The epigenetically active small chemical N-methyl pyrrolidone (NMP) prevents estrogen depletion induced osteoporosis

Currently, there are several treatments for osteoporosis however; they all display some sort of limitation and/or side effects making the need for new treatments imperative. We have previously demonstrated that NMP is a bioactive drug which enhances bone regeneration in vivo and acts as an enhancer of bone morphogenetic protein (BMP) in vitro. NMP also inhibits osteoclast differentiation and attenuates bone resorption.In the present study, we tested NMP as a bromodomain inhibitor and for osteoporosis prevention on ovariectomized (OVX) induced rats while treated systemically with NMP. Female Sprague–Dawley rats were ovariectomized and weekly NMP treatment was administrated 1 week after surgery for 15 weeks. Bone parameters and related serum biomarkers were analyzed. 15 weeks of NMP treatment decreased ovariectomy-induced gained weight in average by 43% and improved bone mineral density (BMD) and bone volume over total volume (BV/TV) in rat femur on average by 25% and 41% respectively. Moreover, mineral apposition rate and bone biomarkers of bone turnover in the treatment group were at similar levels with those of the Sham group.Due to the function of NMP as a low affinity bromodomain inhibitor and its mechanism of action involving osteoblasts/osteoclasts balance and inhibitory effect on inflammatory cytokines, NMP is a promising therapeutic compound for the prevention of osteoporosis.     

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.     

Health Care Utilization and Unmet Needs in Chinese Older Adults With Multimorbidity and Functional Impairment

ObjectivesChina has the world's largest aging population, of which 46% have multimorbidity and 38% have functional impairment. Older adults with multimorbidity often suffer functional impairment as well; however, it is not clear how current health care services have been used in this population. This study aimed to compare health care utilization among Chinese older adults at different levels of chronic disease and functional impairment.DesignA cross-sectional design. Multivariate 2-part models were used to examine the probability and frequency of health care utilization.Setting and ParticipantsData were from 5166 adults aged 65 or older from the 2015 wave of the China Health and Retirement Longitudinal Study. The sample included 22% without any chronic condition, 27% with 1 chronic condition, 44% with multimorbidity, and 7% with multimorbidity and functional impairment.MeasuresHealth care utilization included outpatient visits, inpatient visits, and unmet hospitalization needs.ResultsAs the number of chronic conditions and functional impairments increased, older adults tend to access health care more. Older adults with both multimorbidity and functional impairment tend to use health care services most, but still reported the highest level of unmet hospitalization needs among all groups.Conclusions and ImplicationsChinese older adults with multimorbidity and functional impairment may have experienced multiple barriers in accessing health care. Social programs should be created to make health care more accessible among older adults. The health care delivery system could be oriented to home-based medical care, which have been found effective in delivering high-quality care and reducing health care costs.     

Oblique lumbar interbody fusion combined with stress end plate augmentation and anterolateral screw fixation for degenerative lumbar spinal stenosis with osteoporosis: a matched-pair case-controlled study

