A variable mineralization time and solution concentration intervene in the microstructure of biomimetic mineralized collagen and potential osteogenic microenvironment.

The absence of a conducive bone formation microenvironment between fractured ends poses a significant challenge in repairing large bone defects. A promising solution is to construct a bone formation microenvironment that mimics natural bone tissue. Biomimetic mineralized collagen possesses a chemical composition and microstructure highly similar to the natural bone matrix, making it an ideal biomimetic bone substitute material. The microstructure of biomimetic mineralized collagen is influenced by various factors, and its biomineralization and microstructure, in turn, affect its physicochemical properties and biological activity. We aimed to utilize mineralization time and solution concentration as variables and employed the polymer-induced liquid precursor strategy to fabricate mineralized collagen with diverse microstructures, to shed light on how mineralization parameters impact the material microstructure and physicochemical properties. We also investigated the influence of microstructure and physicochemical properties on cell biocompatibility and the bone-forming microenvironment. Through comprehensive characterization, we examined the physical and chemical properties of I-EMC under various mineralization conditions and assessed the in vitro and in vivo biocompatibility and osteogenic performance. By investigating the relationship between mineralization parameters, material physicochemical properties, and osteogenic performance, we revealed how microstructures influence cellular behaviors like biocompatibility and osteogenic microenvironment. Encouragingly, mineralization solutions with varying concentrations, stabilized by polyacrylic acid, successfully produced intrafibrillar and extrafibrillar mineralized collagen. Compared to non-mineralized collagen, all mineralized samples demonstrated improved bone-forming performance. Notably, samples prepared with a 1× mineralization solution exhibited relatively smooth surfaces with even mineralization. Extending the mineralization time enhanced the degree of mineralization and osteogenic performance. Conversely, samples prepared with a 2× mineralization solution had rough surfaces with large calcium phosphate particles, indicating non-uniform mineralization. Overall, our research advances the potential for commercial production of mineralized collagen protein products, characterized by dual biomimetic properties, and their application in treating various types of bone defects.

3D-printed PCL scaffolds with anatomy-inspired bionic stratified structures for the treatment of growth plate injuries.

The growth plate is a cartilaginous tissue with three distinct zones. Resident chondrocytes are highly organized in a columnar structure, which is critical for the longitudinal growth of immature long bones. Once injured, the growth plate may potentially be replaced by bony bar formation and, consequently, cause limb abnormalities in children. It is well-known that the essential step in growth plate repair is the remolding of the organized structure of chondrocytes. To achieve this, we prepared an anatomy-inspired bionic Poly(ε-caprolactone) (PCL) scaffold with a stratified structure using three-dimensional (3D) printing technology. The bionic scaffold is engineered by surface modification of NaOH and collagen Ⅰ (COL Ⅰ) to promote cell adhesion. Moreover, chondrocytes and bone marrow mesenchymal stem cells (BMSCs) are loaded in the most suitable ratio of 1:3 for growth plate reconstruction. Based on the anatomical structure of the growth plate, the bionic scaffold is designed to have three regions, which are the small-, medium-, and large-pore-size regions. These pore sizes are used to induce BMSCs to differentiate into similar structures such as the growth plate. Remarkably, the X-ray and histological results also demonstrate that the cell-loaded stratified scaffold can successfully rebuild the structure of the growth plate and reduce limb abnormalities, including limb length discrepancies and angular deformities in vivo. This study provides a potential method of preparing a bioinspired stratified scaffold for the treatment of growth plate injuries.

Bisphosphonate-incorporated coatings for orthopedic implants functionalization.

