MB2033, an anti-PD-L1 × IL-2 variant fusion protein, demonstrates robust anti-tumor efficacy with minimal peripheral toxicity.

Interleukin-2 (IL-2), a cytokine with pleiotropic immune effects, was the first approved cancer immunotherapy agent. However, IL-2 is associated with systemic toxicity due to binding with its ligand IL-2Rα, such as vascular leakage syndrome, limiting its clinical applications. Despite efforts to extend the half-life of IL-2 and abolish IL-2Rα interactions, the risk of toxicity remains unresolved. In this study, we developed the bispecific fusion protein MB2033, comprising a novel IL-2 variant (IL-2v) connected to anti-programmed death ligand 1 (PD-L1) via a silenced Fc domain. The IL-2v of MB2033 exhibits attenuated affinity for IL-2Rßγ without binding to IL-2Rα. The binding affinity of MB2033 for PD-L1 is greater than that for IL-2Rßγ, indicating its preferential targeting of PD-L1+ tumor cells to induce tumor-specific immune activation. Accordingly, MB2033 exhibited significantly reduced regulatory T cell activation, while inducing comparable CD8+ T cell activation to recombinant human IL-2 (rhIL-2). MB2033 induced lower immune cell expansion and reduced cytokine levels compared with rhIL-2 in human peripheral blood mononuclear cells, indicating a decreased risk of peripheral toxicity. MB2033 exhibited superior anti-tumor efficacy, including tumor growth inhibition and complete responses, compared with avelumab monotherapy in an MC38 syngeneic mouse model. In normal mice, MB2033 was safer than non-α IL-2v and tolerable up to 30 mg/kg. These preclinical results provide evidence of the dual advantages of MB2033 with an enhanced safety and potent clinical efficacy for cancer treatment.

Comparative In Vivo Study of Solid-Type Pure Hyaluronic Acid in Thread Form: Safety and Efficacy Compared to Hyaluronic Acid Filler and Polydioxanone Threads.

INTRODUCTION: Although various products are commonly used for skin rejuvenation, solid-type hyaluronic acid (HA) as an injectable form has not been researched or utilized. This study aimed to demonstrate the safety and efficacy of solid-type HA in thread form, which differs from the conventional gel-type HA commonly used. METHOD: Solid-type HA threads, conventional HA fillers, and polydioxanone (PDO) threads were inserted into the dorsal subcutaneous layer of mice. Photographs were taken on days 0, 1, 3, and 7, and on day 7, the samples were harvested for histological analysis. Inflammatory reactions and detection of collagen were confirmed through tissue staining, and real-time PCR was conducted to quantify collagen synthesis. RESULTS: In the histological analysis, the PDO threads exhibited a greater inflammatory response compared to the HA threads. Masson's trichrome staining revealed a higher degree of collagen synthesis in the HA thread group compared to the HA filler group. While collagen type 1 expression was significantly higher in the PDO thread group than in the HA thread group, the HA thread group showed higher expression levels of collagen type 3. Furthermore, the PDO thread group demonstrated a statistically significant increase in TGF-ß1 compared to the HA group. CONCLUSION: This in vivo study demonstrated the stable application of solid-type pure HA threads and their potential for inducing collagen production, while also yielding a low inflammatory response. The findings highlight the promising applications of solid-type HA in the field of cosmetic dermatology. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Correction: A Bone Metastasis Nude Mouse Model Created by Ultrasound Guided Intracardiac Injection of Breast Cancer Cells: the Micro-CT, MRI and Bioluminescence Imaging Analysis.

[This corrects the article on p. 57 in vol. 64.].

Anti-Arthritogenic Property of Interleukin 10-Expressing Human Amniotic MSCs Generated by Gene Editing in Collagen-Induced Arthritis.