BACKGROUND CONTEXTOblique lumbar interbody fusion (OLIF) has been proven to be effective in treating degenerative lumbar spinal stenosis (DLSS). Whether OLIF is suitable for treating patients with DLSS with osteoporosis (OP) is still controversial. Bone cement augmentation is widely used to enhance the internal fixation strength of osteoporotic spines. However, the effectiveness of OLIF combined with bone cement stress end plate augmentation (SEA) and anterolateral screw fixation (AF) for DLSS with OP have not confirmed yet.PURPOSETo evaluate the clinical, radiological, and functional outcomes of OLIF-AF versus OLIF-AF-SEA in the treatment of DLSS with OP.STUDY DESIGNRetrospective case-control study.PATIENT SAMPLEA total of 60 patients with OP managed for DLSS at L4–L5.OUTCOME MEASURESVisual analog scale (VAS) score of the lower back and leg, Oswestry Disability Index (ODI), disk height (DH), lumbar lordosis (LL), segmental lordosis (SL), cage subsidence and fusion rate.METHODSThe study was performed as a retrospective matched-pair case‒controlled study. Patients with OP managed for DLSS at L4–L5 between October 2017 and June 2020 and completed at least 2 years of follow-up were included, which were 30 patients treated by OLIF-AF and 30 patients undergoing OLIF-AF-SEA. The demographics and radiographic data, fusion status and functional outcomes were therefore compared to evaluate the efficacy of the two approaches.RESULTSPain and disability improved similarly in both groups at the 24-month follow-up. However, the SEA group had lower pain and functional disability at 3 months postoperatively (p<.05). The mean postoperative disc height decrease (△DH) was significantly lower in the SEA group than in the control group (1.17±0.81 mm vs 2.89±2.03 mm; p<.001). There was no significant difference in lumbar lordosis (LL) or segmental lordosis (SL) between the groups preoperatively and 1 day postoperatively. However, a statistically significant difference was observed in SL and LL between the groups at 24 months postoperatively (p<.05). CS was observed in 4 cases (13.33%) in the SEA group and 17 cases (56.67%) in the control group (p<.001). A nonsignificant difference was observed in the fusion rate between the SEA and control groups (p=.347) at 24 months postoperatively.CONCLUSIONSThis study revealed that OLIF-AF-SEA was safe and effective in the treatment of DLSS with OP. Compared with OLIF-AF, OLIF-AF-SEA results in a minor postoperative disc height decrease, a lower rate of CS, better sagittal balance, and no adverse effect on interbody fusion.     

Enhanced immunostimulatory effects of DNA-encapsulated peptide hydrogels

DNA that encodes tumor-specific antigens represents potential immunostimulatory agents. However, rapid enzymatic degradation and fragmentation of DNA during administration can result in limited vector expression and, consequently, poor efficacy. These challenges have necessitated the use of novel strategies for DNA delivery. Herein, we study the ability of cationic self-assembling peptide hydrogels to encapsulate plasmid DNA, and enhance its immunostimulatory potential in vivo. The effect of network charge on the gel's ability to retain the DNA was assessed employing three gel-forming peptides that vary systematically in formal charge. The peptide HLT2, having a formal charge of +5 at neutral pH, was optimal in encapsulating microgram quantities of DNA with little effect on its rheological properties, allowing its effective syringe delivery in vivo. The plasmid, DNA(TA), encapsulated within these gels encodes for a melanoma-specific gp100 antigen fused to the alarmin protein adjuvant HMGN1. Implantation of DNA(TA)-loaded HLT2 gels into mice resulted in an acute inflammatory response with the presence of polymorphonuclear cells, which was followed by infiltrating macrophages. These cellular infiltrates aid in the processing of encapsulated DNA, promoting increased lymphoproliferation and producing an enhanced immune response mediated by CD4+/IFNγ+ expressing Th1 cells, and complemented by the formation of gp100-specific antibodies.     

突出椎间盘自然吸收现象的回顾性研究

目的研究突出椎间盘自然吸收的现象,为腰椎间盘突出症的非手术或手术治疗选择提供依据。方法对18例发生突出椎间盘自然吸收现象患者的病程、症状、体征及影像学资料进行回顾性分析。结果所有患者均为破碎型突出。18例均获随访,时间6~72(17±15)个月。突出物吸收率:完全消失12例,显著缩小6例。其中1例后纵韧带破裂者遗留少许腰痛,跟腱反射未恢复,但能正常工作及生活;另有1例腰腿痛复发,影像学显示突出间盘缩小后再次大块脱出,后纵韧带破裂;其余患者症状体征完全恢复,腰椎主动活动自如。结论腰椎间盘突出症如果后纵韧带完整,即使突出物巨大,症状重,只要没有马尾综合征或进行性单根神经根麻痹,都可以进行非手术治疗,且预后良好;但椎间盘吸收后在合适的条件下可再次突出。     