Bisphosphonates (BPs), the stable analogs of pyrophosphate, are well-known inhibitors of osteoclastogenesis to prevent osteoporotic bone loss and improve implant osseointegration in patients suffering from osteoporosis. Compared to systemic administration, BPs-incorporated coatings enable the direct delivery of BPs to the local area, which will precisely enhance osseointegration and bone repair without the systemic side effects. However, an elaborate and comprehensive review of BP coatings of implants is lacking. Herein, the cellular level (e.g., osteoclasts, osteocytes, osteoblasts, osteoclast precursors, and bone mesenchymal stem cells) and molecular biological regulatory mechanism of BPs in regulating bone homeostasis are overviewed systematically. Moreover, the currently available methods (e.g., chemical reaction, porous carriers, and organic material films) of BP coatings construction are outlined and summarized in detail. As one of the key directions, the latest advances of BP-coated implants to enhance bone repair and osseointegration in basic experiments and clinical trials are presented and critically evaluated. Finally, the challenges and prospects of BP coatings are also purposed, and it will open a new chapter in clinical translation for BP-coated implants.

Functionalization of biomimetic mineralized collagen for bone tissue engineering.

Mineralized collagen (MC) is the basic unit of bone structure and function and is the main component of the extracellular matrix (ECM) in bone tissue. In the biomimetic method, MC with different nanostructures of neo-bone have been constructed. Among these, extra-fibrous MC has been approved by regulatory agencies and applied in clinical practice to play an active role in bone defect repair. However, in the complex microenvironment of bone defects, such as in blood supply disorders and infections, MC is unable to effectively perform its pro-osteogenic activities and needs to be functionalized to include osteogenesis and the enhancement of angiogenesis, anti-infection, and immunomodulation. This article aimed to discuss the preparation and biological performance of MC with different nanostructures in detail, and summarize its functionalization strategy. Then we describe the recent advances in the osteo-inductive properties and multifunctional coordination of MC. Finally, the latest research progress of functionalized biomimetic MC, along with the development challenges and future trends, are discussed. This paper provides a theoretical basis and advanced design philosophy for bone tissue engineering in different bone microenvironments.

Three-Dimensional Printing Strategies for Irregularly Shaped Cartilage Tissue Engineering: Current State and Challenges.

Although there have been remarkable advances in cartilage tissue engineering, construction of irregularly shaped cartilage, including auricular, nasal, tracheal, and meniscus cartilages, remains challenging because of the difficulty in reproducing its precise structure and specific function. Among the advanced fabrication methods, three-dimensional (3D) printing technology offers great potential for achieving shape imitation and bionic performance in cartilage tissue engineering. This review discusses requirements for 3D printing of various irregularly shaped cartilage tissues, as well as selection of appropriate printing materials and seed cells. Current advances in 3D printing of irregularly shaped cartilage are also highlighted. Finally, developments in various types of cartilage tissue are described. This review is intended to provide guidance for future research in tissue engineering of irregularly shaped cartilage.

Application of multidirectional stitching technology in a laparoscopic suturing instructional program: a randomized controlled trial.

BACKGROUND: Surgeon suturing technology plays a pivotal role in patient recovery after laparoscopic surgery. Intracorporal suturing and knot tying in minimally invasive surgery are particularly challenging and represent a key skill for advanced procedures. In this study, we compared the application of multidirectional stitching technology with application of the traditional method in a laparoscopic suturing instructional program. METHODS: We selected forty residents within two years of graduation to assess the specialized teaching of laparoscopic suturing with laparoscopic simulators. The forty students were randomly divided into two groups, a control group and an experimental group, with twenty students in each group. The control group was scheduled to learn the traditional suture method, and the experimental group applied multidirectional stitching technology. The grades for suturing time, thread length, accuracy of needle entry, stability of the knot, tissue integrity, and tightness of the tissue before and after the training program were calculated. RESULTS: There was no significant difference between the two groups before the learning intervention. After the program, both groups significantly improved in each subject. There were significant differences between the control group and the experimental group in suture time (P = 0.001), accuracy of needle entry and exit (P = 0.035), and whether the suture tissue had cracks (P = 0.030). However, the two groups showed non-significant differences in thread length (P = 0.093), stablity of the knot (P = 0.241), or tightness of the tissue (P = 0.367). CONCLUSIONS: Multidirectional stitching technology improves the efficiency and effectiveness of traditional laparoscopic suture instructional programs. It might be a practicable, novel training method for acquiring proficiency in manual laparoscopic skills in a training setting.

