术前预康复对全髋关节置换术后功能锻炼及运动耐力的影响

目的 探讨术前预康复在全髋关节置换（THA）术后患者关节功能和运动耐力中的干预效果。方法 80例THA患者随机分为实验组与对照组,每组各40例。对照组接受常规术前教育,实验组接受预康复训练。两组患者均在入院、术前1天、术后第2天、术后1周、术后2周使用Harris髋关节功能量表 (HHS)、Charnley髋关节功能评分量表（CHS）和6分钟步行试验（6MWT）来评估患者的关节功能及运动耐力状况。使用t检验、重复测量分析评估其干预效果。结果 经预康复训练后,实验组不同时间点HHS、CHS和6MWT有统计学意义(P<0.05);且组别和时间在HHS、CHS和6MWT上有交互作用。实验组HHS在术前1天、术后1周、术后2周均优于对照组（t=3.594、2.437、5.891,P<0.05）;实验组CHS在术前1天、术后1周、术后2周均优于对照组（t=2.318、3.724、6.439,P<0.05）;实验组6MWT在术前1天、术后1周、术后2周均优于对照组（t=3.878、5.891、8.750,P<0.05）。简单效应示,术前预康复对改善患者的HHS、CHS和6MWT直接及持续作用有统计学意义(P<0.05)。结论 术前预康复可改善THA术后患者关节功能和提升运动耐力,且随着时间改变,效果显著。     

Forkhead box protein P1 is a useful marker for the diagnosis of mucinous minimal deviation adenocarcinoma of uterine cervix

Mucinous minimal deviation adenocarcinoma (MDA) is a rare highly differentiated tumor of uterine cervix, of which the confusing histopathology resembling some benign lesions usually makes difficulty for pathologic diagnosis. The expression of forkhead box protein P1 (FOXP1) is found in some kinds of human tumors and is considered to be associated with the progression of the tumors. The purpose of this study is to detect the FOXP1 expression in MDA and evaluate its possible role in the diagnosis of MDA. Twenty-two MDA cases and 20 control cases consisting of 10 cases of lobular endocervical glandular hyperplasia and 10 cases of normal endocervical tissue were included in this study. All available clinical data were collected and immunostaining for FOXP1, carcinoembryonic antigen (CEA), human milk fat globule antigen 1 (HMFG1), estrogen receptor, and progesterone receptor were performed on these cases. The nuclear/cytoplasmic expression of FOXP1 was found in 18 of 22 MDA cases while in 1 of 20 control cases, which showed statistical significance (P = .000). The cytoplasmic CEA expression was found in 14 of 22 MDA cases and 2 of 20 control cases (P = .000), whereas cytoplasmic HMFG1 expression was found in 10 of 22 MDA cases and 4 of 20 control cases (P = .081). No statistical difference was found between FOXP1 and CEA expression (P = .083) or between FOXP1 and HMFG1 expression (P = .375) in MDA. Neither estrogen receptor nor PR expression was found in MDA. The significant expression of FOXP1 in MDA may be helpful to some extent in the pathologic diagnosis of cervical MDA. A widened observation range and further researches are needed to elucidate the potential mechanism.     

Utility of the Roche Cobas 4800 for detection of high-risk human papillomavirus in formalin-fixed paraffin-embedded oropharyngeal squamous cell carcinoma

Clinical laboratories are expected to reliably identify human papilloma virus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) for prognostic and potential therapeutic applications. In addition to surrogate p16 immunohistochemistry (IHC) testing, DNA-based HPV-specific testing strategies are widely utilized. Recognizing the efficiency of the Roche Cobas 4800 platform for testing gynecological cytology specimens for high-risk HPV, we elected to evaluate the potential utility of this platform for testing formalin-fixed paraffin-embedded (FFPE) OPSCC tissue. Using the Roche Linear Array assay for comparison, we tested twenty-eight samples (16 primary OPSCC, 2 lymph node metastases from primary OPSCC, 1 oral tongue carcinoma, 3 benign squamous papillomas, and 3 non-oropharyngeal carcinoma tissues). Excluding two invalid results, the Roche Cobas 4800 testing resulted in excellent inter-assay concordance (25/26, 96.2%) and 100% concordance for HPV-16/HPV-18 positive samples. This data suggests that the Roche Cobas 4800 platform may be a cost-effective method for testing OPSCC FFPE tissues in a clinical molecular pathology laboratory setting.     

