Psammaplysene A诱导的叉头转录因子O1A蛋白表达对乳腺癌细胞增殖凋亡的影响

目的 探讨Psammaplysene A(PsA)诱导叉头转录因子O1A蛋白(FOXO1A)表达对人乳腺癌细胞株MCF-7及SKBR3增殖和凋亡的影响.方法 用PsA干预2株细胞后,激光共聚焦显微镜(CSM)观察FOXO1A蛋白在细胞中表达;噻唑蓝(MTT)法检测细胞增殖;流式细胞仪(FCM)分析细胞凋亡和周期变化;Western blot检测B细胞淋巴瘤/白血病-2蛋白家族促凋亡调节蛋白(Bim)表达.结果 FOXO 1A蛋白定位于胞核中,PsA诱导后其表达明显增加,细胞发生凋亡,生长减慢.分别用0.1 μmol/L和1.0 μmol/L的PsA干预2株细胞后,凋亡率分别为(16.3±1.4)％和(32.5±2.3)％;(13.7±1.9)％和(30.3±1.6)％;Bim蛋白增加,和阴性对照组比较差异有统计学意义(P＜0.01).结论 PsA通过诱导FOXO1A蛋白表达抑制了乳腺癌细胞增殖,促进凋亡,其机制可能与Bim蛋白激活有关.FOXO1A基因有望成为乳腺癌基因治疗的有效靶点.     

老年髋部骨折患者术后对侧髋部骨折发生因素的Meta分析

目的通过Meta分析评价影响老年髋部骨折患者术后对侧髋部骨折的相关因素。方法检索Pubmed、Cochrane、中国生物医学文献数据库、CNKI中国期刊全文数据库、万方数据库自2005年1月至2018年4月国内外正式刊物上公开发表的有关老年髋部骨折术后对侧髋部骨折相关因素的文献,严格评价质量及提取相关资料,获取患者的性别、年龄(>65岁)、吸烟、初次髋部骨折类型、骨质疏松症(Singh指数≥4为骨质疏松)、伴有原发性高血压、伴有帕金森病、伴有脑卒中、伴有老年痴呆症、伴有白内障、伴有类风湿关节炎、伴有糖尿病、初次骨折内固定种类、患者治疗配合的依从性。运用RevMan5.0软件进行统计分析,评估各项指标的优势比(OR)和95%可信区间(CI)。结果共纳入17项研究13717例老年髋部骨折患者,发生对侧髋部骨折1504例。影响老年髋部骨折术后对侧髋部骨折的相关因素有患者年龄(OR=-3.55,95%CI:-5.60^-1.50,P<0.001)、骨质疏松症(OR=2.38,95%CI:1.36~4.17,P=0.002)、伴有帕金森病(OR=4.54,95%CI:2.74~7.53,P<0.001)、脑卒中(OR=0.33,95%CI:0.18~0.59,P<0.001)、老年痴呆症(OR=0.43,95%CI:0.29~0.62,P<0.001)、白内障(OR=0.37,95%CI:0.22~0.63,P<0.001)、类风湿关节炎(OR=0.32,95%CI:0.21~0.50,P<0.001)、糖尿病(OR=0.65,95%CI:0.47~0.91,P=0.01)、初次骨折内固定种类(OR=0.51,95%CI:0.30~0.85,P=0.01)、治疗配合依从性(OR=0.36,95%CI:0.21~0.64,P<0.001),而与性别(OR=1.07,95%CI:0.45~2.56,P=0.88)、吸烟(OR=0.86,95%CI:0.40~1.86,P=0.70)、初次髋部骨折类型(OR=0.97,95%CI:0.60~1.57,P=0.90)、伴有原发性高血压(OR=0.70,95%CI:0.41~1.21,P=0.20)无关。结论影响老年髋部骨折患者术后对侧髋部骨折的相关因素有年龄偏大、伴有骨质疏松症、帕金森病、脑卒中、老年痴呆症、白内障、类风湿关节炎、糖尿病、初次骨折内固定种类、治疗配合依从性差。而患者性别、吸烟、骨折类型、伴有原发性高血压目前尚无足够的证据与对侧髋部骨折有关。     

Risk factors for hip fracture in a high incidence area: A case-control study from Oslo,Norway

