Microtubule disruption synergizes with STING signaling to show potent and broad-spectrum antiviral activity.

The activation of stimulator of interferon genes (STING) signaling induces the production of type I interferons (IFNs), which play critical roles in protective innate immunity for the host to defend against viral infections. Therefore, achieving sustained or enhanced STING activation could become an antiviral immune strategy with potential broad-spectrum activities. Here, we discovered that various clinically used microtubule-destabilizing agents (MDAs) for the treatment of cancer showed a synergistic effect with the activation of STING signaling in innate immune response. The combination of a STING agonist cGAMP and a microtubule depolymerizer MMAE boosted the activation of STING innate immune response and showed broad-spectrum antiviral activity against multiple families of viruses. Mechanistically, MMAE not only disrupted the microtubule network, but also switched the cGAMP-mediated STING trafficking pattern and changed the distribution of Golgi apparatus and STING puncta. The combination of cGAMP and MMAE promoted the oligomerization of STING and downstream signaling cascades. Importantly, the cGAMP plus MMAE treatment increased STING-mediated production of IFNs and other antiviral cytokines to inhibit viral propagation in vitro and in vivo. This study revealed a novel role of the microtubule destabilizer in antiviral immune responses and provides a previously unexploited strategy based on STING-induced innate antiviral immunity.

A transcription factor complex in Dictyostelium enables adaptive changes in macropinocytosis during the growth-to-development transition.

Macropinocytosis, an evolutionarily conserved endocytic pathway, mediates nonselective bulk uptake of extracellular fluid. It is the primary route for axenic Dictyostelium cells to obtain nutrients and has also emerged as a nutrient-scavenging pathway for mammalian cells. How cells adjust macropinocytic activity in various physiological or developmental contexts remains to be elucidated. We discovered that, in Dictyostelium cells, the transcription factors Hbx5 and MybG form a functional complex in the nucleus to maintain macropinocytic activity during the growth stage. In contrast, during starvation-induced multicellular development, the transcription factor complex undergoes nucleocytoplasmic shuttling in response to oscillatory cyclic adenosine 3',5'-monophosphate (cAMP) signals, which leads to increased cytoplasmic retention of the complex and progressive downregulation of macropinocytosis. Therefore, by coupling macropinocytosis-related gene expression to the cAMP oscillation system, which facilitates long-range cell-cell communication, the dynamic translocation of the Hbx5-MybG complex orchestrates a population-level adjustment of macropinocytic activity to adapt to changing environmental conditions.

Over-expression of microRNA-145 Elevating Autophagy Activities via Downregulating FRS2 Expression.

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic and progressive joint diseases characterized by cartilage degeneration and chondrocyte death. In this study, we aimed to identify the modulation effect of miR-145 on chondrocytes' autophagy during the development of OA. BACKGROUND: Osteoarthritis (OA) is one of the most prevalent types of chronic and progressive joint disorder with the symptoms of joint pain and stiffness, and it leads to disability at the end stage. In recent years, microRNA-145 (miR-145) has been found to activate autophagy in various cell types, including mesenchymal stem cells, cardiomyocytes, and osteosarcoma cells. However, it is unknown whether miR-145 regulates the progression of OA by influencing chondrocyte autophagy. METHODS: Before investigating the regulatory effect of miR-145 on the autophagic activity of chondrocytes, the expression of miR-145 in human joint samples was analyzed. The targeting relationship between miR-145 and FRS2 was detected by dual luciferase assay. The effect of FRS2 and miR-145 on the autophagic activity of chondrocytes was observed by bidirectional expression of FRS2 and miR-145. RESULTS: The miR-145 expression and LC3-II/LC3-I ratio were significantly decreased and the SQSTM1 expression was increased in OA patients. The miR-145 overexpression in C20A4 cells increased LC3-II/LC3-I ratio, decreased SQSTM1 expression, and was positively correlated with autophagic activity. Under oxidative stress, miR-145 overexpression significantly improved chondrocyte viability through autophagy stimulation. FRS2 is a potential target of miR-145 via a binding sequence within its 3' UTR. FRS2 acts as the downstream mediator of miR-145 to suppress autophagy through activating PI3K/Akt/mTOR pathways. CONCLUSION: The miR-145 acts as a protective factor against chondrocytes by regulating miRFRS2- autophagy axis. The decrease of miR-145 in articular synovial fluid may turn out to be an important marker for early diagnosis of OA, and modulation of miR-145 may represent a promising therapeutic strategy for OA.