Unmedicated patients with schizophrenia in economically underdeveloped areas of China.

OBJECTIVES: Untreated schizophrenia commonly leads to poor prognosis. The medication treatment rate of schizophrenia patients in economically underdeveloped areas of China has not been well-studied. This study aimed to examine the pattern of unmedicated schizophrenia patients in economically underdeveloped rural and urban areas of China. METHOD: A total of 4240 schizophrenia patients in Lanzhou (1720 rural and 2520 urban patients) registered in the community mental-health service system in Lanzhou, Gansu province were included. Their socio-demographic and clinical characteristics including medication treatment status were collected and analyzed. RESULTS: The proportion of unmedicated schizophrenia patients was 22.5% (n = 953) in the whole sample, with 32.3% (556/1720) in rural and 15.8% (397/2520) in urban patients (X2=161.1, P < 0.001). Multiple logistic regression analyses revealed that unmedicated schizophrenia patients in rural area were more likely to be older (OR=1.02, 95%CI: 1.01-1.03), male (OR=1.35, 95%CI: 1.07-1.71), unmarried (OR=0.71, 95%CI: 0.55-0.91), and have lower educational level (OR=0.39, 95%CI: 0.24-0.65), longer illness duration (OR=1.01, 95%CI: 1.00-1.02) and less frequent admissions (OR=0.46, 95%CI: 0.38-0.54). In contrast, unmedicated patients in urban area were more likely to be older (OR=1.01, 95%CI: 1.00-1.02), unmarried (OR=0.77, 95%CI: 0.61-0.98), employed (OR=2.38, 95%CI: 1.87-3.04), and have lower educational level (OR=0.49, 95%CI: 0.37-0.65), better financial status (OR=0.60, 95%CI: 0.48-0.76) and less frequent admissions (OR=0.81, 95%CI: 0.75-0.87). CONCLUSIONS: The rate of unmedicated schizophrenia patients is high in economically underdeveloped areas of China, particularly in rural areas. Effective policies and measures should be implemented urgently to improve the treatment rate in this population.

Bending Experiment and Mechanical Properties Analysis of Composite Sandwich Laminated Box Beams.

The failure modes, ultimate load, stiffness performance, and their influencing factors of a composite sandwich laminated box beam under three-point bending load are studied by an experiment, finite element model, and analytical method. The three-point bending experiment was carried out on three different core composite sandwich laminated box beams, and the failure modes and bearing capacity were studied. With the use of composite progressive damage analysis and the core elastoplastic constitutive model, the finite element model of the composite sandwich laminated box beam was established, and the three-point bending failure process and failure modes were analyzed. The analytical model was established based on the Timoshenko beam theory. The overall bending stiffness and shear stiffness of the composite sandwich laminated box beam were calculated by the internal force-displacement relationship. The results show that the composite sandwich laminated box beam mainly suffers from local crushing failure, and the errors between the finite element simulation and the experiment result were within 7%. The analytical model of the composite sandwich laminated box beam can approximately predict the overall stiffness parameters, while the maximum error between theoretic results and experimental values was 5.2%. For composite aluminum honeycomb sandwich laminated box beams with a ratio of span to height less than 10, the additional deflection caused by shear deformation has an error of more than 25%. With the ratio of circumferential layers to longitudinal layers increasing, the three-point bending ultimate load of the composite sandwich laminated box beam increases, but the ratio of the overall stiffness to mass reduces. The use of low-density aluminum foam and smaller-wall-thickness cell aluminum honeycombs allows for the more obvious benefits of light weight.

Hidden blood loss and its risk factors in patients undergoing laparoscopy and laparotomy for cervical cancer management.