Although stem cells are promising tools for the treatment of arthritis, their therapeutic effects remain controversial. In this study, we investigated the therapeutic properties of interleukin (IL)-10-overexpressing human amniotic mesenchymal stem cells (AMMs) generated via gene editing in a collagen-induced mouse model. IL-10 was inserted into the genomic loci of AMMs via transcription activator-like effector nucleases. In vitro immunomodulatory effects of IL-10-overexpressing AMMs (AMM/I) were evaluated and their anti-arthritogenic properties were determined in collagen-induced arthritis (CIA) mice. Transplantation of AMM/I attenuates CIA progression. In addition, the regulatory T cell population was increased, while T helper-17 cell activation was suppressed by AMM/I administration in CIA mice. Consistently, AMM/I injection increased proteoglycan expression, while reducing inflammation and the expression levels of the pro-inflammatory factors, IL-1 ß, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor- α, in joint tissues. In conclusion, use of IL-10-edited human AMM/I may be a novel therapeutic strategy for the treatment of arthritis.

Effects of Location and Volume of Intraosseous Cement on Adjacent Level of Osteoporotic Spine Undergoing Kyphoplasty: Finite Element Analysis.

OBJECTIVE: Kyphoplasty (KP) is a surgery used to reduce pain and increase stability by injecting medical bone cement into broken vertebrae. The purpose of this study was to determine the ideal amount of cement and injection site by analyzing forces with the finite element method. METHODS: We modeled the anatomical structure of the vertebra and injected the cement at T12. By increasing the amount of cement from 1 cc to 22 cc, stress applied to T11 and L1 cortical was calculated. In addition, stress applied to the adjacent KP level was calculated with different injection sites (medial, anterosuperior, posterosuperior, anteroinferior, and posteroinferior). After 5 cc cement was inserted, adjacent end plate stress was analyzed. RESULTS: In this study, break point adjacent bone stress according to the capacity of cement was bimodal. Flexion/extension and lateral bending conditions showed similar break points (11.5-11.7 cc and 18.5-18.6 cc, respectively). When cement injection was changed, front under and back under had the highest stress values among various parts, whereas the center position showed the lowest stress value. CONCLUSIONS: With increasing amount of bone cement, stress on the upper and lower end plates of the cemented segment increased significantly. Thus, increasing cement amount to be more than 11.5 cc has a potential risk of adjacent fracture. Centrally injected bone cement can lower the risk of adjacent fracture after percutaneous KP.

Cortical Trajectory Screw Fixation in Lumbar Spine Surgery: A Review of the Existing Literature.

Posterior lumbar fusion is a safe and effective surgical method for diseases, such as lumbar stenosis, spondylolisthesis, lumbar instability, spinal deformity, and tumor. Pedicle screw (PS) fixation was first introduced by Bouche and has been adopted as the gold standard for posterior lumbar fusion. Santoni and colleagues introduced a new methodological screw insertion technique that uses a cortical bone trajectory (CBT), described as that from a medial to lateral path in the transverse axial plane and caudal to the cephalad path in the sagittal plane through the pedicle for maximum contact of the screw with the cortical bone. Owing to the lower invasiveness, superior cortical bone contact, and reduced neurovascular injury incidence, the CBT technique has been widely used in posterior lumbar fusion; however, these advantages have not been proven in clinical/radiological and biomechanical studies. We designed the present study to review the existing evidence and evaluate the merit of CBT screw fixation. Six electronic databases were searched for relevant articles published in August 2020 using the search terms "cortical bone trajectory," "CBT spine," "CBT fixation," "cortical pedicle screws," and "cortical screws." Studies were analyzed and divided into the following groups: "biomechanics investigation," "surgical technique," and "clinical/radiological studies." Most studies compared CBT and PS fixation, and the CBT screw fixation method showed better or similar outcomes.

Anti-Inflammatory and Anti-Allergic Effects of Saponarin and Its Impact on Signaling Pathways of RAW 264.7, RBL-2H3, and HaCaT Cells.