SMPDL3A is a cGAMP-degrading enzyme induced by LXR-mediated lipid metabolism to restrict cGAS-STING DNA sensing.

Lipid metabolism has been associated with the cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) stimulator of interferon genes (STING) DNA-sensing pathway, but our understanding of how these signals are integrated into a cohesive immunometabolic program is lacking. Here, we have identified liver X receptor (LXR) agonists as potent inhibitors of STING signaling. We show that stimulation of lipid metabolism by LXR agonists specifically suppressed cyclic GMP-AMP (cGAMP)-STING signaling. Moreover, we developed cyclic dinucleotide-conjugated beads to biochemically isolate host effectors for cGAMP inhibition, and we found that LXR ligands stimulated the expression of sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A), which is a 2'3'-cGAMP-degrading enzyme. Results of crystal structures suggest that cGAMP analog induces dimerization of SMPDL3A, and the dimerization is critical for cGAMP degradation. Additionally, we have provided evidence that SMPDL3A cleaves cGAMP to restrict STING signaling in cell culture and mouse models. Our results reveal SMPDL3A as a cGAMP-specific nuclease and demonstrate a mechanism for how LXR-associated lipid metabolism modulates STING-mediated innate immunity.

Does the timing of surgery affect outcomes in young and middle-aged patients undergoing surgical stabilization of rib fractures? Feedback was based on real data from physicians, patients, and family caregivers.

BACKGROUND: There is a general clinical consensus that early surgical stabilization of rib fractures (SSRF, ≤ 48-72 h after admission) can benefit patients, and this is only regarding the surgeon's opinions. This study assessed the true outcomes of young and middle-aged patients at different surgical timings. METHODS: This retrospective cohort study was conducted among patients aged 30-55 years who were hospitalized with a diagnosis of isolated rib fractures and underwent SSRF between July 2017 and September 2021. The patients were divided into early (≤ 3 days), mid- (4-7 days) and late (8-14 days) groups, according to the interval (days) between surgery and injury date. The impact of different surgical timings on clinical outcomes, patients, and families was assessed by comparing SSRF-related data during hospitalization and follow-up studies of clinicians, patients themselves, and family caregivers 1-2 months after surgery. RESULTS: In this study, 155 complete patient data were finally included, including 52, 64, and 39 patients in the early, mid, and late groups, respectively. Length of operation, preoperative closed chest drainage rate, length of hospital stay, intensive care unit length of stay, duration of invasive mechanical ventilation in the early group were lower than those in the intermediate and late groups. Additionally, hemothorax and excess pleural fluid incidence after SSRF was lower in the early group than in the intermediate and late groups. Postoperative follow-up results showed that patients in the early group had higher SF-12 physical component summary scores and shorter duration of absence from work. Family caregivers had lower Zarit Burden Interview scores than those in the mid- and late groups. CONCLUSION: From the experience of our institution's SSRF, early surgery is safe and offers additional potential benefits for young and middle-aged patients and families with isolated rib fractures.

NF-κB activation enhances STING signaling by altering microtubule-mediated STING trafficking.

