Molybdenum disulfide (MoS2), as a member of potential in biomedical applications due to its unique chemical-physical properties, photo-electronic properties, and biocompatibility. MoS2 nanostructures have recently been shown to be multifunctional nanotheranostic agents for neuroprotection and maintenance of endothelial homeostasis. However, whether ultrasmall MoS2 quantum dots (QD) participate in preventing the impairment of the endothelial barrier elicited by proinflammatory stimuli and the associated underlying mechanisms remain elusive yet. Herein, we set out to explore the protective effects of MoS2 QD on inflammatory endothelial barrier dysfunction and macrophage plasticity. We revealed an inhibitory effect of MoS2 QD on endothelial barrier impairment and monocyte-endothelial cell interactions, including monocyte adhesion and transmigration, and this might be associated with a reduced activation of focal adhesion kinase (FAK). Importantly, using an in vitro macrophage polarization system, we revealed that MoS2 QD altered macrophage plasticity via inhibiting M1-macrophage polarization, and the reduction in nuclear factor-KB (NF-KB) activation and promotion of mitophagy by MoS2 QD was involved in preventing M1 macrophage polarization. Taken together, these findings suggested potential therapeutic applications of MoS2-based bioactive nanoagents to attenuate inflammatory endothelial barrier dysfunctions that are provoked by macrophage-mediated endothelial activation.

The integration of reactive oxygen species (ROS)-based chemodynamic therapy (CDT) and photodynamic therapy (PDT) has attracted enormous attention for synergistic antitumor therapies. However, the strategy is severely hampered by tumor hypoxia and overproduced antioxidant glutathione (GSH) in the tumor microenvironment. Inspired by the concept of metal coordination-based nanomedicines, we proposed an effective strategy for synergistic cancer treatment in response to the special tumor microenvironmental properties. Herein, we present novel metal-coordinated multifunctional nanoparticles (NPs) by the Cu2+-triggered assembly of photosensitizer indocyanine green (ICG) and hypoxia-activated anticancer prodrug tirapazamine (TPZ) (Cu-ICG/TPZ NPs). After accumulating within tumor sites via the enhanced permeability and retention (EPR) effect, the Cu-ICG/TPZ NPs were capable of triggering a cascade of combinational therapeutic reactions, including hyperthermia, GSH elimination, and Cu+-mediated •OH generation and the subsequent hypoxia-triggered chemotherapeutic effect of TPZ, thus achieving synergistic tumor therapy. Both in vitro and in vivo evaluations suggested that the multifunctional Cu-ICG/TPZ NPs could realize satisfactory therapeutic efficacy with excellent biosafety. These results thus suggested the great potential of Cu-ICG/TPZ NPs to serve as a metallodrug nanoagent for synergetically enhanced tumor treatment.

Mitochondrial dynamics is crucial to cellular metabolic homeostasis, development, and remodeling. However, the perturbation of mitochondrial dynamics impairs endothelial functions, leading to numerous diseases, including cardiovascular diseases. The few-layered molybdenum disulfide (MoS2)-based nanoagents hold great potential as therapeutic agents for various disorders. Herein, we investigated whether flower-like MoS2 nanosheets (FL-MoS2) promote mitochondrial homeostasis via modulating mitochondrial dynamics in endothelial cells. Our results demonstrated that mitochondrial elements become dramatically elongated in endothelial cells in response to FL-MoS2, suggesting that FL-MoS2 promotes mitochondrial fusion rather than fission. The molecular mechanisms mediating mitochondrial fusion by FL-MoS2 involved the upregulation of pro-fusion proteins as well as a decrease in mitochondrial translocation of dynamin-related protein 1 (Drp 1). Consistently, we demonstrated that FL-MoS2 maintains mitochondrial homeostasis through regulating transcription factor EB (TFEB)-mediated mitochondrial dynamics and biogenesis. In addition, we established that mitochondrial tubulation in response to FL-MoS2 protects endothelial cells from mitochondrial impairments induced by tumor necrosis factor (TNF) alpha. Our results revealed the unique ability of MoS2-based nanoagents to modulate mitochondrial homeostasis, contributing to improvements in endothelial functions.

