An overview of current research on cancer stem cells: a bibliometric analysis.

BACKGROUND: Cancer stem cells (CSCs) represent a potential mechanism contributing to tumorigenesis, metastasis, recurrence, and drug resistance. The objective of this study is to investigate the status quo and advancements in CSC research utilizing bibliometric analysis. METHODS: Publications related to CSCs from 2010 to 2022 were collected from the Web of Science Core Collection database. Various analytical tools including CiteSpace, VOSviewer, Scimago Graphica, and GraphPad Prism were used to visualize aspects such as co-authorship, co-occurrence, and co-citation within CSC research to provide an objective depiction of the contemporary status and developmental trajectory of the CSC field. RESULTS: A total of 22,116 publications were included from 1942 journals written by 95,992 authors. Notably, China emerged as the country with the highest number of publications, whereas the United States exerted the most significant influence within the field. MD Anderson Cancer Center emerged as the institution making the most comprehensive contributions. Wicha M.S. emerged as the most prolific and influential researcher. Among journals, Cancers emerged as a focal point for CSC research, consistently publishing a wealth of high-quality papers. Furthermore, it was observed that most journals tended to approach CSC research from molecular, biological, and immunological perspectives. The research into CSCs encompassed a broad array of topics, including isolation and enrichment techniques, biomarkers, biological characteristics, cancer therapy strategies, and underlying biological regulatory mechanisms. Notably, exploration of the tumor microenvironment and extracellular vesicles emerged as burgeoning research frontiers for CSCs. CONCLUSION: The research on CSCs has garnered growing interest. A trend toward multidisciplinary homogeneity is emerging within the realm of CSCs. Further investigation could potentially center on the patients of extracellular vesicles and the tumor microenvironment in relation to CSCs.

The inhibition of Beclin1-dependent autophagy sensitizes PTC cells to ABT737-induced death.

ABT737 is used as a specific BCL2 inhibitor, which can treat papillary thyroid carcinoma (PTC). However, the effect of ABT737 on PTC cell apoptosis is limited. Moreover, BCL2 inhibition causes the activation of Beclin1-dependent autophagy. Our study aimed to explore the effects of autophagy and Beclin1 on ABT737 efficacy in PTC. The experimental data showed that ABT737 synchronously enhanced autophagic activity and apoptosis level in PTC cells. ABT737 also promoted the dissociation of BCL2-Beclin1 and BCL2-Bax complexes. Autophagy inhibitors, Bafilomycin A1 and 3-MA, enhanced the inhibitory effect of ABT737 on the survival and function in PTC cells. Consistently, autophagy inhibition with Beclin1 pharmacological inhibitor (spautin-1) also enhanced the efficacy of ABT737. Additionally, ABT737 at low-dose promoted LC3 conversion in PTC cells, and did not affect PTC cell apoptosis and survival. However, The efficacy of low-dose of ABT737 in PTC cell apoptosis and survival was displayed with the addition of Bafilomycin A1, 3-MA or spautin-1. In conclusion, the limited role of ABT737 in PTC cell apoptosis is attributed to its promoting effect on Beclin1-dependent autophagy. Therefore, autophagy inhibition based on Beclin1 downregulation can enhance the sensitivity of PTC cells to ABT737-induced death.

Tensile Property of 7075 Aluminum Alloy with Strengthening Layer by Laser Remelting-Cladding Treatment.

The Ni60-SiC-CeO2 strengthening layer with deep remelting pools was constructed on the surface of 7075 aluminum alloy using the laser remelting-cladding processing method, and a soft and hard interphase was prepared on the matrix by the interval of laser remelting, which was inspired by soft-hard interphase structure with excellent crack inhibition performance from the natural world. The microstructure and microhardness of the remelting region and the remelting-cladding region of the strengthening layer were studied. The tensile characteristics of two distinct strengthening layers were investigated in the laboratory. The results showed that the grain size of remelting pools is finer, and the microhardness is higher than that of the matrix, which makes crack propagation more difficult. In addition, the results show that the strengthening layer has compact and flawless microstructure and has been metallurgically integrated with the matrix, and the microhardness of the regions treated by laser cladding and laser remelting-cladding has been improved obviously. Toughness has improved, as has the problem of toughness reduction after cladding ceramic particles. The sample's strength is also significantly greater than that of the untreated sample.