Saponarin{5-hydroxy-2-(4-hydroxyphenyl)-6-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-7-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one}, a flavone found in young green barley leaves, is known to possess antioxidant, antidiabetic, and hepatoprotective effects. In the present study, the anti-inflammatory, anti-allergic, and skin-protective effects of saponarin were investigated to evaluate its usefulness as a functional ingredient in cosmetics. In lipopolysaccharide-induced RAW264.7 (murine macrophage) cells, saponarin (80 µM) significantly inhibited cytokine expression, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, inducible nitric oxide synthase, and cyclooxygenase (COX)-2. Saponarin (80 µM) also inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 involved in the mitogen-activated protein kinase signaling pathway in RAW264.7 cells. Saponarin (40 µM) significantly inhibited ß-hexosaminidase degranulation as well as the phosphorylation of signaling effectors (Syk, phospholipase Cγ1, ERK, JNK, and p38) and the expression of inflammatory mediators (tumor necrosis factor [TNF]-α, IL-4, IL-5, IL-6, IL-13, COX-2, and FcεRIα/γ) in DNP-IgE- and DNP-BSA-stimulated RBL-2H3 (rat basophilic leukemia) cells. In addition, saponarin (100 µM) significantly inhibited the expression of macrophage-derived chemokine, thymus and activation-regulated chemokine, IL-33, thymic stromal lymphopoietin, and the phosphorylation of signaling molecules (ERK, p38 and signal transducer and activator of transcription 1 [STAT1]) in TNF-α- and interferon (IFN)-γ-stimulated HaCaT (human immortalized keratinocyte) cells. Saponarin (100 µM) also significantly induced the expression of hyaluronan synthase-3, aquaporin 3, and cathelicidin antimicrobial peptide (LL-37) in HaCaT cells, which play an important role as skin barriers. Saponarin remarkably inhibited the essential factors involved in the inflammatory and allergic responses of RAW264.7, RBL-2H3, and HaCaT cells, and induced the expression of factors that function as physical and chemical skin barriers in HaCaT cells. Therefore, saponarin could potentially be used to prevent and relieve immune-related skin diseases, including atopic dermatitis.

TGF-ß1 overexpressing human MSCs generated using gene editing show robust therapeutic potential for treating collagen-induced arthritis.

Transforming growth factor ß (TGF-ß) plays a pivotal role in cartilage differentiation and other functions of mesenchymal stem cells (MSCs). In this study, we investigated the therapeutic potential of TGF-ß1 overexpressing amniotic MSCs (AMMs) generated using gene editing in a mouse model of damaged cartilage. The TGF-ß1 gene was inserted into a safe harbor genomic locus in AMMs using transcription activator-like effector nucleases. The chondrogenic properties of TGF-ß1-overexpressing AMMs (AMM/T) were characterized using reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR, and histological analysis, and their therapeutic effects were evaluated in mouse model of collagen-induced arthritis (CIA). AMM/T expressed cartilage-specific genes and showed intense Safranin O and Alcian blue staining. Furthermore, injecting AMM/T attenuated CIA progression compared with AMM injection, and increased the regulatory T (Treg) cell population, while suppressing T helper (Th)17 cell activation in CIA mice. Proinflammatory factors, such as interleukin-1ß (IL-1ß), IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α were significantly decreased in AMM/T injected CIA mice compared with their AMM injected counterparts. In conclusion, genome-edited AMMs overexpressing TGF-ß1 may be a novel and alternative therapeutic option for protecting cartilage and treating inflammatory joint arthritis.

Three-dimensional Differentiated Human Mesenchymal Stem Cells Exhibit Robust Antifibrotic Potential and Ameliorates Mouse Liver Fibrosis.

Recently, three-dimensional (3D)-cultured adipose mesenchymal stem cells (ASCs) have provided an effective therapy for liver fibrosis. This study aimed to enhance the potential of human ASCs for antifibrosis or hepatocyte regeneration using a 3D culture system and investigate their therapeutic mechanism in experimental liver fibrosis. ASC-3Dc were generated in a 3D culture system and stimulated with four growth factors, namely epidermal growth factor, insulin-like growth factor (IGF)-1, fibroblast growth factor-2, and vascular endothelial growth factor-A. The expression levels of antifibrotic or hepatic regeneration factors were then measured using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The therapeutic effects of ASC-3Dc were determined using a liver fibrosis model induced by thioacetamide. Histological analysis was performed to elucidate the therapeutic mechanism. ASC-3Dc exhibited high levels of hepatocyte growth factor (HGF), IGF-1, stromal cell-derived factor (SDF)-1 genes, and protein expression. In addition, injecting ASC-3Dc significantly prevented hepatic fibrosis and improved liver function in vivo. Moreover, high numbers of ki-67-expressing hepatocytes were detected in the ASC-3Dc-injected livers. Albumin-expressing ASC-3Dc engrafted in fibrotic livers augmented HGF expression. Thus, short-term 3D-cultured ASCs may be a novel alternative to the conventional treatment for liver damage in clinical settings.