article: A comparative study between two types of cervical laminoplasty on the postoperative deep-extensor volume and axial neck pain, minimum two-year follow-up - Panminerva Medica 2022 December;64(4):572-4 - Minerva Medica - Journals

Molybdenum disulfide quantum dots (MoS2 QDs) represent an emerging class of two-dimensional (2D) atomically layered transition metal dichalcogenide nanostructures with few nanometers in lateral size, which show attractive potential as versatile platforms for theranostic applications in various neurological disorders. However, the potential impacts of MoS2 QDs on microglia remain unclear. In this report, we showed that exposure of microglia to MoS2 QDs triggered NLRP3 inflammasome activation as revealed by the cleavage of the inactive precursor of caspase-1 to its active form and the increased release of downstream pro-inflammatory cytokines, resulting in microglia cell death that occurred through caspase-1-dependent pyroptosis. We also found that MoS2 QDs activated autophagy, and suppression of autophagy by specific inhibitors potentiated MoS2 QD-induced pyroptosis. Additionally, MoS2 QDs stimulated mitochondria-derived reactive oxygen species (mtROS) generation in BV-2 cells. However, ROS scavengers could diminish the MoS2 QD-mediated NLRP3 inflammasome activation and pyroptotic cell death in microglia. Overall, our findings identified pyroptosis as a cellular response to MoS2 QD exposure in microglial cells, affording novel insights into the neurotoxicity of MoS2 QDs and facilitating the rational design and application of functional MoS2 QDs in neuroscience.

An electrochemical sensor based on core-shell nanostructured copper sulfide@Prussian blue composites (CuS@PB) was investigated for ascorbic acid (AA) detection. CuS nanoparticles (NPs) were prepared by a hydrothermal method, then core-shell CuS@PB nanohybrid was fabricated through in situ synthesis of PB on CuS NPs. Taking advantage of their enhanced properties, a novel electrochemical AA sensor was developed by drop-coating of CuS@PB nanohybrid on glassy carbon electrode (GCE). As expected, electrochemical observations showed that CuS@PB/GCE presented higher electrocatalytic performance of AA than PB/GCE, with a wide linear range (5-3875 mu M, R = 0.9997), fast response time (<3 s), high sensitivity (256.91 mu AmM(-1)cm(-2)), as well as a low limit of detection (0.24 mu M at a signal-tonoise ratio of 3). Additionally, the CuS@PB/GCE showed excellent reproducibility, storage stability, anti-interference, and selectivity. The application of a CuS @PB/GCE sensor for an AA assay in beverage samples achieved satisfactory results, demonstrating great prospects for the quantitative detection of AA in various fields.

目的:研究小切口微型钢板结合不同螺钉固定治疗跟骨粉碎性骨折的疗效.方法:选择本院2016年7月至2018年7月纳入的104例跟骨粉碎性骨折患者作为研究对象,按照随机数字表法分为两组(各52例),试验组采取跗骨窦小切口微型钢板拉力螺钉结合锁定螺钉固定,对照组采取相同切口全部锁定螺钉固定,对比两组治疗结果.结果:治疗前两组的跟骨高度、跟骨宽度相比无差异,治疗后试验组跟骨高度及宽度均优于对照组,差异有统计学意义(P＜0.05).试验组关节面平整效果的优良率90.38％,明显高于对照组78.85％,差异有统计学意义(P＜0.05).试验组并发症发生率5.77％,明显低于对照组17.31％,差异有统计学意义(P＜0.05).治疗前两组的疼痛视觉模拟评分(VAS)和美国矫形外科足踝协会足功能评分(AOFAS),差异无统计学意义(P＞0.05),治疗后试验组各项评分均优于对照组,差异有统计学意义(P＜0.05).结论:小切口微型钢板拉力螺钉结合锁定螺钉固定运用于跟骨粉碎性骨折中效果明显,可有效改善跟骨高度及宽度,减少并发症产生,促进关节面平整,减轻疼痛,改善踝关节功能.