It is widely known that stimulator of interferon genes (STING) can trigger nuclear factor κB (NF-κB) signaling. However, whether and how the NF-κB pathway affects STING signaling remains largely unclear. Here, we report that Toll-like receptor (TLR)-, interleukin-1 receptor (IL-1R)-, tumor necrosis factor receptor (TNFR)-, growth factor receptor (GF-R)-, and protein kinase C (PKC)-mediated NF-κB signaling activation dramatically enhances STING-mediated immune responses. Mechanistically, we find that STING interacts with microtubules, which plays a crucial role in STING intracellular trafficking. We further uncover that activation of the canonical NF-κB pathway induces microtubule depolymerization, which inhibits STING trafficking to lysosomes for degradation. This leads to increased levels of activated STING that persist for a longer period of time. The synergy between NF-κB and STING triggers a cascade-amplified interferon response and robust host antiviral defense. In addition, we observe that several gain-of-function mutations of STING abolish the microtubule-STING interaction and cause abnormal STING trafficking and ligand-independent STING autoactivation. Collectively, our data demonstrate that NF-κB activation enhances STING signaling by regulating microtubule-mediated STING trafficking.

Identification of differentially expressed autophagy genes associated with osteogenic differentiation in human bone marrow mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cells derived from human tissues have been widely used for tissue regeneration because of their strong self-renewal capacity and multi-potential properties. Autophagy plays a vital role in maintaining bone homeostasis. However, the mechanism underlying this role for autophagy in the osteogenic differentiation of mesenchymal stem cells remains to be elucidated. METHODS: Two microarray datasets were downloaded from the GEO database. Fourteen bone marrow mesenchymal stem cell samples comprising control and induction groups were selected to identify differentially expressed autophagy-related genes via multiple bioinformatics approaches, followed by functional analysis. Interactions among differentially expressed autophagy genes, miRNAs, and transcription factors were analyzed and visualized using Cytoscape software. The association between hub differentially expressed genes and autophagy was validated by qRT-PCR. RESULTS: Ten autophagy-related genes (including VPS8, NDRG4, and CYBB) were identified as osteogenic hub genes. Correlation analysis revealed that CYBB was highly correlated with the sensitivity to multiple drugs, such as imexon, megestrol acetate, and isotretinoin. The regulatory network displayed a complex connection among miRNAs, transcription factors, and differentially expressed autophagy genes. Friends' analysis showed that NDRG4 was highly closely related to other hub genes (P < 0.05). Furthermore, NDRG4 expression was downregulated in the induction group (P < 0.01). NDRG4 was significantly correlated with infiltrating immune cells, including monocytes, eosinophils, type 17 T helper cells, neutrophils, activated CD8 T cells, and immature B cells. Levels of the 10 autophagy-related genes (including VPS8, NDRG4, and CYBB) were successfully validated based on in vitro experiments. CONCLUSION: We identified candidate molecules to further investigate their functions in osteogenesis, providing novel insights into the role of autophagy in mesenchymal stem cell differentiation.

COVID-19 Shock and the Time-Varying Volatility Spillovers Among the Energy and Precious Metals Markets: Evidence From A DCC-GARCH-CONNECTEDNESS Approach.

The outbreak of the COVID-19 epidemic intensified the volatility of commodity markets (the energy and precious metals markets), which created a significant negative impact on the volatility spillovers among these markets. It may also have triggered a new volatility risk contagion. In this paper, we introduce the DCC-GARCH-CONNECTEDNESS approach to explore the volatility spillover level and multi-level spillover structure characteristics among the commodity markets before and during the COVID-19 epidemic in order to clarify the new volatility risk contagion patterns across the markets. The results implied several conclusions. (i) The COVID-19 epidemic has significantly improved the total volatility spillover level of the energy and precious metals markets and has enhanced the risk connectivity among the markets. (ii) The COVID-19 epidemic has amplified the volatility of the crude oil market, making it the main volatility spillover market, namely the source of volatility risk contagion. (iii) The COVID-19 epidemic outbreak enhanced the external risk absorption capacity of the natural gas and silver markets, and the absorption level of the external volatility spillover improved significantly. Furthermore, the risk absorption capacity of the gold market weakened, while the gold market has remained the endpoint of external volatility risk during the epidemic and has acted as a risk stabilizer. (iv) The volatility spillover among markets has clear time-varying characteristics and a positive connectedness with the severity of the COVID-19 epidemic. As the severity of the COVID-19 epidemic increases, the volatility risk connectivity among the markets rapidly increases.