PHACTR1 promotes the mobility of papillary thyroid carcinoma cells by inducing F-actin formation.

Papillary thyroid carcinoma (PTC) limits effective biomarkers for predicting prognosis and targeted therapy. Phosphatase and actin regulator 1 (PHACTR1) is a mobility-promoting molecule due to its regulation on F-actin formation, which is valuable for the investigation of PTC. Our study aimed to investigate the relationship between PHACTR1 and PTC carcinogenesis, especially mobility. Our results displayed that PHACTR1 expression was elevated in metastatic or larger PTC tissues. In addition, PTC cells K1 with more obvious mobility had higher PHACTR1 expression whereas weakly mobile cells TPC-1 was contrary. Moreover, PHACTR1 silencing inhibited the invasion, migration and tumorigenicity of K1 cells, while PHACTR1 overexpression promoted the invasion, migration and tumorigenicity in TPC-1 cells. Furthermore, PHACTR1 overexpression increased the fluorescent intensity of F-actin in TPC-1 cells. Importantly, the enhanced invasion and migration in TPC-1 cells caused by PHACTR1 overexpression were significantly reversed by the disruption of F-actin assembly with swinholide A. In conclusion, PHACTR1 can promote the mobility of PTC cells, which results in the carcinogenesis of PTC. PHACTR1-regulated F-actin formation determines the mobility of PTC cells. Therefore, PHACTR1 can function as a potential biomarker for predicting prognosis and targeting therapy in PTC.

Evaluation and Application of Silk Fibroin Based Biomaterials to Promote Cartilage Regeneration in Osteoarthritis Therapy.

Osteoarthritis (OA) is a common joint disease characterized by cartilage damage and degeneration. Traditional treatments such as NSAIDs and joint replacement surgery only relieve pain and do not achieve complete cartilage regeneration. Silk fibroin (SF) biomaterials are novel materials that have been widely studied and applied to cartilage regeneration. By mimicking the fibrous structure and biological activity of collagen, SF biomaterials can promote the proliferation and differentiation of chondrocytes and contribute to the formation of new cartilage tissue. In addition, SF biomaterials have good biocompatibility and biodegradability and can be gradually absorbed and metabolized by the human body. Studies in recent years have shown that SF biomaterials have great potential in treating OA and show good clinical efficacy. Therefore, SF biomaterials are expected to be an effective treatment option for promoting cartilage regeneration and repair in patients with OA. This article provides an overview of the biological characteristics of SF, its role in bone and cartilage injuries, and its prospects in clinical applications to provide new perspectives and references for the field of bone and cartilage repair.

Long noncoding RNA (lncRNA) H19: An essential developmental regulator with expanding roles in cancer, stem cell differentiation, and metabolic diseases.

Recent advances in deep sequencing technologies have revealed that, while less than 2% of the human genome is transcribed into mRNA for protein synthesis, over 80% of the genome is transcribed, leading to the production of large amounts of noncoding RNAs (ncRNAs). It has been shown that ncRNAs, especially long non-coding RNAs (lncRNAs), may play crucial regulatory roles in gene expression. As one of the first isolated and reported lncRNAs, H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis, development, tumorigenesis, osteogenesis, and metabolism. Mechanistically, H19 mediates diverse regulatory functions by serving as competing endogenous RNAs (CeRNAs), Igf2/H19 imprinted tandem gene, modular scaffold, cooperating with H19 antisense, and acting directly with other mRNAs or lncRNAs. Here, we summarized the current understanding of H19 in embryogenesis and development, cancer development and progression, mesenchymal stem cell lineage-specific differentiation, and metabolic diseases. We discussed the potential regulatory mechanisms underlying H19's functions in those processes although more in-depth studies are warranted to delineate the exact molecular, cellular, epigenetic, and genomic regulatory mechanisms underlying the physiological and pathological roles of H19. Ultimately, these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.