Evaluation of patients with pathological fractures treated by standard trauma principles but neglecting the underlying malign bone disease

IntroductionThere are several studies in the literature about pathological fractures but almost no information about patients whose pathological fracture caused by a malignant lesion misdiagnosed and treated as a simple fracture. The aim of this study was to investigate patient and fracture characteristics, and outcomes in cases where fractures occurred in the presence of a malign pathology but were treated as simple fractures.Patients and MethodsCases of malign bone lesions between 2000 and 2020 were retrospectively reviewed. Patients with a final diagnosis of malign bone lesion but whose pathological fractures were treated ignoring the underlying malign bone disease were included. Demographic, clinical and outcome data were collected from patient's medical records and analyzed.ResultsSix patients met the inclusion criteria. Three of the patients were female and the cohort mean age was 56.8 ± 21.8 years at the time of admission. Patient diagnoses were: renal cell carcinoma metastasis (n = 1); colon cancer metastasis (n = 1); chondrosarcoma (n = 2); osteosarcoma (n = 1); and undifferentiated pleomorphic sarcoma of bone (n = 1). In all cases surgical management differed from those that should have been applied if the pathological fracture had been identified. Furthermore, surgical management after definitive histological diagnosis were more aggressive compared to if the malignancy had been identified at first admission. All patients died after a mean follow-up of 16.67 ± 11.7 months and the complication rate was 100%.ConclusionWhen a pathological fracture is misdiagnosed and managed as a simple bone fracture, outcomes are extremely poor. In these situations, remedial surgery is more extensive, with increased complication rates and there is poor life expectancy.     

Risk factors for loss to follow up of pelvis and acetabular fractures

IntroductionPelvic and acetabular fracture incidence is increasing worldwide for more than four decades. There is currently no evidence examining risk factors for loss to follow up in patients with these injuries.MethodsPatients presenting with pelvic and/or acetabular fractures at our institution between 2015 and 2020 were included. Demographic, injury, treatment, and follow up information was included. Excluded patients were those who sustained a pathologic fracture, has a course of treatment prior to transfer to our centre, or expired prior to discharge.Results446 patients, 263 with a pelvic ring injury, 172 with an acetabular fracture, and 11 with combined injuries were identified. 271 (61%) of patients in our cohort followed up in Orthopaedic clinic (p = 0.016). With an odds ratio of 2.134, gunshot wound mechanism of injury was the largest risk factor for loss to follow up (p = 0.031) followed by male sex (OR= 1.859) and surgery with general trauma surgery (OR=1.841). The most protective risk factors for follow up with Orthopaedic surgery were operatively treated pelvic and acetabular fractures (OR=0.239) and Orthopaedic Surgery as the discharging service (OR=0.372).DiscussionNumerous risk factors exist for loss to follow up including male sex, ballistic mechanism, and discharging service. Investigation into interventions to improve follow up in these patients are warranted.     

Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice

Polyethylene glycol (PEG)-coated (pegylated) gold nanoparticles (AuNPs) have been proposed as drug carriers and diagnostic contrast agents. However, the impact of particle characteristics on the biodistribution and pharmacokinetics of pegylated AuNPs is not clear. We investigated the effects of PEG molecular weight, type of anchoring ligand, and particle size on the assembly properties and colloidal stability of PEG-coated AuNPs. The pharmacokinetics and biodistribution of the most stable PEG-coated AuNPs in nude mice bearing subcutaneous A431 squamous tumors were further studied using ¹¹¹In-labeled AuNPs. AuNPs coated with thioctic acid (TA)-anchored PEG exhibited higher colloidal stability in phosphate-buffered saline in the presence of dithiothreitol than did AuNPs coated with monothiol-anchored PEG. AuNPs coated with high-molecular-weight (5000 Da) PEG were more stable than AuNPs coated with low-molecular-weight (2000 Da) PEG. Of the 20-nm, 40-nm, and 80-nm AuNPs coated with TA-terminated PEG₅₀₀₀, the 20-nm AuNPs exhibited the lowest uptake by reticuloendothelial cells and the slowest clearance from the body. Moreover, the 20-nm AuNPs coated with TA-terminated PEG₅₀₀₀ showed significantly higher tumor uptake and extravasation from the tumor blood vessels than did the 40- and 80-nm AuNPs. Thus, 20-nm AuNPs coated with TA-terminated PEG₅₀₀₀ are promising potential drug delivery vehicles and diagnostic imaging agents.     