A defective lysosome-autophagy degradation pathway contributes to a variety of endothelial-to-mesenchymal transition (EndMT)-related cardiovascular diseases. Molybdenum disulfide quantum dots (MoS2 QDs) are nanoscale sizes in the planar dimensions and atomic structures of transition metal dichalcogenides (TMDs) materials with excellent physicochemical and biological properties, making them ideal for various biomedical applications. In this study, water-soluble MoS2 QDs with an average diameter of about 3.4 nm were synthesized by using a sulfuric acid-assisted ultrasonic method. The as-prepared MoS2 QDs exhibited low cytotoxicity of less than 100 μg/mL in both human umbilical vein endothelial cells and human coronary artery endothelial cells and showed novel biological properties to prevent EndMT and promote angiogenesis in vitro. We found that MoS2 QDs treatment-induced transcription factor (TFEB) mediated lysosomal biogenesis, which could cause autophagy activation. Importantly, using in vitro transforming growth factor (TGF)-β-induced EndMT model, we demonstrated that the cardiovascular protective effect of MoS2 QDs against EndMT acted through triggering TFEB nucleus translocation and restoring an impairment of autophagic flux, whereas genetic suppression of TFEB impaired the protective action of MoS2 QDs against EndMT. Taken together, these results gain novel insights into the mechanisms by which MoS2 QDs regulate EndMT and facilitate the development of MoS2-based nanoagents for the treatment of EndMT-related cardiovascular diseases.

目的 探讨老年髋部骨折合并骨质疏松出院患者的延续护理效果.方法 选取2016年5月至2017年12月老年髋部骨折合并骨质疏松患者124例,均在我院治疗后出院,并进行随机分组每组62例,对照组实施常规护理,观察组实施延续性护理干预.比较两组患者出院后1周、第1个月以及第3个月的用药依从性情况和生活质量评分,评估两组患者的护理满意度.结果 观察组与对照组患者出院后1周的用药依从性评分相比较差异无统计学意义(P>0.05).观察组患者出院后第1个月以及第3个月的依从性均明显高于对照组(P<0.05).观察组的身体疼痛、躯体功能、生命活力、社会功能、情感职能、生理职能、总体健康、精神健康等8项生活质量评分均明显高于对照组差异具有可比性,有统计学意义(P<0.05).同时观察组的护理满意度显著高于对照组,差异有统计学意义(P<0.05).结论 给予老年髋部骨折合并骨质疏松出院患者延续护理干预,有利患者保持较高的用药依从性,增加患者对护理的满意度,对进一步改善患者的生活质量有积极意义,值得临床借鉴和推广应用.

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its agonistic receptors have been identified as highly promising antitumor agents preferentially eliminating cancer cells with minimal damage, the emergence of TRAIL resistance in most cancers may contribute to therapeutic failure.Thus, there is an urgent need for new approaches to overcome TRAIL resistance.Gold nanoparticles (AuNPs) are one of the most promising nanomaterials that show immense antitumor potential via targeting various cellular and molecular processes; however, the effects of AuNPs on TRAIL sensitivity in cancer cells remain unclear.In this study, we found that AuNPs combined with TRAIL exhibited a greater potency in promoting apoptosis in non-small-cell lung cancer (NSCLC) cells compared with TRAIL alone, suggesting that AuNPs sensitize cancer cells to TRAIL.Further experiments demonstrated that the combination of TRAIL and AuNPs was more effective in causing excessive mitochondrial fragmentation in cancer cells accompanied by a dramatic increase in mitochondrial recruitment of dynamin-related protein 1 (Drp1), mitochondrial dysfunctions, and enhancement of autophagy induction.Small interfering RNA (siRNA) silencing of Drp1 or inhibition of autophagy could effectively alleviate apoptosis in cells exposed to TRAIL combined with AuNPs.In vivo studies revealed that AuNPs augmented TRAIL sensitivity in tumor-bearing mice.Our data indicated that AuNPs potentiate apoptotic response to TRAIL in NSCLC cells through Drp1-dependent mitochondrial fission, and TRAIL combined with AuNPs can be a potential chemotherapeutic strategy for the treatment of NSCLC.