Joint fluid interleukin-6 combined with the neutral polymorphonuclear leukocyte ratio (PMN%) as a diagnostic index for chronic periprosthesis infection after arthroplasty.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice. Many novel serum and joint fluid biomarkers have important implications for the diagnosis of PJI. The presented study evaluated the value of joint fluid interleukin-6 (IL-6) combined with the neutral polymorphonuclear leukocyte (PMN%) ratio for chronic PJI diagnosis after arthroplasty. MATERIALS AND METHODS: Sixty patients with chronic PJI or aseptic failure who underwent hip or knee revision from January 2018 to January 2020 in our department were included in this retrospective study. According to the 2013 MSIS diagnostic criteria, the 60 patients were divided into a PJI group and a non-PJI group (30 patients per group). We collected the joint fluid before surgery and determined the level of IL-6 and the PMN% by ELISA, and the differences between the two groups were compared. The diagnostic efficacy of joint fluid IL-6 combined with PMN% in chronic PJI was analyzed using a receiver operating characteristic curve (ROC curve). RESULTS: The diagnosis of PJI using joint fluid IL-6 combined with PMN% presented an area under the curve of 0.983, which was more accurate than the areas under the curve for diagnosis using IL-6 and PMN% individually (0.901 and 0.914, respectively). The optimal threshold values for IL-6 and PMN% were 662.50 pg/ml and 51.09%, respectively. Their sensitivity and specificity were 96.67% and 93.33%, respectively. The accuracy of the diagnosis of PJI was 95.00%. CONCLUSIONS: Joint fluid IL-6 combined with PMN% can be used as an auxiliary method to detect chronic infection around the prosthesis after hip/knee arthroplasty. LEVEL OF EVIDENCE: Patients who underwent hip/knee revision at the First Hospital of Chongqing Medical University for periprosthetic infection or aseptic failure of the prosthesis after hip/knee arthroplasty from January 2018 to January 2020 were included. Trial registration This study was approved by the ethics committee of the First Hospital of Chongqing Medical University on September 26, 2018 (local ethics committee number: 20187101) and registered with the China Clinical Trials Registry (registration number: ChiCTR1800020440) with an approval date of December 29, 2018.

Case Report: Paroxysmal weakness of unilateral limb as an initial symptom in anti-LGI1 encephalitis: a report of five cases.

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common kind of autoimmune encephalitis following anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Anti-LGI1 encephalitis is characterized by cognitive impairment or rapid progressive dementia, psychiatric disorders, epileptic seizures, faciobrachial dystonic seizures (FBDS), and refractory hyponatremia. Recently, we found an atypical manifestation of anti-LGI1 encephalitis, in which paroxysmal limb weakness was the initial symptom. In this report, we describe five cases of anti-LGI1 encephalitis with paroxysmal limb weakness. Patients had similar presentations, where a sudden weakness involving a unilateral limb was observed, which lasted several seconds and occurred dozens of times each day, with the anti-LGI1 antibody being positive in both serum and cerebrospinal fluid (CSF). FBDS occurred after a mean of 12 days following paroxysmal limb weakness in three of five patients (Cases 1, 4, and 5). All patients were given high-dose steroid therapy, which had a good effect on their condition. Based on this report, we suggest that paroxysmal unilateral weakness may be a kind of epilepsy and be connected to FBDS. As an unusual neurological presentation, paroxysmal weakness can be included in the clinical manifestations of anti-LGI1 encephalitis, helping to raise awareness of the recognition of anti-LGI1 encephalitis in patients with this symptom and leading to early diagnosis and early treatment, which would contribute to improved clinical outcomes.

Downregulation of Bmal1 Expression in Celiac Ganglia Protects against Hepatic Ischemia-Reperfusion Injury.