The aim of this population-based matched case-control study was to evaluate the effect of risk factors for hip fracture in Oslo, Norway, which has some of the highest incidence rates ever reported. The study population comprised all non-institutionalized persons 50 years or older living in the catchment area of two Oslo hospitals, and cases were 246 patients admitted for hip fracture during a 1-year period. The controls were randomly selected from the study population, matched 1:1 for age and sex. Hip fracture was associated with lean body stature, smoking, low grip strength and decreased levels of physical activity, and inversely with length of education. In addition, hip fracture was inversely related to indicators of total food intake (number of meals per day, frequency of dinners, and slices of bread per day). A relation between hip fracture and low vitamin D intake was also suggested, whereas no association with dietary calcium intake was found. Finally, increased risk of fracture was seen in persons reporting two or more hospital admissions in the previous 2 years, and in those reporting weight reduction due to poor appetite during the previous year. In conclusion, the risk factor pattern for hip fracture was much the same in the elderly population of Oslo as previously described in other populations with a lower incidence of fracture. This study also indicates a relation between hip fracture and low food intake.     

A case of pathological fracture caused by vitamin D insufficiency in a young athlete and a review of the literature

Our patient is a 16-year-old boy basketballer with no significant medical history or previous injuries. He fell on his right hip during jogging and sustained a right superior-posterior hip dislocation with a Pipkin type 2 fracture of the femoral head. Manipulation and reduction under sedation then general anaesthesia was unsuccessful he underwent open reduction and internal fixation.Because his fall was of low energy, an endocrinologist was consulted to rule out primary contributing factors to his fracture dislocation. He was found to have insufficient levels of vitamin D (22.4 μg/l) which was replaced subsequently. Other hormonal investigations were unremarkable. The Bone Mineral Density of his left femoral neck measured 1.098, corresponding to a Z-score of 1.1 (normal). At 2 months post operation, our patient was pain free and able to ambulate without aid. Follow up Xrays showed satisfactory alignment with no evidence of osteonecrosis.We conducted a literature search on pubmed with keywords: Hip, dislocation, fracture, minimal trauma, atraumatic, vitamin D deficiency. We then excluded post-operative dislocations and found 4 articles reporting minimal or atraumatic hip dislocations.Posterior hip dislocations have been reported in literature to be a high energy trauma, usually due to an axial load on the femur, typically with hip flexed and adducted. Complex posterior fracture-dislocation of the native hip joint in adults is usually caused by road traffic accidents or falls from heights.Native hip dislocations in adults associated with minimal or no trauma are rarely reported in literature, and are mostly due to hip dysplasia, arthritis, connective tissue disorders or spastic muscular paralysis. Of note there are no reports of vitamin D deficiency causing a hip fracture dislocation.This is the first known case of an athlete sustaining a vitamin D insufficiency fracture. In patients presenting with posterior hip dislocations after minimal or no trauma, underlying causes must be excluded. More research is necessary to investigate the relationship between vitamin D insufficiency and hip dislocations.     

Incidence and risk factors of occult posterior malleolar fracture in patients with spiral distal tibial fracture: Reexamination and analysis

ObjectiveTo evaluate the incidence and risk factors for posterior malleolar fractures (PMFs) in patients with spiral distal tibial fractures (SDTFs).MethodsIn a retrospective study, 248 adults with SDTFs who underwent treatment were enrolled between November 2017 and May 2020. In a prospective study, we recruited 113 consecutive, skeletally mature patients with SDTFs who were identified from the trauma clinic of our hospital between June 2020 and May 2021. Radiographs and CT scans of the ankle region on the affected side were obtained to determine the presence of PMFs. If the CT scan was negative, additional MRI examination of the ankle was performed as a supplementary protocol in the prospective study. Univariate analysis and multivariate analysis were conducted to analyze the risk factors.ResultsIn the retrospective study, the incidence of PMFs associated with simple SDTFs was 74.0% (105/142), which was significantly lower than 90.8% (69/76) in the prospective study. Independent predictors of PMFs in patients with simple SDTFs identified by multivariate analysis in the retrospective study were age (OR = 1.07; P = 0.001) and external rotation of the proximal tibia (OR = 3.36; P = 0.027) and those in the prospective study were osteoporosis (OR = 0.04; P = 0.007) and spiral fibula fractures (OR = 16.05; P = 0.046).ConclusionThis study reexamined the high incidence of concurrent PMFs. Additionally, ankle radiographs and CT scans were recommended for all simple SDTF patients. For simple SDTF patients with negative CT scans, especially those caused by external rotation of the proximal tibia, combined with nonosteoporotic or spiral fibula fractures, additional MRI examinations are recommended.     

