皮肤恶性黑色素瘤(CMM)是皮肤来源的高度恶性肿瘤,发病率不高,但恶性程度高,致死率高,早期可发生转移.准确地判定肿瘤分期并行规范的治疗可明显改善预后,提高患者生存率.外科手术仍是CMM治疗的基础.随着分子检测的开展,靶向和免疫等精准治疗的快速进展,局部不可切除或晚期的CMM治疗显著获益,但仍需继续探索.本文就近年来对该病的治疗研究进展作如下综述.

BACKGROUND:DICER1-AS1 is reported to promote the progression and disturb the cell cycle in osteosarcoma; however, its mechanism has rarely been studied.MATERIALS AND METHODS:DICER1-AS1 expression levels were evaluated by qPCR and fluorescence in situ hybridization (FISH). The total, nuclear, and cytosolic levels of CDC5L were measured by western blotting and immunofluorescence (IF). Cell proliferation, apoptosis, and cell cycle analyses were conducted using the colony formation, CCK-8 assay, terminal transferase-mediated UTP nick end-labeling kit (TUNEL) assay, and flow cytometry. Levels of cell proliferation-, cell cycle-, and cell apoptosis-related proteins were determined by western blotting. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to evaluate the relationship between DICER1-AS1 and CDC5L.RESULTS:LncRNA DICER1-AS1 was highly expressed in samples of osteosarcoma tissue and in osteosarcoma cell lines. DICER1-AS1 knockdown inhibited cell proliferation, promoted cell apoptosis, and disturbed the cell cycle. Moreover, DICER1-AS1 was found to bind with CDC5L, and knockdown of DICER-AS1 inhibited the nuclear transfer of CDC5L. DICER1-AS1 knockdown also reversed the effects of CDC5L overexpression on cell proliferation, apoptosis, and the cell cycle. Moreover, CDC5L inhibition suppressed cell proliferation, promoted cell apoptosis, and disturbed the cell cycle, and those effects were further enhanced by DICER1-AS1 knockdown. Finally, DICER1-AS knockdown inhibited tumor growth and proliferation, and promoted cell apoptosis in vivo.CONCLUSION:LncRNA DICER1-AS1 knockdown inhibits the nuclear transfer of CDC5L protein, arrests the cell cycle, and induces apoptosis to suppress the development of osteosarcoma. Our results suggest a novel target (DICER1-AS1) for treatment of osteosarcoma.

As an insidious metabolic bone disease, osteoporosis plagues the world, with high incidence rates. Patients with osteoporosis are prone to falls and becoming disabled, and their cone fractures and hip fractures are very serious, so the diagnosis and treatment of osteoporosis is very urgent. Extracellular vesicles (EVs) are particles secreted from cells to the outside of the cell and they are wrapped in a bilayer of phospholipids. According to the size of the particles, they can be divided into three categories, namely exosomes, microvesicles, and apoptotic bodies. The diameter of exosomes is 30–150 nm, the diameter of microvesicles is 100–1000 nm, and the diameter of apoptotic bodies is about 50–5000 nm. EVs play an important role in various biological process and diseases including osteoporosis. In this review, the role of EVs in osteoporosis is systematically reviewed and some insights for the prevention and treatment of osteoporosis are provided.

The complex bone regeneration microenvironment puts high demands on orthopedic implants. The implants are not only desired to satisfy the meeting of the biomechanical properties, but should also possess capabilities to promote osseointegration and bone immune regulation. PEEK is a promising polymeric material for bone implants due to its suitable mechanical properties that well match natural cortical bone tissue. However, its inert biological properties limit its application. As a newly-developed bioactive polysaccharides complex, strontium Eucommia ulmoides polysaccharides (EUP-Sr) has been proved to have capabilities including promoting osteogenesis and regulating bone immunity. In this study, in order to improve the bioactivities of PEEK, we introduce EUP-Sr to the PEEK surface via polydopamine-based coating and form a bioactive PEEK named DPEEK@EUP-Sr. The as-fabricated DPEEK@EUP-Sr was systematically investigated through scanning electron microscopy, X-ray photoelectron spectroscopy, water contact angle analysis to verify the successful introduction of EUP-Sr to PEEK, and in vitro biological experiments including cell proliferation and RT-PCR analysis suggested that the DPEEK@EUP-Sr can effectively promote the proliferation of preosteoblast MC3T3-E1, and exhibit significant anti-inflammation and osteogenesis effects, and so should be beneficial for osteointegration between bone and implants.