Treatment of typical trampoline fracture of the proximal tibia in children: results of minimum 1 year follow-up.

PURPOSE: To evaluate the results of trampoline fracture of the proximal tibia treated with either external fixator or conservative management at a minimum 1-year follow-up. METHODS: A retrospective review was performed on 22 children who between January 2005 and November 2013 presented with proximal metaphyseal fracture due to trampoline injury. Proximal metaphyseal fractures in 22 pediatric patients were clinically and radiologically evaluated. Of 22 subjects, 9 were male, 13 were female, and mean age was 4.2 years (range 2-7). RESULTS: In terms of comorbid injury, 1 proximal humerus fracture, two distal humerus fractures were present. Injury mechanism-wise, jumping with companions who had a weight difference accounted for 16, similar age, but jumping with multiple companions were three, direct crush were three. There were no differences in the valgus angle or length of the legs during the 2 year follow-up period. However, epiphyseal tibia shaft angle significantly decreased and proximal epiphysis was found to be flat compared to the contralateral side. CONCLUSION: Jumping with companion with a large difference in body weight, the first experience of jumping on trampoline and state of extension of knee at the time of injury was revealed to be risk factors for trampoline fractures. During a follow-up period of 1 year or longer, it was concluded that valgus deformity of lower extremity or leg length discrepancy were not noticeable.

Maximizing Thread Usage for Facial Rejuvenation: A Preliminary Patient Study.

BACKGROUND: Surgical facial rejuvenation techniques with thread lifting have gained popularity. To effectively rejuvenate an aging face, it is necessary to perform both soft tissue envelop repositioning and volume restoration procedures. With the trend toward less invasive techniques and long-lasting results with minimal complications, many surgeons have continued changing the techniques. OBJECTIVES: In the present study, we developed the 4 M (Multi-target, Multi-vector, Multi-layer, Multi-material) thread lift technique for long-lasting results. METHODS: A prospective study was conducted on 73 patients who underwent the 4 M thread lifting procedure between January 2016 and February 2018. To evaluate the surgical outcomes objectively, two plastic surgeons compared photographs using a 5-point Global Aesthetic Improvement Scale (GAIS) at 1, 3, 6, 12, 18, and 24 months of follow-up. RESULTS: Based on the GAIS objective assessment, in most patients (85%) experienced better than 3 score ("improved") changes. Approximately 42.5% of the patients experienced better than 4 score ("much improved") changes. The mean GAIS grade improved significantly (p < 0.005) without decline throughout a period of 12 months. No serious adverse complication was observed except one patient, who experienced skin irregularities and dimpling for up to 9 months after the procedure. CONCLUSIONS: This 4 M thread lifting is the multiple layer lifting and rejuvenation using different materials in addition to the multiple targets. Using the concepts of structural rejuvenation, the 4 M thread lifting technique presented modest to significant improvement, maintaining good results at 12 months after procedure. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

HGF and IL-10 expressing ALB::GFP reporter cells generated from iPSCs show robust anti-fibrotic property in acute fibrotic liver model.