The unique physicochemical properties of graphene and its derivatives enable their application in the diagnostics and therapy of central nervous system (CNS) diseases. However, the potential impacts of surface properties of functionalized graphene on microglia remain poorly understood. Herein, we used graphene oxides (GO), polyethylene glycol (PEG)- and polyethylenimine (PEI)-functionalized GO, which possess different surface charges, to investigate their effects on microglia by focusing on mitochondrial dynamics. The positively charged GO-PEI was found to promote mitochondrial fission as observed in BV-2 cells with mitochondria labeled by DsRed2-mito, indicating that alterations in mitochondrial dynamics depend on the surface properties of graphene. Concurrent to mitochondrial fragmentation, treatment with positively charged GO-PEI induced an increase in mitochondrial recruitment of dynamin-related protein (Drp1). Additionally, GO-PEI treatment also led to apoptotic and autophagic cell death. However, Drp1 silencing by small interfering RNA (siRNA) could effectively attenuate GO-PEI-induced apoptotic and autophagic cell death, indicating that mitochondrial fragmentation occurs upstream of GO-PEI-mediated toxicity in microglia. Overall, our study indicated that positively charged GO-PEI might cause deleterious influence on the central immune homeostasis by Drp1-dependent mitochondrial fragmentation, and provide the strategies for the rational design of graphene-based materials in neuroscience.

Prion disorders are progressive neurodegenerative diseases characterized by extensive neuronal loss, which is linked to the extracellular accumulation of the scrapie isoform (PrPSC) of the normal cellular prion protein (PrPC). As microglial activation is a central event in pathogenesis of prion disease, the strategies that reduce microglial activation may have therapeutic benefits. In this study, the neuroprotective effects of hydroxylated C60(C60-OH) and amino modified-C60(C60-NH2) were evaluated by using PrP(106-126)-stimulated BV-2 cells as a model of activated microglia. Herein, we showed that microglial activation in response to PrP(106-126) was effectively attenuated by pretreatment with C60-OH as compared with C60-NH2. C60-OH significantly inhibited the excessive production of inflammatory mediators, such as prostaglandin E2 (PGE2), nitric oxide (NO), tumor necrosis factors (TNF)-α, interleukin (IL)-1β, and IL-6, and blocked the expression of cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase (iNOS) in PrP(106-126)-stimulated BV-2 cells. C60-OH exerted anti-inflammatory potential by up-regulating the expression of antioxidant enzymes via activation of nuclear factor erythroid 2-related factor 2 (Nrf2). The inhibitory effect of C60-OH against PrP(106-126)-induced inflammatory response was abolished by siRNA of Nrf2. In addition, conditioned culture media taken from PrP(106-126)-stimulated microglia cause apoptotic neuronal cell death, which was suppressed by pretreatment with C60-OH. Take together, these results suggest that C60-OH protects neuronal cells against PrP(106-126)-mediated neurotoxicity through activation of Nrf2 pathway, and provides evidence that fullerene derivatives may have therapeutic potential in prion diseases.

Objective To investigate the medium-term efficacy of total hip replacement with CFP handle prosthesis.Methods Thirty-two patients (34 hips) undergoing total hip replacement with CFP handle prosthesis were selected.The preoperative diagnosis was:femoral neck fracture in 6 cases,femoral head necrosis in 12 cases,osteoarthritis in 10 cases,ankylosing spondylitis in 3 cases,and pigmentation villi nodular synovitis in 1 case.Ten days,1 month,6 months,and 1 year (a year later) after surgery,the hip joint function and X ray film performance were followed up.Results There was no complication such as infect and injury of blood vessel and nerve.Postoperative X ray film showed the femoral handle prosthesis position was good.The average Harris hip score was 32.6 (20-53) scores before surgery,and back to 95.3(90-100) scores after surgery,no patients needed revision surgery.Postoperative Engh score was above 10 scores after half a year.Conclusion The medium-term efficacy of total hip replacement with CFP handle prosthesis is good,and can be used as one of the choice of primary total hip replacement.