Hepatic ischemia-reperfusion injury (HIRI) significantly contributes to liver dysfunction following liver transplantation and hepatectomy. However, the role of the celiac ganglion (CG) in HIRI remains unclear. Adeno-associated virus was used to silence Bmal1 expression in the CG of twelve beagles that were randomly assigned to the Bmal1 knockdown group (KO-Bmal1) and the control group. After four weeks, a canine HIRI model was established, and CG, liver tissue, and serum samples were collected for analysis. The virus significantly downregulated Bmal1 expression in the CG. Immunofluorescence staining confirmed a lower proportion of c-fos+ and NGF+ neurons in TH+ cells in the KO-Bmal1 group than in the control group. The KO-Bmal1 group exhibited lower Suzuki scores and serum ALT and AST levels than the control group. Bmal1 knockdown significantly reduced liver fat reserve, hepatocyte apoptosis, and liver fibrosis, and it increased liver glycogen accumulation. We also observed that Bmal1 downregulation inhibited the hepatic neurotransmitter norepinephrine, neuropeptide Y levels, and sympathetic nerve activity in HIRI. Finally, we confirmed that decreased Bmal1 expression in CG reduces TNF-α, IL-1ß, and MDA levels and increases GSH levels in the liver. The downregulation of Bmal1 expression in CG suppresses neural activity and improves hepatocyte injury in the beagle model after HIRI.

Detection of inguinal lymph nodes is promising for the diagnosis of periprosthetic joint infection.

Background: Localized inguinal lymphadenopathy often represents lower extremity pathogen infection, while normalized lymphadenopathy is associated with infection regression. We hypothesized that inguinal lymph nodes (LNs) were enlarged in Periprosthetic Joint Infection (PJI) patients and that normalized inguinal LNs would be a promising way to determine the timing of reimplantation. Methods: We prospectively enrolled 176 patients undergoing primary and revision hip or knee arthroplasty. All patients underwent ultrasound examination of inguinal LNs preoperatively. The diagnostic value of inguinal LNs in PJI was evaluated by the receiver operating characteristic (ROC) curve. Results: The median level of inguinal LNs was 26mm in the revision for PJI group compared with 12 mm in the aseptic revision group (p< 0.0001). The size of the inguinal LNs well distinguishes PJI from aseptic failure (AUC= 0.978) compare with ESR (AUC= 0.707) and CRP (AUC= 0.760). A size of 19mm was determined as the optimal threshold value of the inguinal LNs for the diagnosis of PJI, with a sensitivity of 92% and specificity of 96%. Conclusion: Ultrasonic analysis of inguinal LNs is a valuable piece of evidence for the diagnosis of PJI and evaluation of persistent infection.

ADAMTS1 induces epithelial-mesenchymal transition pathway in non-small cell lung cancer by regulating TGF-ß.

Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers. Identifying key molecular targets related to the initiation, development, and metastasis of lung cancer is important for its diagnosis and target therapy. The ADAMTS families of multidomain extracellular protease enzymes have been reported to be involved in many physiological processes. In this study, we found that ADAMTS1 was highly expressed in NSCLC tissues, which promoted cell proliferation, migration, invasion, and epithelial to mesenchymal transition (EMT) of NSCLC cells. In the NSCLC tumor metastasis model involving nude mice, overexpression of ADAMTS1 promoted EMT and lung metastasis of tumor cells. Moreover, ADAMTS1 positively regulated TGF-ß expression, and TGF-ß was highly expressed in NSCLC tumor tissues. si-TGF-ß or inhibition of TGF-ß expression through the short peptide KTFR on ADAMTS1 protein could reverse the oncogenic effects of ADAMTS1 on lung cancer cells. Taken together, ADAMTS1 functioned as an oncogene in NSCLC cells by promoting TGF-ß expression, indicating that ADAMTS1 has important regulatory roles in the progression of NSCLC.

[Clinical effect of simultaneous implantation and maxillary sinus floor elevation with or without bone graft].

PURPOSE: To investigate the difference of osteogenic effect and stability of maxillary sinus implants 6 months after maxillary sinus elevation with or without bone grafting. METHODS: A total of 150 patients with maxillary sinus floor lift and simultaneous implantation in Lishui People's Hospital from December 2019 to December 2021 were divided into group A (internal maxillary sinus lift + bone grafting) and group B (internal lift without bone grafting). Preoperative and postoperative CBCT data and implant stability of all patients were measured and analyzed to compare whether there were differences in clinical efficacy between the two groups. SPSS 25.0 software package was used for data analysis. RESULTS: A total of 199 implants were implanted, the implant retention rate was 97.6% in group A and 95.7% in group B one year after surgery, with no significant difference between the two groups(P＞0.05). There was no significant difference in residual bone height(RBH) and gray scale value (HU) between the two groups before and 6 months after operation (P＞0.05). There was no significant difference in ISQ value between the two groups during operation and 6 months after operation(P＞0.05). CONCLUSIONS: In cases with the remaining alveolar bone height of 3～8 mm and the planned lifting height of 3～4 mm, maxillary sinus floor lifting procedure achieved good clinical results in both groups with or without bone grafting, which indicated that bone grafting had little effect on retention rate and stability of the implants.