LL-37 transports immunoreactive cGAMP to activate STING signaling and enhance interferon-mediated host antiviral immunity.

Cyclic 2',3'-GMP-AMP (cGAMP) binds to and activates stimulator of interferon genes (STING), which then induces interferons to drive immune responses against tumors and pathogens. Exogenous cGAMP produced by infected and malignant cells and synthetic cGAMP used in immunotherapy must traverse the cell membrane to activate STING in target cells. However, as an anionic hydrophilic molecule, cGAMP is not inherently membrane permeable. Here, we show that LL-37, a human host defense peptide, can function as a transporter of cGAMP. LL-37 specifically binds cGAMP and efficiently delivers cGAMP into target cells. cGAMP transferred by LL-37 activates robust interferon responses and host antiviral immunity in a STING-dependent manner. Furthermore, we report that LL-37 inducers vitamin D3 and sodium butyrate promote host immunity by enhancing endogenous LL-37 expression and its mediated cGAMP immune response. Collectively, our data uncover an essential role of LL-37 in innate immune activation and suggest new strategies for immunotherapy.

Clinical Application Effects of Different Preoperative Blood Management Schemes in Older Patients with Delayed Intertrochanteric Fracture Surgery.

Introduction: Research on preoperative blood management in older patients with delayed surgery for intertrochanteric fracture is scarce, especially regarding hematopoiesis and hemostasis. We assessed the effectiveness of optimized blood management programs in older patients undergoing delayed surgery for intertrochanteric fractures. Methods: This retrospective study included 456 patients who underwent delayed surgery for intertrochanteric fractures. According to the optimized blood management plan, the patients were divided into four groups: group A was the control group; group B received 1 g of tranexamic acid (TXA) intravenously at admission; group C underwent sequential TXA treatment after admission until 1 day before surgery (1 g/day); and group D received iron supplements (200 mg/day) in addition to the treatment administered to group C, with or without recombinant human erythropoietin (rHuEPO; 40,000 IU). The primary outcomes were preoperative hidden blood loss (HBL), preoperative allogeneic blood transfusion (ABT) rate, hemoglobin (Hb) change, and actual Hb drop. Results: The Hb reduction, calculated HBL, and hospitalization duration in groups C and D were significantly lower than those in groups A and B. The preoperative ABT rates in groups C and D were significantly lower than those in groups A and B, with no significant difference between groups C and D. Discussion: The results of this study suggested that iron supplementation (with or without rHuEPO) combined with the sequential IV TXA scheme did not show a better clinical effect than the sequential IV TXA scheme in the management of patients undergoing delayed surgery for intertrochanteric fractures. Therefore, further evaluation is needed before recommending iron supplements and rHuEPO in older patients.

Effects of runt-related transcription factor 2 (RUNX2) on the autophagy of rapamycin-treated osteoblasts.

Autophagy occurs throughout the development and maturation of bone tissues and various types of bone cells and plays a vital role in osteoporosis progression. This study aimed to explore the role of runt-related transcription factor 2 (RUNX2) in osteoblast autophagy and its related molecular mechanisms. MC3T3-E1 cells were treated with different concentrations of rapamycin, and their viability was determined using a cell counting Kit-8 (CCK-8). The cells were then transfected with si-RUNX2 and RUNX2 overexpression plasmids, and the viability of these rapamycin-treated cells was measured using CCK-8, while the expression of autophagy-related genes/proteins and osteoblast differentiation-related genes was determined using Western blotting and RT-qPCR. Finally, Alizarin red staining was used to observe osteoblast mineralization, and transmission electron microscopy was employed to detect autophagosomes in cells administered different treatments. Rapamycin significantly inhibited cell viability and promoted cell autophagy compared with the control (P < 0.05). Cells with RUNX2 knockdown and overexpression were successfully established. Further, RUNX2 overexpression was found to significantly enhance the viability and osteoblast mineralization of rapamycin-treated cells and suppress cell autophagy. RUNX2 overexpression also increased p-p38MAPK/p38MAPK levels and ALP, OCN, and OSX expression, and markedly downregulated Beclin-1, LC3-II/LC3-I, p62, ATG1, p-Beclin-1, and ATG5 levels (P < 0.05). However, the trends after RUNX2 knockdown opposed those observed after RUNX2 overexpression. RUNX2 may regulate osteoblast differentiation and autophagy by mediating autophagy-related and osteoblast differentiation-related genes/proteins, as well as the p38MAPK signaling pathway.