Background Gluteal muscle contracture (GMC) may cause abnormal spinal alignment as well as hip and pelvic deformities. The spine-pelvis alignment of GMC patients is unclear. This study aimed to describe the spine-pelvis sagittal alignment in patients with GMC and to explore the impact of GMC on the pathogenesis of low back pain (LBP). Methods Radiological analysis was performed in 100 patients with GMC and 100 asymptomatic volunteers who acted as the control group. Sagittal parameters were measured by two independent raters and their averages were presented on lateral radiographs of the whole spine, including pelvic incidence (PI), sagittal vertical axis (SVA), pelvic tilt (PT), lumbar lordosis (LL), sacral slope (SS), thoracic kyphosis (TK), and the relationship between PI and LL (expressed as PI-LL). All cases were categorized into one of three classes based on the apex position of lumbar lordosis and were further divided into three groups by the PI value. The GMC and control parameters were compared and the correlations between the parameters in the GMC group were analysed. Results The PI value of the GMC group was significantly less than that of the control group (42.38 ± 10.90° vs 45.68 ± 7.49°, P < 0.05). There was no difference found between the key parameters (SVA, PT, and PI-LL), which correlated with outcomes in adult deformity. No differences of SS were found between the two groups (P > 0.05). The GMC group showed lower average LL (42.77 ± 10.97° vs 46.41 ± 9.07°) and TK (17.34 ± 9.50° vs 20.45 ± 8.02°) compared with the control group (P < 0.05). LL was correlated with PI, SS, PT, TK (P < 0.01) and SVA (P < 0.05). TK and SVA were not correlated with any parameters except LL and pairwise correlations were found among PI, SS, and PT. There were no differences found between the distributions of the lumbar lordosis apex of GMC and the control but the range of SS in apex groups 3 and 4 did differ. GMC patients had the most small-PI value (44%) while approximately 64% of asymptomatic individuals had a normal PI. Interobserver variability was sufficient for all parameters calculated by the intraclass correlation coefficient (ICC). Conclusions Gluteal muscle contracture causes a low PI which may contribute to low back pain. Patients with GMC present the same global sagittal spinal-pelvic balance as asymptomatic individuals due to a compensatory mechanism through excessive flat lumbar and thoracic curves. Future studies on the relationship between spinal-pelvic sagittal and coronal alignment and low back pain are needed to understand the mechanical forces involved in the onset of GMC.

Objective To gain a greater understanding of anomalous insertions of the anterior horn of the medial meniscus through evaluation of a rare case and a review of the existing literature on medial meniscus malformations. Methods This report describes a 26-year-old man with an anomalous insertion of the anterior horn of the medial meniscus combined with symptomatic hypertrophy of the anterior horn and a synovial cyst. We also conducted a review of the existing literature on medial meniscus malformations using five major scholarly literature databases and search engines. Results The literature review revealed that the incidence of anomalous insertions of the anterior horn of the medial meniscus is 0.5% to 2.8%. Not all patients undergo surgical excision; some are only symptomatically treated. In our patient, the arthroscopic view was consistent with the imaging characteristics. No special operation was performed to treat the anomalous insertion. At the 18-month follow-up, the patient had no symptom recurrence and had returned to practicing sports. Conclusion The pain during hyperextension in our patient was caused by a cyst and anterior horn hypertrophy. If the symptoms in such cases are not caused by the anomalous insertion, no special treatment is needed.

Objective: Although running causes inevitable stress to the joints, data regarding its effect on the cartilage of the knee are conflicting. This systematic review and meta-analysis aimed to evaluate the effect of running on knee joint cartilage. Methods: PubMed, EMBASE, SportDiscus, and Cochrane Library databases were searched to identify randomized controlled trials (RCTs) and cohort studies. The outcome indicators were cartilage oligomeric matrix protein (COMP), cartilage volume and thickness, and T2. Results: A total of two RCTs and 13 cohort studies were included. There was no significant difference in cartilage volume between the running and control groups (MD, -115.88 U/I; 95% CI, -320.03 to 88.27; p = 0.27). However, running would decrease cartilage thickness (MD, -0.09 mm; 95%CI, -0.18 to -0.01; p = 0.03) and T2 (MD, -2.78 ms; 95% CI, -4.12 to -1.45; p < 0.001). Subgroup analysis demonstrated that COMP immediately or at 0.5 h after running was significantly increased, but there were no significant changes at 1 h or 2 h. Conclusions: Running has advantages in promoting nutrition penetrating into the cartilage as well as squeezing out the metabolic substance, such as water. Our study found that running had a short-term adverse effect on COMP and did not affect cartilage volume or thickness. (C) 2020 Published by Elsevier Ltd.

