Tandem Vinylogous Aldol and Intramolecular [2 + 2] Cycloaddition toward Benzocyclobutenes by UV Light Photocatalysis.

A facile and efficient radical tandem vinylogous aldol and intramolecular [2 + 2] cycloaddition reaction for direct synthesis of cyclobutane-containing benzocyclobutenes (BCBs) under extremely mild conditions without using any photocatalysts is reported. This approach exhibited definite compatibility with functional groups and afforded new BCBs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost, and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Visible-Light-Mediated Catalyst-Free [2+2] Cycloaddition Reaction for Dihydrocyclobuta[b]naphthalene-3,8-diones Synthesis under Mild Conditions.

A facile and efficient visible-light-mediated method for directly converting 1,4-naphthoquinones into dihydrocyclo-buta[b]naphthalene-3,8-diones (DHCBNDOs) under mild and clean conditions without using any photocatalysts is reported. This approach exhibited favorable compatibility with functional groups and afforded a series of DHCBNDOs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Microfracture versus Enhanced Microfracture Techniques in Knee Cartilage Restoration: A Systematic Review and Meta-Analysis.

This study aimed to compare the efficacy and safety of the microfracture (MFx) and microfracture augmented (MFx + ) techniques for the treatment of cartilage defects of the knee. The PubMed and EMBASE databases were searched from 1 January, 1950 to 1 May, 2019. RevMan5.3 was used to perform statistical analysis. Relative risk was calculated for binary variables, and weighted mean difference and standardized mean difference (SMD) were measured for continuous variables. The 95% confidence interval (CI) of each variable was assessed. Thirteen trials with 635 patients were included. There was a significant difference in the Lysholm's score (SMD = 0.26, 95% CI: 0.01-0.50, p = 0.04) and magnetic resonance observation of cartilage repair tissue score (SMD = 14.01, 95% CI: 8.01-20.02, p < 0.01) between the MFx and MFx+ groups. There was no significant difference in the Western Ontario and McMaster Universities Osteoarthritis Index score (SMD = - 12.40, 95% CI: -27.50 to 32.71, p = 0.11), International Knee Documentation Committee score (SMD = 8.67, 95% CI: -0.92 to 18.27, p = 0.08), visual analog scale score (SMD = - 0.20, 95% CI: -2.45 to 0.96, p = 0.57), Tegner's score (SMD = 0.26, 95% CI: -0.67 to 1.18, p = 0.59), modified Cincinnati's score (SMD = - 4.58, 95% CI: -14.31 to 5.14, p = 0.36) and modified International Cartilage Repair Society pain score (SMD = 0.09, 95% CI: -0.37 to 0.55, p = 0.70) between the groups. Results of the pooled analyses of the MFx+ and MFx groups suggested that the MFx+ technique is slightly superior to the MFx technique for the treatment of articular cartilage defects of the knee. Further research is required and future studies should include assessments of the outcomes at long-term follow-ups. Trial registration number is PROSPERO CRD42019135803.

Hip Arthroscopic Reduction and Fixation for Adolescent Acetabular Posterior Wall Fracture: A Case Report.

BACKGROUND: Posterior wall fracture is the most common type of acetabular fracture, the traditional open reduction and fixation through the Kocher-Langenbeck approach required a large incision and extensive muscle and soft tissue dissection, resulting in more blood loss, more complications and delayed recovery after the operation. Hip arthroscopy has been widely used in clinical practice but rarely reported in acetabular fractures. CASE PRESENTATION: We present the case of a 14-year-old boy with acetabular posterior wall fracture who was treated with hip arthroscopy reduction and fixation using anchors. He began to walk with partial weight-bearing assisted by double crutches, and returned to school with crutches at 3 days after surgery. Although hip arthroscopy is technically more demanding, it's an optimal choice for selected patients of acetabular fracture with the advantages of less invasive and faster postoperative recovery.

Augmented Microfracture Technique Versus Microfracture in Talar Cartilage Restoration: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to compare the efficacy and safety between the microfracture (MFx) and augmented microfracture (MFx+) techniques for articular cartilage defects of the talus (OLTs). PubMed and EMBASE were searched from January 1950 to October 2020. Only randomized controlled trials, quasi-randomized controlled trials, and observational studies (retrospective and prospective) applying MFx and MFx+ techniques to treat talar cartilage defects were selected. Ten trials with 492 patients were included. There was significant difference in final American Orthopaedic Foot & Ankle Society score (AOFAS) (mean difference [MD] = 7.07; 95% confidence interval [CI], 3.70-10.44; p < .01), AOFAS change (MD = 7.97; 95% CI, 4.27-11.66; p < .01), visual analog scale (VAS) change score (MD = 0.44; 95% CI, 0.29-0.59; p < .01), Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score (MD = 12.51; 95% CI, 7.16-17.86; p < .01), complication (RR = 0.33; 95% CI, 0.16-0.69; p < .01), and revision (Relative risk = 0.34; 95% CI, 0.15-0.77; p < .05), between the MFx and MFx+ groups. No significant difference was observed for final VAS pain score (MD = -0.53; 95% CI, -1.2 to 1.05; p = .13) and Tegner scale (MD = 0.31; 95% CI, -1.05 to 1.66; p = .66) in either group. Our results suggest that augmented microfracture is superior to microfracture alone in the treatment of talar OLTs based on the AOFAS, MOCART, VAS score, complication rate, and revision ratio. Therefore, microfracture with augmentation should be considered as a treatment for OLTs of talus. However, more randomized trials are still required to determine the long-term superiority of MFx+.