Dose tranexamic acid reduce blood loss associated with simultaneous bilateral distal tibial tubercle-high tibial osteotomy?

BACKGROUND: Simultaneous bilateral distal tibial tubercle high tibial osteotomy (SBDTT-HTO) can result in increased blood loss. The aim of this study is to evaluate the actual hemostatic effect of different tranexamic acid (TXA) treatment regimen in SBDTT-HTO. METHODS: We conducted a retrospective case-control study including 54 patients who underwent SBDTT-HTO. The single-dose group (n = 18) received 1 g of intravenous TXA 15-30 min before surgery, the two-dose group (n = 18) received an additional 1 g of intravenous TXA 6 h after surgery, and the multiple-dose group (n = 18) received an additional 1 g intravenous TXA per-day until discharge. Blood loss, hemoglobin levels, occurrence of any adverse events,functional analysis, quality of life, and pain assessmentswere compared among the three groups. RESULTS: The total blood loss, hidden blood loss, drainage volumes, and haemoglobin level in the multiple-dose group all occupy a significant advantage.(p < 0.05). In addition, better quality of life were observed in patients belonging to the multiple-dose group then single-dose group.(p < 0.05). CONCLUSIONS: Based on our results, for patients undergoing SBDTT-HTO, sequential intravenous TXA administration can effectively and safely reduce blood loss,maintain postoperative Hb levels,and with the advantage of accelerating recovery.

Modified negative-pressure wound therapy for linear blister formation prevention around foam dressings: technical note and case series.

BACKGROUND: Linear blisters (LBs) often occur around dressings when negative-pressure wound therapy (NPWT) is used to cover open wounds. Tension blisters may increase the wound infection incidence rate, delay the start of operation, and prolong the duration of hospital stay. Currently, there are no established methods for the prevention of LB formation around dressings, which remains to be a major concern in clinical applications. Therefore, we developed a novel, simple, reproducible, and convenient method for preventing LB formation around NPWT dressings. METHOD: Fifty-three cases of Gustilo type II and III open fractures under NPWT were considered. NPWT was used on every wound after debridement. All patients were divided into a conventional group (27 cases, 33 wounds) and a novel group (26 cases, 27 wounds) based on the difference in the NPWT dressing appearance. A healthy volunteer with intact skin was also included to perform the detailed process of NPWT. LBs occurring on intact skin around the dressings were observed and recorded when the dressing was removed 3 days after the operation. The occurrence of LB formation and wound infection was considered as categorical data and compared between the two groups using a chi-square test. The duration of hospital stay was considered as numerical data and compared between the two groups using two independent t tests. RESULTS: The percentage of occurrence of LB formation around dressings in the conventional group was 27.3%, whereas it was merely 3.7% in the novel group (P = 0.037). The infection incidence rate in the conventional group was 30.3%, whereas that in the novel group was 25.9%; however, no statistical difference was observed between the two groups (P = 0.708). The average duration of hospital stay in the conventional group was 14.39 ± 4.55 days, whereas that in the novel group was 11.04 ± 3.47 days (P = 0.003). CONCLUSION: Thus, changing the NPWT dressing appearance can prevent LB formation around dressings, providing an effective method to improve NPWT application. Modified NPWT dressings also shorten the duration of hospital stay, but do not significantly decrease the incidence of wound infection.