BACKGROUND: Cell therapy using hepatocytes derived from stem cells has been regarded as a promising alternate to liver transplantation. However, the heterogeneity of these hepatocytes makes them unsuitable for therapeutic use. To overcome this limitation, we generated homogenous hepatocyte like induced hepatocyte-like (iHep) cells. METHODS: iHep cells were generated from induced pluripotent stem cells (iPSCs) integrated with the albumin (ALB) reporter gene. The therapeutic properties of these iHep cells were investigated after transplantation in fibrotic liver tissues of a mouse model. RESULTS: The iHep cells expressed hepatocyte specific genes and proteins, and exhibited high levels of hepatocyte growth factor (HGF) and interleukin (IL)-10 expressions. Transplantation of iHep cells significantly decreased thioacetamide (TAA)-induced liver fibrosis, apoptotic cells in the liver, and ameliorated abnormal liver function. Liver tissues engrafted with iHep cells exhibited decreased expression of pro-inflammatory factors such as transforming growth factor (TGF)-ß, IL-6, and monocyte chemo attractant protein (MCP)-1. Furthermore, an increased number of proliferating hepatocytes and human albumin-expressing iHep cells were detected in mice liver. CONCLUSIONS: This study has investigated and proven the liver regeneration potential of genome-edited iHep cells and promises to be a strong foundation for further studies exploring cell therapy as an alternative therapeutic option for the treatment of liver fibrosis.

Biomechanical comparison of single-bundle versus double-bundle anterior cruciate ligament reconstruction: a meta-analysis.

BACKGROUND: Of the many issues regarding surgical techniques related to anterior cruciate ligament reconstruction (ACLR), single-bundle (SB) or double-bundle (DB) ACLR is one of the most debated topics. However, it is unclear which of the techniques yields better outcomes after ACLR for ACL injury. The purpose of this meta-analysis was to compare the benefits of SB versus DB ACLR in terms of biomechanical outcomes. METHODS: The electronic databases MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched for relevant articles comparing the outcomes of SB-ACLR versus DB-ACLR that were published until November 2019. RESULTS: Seventeen biomechanical studies were included. The anterior laxity measured using the anterior drawer test showed significantly better results in DB-ACLR when compared with SB-ACLR. In addition, outcomes of the anterior tibial translation test under a simulated pivot shift presented with better results at low flexion and 30° in DB-ACLR, compared with SB-ACLR. However, there were no significant biomechanical differences between the groups in internal rotation. CONCLUSIONS: The present study demonstrated that both techniques for ACLR are associated with restoration of normal knee kinematics. DB-ACLR is superior to SB-ACLR in terms of restoration of anteroposterior stability. However, which technique yields better improvement in internal rotation laxity, and internal rotation laxity under a simulated pivot shift at a specific angle, remains unclear. LEVEL OF EVIDENCE: This is a level II meta-analysis.

Effects of Apigenin on RBL-2H3, RAW264.7, and HaCaT Cells: Anti-Allergic, Anti-Inflammatory, and Skin-Protective Activities.

Apigenin (4',5,7-trihydroxyflavone, flavonoid) is a phenolic compound that is known to reduce the risk of chronic disease owing to its low toxicity. The first study on apigenin analyzed its effect on histamine release in the 1950s. Since then, anti-mutation and antitumor properties of apigenin have been widely reported. In the present study, we evaluated the apigenin-mediated amelioration of skin disease and investigated its applicability as a functional ingredient, especially in cosmetics. The effect of apigenin on RAW264.7 (murine macrophage), RBL-2H3 (rat basophilic leukemia), and HaCaT (human immortalized keratinocyte) cells were analyzed. Apigenin (100 µM) significantly inhibited nitric oxide (NO) production, cytokine expression (interleukin (IL)-1ß, IL6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase [iNOS]), and phosphorylation of mitogen-activated protein kinase (MAPK) signal molecules, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) in RAW264.7 cells. Apigenin (30 M) also inhibited the phosphorylation of signaling molecules (Lyn, Syk, phospholipase Cγ1, ERK, and JNK) and the expression of high-affinity IgE receptor FcεRIα and cytokines (tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-6, IL-13, and COX-2) that are known to induce inflammation and allergic responses in RBL-2H3 cells. Further, apigenin (20 µM) significantly induced the expression of filaggrin, loricrin, aquaporin-3, hyaluronic acid, hyaluronic acid synthase (HAS)-1, HAS-2, and HAS-3 in HaCaT cells that are the main components of the physical barrier of the skin. Moreover, it promoted the expression of human ß-defensin (HBD)-1, HBD-2, HBD-3, and cathelicidin (LL-37) in HaCaT cells. These antimicrobial peptides are known to play an important role in the skin as chemical barriers. Apigenin significantly suppressed the inflammatory and allergic responses of RAW264.7 and RBL cells, respectively, and would, therefore, serve as a potential prophylactic and therapeutic agent for immune-related diseases. Apigenin could also be used to improve the functions of the physical and chemical skin barriers and to alleviate psoriasis, acne, and atopic dermatitis.