Risk factors for fracture of the shafts of the tibia and fibula in older individuals

A case-control study to identify risk factors for fracture of the shafts of the tibia and fibula among persons 45 years of age and older was undertaken in five Northern California Kaiser Permanente Medical Centers during 1996–2001. One hundred seventy-nine cases of newly diagnosed fracture of the tibia/fibula shaft and 2,399 controls sampled from the membership lists of the same five medical centers were included. Information on potential risk factors was obtained by a standardized questionnaire administered by trained interviewers. The number of previous fractures was associated with an increased risk [adjusted odds ratio (OR) (95% confidence interval) =1.49 (1.09–2.03) per previous fracture]. Attributes known or thought to be associated with protection against loss of bone mass, including high body mass index [adjusted OR =0.82 (0.69–0.97) per 5 kg/m² increase], having ever used thiazide diuretics or water pills for at least 1 year [adjusted OR =0.62 (0.38–1.02)], and current use of menopausal hormone therapy among females [adjusted OR =0.84 (0.53–1.32)] tended to show decreased risks. Factors generally associated with lower bone mass, such as current cigarette smoking [OR =1.55 (1.01–2.39)] and, to some extent, lack of physical activity [OR =1.31 (0.87–1.96) for the lowest quartile compared to the upper three quartiles], tended to demonstrate increased risks. The number of falls in the past year and risk factors for falls were not associated with tibia/fibula shaft fractures, and indicators of health status were weakly and inconsistently associated with risk. Thus, this study suggests that risk factors for low bone mass, but not health status or risk factors for falls, may be important in the etiology of fracture of the shaft of the tibia/fibula in older individuals.     

Incidence and risk factors of surgical site infection after intertrochanteric fracture surgery: A prospective cohort study

Surgical site infection (SSI) is a challenging complication after intertrochanteric fracture surgery but without a large‐sample size study to investigate the incidence and risk factors of it. The present study was to investigate the incidence and risk factors of SSI after intertrochanteric fracture surgery. A total of 1941 patients underwent intertrochanteric fracture surgery between October 2014 and December 2018 were included. Demographic data, surgical variables, and preoperative laboratory indexes were obtained from a prospective database and reviewed by hospital records. The optimum cut‐off value for quantitative data was detected by receiver operating characteristic analysis. The univariate analysis and multivariable analysis were conducted to analyse the risk factors. In total, 25 patients (1.3%) developed SSI, including 22(1.1%) superficial infection and 3(0.2%) deep infection. After adjustment of multiple variables, gender (odds ratio[OR] 2.64, P = .024), time to surgery>4 days (OR 2.41, P = .046), implant (intramedullary or extramedullary devices) (OR 2.96, P = .036), ALB<35 g/L (OR 2.88, P = .031) remained significant factors. In conclusion, the incidence of SSI after intertrochanteric fractures surgery was 1.3%, with 1.1% for superficial and 0.2% for deep infection. Gender, time to surgery>4 days, the implant (intramedullary or extramedullary devices), and ALB<35 g/L were independent risk factors for the rate of SSI.     