Fullerene (C60) derivatives, a unique class of compounds with potent antioxidant properties, have been reported to exert a wide variety of biological activities including neuroprotective properties. Mitochondrial dynamics are an important constituent of cellular quality control and function, and an imbalance of the dynamics eventually leads to mitochondria disruption and cell dysfunctions. This study aimed to assess the effects of carboxylic acid C60 derivatives (C60–COOH) on mitochondrial dynamics and elucidate its associated mechanisms in lipopolysaccharide (LPS)-stimulated BV-2 microglial cell model. Using a cell-based functional screening system labeled with DsRed2-mito in BV-2 cells, we showed that LPS stimulation led to excessive mitochondrial fission, increased mitochondrial localization of dynamin-related protein 1 (Drp1), both of which were markedly suppressed by C60–COOH pretreatment. LPS-induced mitochondria reactive oxygen species (ROS) generation and collapse of mitochondrial membrane potential (ΔΨm) were also significantly inhibited by C60–COOH. Moreover, we also found that C60–COOH pretreatment resulted in the attenuation of LPS-mediated activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling, as well as the production of pro-inflammatory mediators. Taken together, these findings demonstrated that carboxylic acid C60 derivatives may exert neuroprotective effects through regulating mitochondrial dynamics and functions in microglial cells, thus providing novel insights into the mechanisms of the neuroprotective properties of carboxylic acid C60 derivatives.

Objective To compare the outcome of proximal femoral nail anti-rotation (PFNA)versus anatomical locking plate (ALP) in treatment of unstable intertrochanteric fracture.Methods The study included 89 patients who had received PFNA fixation (PFNA group,n =45) or ALP fixation (ALP group,n =44) for unstable intertrochanteric fracture between February 2008 and September 2009.Operation time,amount of bleeding,drainage volume,postoperative complications,fracture healing time and hip joint score after fracture healing were compared between two groups.Results Mean operation time in PFNA group was obviously shorter than that in ALP group (61.4 minutes vs 114.8 minutes,P ＜0.01).Mean amount of bleeding and drainage volume were significantly lower in PFNA group than in ALPgroup (119.3 mlvs 136.8ml,P＜0.01; 74.9mlvs80.3 ml,P＜0.01).While,PFNA group was not significantly different from ALP group with regard to average fracture healing time and Harris hip joint score after fracture healing (4 months vs 4.1 months,P ＞ 0.05; 91.2 points vs 89.8 points,P ＞0.05).Two patients had poor fracture reduction in PFNA group,but all patients had good fracture reduction in ALP group.No obvious adverse postoperative complications occurred in PFNA group,but one patient had fracture nonunion in ALP group.Conclusions PFNA and ALP fixation of unstable intertrochanteric fracture present insignificant differences in fracture healing time,postoperative complications and hip joint function after fracture healing.Whereas,PFNA is more suitable for the elder patients on account of shorter operation time and less intraoperative bleeding.

Objective To study whether CT imaging technology combined with computer program-ming can be used to quantitatively evaluate the initial stability of the tapered femoral component at the proximal femur. Methods Thirty patients who had undergone total hip arthroplasty were included in this study.Anteroposterior and lateral radiographs and spiral CT scans were taken for their tapered stems of femoral component inserted into their medullary cavities of Type A or Type B. The sectional views of CT scans were programmed on computer for calculation of the contact areas between the 4 zones of the tapered stems and the cancellous and cortical bone at the medullary cavity. Results The X-rays and the sectional views of CT showed the 3-point fixation pattern was obtained by the femoral stems in the medullary cavity. The contact areas between the 4 zones of the tapered stems and the cancellous and cortical bone at the medullary cavity were 22. 9%, 13.6% 7.9%, and 3.3% respectively. Conclusion It is possible to use CT imaging combined with computer programming as a quantitative method to evaluate the contact areas between the tapered com-ponent and the proximal femur following total hip arthroplasty.