A novel role for α-viniferin in suppressing angiogenesis by blocking the VEGFR-2/p70S6K signaling pathway.

Angiogenesis plays important roles in pathological conditions such as cancer and inflammation as well as normal tissue development and homeostasis. Here, we investigated the effects and molecular mechanisms of α-viniferin, an oligostilbene isolated from Caragana sinica, on human umbilical vein endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. α-viniferin treatment inhibited mitogen-induced HUVEC proliferation by retinoblastoma protein hypophosphorylation. In addition, α-viniferin suppressed mitogen-induced HUVEC adhesion, migration, invasion, and microvessel outgrowth. These anti-angiogenic activities of α-viniferin might be mediated through downregulation of cell cycle-related proteins, vascular endothelial growth factor receptor-2 (VEGFR-2), and matrix metalloproteinase-2. Furthermore, inactivation of VEGFR-2/p70 ribosomal S6 kinase signaling pathway was found to be involved in α-viniferin-mediated modulation of endothelial cell responses. Our results demonstrate the pharmacological functions and molecular mechanisms of α-viniferin in regulating angiogenesis, suggesting the therapeutic potential of α-viniferin to treat and prevent various angiogenesis-related diseases.

Ergosterol Peroxide from the Medicinal Mushroom Ganoderma lucidum Inhibits Differentiation and Lipid Accumulation of 3T3-L1 Adipocytes.

Ergosterol peroxide is a natural compound of the steroid family found in many fungi, and it possesses antioxidant, anti-inflammatory, anticancer and antiviral activities. The anti-obesity activity of several edible and medicinal mushrooms has been reported, but the effect of mushroom-derived ergosterol peroxide on obesity has not been studied. Therefore, we analyzed the effect of ergosterol peroxide on the inhibition of triglyceride synthesis at protein and mRNA levels and differentiation of 3T3-L1 adipocytes. Ergosterol peroxide inhibited lipid droplet synthesis of differentiated 3T3-L1 cells, expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAT/enhancer-binding protein alpha (C/EBPα), the major transcription factors of differentiation, and also the expression of sterol regulatory element-binding protein-1c (SREBP-1c), which promotes the activity of PPARγ, resulting in inhibition of differentiation. It further inhibited the expression of fatty acid synthase (FAS), fatty acid translocase (FAT), and acetyl-coenzyme A carboxylase (ACC), which are lipogenic factors. In addition, it inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) involved in cell proliferation and activation of early differentiation transcription factors in the mitotic clonal expansion (MCE) stage. As a result, ergosterol peroxide significantly inhibited the synthesis of triglycerides and differentiation of 3T3-L1 cells, and is, therefore, a possibile prophylactic and therapeutic agent for obesity and related metabolic diseases.

No differences in mid- to long-term outcomes of computer-assisted navigation versus conventional total knee arthroplasty.

