扭伤 14 例，膝关节过伸、内翻暴力致伤 3 例。骨软骨骨折部位：髌骨 8 例，股骨外髁 4 例，股骨内髁 1 例，胫骨平台 4 例。新鲜骨折 15 例，陈旧性骨折 2 例。术前膝关节 Lysholm 评分为（31.6±2.3）分。14 例骨软骨骨折切开复位后，根据骨质情况分别选择可吸收棒（9 例）、可吸收软骨钉（3 例）或可吸收缝线（2 例）固定；3 例骨块位于胫骨内侧平台边缘非负重区直接取出。结果术后 1 例发生切口脂肪液化，再次清创后愈合；其余患者切口均Ⅰ期愈合。患者均获随访，随访时间 6 个月～2 年，平均 13 个月。14 例行内固定患者中，13 例骨折愈合良好，1 例髌骨骨软骨骨折未愈合；3 例非负重区骨软骨取出患者，随访期间未见膝关节内侧关节间隙变窄及创伤性关节炎发生。术后 1 年，膝关节 Lysholm 评分为（91.3±1.1）分，较术前明显改善（t=7.136，P=0.001）。 结论对于膝关节骨软骨损伤，骨软骨骨块带有全层松质骨时可选择切开复位内固定，带点状松质骨时可直接取出。     

Does CETP rs5882, rs708272, SIRT1 rs12778366, FGFR2 rs2981582, STAT3 rs744166, VEGFA rs833068, IL6 rs1800795 polymorphisms play a role in optic neuritis development?

Objectives: Optic neuritis (ON) is defined as inflammation of the optic nerve, which is mostly idiopathic. However, it can be associated with various causes (demyelinating lesions, autoimmune disorders, infectious and inflammatory conditions). Inflammatory demyelinating disorder of the optic nerve can be associated with multiple sclerosis. It is thought that CETP, SIRT1, FGFR2, STAT3, VEGFA and IL6 genes play a key role in this autoimmune inflammatory disease. The aim of our study was to determine if the frequency of the CETP, SIRT1, FGFR2, STAT3, VEGFA and IL6 gene polymorphisms have an influence on the development of acute ON.

Methods: The study enrolled patients with ON and a random sample of healthy population. The genotyping test of the CETPrs5882,rs708272, SIRT1rs12778366, FGFR2rs2981582, STAT3rs744166, VEGFArs833068, IL6rs1800795 polymorphisms was carried out using the RT-PCR method.

Results: Our study determined that the G/A genotype of CETPrs708272 was associated with two-fold-decreased odds of ON development under the codominant (OR = 0.495;95%CI:0.256–0.959) and overdominant (OR = 0.501;95%CI:0.280–0.895) models. Also, each allele C at VEGFArs833068 was associated with 1.7-fold increased odds of ON development under the additive model (OR = 1.733;95%CI:1.148–2.615). Furthermore, IL6 rs1800795 G/G genotype was associated with increased odds of ON development under the codominant (OR = 2.869;95%CI:1.280–6.434) and recessive (OR = 2.315;95%CI:1.251–4.285) models.

Conclusions: We revealed that the genotypes of CETPrs708272 G/A, IL6rs1800795 G/G, and each allele C at VEGFArs833068 were associated with ON. CETPrs708272 G/G genotype was associated with decreased by 62% odds of ON with MS development under the recessive (OR = 0.379;95%CI:0.155–0.929; p = .034) model.     

Stabilization and formulation of a recombinant Human Cytomegalovirus vector for use as a candidate HIV-1 vaccine

Live attenuated viral vaccine/vector candidates are inherently unstable and infectivity titer losses can readily occur without defining appropriate formulations, storage conditions and clinical handling practices. During initial process development of a candidate vaccine against HIV-1 using a recombinant Human Cytomegalovirus vector (rHCMV-1), large vector titer losses were observed after storage at 4 °C and after undergoing freeze-thaw. Thus, the goal of this work was to develop candidate frozen liquid formulations of rHCMV-1 with improved freeze-thaw and short-term liquid stability for potential use in early clinical trials. To this end, a virus stability screening protocol was developed including use of a rapid, in vitro cell-based immunofluorescence focus assay to quantitate viral titers. A library of ∼50 pharmaceutical excipients (from various known classes of additives) were evaluated for their effect on vector stability after freeze-thaw cycling or incubation at 4 °C for several days. Certain additives including sugars and polymers (e.g., trehalose, sucrose, sorbitol, hydrolyzed gelatin, dextran 40) as well as removal of NaCl (lower ionic strength) protected rHCMV-1 against freeze-thaw mediated losses in viral titers. Optimized solution conditions (e.g., solution pH, buffers and sugar type) slowed the rate of rHCMV-1 titer losses in the liquid state at 4 °C. After evaluating various excipient combinations, three new candidate formulations were designed and rHCMV-1 stability was benchmarked against both the currently-used and a previously reported formulation. The new candidate formulations were significantly more stable in terms of reducing rHCMV-1 titer losses after 5 freeze-thaw cycles or incubation at 4 °C for 30 days. This case study highlights the utility of semi-empirical design of frozen liquid formulations of a live viral vaccine candidate, where protection against infectivity titer losses due to freeze-thaw and short-term liquid storage are sufficient to enable more rapid initiation of early clinical trials.