OBJECTIVE:To summarize the surgical technique and the clinical results of small acetabular components combined with medial protrusio technique in primary total hip arthroplasty (THA) for the treatment of Crowe type IV congenital hip dislocation (CHD).METHODS:From January 2000 to December 2005, total 14 patients (16 hips) of Crowe type IV CHD underwent cementless THA (12 unilateral, 2 bilateral) with this new technique. There were 2 males and 12 females with an average age of 49 years (range, 38 to 75 years). The indications for surgery was severe hip pain and leg length discrepancy with difficulty in walking and activating. Cup design: Duraloc (Depuy, Warsaw, USA) in 10 hips, Pressfit S II (LINK, Germany) in 6 hips. The outside diameter of the cup was 42 to 44 mm; and the thickness of the polyethylene liner was 6 to 7 mm. Total hip replacement were performed with the medial protrusion technique to stabilize the fit of a hemispherical metal cup in the acetabulum. The hip functions were evaluated by Harris hip score. The muscle strength of the gluteus medius and gait were respectively evaluated in accordance with the standards of five and four classes.RESULTS:The X-ray showed that the average superolateral bone coverage in these 16 hips (none of which had bone graft) was more than 98 percent. The cup was an average of (5.8 +/- 1.2) mm medial and (6.2 +/- 1.7) mm superior to the Ranawat triangle. The follow-up period ranged from 3 to 9 years. The Harris hip score improved from 25 to 32 preoperatively to 90 to 98 1 year postoperatively. X-ray showed that perforated area of the medial acetabulum were repaired with healed bone mud 4 to 8 months after operation. The rate of linear wear of the polyethylene liner averaged (0.10 +/- 0.03) mm each year. Until now, no aseptic loosening or osteolysis was identified around the acetabulum components, no acetabular components were revised for loosening or other reasons.CONCLUSION:Small acetabular components combined with medial protrusio technique is a simple, reliable and flexible surgical technique. Early and mid-term result in total hip arthroplasty with this technique for the treatment of Crowe type IV CHD is satisfactory.

Objective To identify the relationship of the femoral morphology with the sex and age, analyze and compare the two methods of defining the morphology of marrow cavity.Methods AP and lateral radiography of the hip joint was made in 45 patiens who accepted total hip arthroplasty.The anatomic parameters of the proximal femur were measured on those radiography.The femoral morphology was analyzed using Dorr criteria and Noble class respectively.Results (1)The anatomic parameters of the proximal femur were not correlated with the age in male.(2)The inner diameter of canal 10 em distal to the lesser trochanter, isthmus width and canal to calar isthmus rate were positively correlated with age in female.(3)The medial cortical and lateral cortical thickness 10 cm distal to the lesser trochanter,cortical index and canal-flare index were negatively correlated with age in female.(4)According to Dorr criteria,13 femora were classified as type A,20 as type B,and 12 as type C.According to Noble class,4 femora were classified as champagne type,34 as normal type,and 7 as stove pipe type.Conclusions The femoral morphology don't change with age in male.The width of femoral canal increase with age in female.Type C of Dorr criteria contains all of stove pipe type and a portion of normal type.

Objective To summarize the surgical technique and the clinical result of subtrochanteric shortening with overlapping femoral resection in primary total hip arthroplasty(THA)for Crowe type Ⅳadult dislocated hip (ADH).Methods From January 2000 to December 2003,11 primary hip arthroplasties were Derformed in Crowe Ⅳadult hip dislocation using a subtrochanteric shortening with overlapping femoral resection.There were 3 men and 5 women with an average age of 48 years (range 40-57 years).Subtrochanteric shortening with overlapping femoral resection and"V"shaped derotational osteotomy were performed for all cases without soft tissue release.The proximal femoral shaft splitting was used in 6 hips.Resnits The mean follow-up was 5 years (range 3-7 years).No operation was complicated by dislocation,or deep infection.Length of the reseeted subtrochanteric femour averaged 4.5 cm(4-6 cm).No hip reduction was encountered difficultly,and no nerve palsies and lax dislocation of the hip occurred.X-ray showed all acetabular cups were placed at the anatomical position,all osteotomies healed by 3-6 months.The Harris hip score improved from 25-32 to 90-98.Limb-length discrepancy was restored to an average of 3 cm after surgerv.No acetabular and femoral components need revision.No aseptic loosening or osteolysis was identified around the femoral or acetabulum components.Conclusion Subtrochanteric shortening osteotomy is a safe and predictable method of restoring the anatomic hip center in Crowe Ⅳ adult hip dislocation.

目的探讨生物活性玻璃加自体骨后外侧融合治疗腰椎峡部不连的临床疗效。方法对45例(90处)腰椎峡部不连患者,采用椎板减压取得骨粒或者用自体骼骨与生物活性玻璃混合于不连节段后外侧进行治疗。结果45例均随访12个月,根据邹德威的术后临床功能评价标准,临床疗效优良率达到98%,根据术后X线检查结果,1年的融合率达98%。结论采用该方法治疗腰椎峡部不连,融合率较高,临床效果较好,方法可行。