PURPOSE: Accurate implant position in total knee arthroplasty (TKA) can potentially lead to better long-term functional outcomes and implant survival. Recent studies on whether better clinical results could be obtained from computer-navigated or conventional TKA were inconclusive. In addition, recent reviews only included short-term follow-up studies without performing quantitative mid- to long-term follow-up analysis. Thus, the purpose of the present study was to perform a meta-analysis comparing mid- to long-term clinical outcomes (such as knee scoring and functional results) and radiological outcomes (such as normal alignment of the limb axis or component) between computer-navigated TKA and conventional TKA to determine which method of TKA could obtain better clinical and radiological results. METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and SCOPUS electronic databases were searched for relevant articles published through August 2018 that compared outcomes of computer-navigated TKA and conventional TKA. Data search, extraction, analysis, and quality assessment were performed according to the Cochrane Collaboration guidelines. Clinical and radiological outcomes of both techniques were evaluated using various outcome measures. RESULTS: Seven randomized controlled trials were included. Based on Knee Society Scores, the Western Ontario and McMaster Universities Osteoarthritis Index, pain, and range of motion, there were no significant differences in clinical outcomes between the two techniques. Based on outliers from the normal axis, outliers of femoral components in the coronal plane, and outliers of tibial components in the coronal plane, radiologic outcomes showed no significant differences between the two techniques either. CONCLUSIONS: The present study revealed that there were no significant differences in clinical or radiological outcomes between computer-navigated TKA and conventional TKA. It remains unclear which TKA technique yields better results in terms of mid- to long-term clinical and radiological outcomes. LEVEL OF EVIDENCE: I.

A Meta-analysis of Studies of Volar Locking Plate Fixation of Distal Radius Fractures: Conventional versus Minimally Invasive Plate Osteosynthesis.

BACKGROUND: Open reduction and internal fixation using a volar locking plate has been increasingly performed for distal radius fractures. Both conventional and minimally invasive plate osteosynthesis (MIPO) techniques are widely used to treat distal radius fractures. However, it is unclear which of the techniques yields better outcomes after surgery for distal radius fractures. The purpose of this meta-analysis was to compare the benefits of conventional and MIPO techniques for distal radius fractures in terms of clinical outcomes. METHODS: Medline, Embase, and the Cochrane Central Register of Controlled Trials electronic databases were searched for articles comparing the outcomes of the conventional and MIPO techniques and published up until July 2017. Data search, extraction, analysis, and quality assessment were performed based on the Cochrane Collaboration guidelines. Clinical outcomes were evaluated using various outcome measures. RESULTS: Four clinical studies were included in the analysis. No significant clinical differences were found between the techniques in clinical hand scoring, grip strength, and range of motion. However, patient satisfaction after surgery was significantly higher in the MIPO group than that in the conventional group (standard mean difference, -0.54; 95% confidence interval [CI], -0.79 to -0.29; I2 = 0%). Furthermore, although there were no significant differences in volar tilt and ulnar variance between the two groups, radial inclination revealed a significant difference between the two groups (radial inclination: weighted mean difference, 1.20; 95% CI, 0.25 to 2.15; I2 = 19%). CONCLUSIONS: Both conventional and MIPO techniques were effective for patients with distal radius fractures. Despite limited high quality evidence to compare osteosynthesis with a volar locking plate via the conventional and MIPO techniques, the present study showed that the MIPO technique was associated with more favorable patient satisfaction.

PKM2 enhances cancer invasion via ETS-1-dependent induction of matrix metalloproteinase in oral squamous cell carcinoma cells.

OBJECTIVES: This study aimed at investigating the molecular mechanism underlying PKM2-mediated cancer invasion. MATERIALS & METHODS: To optimize the investigation of PKM2-specific effects, we used two immortalized oral cell lines. The two cell lines drastically differed in PKM2 expression level, particularly in the level of nuclear PKM2, and subsequently in glucose metabolism and tumorigenicity. RESULTS: Knockdown of PKM2 reduced not only the glucose metabolism but also the invasive activity by curtailing the expressions of matrix metalloproteinases (MMP): PKM2 could modulate MMP-9 expression by regulating ETS-1 inside the nucleus. These results were further confirmed in an oral squamous cell carcinoma (OSCC) cell line. In correspondence with in vitro findings, clinicopathological data from OSCC patients indicated strong association between PKM2 expression and poor survival rate. Additionally, upon analysis of public database, significant positive correlation was found between PKM2 and ETS-1 in OSCC. CONCLUSION: Collectively, this study unveiled the molecular mechanism underlying PKM2-mediated cancer invasion, thereby providing novel targets for therapeutics development against invasive OSCC.