PURPOSE: Laparoscopy and laparotomy are the two most common surgical options used to treat women with early-stage cervical cancer. This study aimed to examine the volume of hidden blood loss (HBL) between laparoscopy and laparotomy for cervical cancer and to identify its risk factors. METHODS: Sixty-one patients treated with laparotomy and 50 patients treated with laparoscopy were enrolled in this study. Their medical data were collected to calculate the HBL according to the Nadler and Gross formula, and its risk factors were identified by multiple linear regression analysis. RESULTS: The visible blood loss was 574.9 ± 271.6 mL in the laparotomy surgery; however, the HBL was 345.2 ± 258.6 mL, accounting for 38.3 ± 21.4% of true TBL. The visible blood loss in the laparoscopy group was 168.9 ± 121.9 mL, and the HBL was 185.1 ± 130.5 mL (52.3 ± 28.1% of true TBL). The HBL blood loss in laparotomy was more than laparoscopy (p < 0.01). Multiple linear regression analysis suggested that patient age (p = 0.012), surgical time (p = 0.037) and pathological tumour type (p = 0.014) were independent risk factors contributing to HBL in laparotomy. Meanwhile, the following risk factors were positively correlated with HBL in laparoscopy: pre-operative value of Hb (p = 0.002), pre-operative value of Hct (p = 0.003), surgical time (p = 0.035), pathological tumour type (p = 0.036) and diabetes mellitus (p = 0.022). Ten and eight patients had pre-operative anaemia in the laparotomy group and the laparoscopy group, respectively, and 54 and 29 post-operatively. CONCLUSIONS: HBL is seriously underestimated, and accounts for a large percentage of total blood loss both in laparotomy and laparoscopy for cervical cancer. Additionally, age, pathological tumour type, pre-operative value of Hb and Hct, surgical time and diabetes mellitus have the potential to increase HBL. A correct understanding of HBL can ensure patient safety and improve post-operative rehabilitation.

Multimodal intraoperative monitoring during surgical correction of scoliosis to avoid neurologic damage.

The purpose of this study was to evaluate the application of multimodal intraoperative monitoring (MIOM) system in patients with congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS).Twelve patients who underwent posterior surgical correction of scoliosis for CS and AIS from June 2014 to July 2018 were enrolled in this study. During the operation, we monitored the functional status of the spinal cord by MIOM. An abnormal somatosensory evoked potential was defined as a prolonged latency of more than 10% or a peak-to-peak amplitude decline of more than 50% when compared to baseline. An abnormal transcranial motor evoked potential (TcMEP) was defined as a TcMEP amplitude decrease of more than 50%. A normal triggered electromyography response, which presented with the absence of an electrical response on stimulation at 8.2 mA, indicated that the pedicle screw was not in contact with the spinal cord or nerve root.A total of 12 patients underwent MIOM surgery, of which 9 patients with negative MIOM had no significant deterioration of neurological function postoperatively, and exhibited satisfactory surgical correction of scoliosis during follow-ups. However, the remaining 3 patients suffered from MIOM events, 2 patients had normal neurological function, and 1 patient had deteriorated neurological function postoperatively.Using MIOM in CS and AIS surgery could promptly detect iatrogenic neurological injury at the early stage. Therefore, rapid response by appropriate intraoperative interventions can be taken to minimize the injury. Besides, stable MIOM recordings encourage surgeons to correct scoliosis even when the Cobb angle of scoliosis was extremely large.

A screw-view model of navigation aid retrograde transpubic screw fixation for anterior pelvic ring fracture: A case report with 28 months follow-up and technical note.