Effect of Reticulate Unit Spacing on Microstructure and Properties of Biomimetic 7075 Aluminum Alloy by Laser Cladding.

In the context of energy conservation and emission reduction, more and more attention has been paid to the development of lightweight metal materials with both high strength and high toughness. Inspired by the non-smooth surface of natural organisms, a biomimetic surface with various spacing reticulate units of 7075 aluminum alloys was modified by laser cladding. The microstructure, microhardness and tensile properties of the various spacing units with CeO2-SiC-Ni60 were studied. The finer microstructure and the higher microhardness of various spacing units in comparison with that of 7075 aluminum alloys were obtained, no matter the strip-like treated region or the cross-junction region. Moreover, the best combination of strength and toughness of the biomimetic sample with 2.5 mm spacing reticulate unit was discussed. Finally, by combining the microstructure, XRD phase change, thermal gradient effect, thermal expansion coefficient difference and hard phase strengthening mechanism, it was concluded that the 2.5 mm spacing reticulate unit had the best ability to inhibit crack propagation, and the dispersive hard phases of Al3Ni2 and SiC played a major role in stress release of the matrix.

Lactate Mediates the Bone Anabolic Effect of High-Intensity Interval Training by Inducing Osteoblast Differentiation.

BACKGROUND: High-intensity interval training (HIIT) reportedly improves bone metabolism and increases bone mineral density (BMD). The purpose of the present study was to investigate whether lactate mediates the beneficial effects of exercise on BMD, bone microarchitecture, and biomechanical properties in an established osteoporotic animal model. In addition, we hypothesized that lactate-induced bone augmentation is achieved through enhanced osteoblast differentiation and mineralization. METHODS: A total of 50 female C57BL/6 mice were randomly allocated into 5 groups: the nonovariectomized group, the ovariectomized group (OVX), the HIIT group (OVX + HIIT), the HIIT with lactate transporter inhibition group (OVX + HIIT + INH), and the lactate subcutaneous injection group (OVX + LAC). After 7 weeks of intervention, bone mass, bone strength, and bone formation/resorption processes were evaluated via microcomputed tomography (micro-CT), biomechanical testing, histological analysis, and serum biochemical assays; in vitro studies were performed to explore the bone anabolic effect of lactate at the cellular level. RESULTS: Micro-CT revealed significantly increased BMD in both the OVX + HIIT group (mean difference, 41.03 mg hydroxyapatite [HA]/cm 3 [95% CI, 2.51 to 79.54 mg HA/cm 3 ]; p = 0.029) and the OVX + LAC group (mean difference, 40.40 mg HA/cm 3 [95% CI, 4.08 to 76.71 mg HA/cm 3 ]; p = 0.031) compared with the OVX group. Biomechanical testing demonstrated significantly improved mechanical properties in those 2 groups. However, the beneficial effects of exercise on bone microstructure and biomechanics were largely abolished by blocking the lactate transporter. Notably, histological and biochemical results indicated that increased bone formation was responsible for the bone augmentation effects of HIIT and lactate. Cell culture studies showed a marked increase in the expression of osteoblastic markers with lactate treatment, which could be eliminated by blocking the lactate transporter. CONCLUSIONS: Lactate may have mediated the bone anabolic effect of HIIT in osteoporotic mice, which may have resulted from enhanced osteoblast differentiation and mineralization. CLINICAL RELEVANCE: Lactate may mediate the bone anabolic effect of HIIT and serve as a potential inexpensive therapeutic strategy for bone augmentation.