Comparison of topical and intravenous Tranexamic acid for high tibial osteotomy: A retrospective study.

ABSTRACT: High tibial osteotomy (HTO) is a promising surgery that can treat osteoarthritis of the medial septum of the knee. However, the extensive release of soft tissue and the osteotomy gap may produce intraoperative and postoperative bone bleeding. Tranexamic acid (TXA) is an effective blood management strategy, as it competitively inhibits the activation process of plasminogen and prevents fibrinolytic enzymes from degrading fibrin. Therefore, we compared the operative bone bleeding of patients who underwent HTO who received either intravenous (IV) or topical TXA in this research.The medical records of a total of 191 patients (including 72 who received IV TXA, 64 who received topical TXA and 55 control patients) who received open-wedge HTO were retrospectively reviewed from January 2016 to August 2019. There were no obvious demographic differences between the groups. Here, we used independent parameters to assess the efficacy of topical and IV TXA in reducing blood loss.Compared with the IV TXA group, patients receiving topical TXA therapy had greater blood loss (622 ±â€Š231 ml versus 451 ±â€Š231 ml, mean difference 171 mL [95% CI, 87-254]; p < 0.001). The hemoglobin concentration of the IV TXA group was obviously higher than that of the topical medication group. No patients had thromboembolic complications during the entire study period.In our study, it seemed that either IV or topical use of TXA might reduce blood loss after open-wedge HTO, and the blood loss and amount of drainage in the IV TXA group showed huge decreases compared to those in the topical group.

Do the successful revision surgery for humeral nonunion solve all the effects on health-related quality of life? A retrospective cohort study.

BACKGROUND: The aim of this study is to evaluate the effects of successful revision operation on health quality of life(QoL) and functional outcome in humeral nonunion patients. METHODS: This retrospective study included 62 patients with humeral nonunion from Northwest China, who were admitted to the Department of Trauma Surgery, Honghui Hospital between March 2013 and September 2019. The following data were retrospectively evaluated: demographic data, clinical data, imaging findings, and treatment methods. The QoL assessment indicators for humeral nonunion patients included the SF-12 mental component summary (MCS) and physical component summary (PCS),brief pain inventory-severity(BPI-S) and brief pain inventory-interference (BPI-I). The mayo elbow performance score (MEPS) was used to assess the elbow function of the patients. RESULTS: Successful revision surgery significantly improved the patient's PCS, MCS, BPI-S and BPI-I scores (p<0.001). According to the MEPS criteria, the excellent and good rates were 95.16% in this study. The impact of humeral nonunion on mental health was comparable with the reported impact of stroke and type II diabetes (p>0.05).The impact of post-op on physical health was comparable with the reported impact of COPD, silicosis, hypertension, barrentt's esophagus and lower urinary tract symptoms(p>0.05). CONCLUSION: Humeral nonunion is a devastating chronic medical condition that negatively affects both physical and mental health as well as quality of life. Although the effects of pain in the body can be completely relieved by treatment, the entire medical process may cause everlasting psychological trauma to the patient.

Efficacy and Safety of Long-Term Intravenous Tranexamic Acid Administration for Blood Management in Revision Surgery for Femoral Shaft Nonunion: A Retrospective Case-Control Study.