RATIONALE: The purpose of this study was to evaluate the accuracy of a retrograde transpubic screw fixation assisted by a screw-view model of navigation in treating a pelvic fracture. PATIENT CONCERNS: A 30-year-old female patient injured in a motor vehicle accident, displayed symptoms characterized by swelling and pain of the pudendum. DIAGNOSES: The patient was diagnosed with a fracture of the pubic ramus. INTERVENTIONS: We used a screw-view model of navigation to assist our retrograde transpubic screw fixation in this patient. OUTCOMES: In total, 2 screws were inserted into the bilateral pubic ramus and both were excellently positioned. It took 7.4 minutes to design the screws, 8.1 minutes to implant the guidewire, and 39.3 minutes to place the screws. Intraoperative blood loss amounted to 21 mL and the total fluoroscopic time was 3.8 minutes. No clinical complications, such as neurologic, vascular, or urologic injury, infection, screw loosening, or loss of reduction, were found after the operation. Follow-up lasted 28 months. LESSONS: The outcome of our study suggests that the screw-view model of navigation maximizes the retrograde transpubic screw insertion accuracy in the treatment of a pubic ramus fracture, which is made efficient by pain relief and early out-of-bed mobilization. Our suggestion is, therefore, that the relative position between the pubic ramus and the patient tracker must be static to ensure the accuracy of the entire system throughout the operation.

Accuracy and safety of percutaneous periacetabular screw insertion using screw view model of navigation in acetabular fracture: A case report.

RATIONALE: The purpose of this study was to estimate the efficacy and safety of percutaneous periacetabular screw (PPS) insertion assisted by screw view model of navigation (SVMN) to treat fracture of acetabulum. PATIENT CONCERNS: A 61-year-old male patient was injured in a motorcycle accident, which caused pain, swelling, deformity and limited mobility on his right hip. DIAGNOSES: He was diagnosed with fracture of acetabulum. INTERVENTIONS: We used PPS insertion assisted by SVMN to treat fracture of acetabulum in this patient. OUTCOMES: The follow up lasted 24 months. Totally 2 screws were inserted into anterior and posterior column of acetabulum respectively and both of them displayed grade 0. Compared with the preoperative gap and step of fracture displacement, the postoperative ones were significantly reduced. It took 11.7 minutes for designing the screws, 6.7 minutes for implanting the guide wire, and 45.5 minutes for placing the screws. Intraoperative blood loss was 29 mL and total fluoroscopic time was 4.1 minutes. No clinical complications such as nerve vascular injury, infection and screw loosening were found after the operation. LESSONS: The study indicated that SVMN is favorable to the PPS insertion for acetabular fracture. Our lesson is that the relative position between the acetabular and the patient tracker must be static to ensure the accuracy of the entire system throughout the operation.

MiR-206 inhibits proliferation and migration of prostate cancer cells by targeting CXCL11.

BACKGROUND: Our study was aimed at detecting the expression levels of miR-206 in prostate cancer (PCa) tissues and PCa cell lines, and exploring the potential functions of miR-206 by targeting chemokine ligand 11 (CXCL11). METHODS: RT-qPCR was applied to detect the expressions of miR-206 and CXCL11 in PCa tissues and in PCa cell lines. Expression of the CXCL11 protein was detected using Western blot. After manipulating the expression of miR-206 and CXCL11 in PC-3 and DU-145 cells, the changes of cell proliferation and cell cycle were observed through cell counting kit-8 (CCK-8) and flow cytometry. Wound healing and transwell assay were conducted for cell migration and invasion examination in vitro. The luciferase reporter assay was applied to validate the association between miR-206 and CXCL11. RESULTS: MiR-206 was significantly under-expressed in PCa tissues and in PCa cell lines. Up-regulation of miR-206 could inhibit proliferation, migration, invasion and induced G1/G0 arrest of PCa cells, and vice versa. MiR-206 bound to the 3'-UTR of CXCL11 and significantly repressed the luciferase activity. Overexpression of miR-206 decreased the expression level of CXCL11 significantly. CXCL11 mRNA and protein levels were significantly decreased in PCa cells. Downregulation of CXCL11 presented tumor-suppressing effects on PCa cells as miR-206 mimics did. And co-transfection miR-206 attenuated the tumor-promoting effects induced by CXCL11 overexpression. CONCLUSION: Our current finding demonstrated that miR-206 negatively regulated PCa cell proliferation and migration, and arrested cell cycle by targeting CXCL11 as a tumor suppressor in prostate cancer.