Lentivirus-mediated silencing of CNTN1 enhances gefitinib sensitivity by reversing epithelial-mesenchymal transition in lung adenocarcinoma A549 cells.

Contactin-1 (CNTN1), a neuronal cell adhesion molecular, functions in nervous system development and has been associated with carcinogenesis and tumor progression. To investigate the role of CNTN1 in gefitinib resistance in lung adenocarcinoma, lentivirus-mediated short hairpin (sh)RNA was used to silence CNTN1 and its physiological function was analyzed in the A549 cell line. A cell cytotoxicity assay revealed that CNTN1 knockdown enhanced gefitinib sensitivity in the A549 cells. In addition, CNTN1 knockdown, together with gefitinib treatment, resulted in a significant inhibition of colony formation and migration, and promotion of apoptosis. Furthermore, CNTN1 knockdown also reversed the epithelial-mesenchymal transition (EMT) phenotype by increasing E-cadherin protein expression level, and decreasing N-cadherin and vimentin protein expression levels. The PI3K/Akt signaling pathway was also association with the effects of CNTN1 on EMT progression and gefitinib resistance in the A549 cells. Collectively, knockdown of CNTN1 reversed the EMT phenotype and enhanced gefitinib sensitivity in the A549 cells by inhibiting the activation of the PI3K/Akt signaling pathway. These results suggested that CNTN1 may represent a potential therapeutic target for reserving EGFR-tyrosine kinase inhibitor resistance in non-small cell lung cancer.

Efficacy and Safety of Intra-Articular Cell-Based Therapy for Osteoarthritis: Systematic Review and Network Meta-Analysis.

OBJECTIVE: Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of articular cartilage and secondary osteogenesis. Cell-based agents, such as mesenchymal stem cells, have turned into the most extensively explored new therapeutic agents for OA. However, evidence-based research is still lacking. METHODS: We searched public databases up to February 2020 and only included randomized controlled trials. The outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Knee Injury and Osteoarthritis Outcome Score (KOOS), the visual analogue scale (VAS) score, and serious adverse events (SAEs). A network meta-analysis was also performed in this work. RESULTS: We included 13 studies in the meta-analysis. The effect size showed that cell-based therapy did not significantly reduce the WOMAC score at the 6-month follow-up (standard mean difference [SMD] -3.6; 95% confidence interval [CI] -0.90 to 0.18; P = 0.1928). However, cell-based therapy significantly improved the KOOS at the 12-month follow-up (SMD 0.68; 95% CI 0.07-1.30; P = 0.0288) and relieved pain (SMD -1.05; 95% CI -1.46 to -0.64; P < 0.0001). The findings also indicated that high-dosage adipose-derived mesenchymal stem cells (ADMSCs) may be more advantageous in terms of long-term effects. CONCLUSIONS: Cell-based therapy had a better effect on KOOS improvement and pain relief without safety concerns. However, cell-based therapy did not show a benefit in terms of the WOMAC. Allogeneic cells might have advantages compared to controls in the WOMAC and KOOS scores. The long-term effect of high-dose ADMSC treatment for OA is worthy of further study.

Catalyst-Free One-Pot Synthesis of Densely Substituted Pyrazole-Pyrazines as Anti-Colorectal Cancer Agents.

The first catalyst-free post-Ugi cascade methodology was developed for expeditious access to structurally diverse and complex pyrazole-pyrazines in one-pot. This novel cascade reaction features an intramolecular N2-arylation of pyrazoles with allenes at the C-ß position of triple bond. Screening in the colorectal cancer cell lines HCT116 and SW620 validated the feasibility of the methodology for generating bioactive compounds. The lead compound 7h which is active against HCT116 and SW620 with IC50 of 1.3 and 1.8 µM, respectively, can be synthesized and purified in a gram process synthetic scale in 7 hours. The mechanical studies indicated that compound 7h can induce cell cycle arrest in the G2/M phase and inhibit proliferation and viability in human colon cancer cells. Overall, compound 7h is represented as a promising starting point for the development of new anti-colorectal cancer drugs.