股骨粗隆间骨折DHS内固定术后骨折不愈合的危险因素分析

目的分析股骨粗隆间骨折动力髋螺钉（DHS）内固定术后骨折不愈合的原因。方法将自2009-08—2014-01接受DHS内固定治疗的384例股骨粗隆间骨折纳入研究,观察骨折不愈合的情况,并分析性别、年龄、骨折类型、术中操作情况、术后Garden对线指数、颈干角、扶拐下地时间以及合并骨质疏松及糖尿病情况与骨折不愈合发生的相关性。结果384例中368例骨折完全愈合,16例发生骨折不愈合,骨折不愈合发生率4.2%。单因素分析结果：不同性别患者、是否合并骨质疏松、是否处理股骨小粗隆骨块对骨折不愈合的发生率没有影响,差异无统计学意义（P〉0.05）;不同年龄、骨折类型、术中操作情况、术后Garden对线指数、颈干角、扶拐下地时间、合并糖尿病等因素对骨折不愈合的发生率有影响,差异有统计学意义（P〈0.05）。Logistic回归分析：高龄、不稳定骨折、术中螺钉的深度和位置不良、未矫正髋内翻、术后Garden对线指数不满意、颈干角未恢复正常、合并糖尿病是DHS内固定治疗股骨粗隆间骨折术后发生骨折不愈合的危险因素,扶拐下地时间≥6周是发生骨折不愈合的保护因素。结论股骨粗隆间骨折DHS内固定术后骨折不愈合的发生率受到骨折类型、患者自身情况、手术操作情况、术后恢复情况等多种因素的影响,应准确把握危险因素并进行预防。     

应用FRAX工具评估系统性红斑狼疮患者骨折风险及相关因素分析

目的 探讨骨折危险性评估工具(FRAX)评估系统性红斑狼疮(SLE)患者骨质疏松性骨折风险并进行相关因素分析.方法 纳入2018年1月至2019年6月我院治疗的90例SLE患者以及60例正常体检人员,分别设为研究组与对照组.采用双能X线骨密度仪测定骨密度,比较两组骨密度差异;采用FRAX评估SLE患者骨质疏松性骨折风险...     

BMP2及Msx2在特发性高钙尿肾结石患者肾乳头组织表达的研究

目的：研究骨形态发生蛋白2（BMP2）及成骨样细胞转录因子Msx2在特发性高钙尿（IH）肾结石患者肾乳头组织中表达以及探讨其在IH患者结石形成中作用机制。方法：筛选特发性高钙尿肾结石患者8例（IH组）,排除各种已知可能影响血清钙或者尿钙的继发疾病;选择同期因肾肿瘤或非结石所致的无功能肾需行肾切除术的患者8例（NC组）。分别取16例患者肾乳头组织若干,各标本应用实时荧光定量PCR检测BMP2和Msx2mRNA的表达,并应用Westernblot测定两组蛋白质表达水平。结果：IH组BMP2的mRNA表达量为（1．491±0．121）,而NC组BMP2的tuRNA为（1．032±0．034）,两组间表达量差异有统计学意义（P〈0．05）;而1H组与NC组Msx2的mRNA表达量分别为（1．432±0．091）和（1．015±0．017）,两组数据差异有统计学意义（P〈0．05）。Westernblotting检测BMP2蛋白提示NC组和IH组蛋白质表达量分别为（1．475±0．042）和（1．681±0．153）,两组数据差异有统计学意义（P〈0．05）;测定Msx2蛋白水平表达显示NC组为（1．531±0．134）,而IH组（1．603±0．156）,两者差异无统计学意义（P〉0．05）。结论：特发性高钙尿（IH）肾结石患者肾乳头BMP2和Msx2mRNA表达增强为间质异位钙化特征,BMP2信号通路在特发性高钙尿结石患者Randall钙斑形成中具有一定作用。     

Immediate versus delayed intramedullary nailing for open fractures of the tibial shaft: A multivariate analysis of factors affecting deep infection and fracture healing

Background:

The purpose of this study was to evaluate contributing factors affecting deep infection and fracture healing of open tibia fractures treated with locked intramedullary nailing (IMN) by multivariate analysis.

Materials and Methods:

We examined 99 open tibial fractures (98 patients) treated with immediate or delayed locked IMN in static fashion from 1991 to 2002. Multivariate analyses following univariate analyses were derived to determine predictors of deep infection, nonunion, and healing time to union. The following predictive variables of deep infection were selected for analysis: age, sex, Gustilo type, fracture grade by AO type, fracture location, timing or method of IMN, reamed or unreamed nailing, debridement time (≤6 h or >6 h), method of soft-tissue management, skin closure time (≤1 week or >1 week), existence of polytrauma (ISS< 18 or ISS≥18), existence of floating knee injury, and existence of superficial/pin site infection. The predictive variables of nonunion selected for analysis was the same as those for deep infection, with the addition of deep infection for exchange of pin site infection. The predictive variables of union time selected for analysis was the same as those for nonunion, excluding of location, debridement time, and existence of floating knee and superficial infection.