肿瘤相关成纤维细胞促进原代胰腺癌细胞生长及人源性异种移植瘤模型体内成瘤

目的优化人原代胰腺导管癌(PDAC)细胞及肿瘤相关成纤维细胞(CAFs)的分离及培养方法,验证CAFs对原代PDAC细胞的体外生长以及其对高度免疫缺陷模型NOG小鼠体内成瘤的影响,以探索人源性异种移植瘤(PDX)模型构建的新方法。方法首先原代培养手术切除的PDAC组织。以原代PDAC细胞单独培养为对照,观察CAFs和原代PDAC细胞共培养对PDAC细胞传代生长活性的影响。最后在NOG小鼠肩胛部注射混合培养的原代PDAC细胞和CAFs,观察PDX模型建模情况。结果原代PDAC细胞在体外单独培养传代少,均在5代及以内停止生长;与CAFs共培养可促进原代PDAC细胞生长活性,可稳定传至10代以上。NOG小鼠体内注射混合细胞(原代PDAC细胞+CAFs)建模2~3周即可形成肿瘤,而注射CAFs无肿瘤形成。混合细胞法建模有13例(92.9%)成瘤,单一细胞法有9例(64.3%)成瘤,可能因为样本量少,二者成瘤率比较差异无统计学意义(P=0.167);并且肿瘤细胞注射后2、4、6、8周时混合细胞法建模的肿瘤体积均明显大于对应观察时间点单一细胞法建模的肿瘤体积(P<0.01)。结论CAFs对原代PDAC细胞生长传代具有促进作用,原代PDAC细胞与CAFs共培养法可显著提高PDAC原代培养稳定传代,原代PDAC细胞与CAFs混合培养的细胞注射可提高NOG小鼠PDX建模成功率。     

Tests of dorsolateral frontal function correlate with objective tests of postural stability in early to moderate stage Parkinson’s disease

A substantial number of individuals with Parkinson’s disease who display impaired postural stability experience accelerated cognitive decline and an increased prevalence of dementia. To date, studies suggest that this relationship, believed to be due to involvement of nondopaminergic circuitry, occurs later in the disease process. Research has yet to adequately investigate this cognitive-posturomotor relationship especially when examining earlier disease states. To gain greater understanding of the relationship between postural stability and cognitive function/dysfunction we evaluated a more stringent, objective measure of postural stability (center of pressure displacement), and also more specific measures of cognition in twenty-two patients with early to moderate stage Parkinson’s disease. The magnitude of the center of pressure displacement in this cohort was negatively correlated with performance on tests known to activate dorsolateral frontal regions. Additionally, the postural stability item of the UPDRS exhibited poor correlation with the more objective measure of center of pressure displacement and all specific measures of cognition. These results may serve as rationale for a more thorough evaluation of postural stability and cognition especially in individuals with mild Parkinson’s disease. Greater understanding of the relationship between motor and cognitive processes in Parkinson’s disease will be critical for understanding the disease process and its potential therapeutic possibilities.     

The utilization of decellularized tendon slices to provide an inductive microenvironment for the proliferation and tenogenic differentiation of stem cells

The extracellular matrix (ECM) microenvironment for the stem cell niches, including but not limited to the biochemical composition, matrix topography, and stiffness, is crucial to stem cell proliferation and differentiation. The purpose of this study was to explore the capacity of the decellularized tendon slices (DTSs) to induce stem cell proliferation and tenogenic differentiation. Rat adult stem cells, including tendon-derived stem cells (TDSCs) and bone marrow-derived stem cells (BMSCs), were identified to have universal stem cell characteristics. The DTSs were found to retain the native tendon ECM microenvironment cues, including the inherent surface topography, well-preserved tendon ECM biochemical composition and similar stiffness to native tendon. When the TDSCs and BMSCs were cultured on the DTSs respectively, the LIVE/DEAD assay, alamarBlue^® assay, scanning electron microscopy examination and qRT-PCR analysis demonstrated that the DTSs have the capacity to support these stem cells homogeneous distribution, alignment, significant proliferation and tenogenic differentiation. Taken together, the findings of this study indicate that the DTSs can provide a naturally inductive microenvironment for the proliferation and tenogenic differentiation of TDSCs and BMSCs, supporting the use of decellularized tendon ECM as a promising and valuable approach for tendon repair/reconstruction.