Dynamic Perfusion Culture of Human Outgrowth Endothelial Progenitor Cells on Demineralized Bone Matrix In Vitro.

BACKGROUND The aim of this study was to investigate the proliferation, differentiation, and tube formation of human outgrowth endothelial progenitor cells (OECs) cultured with porous demineralized bone matrix (DBM) under a dynamic perfusion system in vitro. MATERIAL AND METHODS OECs were isolated, expanded, characterized, eGFP-transfected and seeded on DBM scaffold and cultured under static or dynamic perfusion conditions, and continuously observed under fluorescence microscope. DBM scaffolds were harvested on day six for RT-PCR and western blot assay to analyze the mRNA and protein expression level of CD34, VE-cadherin, and VEGF. Scanning electron microscope (SEM) was used to observe the tube formation of OECs seeded on DBM scaffolds. RESULTS The results showed the cell density of OECs on DBM was higher when exposed to shear stress generated by a dynamic perfusion system. Shear stress also markedly increased the expression level of VE-cadherin and VEGF and decreased the expression of CD34, at both mRNA and protein levels. SEM showed that the shear-stressed OECs formed tube-like structures inside the pores of DBM scaffolds. CONCLUSIONS A dynamic perfusion system can be used as an innovative method for the rapid vascularization in tissue engineering, which can accelerate the proliferation and differentiation of OECs and the vascularization of implanted scaffolds.

Fabrication and Evaluation of Porous Keratin/chitosan (KCS) Scaffolds for Effectively Accelerating Wound Healing.

OBJECTIVE: To develop a dressing with desired antibacterial activity, good water maintaining ability and mechanical properties for wound healing and skin regeneration. METHODS: The chitosan with different concentrations were added in keratin solution to form porous keratin/chitosan (KCS) scaffolds. The morphological characteristics, chemical composition, wettability, porosity, swelling ratio and degradation of the scaffolds were evaluated. The antibacterial activity was tested by using S. aureus and E. coli suspension for 2 h. And L929 fibroblast cells culture was used to evaluate the cytotoxicity of the KCS scaffolds. RESULTS: The adding of chitosan could increase the hydrophobicity, decrease porosity, swelling ratio and degradation rate of the KCS porous scaffolds. Mechanical properties of KCS scaffolds could be enhanced and well adjusted by chitosan. KCS scaffolds could obviously decrease bacteria number. The proliferation of fibroblast cells in porous KCS patch increased firstly and then decreased with the increase of chitosan concentration. It was appropriate to add 400 µg/mL chitosan to form porous KCS scaffold for achieving best cell attachment and proliferation compared with other samples. CONCLUSION: The porous KCS scaffold may be used as implanted scaffold materials for promoting wound healing and skin regeneration.

Influence of sintering temperature on the characteristics of shale brick containing oil well-derived drilling waste.

INTRODUCTION: The influence of sintering temperature on the physico-mechanical characteristics (such as water absorption, apparent porosity, bulk density, weight loss on ignition, firing shrinkage, and compressive strength), leachability, and microstructure of shale brick containing oil well-derived drilling waste (DW) was investigated. METHODS: The experiments were conducted at a temperature ranging from 950°C to 1,050°C with 30% DW addition. RESULTS: The results indicate that increasing the sintering temperature decreases the water absorption and apparent porosity and increases the shrinkage, density, and compressive strength of sintered specimens. Moreover, the physico-mechanical properties of samples sintered at 1,050°C meet the requirements of the MU20 according to GB/T 5101-2003 (in China). The heavy metal concentrations of the leachate are much lower than the current regulatory limits according to GB16889-2008. CONCLUSION: The results from XRD and SEM show that increasing sintering temperature results in an increase of the high temperature liquid phase, which may have a significant effect on the densification process of the samples.

In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection.

OBJECTIVE: To track superparamagnetic iron oxide nanoparticle (SPIO)-labeled, bone-derived mesenchymal stem cells (MSCs) by in vivo magnetic resonance imaging (MRI) with a 1.5T-system following injection of engineered autologous MSCs into the knee joint cavity in rabbit articular cartilage defect models. METHODS: Rabbit MSCs were labeled with SPIO and a transfection agent. Cell viability, proliferation and differentiation capacity were assessed in vitro using appropriate functional assays. Cells underwent GRE T2*-weighted MRI in vitro. The autologous MSCs seeded in chitosan and glycerophosphate (C-GP) gel were injected into the knee joint cavity of rabbit models for cartilage defects. All rabbits underwent GRE T2*-weighted MRI 1, 4, 8 and 12 weeks post-injection. MR imaging findings were compared histologically. RESULTS: Nanoparticles were stained with Prussian blue and observed by transmission electron microscopy inside the cells. Cell viability, proliferation, and differentiation were comparable between labeled and non-labeled cells. After intra-articular injection of labeled autologous MSCs, marked hypointense signal void areas representing the injected MSCs can be observed for at least 12 weeks on GRE T2*-weighted images. At 12 weeks post-injection, labeled MSCs migrated into the synovial fluid at the suprapatellar bursa, the popliteal space site and subchondral bone of the femur but no MSCs were detected in the defect. Histochemical staining confirmed the presence of Prussian blue-positive cells and BrdU-positive cells. CONCLUSIONS: MRI would be an efficient noninvasive technique to visually track SPIO-labeled seed cells in vivo; the engineered autologous MSCs do not actively participate in the repair of articular cartilage defects following intra-articular injection.