Results:

Six (6.1%; type II Gustilo n=1, type IIIB Gustilo n=5) of the 99 open tibial fractures developed deep infections. Multivariate analysis revealed that timing or method of IMN, debridement time, method of soft-tissue management, and existence of superficial or pin site infection significantly correlated with the occurrence of deep infection (P< 0.0001). In the immediate nailing group alone, the deep infection rate in type IIIB + IIIC was significantly higher than those in type I + II and IIIA (P = 0.016). Nonunion occurred in 17 fractures (20.3%, 17/84). Multivariate analysis revealed that Gustilo type, skin closure time, and existence of deep infection significantly correlated with occurrence of nonunion (P < 0.05). Gustilo type and existence of deep infection were significantly correlated with healing time to union on multivariate analysis (r² = 0.263, P = 0.0001).

Conclusion:

Multivariate analyses for open tibial fractures treated with IMN showed that IMN after EF (especially in existence of pin site infection) was at high risk of deep infection, and that debridement within 6 h and appropriate soft-tissue managements were also important factor in preventing deep infections. These analyses postulated that both the Gustilo type and the existence of deep infection is related with fracture healing in open fractures treated with IMN. In addition, immediate IMN for type IIIB and IIIC is potentially risky, and canal reaming did not increase the risk of complication for open tibial fractures treated with IMN.     

Vitamin D receptor genotype and risk of osteoporotic hip fracture in elderly women of Utah: an effect modified by parity

Introduction The associations between vitamin D receptor (VDR) Bsm I and Fok I genotypes, parity, and risk of osteoporotic hip fracture were evaluated in a statewide population-based case-control study in Utah.Methods Women age 50–89 years with hip fracture (n=882) were ascertained via surveillance of 18 Utah hospitals from 1997 to 2001. Age-matched controls were randomly selected (n=897). Participants were interviewed in their homes, and blood samples were collected for genotyping.Results In logistic regression analyses that controlled for multiple confounders, Bsm I VDR genotype but not Fok I genotype was associated with risk of osteoporotic hip fracture (OR bb vs. BB genotype: 0.68; 95% CI: 0.50, 0.95). In similar analyses, no overall association was observed between parity status and risk of osteoporotic hip fracture. However, the effect of VDR genotype was modified by parity status. Among nulliparous women (n=140), Bsm I genotype was not associated with risk of hip fracture (OR bb vs. BB: 0.82; 95% CI: 0.28, 2.4); among primiparous women (n=133), bb genotype was associated with increased risk of hip fracture (OR bb vs. BB: 3.30; 95% CI: 0.96, 11.29); among multiparous women (n=1,400), bb genotype was associated with decreased risk of hip fracture (OR bb vs. BB: 0.59; 95% CI: 0.42, 0.84).Conclusion VDR Bsm I genotype was associated with risk of hip fracture in Utah women, and this effect was modified by parity status. Hormonal or lifestyle factors related to parity may underlie this interaction.     

No effect of vitamin A intake on bone mineral density and fracture risk in perimenopausal women.

In recent studies from Sweden and the United States, a high vitamin A intake has been associated with low bone mineral density (BMD) and increased fracture risk. In Sweden and the United States, food items such as milk and breakfast cereals are fortified with vitamin A, whereas in Denmark there is no mandatory fortification with vitamin A. In the present study, we investigated relations between vitamin A intake and BMD and fracture risk in a Danish population consuming mostly unfortified food items. Within a population-based cohort study in 2,016 perimenopausal women, associations between BMD and vitamin A intake were assessed at baseline and after 5-year follow-up. Moreover, associations between baseline vitamin A intake and 5-year changes in BMD were studied. Finally, fracture risk was assessed in relation to vitamin A intake. In our cohort, dietary retinol intake (0.53 mg/day) was lower than the intake reported in recent studies form Sweden (0.78 mg/day) and the United States (1.66 mg/day). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin A and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% who had the highest, and those 5% who had the lowest, vitamin A intake. During the 5-year study period, 163 subjects sustained a fracture (cases). Compared to 978 controls, logistic regression analyses revealed no difference in vitamin A intake. Thus, in a Danish population, average vitamin A intake is lower than in Sweden and the United States and not associated with detrimental effects on bone.