Femoral shaft nonunion is a complication that seriously affects physiological functions. We aimed to assess the effectiveness and safety of short- and long-term intravenous tranexamic acid (TXA) administration in the perioperative period of revision surgery for femoral shaft nonunion. In this retrospective study, 53 patients undergoing double-locking plates with channel bone grafting technology for the treatment of femoral shaft nonunion were divided into 3 groups: the patients in group A without use TXA during hospitalization, the patients in group B received intravenous (IV) 1-g TXA at 30 min before the surgery and deep soaked 1-g TXA for 5 min before closing the incision, and then 1-g TXA IV again 6 h after surgery, and the patients in group C received 1-g TXA IV before the operation, 1-g TXA topically during the operation, and subsequent long-term 1-g TXA IV until discharged. The primary outcomes were total blood loss (TBL) and hidden blood loss (HBL). The secondary outcomes included actual hemoglobin (Hb) loss values, transfusion requirement, number of units transfused, postoperative laboratory values (Hb, hematocrit, fibrinogen, and D-dimer), visual analogue scale (VAS) scores, and hospitalization time. The mean TBL was lower in group C than in group A (1168 mL vs. 2714 mL, P < 0.001) and group B (1168 mL vs. 1557 mL, P = 0.008). The differences in HBL volumes were also significant between groups A and C (P < 0.001) and between groups A and B (P < 0.01). The actual Hb loss in the 3 groups showed a consistent trend with TBL, but no significant differences between groups B and C (P = 0.23). On postoperative day (POD) 3, the Hb level was higher in group C than in group A (111.1 g/L vs. 94.6 g/L, P = 0.02). No significant differences were found in VAS, hospital stay, thromboembolic complications, incision-related complications, and TXA adverse reactions among groups. Long-term intravenous TXA during hospitalization can effectively reduce perioperative blood loss, Hb drop, and postoperative hyperfibrinolysis, but is associated with an increased incidence of adverse reactions.

C1orf61 promotes hepatocellular carcinoma metastasis and increases the therapeutic response to sorafenib.

C1orf61 is a specific transcriptional activator that is highly up-regulated during weeks 4-9 of human embryogenesis, the period in which most organs develop. We have previously demonstrated that C1orf61 acts as a tumor activator in human hepatocellular carcinoma (HCC) tumorigenesis and metastasis. However, the underlying molecular mechanisms of tumor initiation and progression in HCC remain obscure. In this study, we demonstrated that the pattern of C1orf61 expression was closely correlated with metastasis in liver cancer cells. Gene expression profiling analysis indicated that C1orf61 regulated diverse genes related to cell growth, migration, invasion and epithelial-mesenchymal transition (EMT). Results showed that C1orf61 promotes hepatocellular carcinoma metastasis by inducing cellular EMT in vivo and in vitro. Moreover, C1orf61-induced cellular EMT and migration are involved in the activation of the STAT3 and Akt cascade pathways. In addition, C1orf61 expression improved the efficacy of the anticancer therapy sorafenib in HCC patients. For the first time, we report a regulatory pathway by which C1orf61 promoted cancer cell metastasis and regulated the therapeutic response to sorafenib. These findings increased our understanding of the molecular events that regulate metastasis and treatment in HCC.

[Extensor digitorum communis split approach combined with loop-plate technique for treatment of ulnar coronoid fracture in terrible triad of elbow].