Osteogenesis is closely complemented by angiogenesis during the bone regeneration process. The development of functional hydrogel bone substitutes that mimic the extracellular matrix is a promising strategy for bone tissue engineering. However, the development of scaffold materials tailored to exhibit sufficient biomechanics, biodegradability, and favorable osteogenic and angiogenic activity continue to present a great challenge. Herein, we prepared a novel magnesium ion-incorporating dual-crosslinked hydrogel through the photocrosslinking of gelatin methacryloyl (GelMA), thiolated chitosan (TCS) and modified polyhedral oligomeric silsesquioxane (POSS) nanoparticles, and active Mg2+ ions were then introduced into system via coordination bonds of MgS, which can be tailored to possess superior mechanical strength, a stable network structure and more suitable pore size and degradation properties. The fabricated GelMA/TCS/POSS-Mg hydrogels effectively promoted cell adhesion, spreading, and proliferation, demonstrating that the introduction of POSS and Mg2+ not only stimulates the osteogenic differentiation of BMSCs but also promotes angiogenesis both in vitro and in vivo, thereby facilitating subsequent bone regeneration in calvarial defects of rats. Taken together, the results of this study indicate that the GelMA/TCS/POSS-Mg hydrogel has promising potential for repairing bone defects by promoting cell adhesion, osteogenesis and vascularization.

Visually monitoring of the residual morphology and quantitatively determining the degradation degree of hydrogels applied in tissue repair therapy in a real-time and noninvasive manner were a crucial technological mean. Despite conventional organic fluorescent molecules commonly used as probe to capture the real-time clues of the labeled hydrogels, they still encounter obstacles, including intrinsic photobleaching, cytotoxicity, and unknown interference factor of degradation caused by the change from polymer structure of hydrogels, thus making it difficult to accurately obtain the information of the hydrogels in vivo . To address the hard nut, we designed the multifunctional hydrogel system with a real-time quantitative aggregation-induced emission fluorescent detection and photoacoustic imaging tracking based on tetraphenylethene (TPE) that possesses the trait of aggregation-induced emission and low photobleaching, bound on the surface of mesoporous dopamine microspheres (MPDAs), and subsequently loaded into the photo-crosslinked injectable hydrogels. In vitro results showed that MPDA-TPE had good compatibility, emitted strong fluorescence when embedded in hydrogels, and maintained stable fluorescence property unless the hydrogels were degraded. Meanwhile, a mathematical formula for the kinetic degradation of hydrogels was established between gravitational and visual degradation in vitro , which can be used to predict in vivo degradation. Furthermore, MPDA possessed the clear photoacoustic imaging effect to provide more accurate clues. The designed hydrogel system holds a potential role in prediction of the in vivo degradation of implanted materials in an accurate, convenient, and real-time noninvasive manner and is a meaningful treatment aid in tissue engineering.

Bone defect therapy based on advanced biocomposite hydrogel scaffolds provide a promising strategy in bone tissue engineering. Inducing bone regeneration that meets the biomechanical, bioactivity and osteoconductivity criteria of bone tissue engineering is highly appealing but challenging. Here, we designed a mineralized, high strength and tough nanocomposite hydrogel by in situ deposition of calcium phosphate hydroxide salt nanohydroxyapatite (HAP) after photopolymerization of gelatin methacryloyl (GelMA), quaternized chitosan (QCS) and functional polyhedral oligomeric silsesquioxane (POSS), in which the POSS nanoparticles served as a physical-chemical crosslinker to reinforce the hydrogel network structure and improved mineralized capacity by silicon in POSS nanoparticle bonding to calcium ions. The fabricated nanocomposite hydrogels have excellent mechanical properties (tensile strength of 328.6 +/- 14.3 kPa and compressive strength of 1.71 +/- 0.24 MPa) and high cytocompatibility, significantly facilitated cell adhesion and upregulated osteodifferentiation. After treatment of a rat skull defect model for 12 weeks, the scaffold of the biomineralized hydrogel remarkably promoted new bone formation and accelerated bone regeneration in situ, suggesting its used as a promising substitute in bone tissue engineering.