分期手术治疗第1跖趾关节巨大痛风石的临床研究

目的:探讨分期手术治疗第1跖趾关节巨大痛风石的近期临床疗效。方法 :自2015年1月至2016年12月,采用分期手术治疗第1跖趾关节巨大痛风石患者12例,全部为男性;年龄45～73岁;右足6例,左足6例;保守治疗2年以上,双能CT检查明确通风石大小及部位;经X线片检查均可见第1跖趾关节骨质破坏。所有患者Ⅰ期手术行痛风病灶的彻底清除及克氏针临时固定,待局部软组织条件稳定后再行跖趾关节的植骨融合内固定手术。比较手术前后血尿酸含量,患肢畸形矫正及并发症情况,采用VAS评分评价疼痛缓解程度。结果:所有患者顺利完成手术,且获得随访,时间9～13个月。12例患者VAS评分由术前的6～9分降低至术后7周的0～1分;血尿酸含量由术前的443～501μmol/L降低至术后7周的307～330μmol/L;术后5～7个月足部第1跖趾关节畸形矫正、外形恢复。术后1例发生切口感染、皮缘坏死,经清创及换药处理后切口愈合。结论:分期手术治疗足部第1跖趾关节巨大痛风石,可矫正关节畸形,恢复第1跖趾关节外形,改善患足疼痛,有利于控制血尿酸含量,且并发症少。     

腕关节镜辅助下切开复位经骨窗植骨内固定治疗桡骨远端die－punch骨折

目的:探讨腕关节镜辅助下切开掌侧经骨窗撬拨复位植骨内固定治疗桡骨远端(Die punch)骨折的临床疗效。方法:自2016年3月至2017年3月,采用腕关节镜辅助下切开复位经骨窗植骨内固定治疗桡骨远端Die punch骨折患者12例,男8例,女4例;年龄20～42岁。术前X线片及CT明确诊断为桡骨远端Die punch骨折。观察患者关节活动度情况,术后12个月采用VAS评分评价疼痛缓解程度,采用Cooney腕关节评分对患者腕关节功能恢复情况进行评估。结果:全部患者无手术并发症,12例患者术后均获随访,时间10～13个月。术后12个月VAS评分0～3分。腕关节掌倾角5°～15°,尺偏角14°～23°,屈伸活动度123°～168°,前臂旋转活动度115°～170°。术后12个月Cooney腕关节评分70～95分;优10例,良1例,可1例。结论:腕关节镜辅助下切开掌侧经骨窗撬拨复位植骨内固定治疗桡骨远端Die punch骨折,术后手腕部功能恢复良好,疼痛症状较轻,临床效果满意。     

手法复位小夹板外固定结合微动理念锻炼治疗肱骨干骨折

目的 :探讨正骨手法复位小夹板外固定结合微动理念锻炼治疗肱骨干骨折的临床疗效。方法 :自2011年3月至2014年2月,采用手法复位小夹板外固定治疗肱骨干骨折患者64例,男28例,女36例;年龄22~67岁,平均38.1岁。按AO/OTA分型:A1型10例,A2型12例,A3型11例;B1型10例,B2型12例,B3型7例;C1型2例,C2型1例,C3型1例。整复后配合微动理念早期功能锻炼。患者均不合并其他部位骨折和血管神经损伤,均无严重内科疾病。随访观察患者骨折愈合及肩肘关节功能恢复情况,并评定疗效。结果:所有患者获随访,时间10~12个月,平均10.3个月。2例复位后3个月少量骨痂生长,改为手术治疗;2例复位后出现桡神经症状,改为手术治疗,其他患者骨性愈合时间8~12周,平均10.2周,骨折达到骨性愈合后,按照Constant-Murley肩关节功能评分评定疗效,平均(93.5±3.2)分,优29例,良29例,可6例,优良率90.3%;按照Mayo肘关节功能评分标准(MEPS),平均(93.7±4.2)分,优35例,良23例,可6例,优良率91.9%。结论 :正骨手法复位小夹板外固定结合微动理念锻炼治疗肱骨干骨折,具有其相应的科学基础和实用价值,整复效果好,费用低廉,能够有效减少并发症,促进患者功能康复。