Multimodal intraoperative monitoring during reduction of spine burst fracture and dislocation prevents neurologic injury.

This study aims to evaluate the application of multimodal intraoperative monitoring (MIOM) in surgical treatment for spine burst fracture and dislocation (SBFD) patients.Eleven patients who underwent posterior reduction and instrumentation (PRI) for SBFD from June 2014 to July 2016 were included into the study. The function of the spinal cord was monitored by MIOM. The muscle strength of the lower extremities and American Spinal Injury Association (ASIA) scores were, respectively, evaluated (before surgery, and at 1, 3, 6, and 12 months after surgery). Furthermore, the extent of reduction was also assessed.Muscle strength recovery, ASIA score changes, and the extent of reduction were correlated with MIOM results. Among the 11 patients who received surgery under MIOM, 8 patients with negative MIOM results during the operation did not demonstrate neurological deterioration postoperatively and exhibited improvements in ASIA scores during follow-ups. However, among the 3 patients who encountered MIOM events (case 4, 7, and 8), 2 patients avoided nerve lesion and 1 patient suffered from neurologic deterioration postoperatively.The application of MIOM technology during PRI surgery may detect spinal cord impairment at the early stage, and operative schemes can be modified before permanent nerve compromise is triggered by surgical manipulation.

Identification of key genes associated with rheumatoid arthritis with bioinformatics approach.

We aimed to identify key genes associated with rheumatoid arthritis (RA).The microarray datasets of GSE1919, GSE12021, and GSE21959 (35 RA samples and 32 normal controls) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in RA samples were identified using the t test in limma package. Functional enrichment analysis was performed using clusterProfiler package. A protein-protein interaction (PPI) network of selected DEGs was constructed based on the Human Protein Reference Database. Active modules were explored using the jActiveModules plug-in in the Cytoscape Network Modeling package.In total, 537 DEGs in RA samples were identified, including 241 upregulated and 296 downregulated genes. A total of 24,451 PPI pairs were collected, and 5 active modules were screened. Furthermore, 19 submodules were acquired from the 5 active modules. Discs large homolog 1 (DLG1) and related DEGs such as guanylate cyclase 1, soluble, alpha 2 (GUCY1A2), N-methyl d-aspartate receptor 2A subunit (GRIN2A), and potassium voltage-gated channel member 1 (KCNA1) were identified in 8 submodules. Plasminogen (PLG) and related DEGs such as chemokine (C-X-C motif) ligand 2 (CXCL2), laminin, alpha 3 (LAMA3), complement component 7 (C7), and coagulation factor X (F10) were identified in 4 submodules.Our results indicate that DLG1, GUCY1A2, GRIN2A, KCNA1, PLG, CXCL2, LAMA3, C7, and F10 may play key roles in the progression of RA and may serve as putative therapeutic targets for treating RA.

Cyclin-dependent kinase inhibitor dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer.

Ovarian cancer is one of the most lethal of woman cancers, and its clinical therapeutic outcome currently is unsatisfied. Dinaciclib, a novel small molecule inhibitor of CDK1, CDK2, CDK5 and CDK9, is assessed in clinical trials for the treatment of several types of cancers. In this study, we investigated the anticancer effects and mechanisms of dinaciclib alone or combined with cisplatin in ovarian cancer. Dinaciclib alone actively induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular ROS levels, which were accompanied by obvious alterations of related proteins such as CDKs, Cyclins, Mcl-1, XIAP and survivin. Pretreatment with N-acety-L-cysteine significantly blocked ROS generation but only partially rescued apoptosis triggered by dinaciclib. Moreover, the combination of dinaciclib with cisplatin synergistically promoted cell cycle arrest and apoptosis, and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. Altogether, dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer, indicating this beneficial combinational therapy may be a promising strategy for treatment of ovarian cancer.