[In vivo MR imaging tracking of supermagnetic iron-oxide nanoparticle-labeled bone marrow mesenchymal stem cells injected into intra-articular space of knee joints: experiment with rabbit].

OBJECTIVE: To evaluate the feasibility of in vivo magnetic resonance imaging (MRI) with 1.5T system tracking of the survival, migration and differentiation of magnetically labeled seed cells-bone marrow-derived mesenchymal stem cells (MSCs) injected into the articular cavity. METHODS: Rabbit MSCs were isolated, purified, expanded, and then coincubated in vitro with supermagnetic iron oxide particles (SPIO) and 5-bromo-2-deoxyuridine (BrdU). Prussian blue staining and transmission electron microscopy were performed to observe the intracellular iron. Some labeled MSCs were subjected to chondrogenic differentiation and the phenotype was examined to assess their chondrogenic differentiation capacity. MSCs colabeled with SPIO nanoparticles and (BrdU were suspended in chitosan and glycerophosphate (C-GP) gel. Eighteen rabbits underwent damage to the femoral trochlea to create cartilage defect models, and randomly divided into 3 groups 1 week later: Group A (n=6) undergoing injection of the MSC suspension in C-GP gel into the intra-articular space of knee joints, Group B (n=6), injected with un-labeled MSC suspension in C-GP gel, and Group C (n=6), without injection. MRI of the knee was performed 1, 4, 8, and 12 weeks after the injection respectively on a certain numbers of rabbits. and then the rabbits were killed with their knee joints taken out to undergo immunohistochemistry. The MR imaging findings were compared with the histological findings. RESULTS: Prussian blue staining and transmission electron microscopy showed intracytoplasmic nanoparticles in the SPIO-labeled cells. Safranin-O staining showed deposition of proteoglycan and type II collagen outside both the labeled and unlabeled MSCs, showing chondrogenesis. GRE T2-weighted MR image showed marked hypointense signal void areas, representing the implanted MSCs, in the intra-articular space after the MSC injection in Group A that persisted for 12 weeks at least; 2 week after the MSC injection hypointense signal could be seen in the defect, which peaked in the signal intensity about 4 weeks later, and then gradually decreased in the signal intensity; and 12 weeks after the injection no recognizable hypointense signal in the defect was detected. Immunohistochemical staining demonstrated the presence of Prussian blue-positive cells and BrdU-positive cells in the tissue sections in the areas corresponding well to the signal intensity loss regions in the MRI images. Group B and Group C showed no signal intensity loss in the intra-articular spaces by GRE T2-weighted MR imaging. Histological observation showed that the defects were repaired with fibrocartilage in Groups A and B, and with fiber tissue in Group C. CONCLUSION: Labeled with SPIO, the MSCs remains their ability of chondrogenic differentiation. It is feasible to track the fate and dynamic redistribution of magnetically labeled MSCs, the seed cells, injected into the articular cavity by 1.5T MRI, an efficient noninvasive technique.

[Analysis of articles and citations in National Journal of Andrology (2000-2002)].

OBJECTIVES: To evaluate the academic status and influence of the National Journal of Andrology (NJA). METHODS: The data of articles and citations in 16 issues of NJA (2000-2002) were collected, then the quality of this journal was evaluated in terms of bibliometric parameters. RESULTS: Except for reviews and translations, the sums of original papers accounted for 183 (53.5%), the articles with citation in 16 issues were 333 (97.08%), and funded project papers accounted for 62 (18.08%). The number of the articles and funded project papers increased every year; the average publishing cycle of the articles was 8.7 months; the average number of authors was 3.7 per article; the average age of the first author was 36.3 years old; the authors distributed in 30 provinces, 43.37% of the authors had senior professional title and 40.80% of the authors had master's or doctor's degrees, the journal had a high rate of self-citation (6.30%). CONCLUSIONS: National Journal of Andrology is a high quality journal, with excellent authors, strong influence and bright future.