OBJECTIVE: To explore the effectivenesss of simple lateral extensor digitorum communis (EDC) split approach combined with loop-plate fixation in the treatment of ulnar coronoid fracture in terrible triad of elbow (TTE). METHODS: The clinical data of 60 patients with TTE who met the selection criteria between January 2015 and May 2018 were retrospectively analyzed. There were 48 males and 12 females, aged from 18 to 60 years (mean, 37.4 years). All the patients were closed fractures. Injury causes included fall injury in 28 cases, falling from height in 20 cases, and traffic accident injury in 12 cases. All patients had no vascular and nerve injury, and the time from injury to operation was 1-14 days, with an average of 4.8 days. The height and size of the fracture of the coronal process were measured by CT and accurate classifications were made. All the 60 patients were treated with simple lateral EDC split approach combined with loop-plate to fix the ulnar coronoid fracture; 20 patients of radial head fracture were fixed with hollow screw, 32 patients with mini-plate fixation, 8 patients with radial head prosthesis replacement; 16 patients with suture and 44 patients with suture anchor to reconstruct lateral collateral ligament complex; 10 patients with residual instability of elbow joint were fixed with hinge external fixator, and others were fixed with adjustable tension brace after operation. Postoperative imaging examination was performed to evaluate fracture healing and complications, such as loosening or breakage of internal fixator, osteoarthritis, and heterotopic ossification, etc. During follow-up, the range of motion (ROM) of the elbow joint was recorded, including elbow flexion, extension, and forearm pronation, supination. Mayo elbow function score system (MEPS) was used to evaluate elbow joint function at last follow-up. RESULTS: All patients were followed up 16-24 months (mean, 20.2 months). All incisions healed by first intention after operation, and no complications such as vascular nerve injury, elbow joint instability, internal fixation failure, and infection occurred; the fracture healing time was 9-17 weeks (mean, 11.7 weeks). Four cases developed elbow stiffness after operation, and all underwent elbow joint lysis with internal fixator removal within 12-15 months after operation; 10 cases developed heterotopic ossification without special treatment. At last follow-up, the ROM of elbow flexion ranged from 85° to 135° (mean, 116°), the ROM of elbow extension ranged from 0° to 20° (mean, 11°), the ROM of forearm pronation ranged from 55° to 75° (mean, 70°), and the ROM of forearm supination ranged from 60° to 90° (mean, 83°). The MEPS score ranged from 55 to 100 (mean, 86.1); the effectiveness were excellent in 40 patients, good in 10 patients, fair in 6 patients, and poor in 4 patients, with an excellent and good rate of 83.3%. CONCLUSION: The simple lateral EDC split approach is fully exposed, and the loop-plate can fix the ulnar coronoid fractures firmly and stably, which can restore the stability of the elbow joint, and the effectiveness is satisfactory.

Comparison of the effectiveness and safety of intravenous and topical regimens of tranexamic acid in complex tibial plateau fracture: a retrospective study.

BACKGROUND: Previous studies have demonstrated the effectiveness and safety of tranexamic acid (TXA) in orthopedic surgery. However, no study has investigated TXA in complex tibial plateau fracture surgery. Therefore, the purpose of this study was to confirm the safety and effectiveness of i.v. (intravenous) TXA and topical TXA. MATERIAL AND METHODS: This was a retrospective analysis of prospectively collected data. The control group received an equal amount of placebo (physiological saline solution); the i.v. group received 1.0 g TXA by intravenous injection before the tourniquet was inflated and before the surgical incision was closed, and the topical group received 3.0 g TXA in 75 mL of physiological saline solution 5 min prior to the final tourniquet release. Perioperative blood loss, vascular events, wound complications, and adverse reactions were compared among the three groups. The pain, knee function, and quality of life (QoL) assessments were based on their corresponding scoring systems. RESULTS: Baseline data were comparable for all groups. The i.v. group showed the best results for total blood loss (TBL) and hidden blood loss (HBL) (424.5 ± 49.4 mL and 219.3 ± 33.4 mL, respectively, all P values < 0.001). Patients in the i.v. group had lesser real Hb decrease than those in the control group (0.9 vs 1.5, P<0.001) and topical group (0.9 vs 1.2, P = 0.026). The blood coagulation level as measured using fibrinolysis (D-dimer) was lower in the i.v. group than in the control and topical groups on POD1 and POD3; however, this difference was not significant; the fibrin-degradation products also showed a similar trend. Patients in the topical group experienced less pain than those in the control group on POD2, POD4, and PO6W. The VAS pain score was 3.6 vs. 4.4 (POD2, P<0.05), 2.8 vs 3.3 (POD4, P<0.05), and 2.1 vs. 2.6 (PO6W, P<0.001) in the topical group vs control group, respectively. No significant differences were identified in vascular events, wound complications, adverse reactions, knee function, and QoL among the three groups. CONCLUSION: To our knowledge, this is the first study that showed both i.v. TXA and topical TXA are safe and effective for complex tibial plateau fractures. The i.v. regimen effectively reduced blood loss during the perioperative period, whereas patients under the topical regimen had less vascular events, wound complications, and a lower incidence of adverse reactions compared to those in the i.v. group. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR-TRC-1800017754 , retrospectively registered from 2018 to 01-01).