Hypoxia-mimicking scaffolds with controlled release of DMOG and PTHrP to promote cartilage regeneration via the HIF-1α/YAP signaling pathway.

Efficiently driving chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) while avoiding undesired hypertrophy remains a challenge in the field of cartilage tissue engineering. Here, we report the sequential combined application of dimethyloxalylglycine (DMOG) and parathyroid hormone-related protein (PTHrP) to facilitate chondrogenesis and prevent hypertrophy. To support their delivery, poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated using a double emulsion method. Subsequently, these microspheres were incorporated onto a poly(l-lactic acid) (PLLA) scaffold with a highly porous structure, high interconnectivity and collagen-like nanofiber architecture to construct a microsphere-based scaffold delivery system. These functional constructs demonstrated that the spatiotemporally controlled release of DMOG and PTHrP effectively mimicked the hypoxic microenvironment to promote chondrogenic differentiation with phenotypic stability in a 3D culture system, which had a certain correlation with the interaction between hypoxia-inducible Factor 1 alpha (HIF-1α) and yes-associated protein (YAP). Subcutaneous implantation in nude mice revealed that the constructs were able to maintain cartilage formation in vivo at 4 and 8 weeks. Overall, this study indicated that DMOG and PTHrP controlled-release PLGA microspheres incorporated with PLLA nanofibrous scaffolds provided an advantageous 3D hypoxic microenvironment for efficacious and clinically relevant cartilage regeneration and is a promising treatment for cartilage injury.

TAT-Beclin 1 represses the carcinogenesis of DUSP4-positive PTC by enhancing autophagy.

BACKGROUND: DUSP4 is a pro-tumorigenic molecule of papillary thyroid carcinoma (PTC). DUSP4 also exists as an autophagic regulator. Moreover, DUSP4, as a negative regulator of MAPK, can prevent Beclin 1 from participating in autophagic response. This study aimed to explore whether TAT-Beclin 1, a recombinant protein of Beclin 1, could inhibit the tumorigenesis of DUSP4-positive PTC by regulating autophagy. METHODS: First, we divided PTC tissues into three groups according to DUSP4 expression levels by immunohistochemical analyses, and evaluated the relationship between autophagic molecules (Beclin 1 and LC3II) and DUSP4 using Western blotting assays. After overexpression of DUSP4 by lentiviral transduction, the in vitro and in vivo roles of TAT-Beclin 1 on DUSP4-overexpressed PTC cells were assessed (including autophagic activity, cell survival and function, and tumor growth). The roles of TAT-Beclin 1 in the survival of DUSP4-silenced PTC cells were also evaluated. RESULTS: Our results showed that the expression levels of autophagic proteins decreased with the increase of DUSP4 expression in PTC tissues. In PTC cells, DUSP4 overexpression-inhibited autophagic activity (including Beclin 1 expression, LC3 conversion rate and LC3-puncta formation) and -promoted cell proliferation and migration were reversed by TAT-Beclin 1 administration. In vivo assays also showed that DUSP4-overexpressed PTC cells had stronger tumorigenic ability and weaker autophagic activity, which was blocked by TAT-Beclin 1 administration. CONCLUSION: TAT-Beclin 1, as an autophagic promoter, could repress the carcinogenesis of DUSP4-positive PTC, which implies that the use of TAT-Beclin 1 for the PTC patients' treatment might be determined according to the DUSP4 level in their tumors.

An engineered (CAGA)12-EGFP cell-based biosensor for high-content and accurate detection of active TGF-ß.

Transforming growth factor-ß (TGF-ß) regulates multiple fundamental physiological processes and is closely related to severe diseases such as cancer, fibrosis, immune disorders and cardiovascular diseases. TGF-ß is thus an important biomarker for clinical diagnosis and prognosis, and a crucial target for therapeutics development. Here we describe a high-content, serum-free, easy-to-use, and cost-effective (CAGA)12-EGFP cell-based biosensor for accurate measurements of active TGF-ß. Together with non-destructive and continuous measurement protocol and data processing method established here, the biosensor is capable of detecting active TGF-ß1 in the range of 0.024-6.25 ng/mL concentration with >91% accuracy and high repeatability. Overall, the engineered (CAGA)12-EGFP biosensor is a powerful tool for detection of active TGF-ß and for mechanistic study of the TGF-ß pathway. The greatly reduced cost and operating simplicity also makes it a highly potent in vitro platform for high-throughput screening of anti-TGF-ß therapeutics.

A three-dimensional (3D) printed simulator as a feasible assessment tool for evaluating hip arthroscopy skills.

PURPOSE: The aims of this study were (1) to develop a three-dimensional (3D) printed simulator that facilitates the simulation of surgical skills for portal placement, intra-articular identification of anatomical structures and arthroscope navigation for hip arthroscopy and (2) to concurrently examine the feasibility of using this simulator as an assessment tool to evaluate trainees' surgical competencies. METHODS: A simulator was developed using a combination of medical imaging, computer-aided design, and 3D printing. A cross-sectional study was conducted with 29 participants divided into 3 subgroups (novice, intermediate and experienced). All participants performed related skills on the simulator, and their performance was evaluated using different assessment parameters. The participants' qualitative feedback regarding the simulator was also collected. The data collated from each group of participants were subsequently compared. RESULTS: Significant differences were observed between the three subgroups of participants with regard to the total checklist score (F2,26 = 11.3), total Arthroscopic Surgical Skill Evaluation score (F2,26 = 92.1), overall final global rating scale score (F2,26 = 49), number of times the participants used fluoroscopy (F2,26 = 7.4), and task completion times (F2,26 = 23.5). The participants' performance in the simulated operation was correlated with their prior clinical experience. There was mainly positive feedback with regard to the fidelity and utility of the simulator in relation to the surgeons' prior clinical experience. CONCLUSIONS: This study demonstrated that a reliable hip arthroscopic simulator can be developed for use by orthopedic surgeons to evaluate their hip arthroscopic skills before performing actual surgical operations. LEVEL OF EVIDENCE: Level III.

The Role of Cartilage Stem/Progenitor Cells in Cartilage Repair in Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease characterized by the loss of cartilage, which seriously affects the quality of patient's life and may even cause permanent sequelae. The treatment of OA is diversified, mostly limited to relieving clinical symptoms. Less invasive treatments that can cure OA are still lacking. With the rise of tissue-cell engineering, stem cell therapy has gradually aroused great interest in treating OA. Cartilage stem/progenitor cells (CSPCs), a type of stem cell found on the surface of articular cartilage, have many similarities with mesenchymal stem cells (MSCs). These cells can be isolated and cultured from animals and humans and exist in articular cartilage over the body, such as the knee joint, patellofemoral joint, and temporomandibular joint. Due to their strong proliferative and chondrogenic differentiation abilities, CSPCs may contribute a lot to cartilage regeneration and repair in OA. We will provide an overview of the biological characteristics of CSPCs and their role in OA in combination with the research progress. Despite some existing limitations, CSPCs still offer an innovative idea for OA treatment with great advantages.

Ufl1 deficiency causes skin pigmentation by up-regulation of Endothelin-1.

Ufmylation (UFM1 modification) is a newly identified ubiquitin-like modification system involved in numerous cellular processes. However, the regulatory mechanisms and biological functions of this modification remain mostly unknown. We have recently reported that Ufmylation family genes have frequent somatic copy number alterations in human cancer including melanoma, suggesting involvement of Ufmylation in skin function and disease. UFL1 is the only known Ufmylation E3-like ligase. In this study, we generated the skin-specific Ufl1 knockout mice and show that ablation of Ufl1 caused epidermal thickening, pigmentation and shortened life span. RNA-Seq analysis indicated that Ufl1 deletion resulted in upregulation of the genes involved in melanin biosynthesis. Mechanistically, we found that Endothelin-1 (ET-1) is a novel substrate of Ufmylation and this modification regulates ET-1 stability, and thereby deletion of Ufl1 upregulates the expression and secretion of ET-1, which in turn results in up-regulation of genes in melanin biosynthesis and skin pigmentation. Our findings establish the role of Ufl1 in skin pigmentation through Ufmylation modification of ET-1 and provide opportunities for therapeutic intervention of skin diseases.