The impact of the union of lesser trochanter fragments after intramedullary fixation of trochanteric femoral fractures: an X-ray based study.

BACKGROUND: Displacement of the lesser trochanter (LT) is not uncommon after managing intertrochanteric femoral fractures and the influence of nonunion of the LT-fragment on clinical outcomes remains controversial. This study aimed to investigate the relationship between the displacement distance and union of the LT-fragment and evaluate the influence of LT-fragment nonunion on hip function and complications. METHODS: This retrospective study included patients with intertrochanteric fractures and displaced LT treated with intramedullary fixation at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from June 2015 to July 2017. The patients were grouped as union and nonunion of the LT-fragment at 1 year. The LT-fragment displacement distance of LT was measured by the anterior-posterior radiographs. RESULTS: Thirty-one and 22 patients showed union and nonunion at 1 year, respectively. The nonunion group had a higher postoperative complication rate than the union group (59% vs. 29%, P = 0.047), especially mechanical complications (45% vs. 6%, P = 0.001). There was no significant difference in hip function between the two groups (P > 0.05). The receiver operating characteristic (ROC) curve revealed an area under the curve of 0.933 of displacement ratio. Patients with a displacement ratio > 0.35 were more likely to have nonunion of the LT-fragment. CONCLUSIONS: The displacement ratio might be a reliable predictor of LT-fragment union. The incidence of postoperative complications might increase with LT-fragment nonunion.

Oxymatrine promotes hypertrophic scar repair through reduced human scar fibroblast viability, collagen and induced apoptosis via autophagy inhibition.

Scars are common complications of burns and trauma, resulting in mental trauma, physical pain, and a heavy financial burden for patients. Specific and effective anti-scarring drugs are lacking in clinical practice. Phytochemicals are easily accessible, low in toxicity, and have various biological and pharmacological properties. Oxymatrine is a phytochemical that regulates autophagy networks. Autophagy is closely related to the maintenance, activity, differentiation, and life-death of skin fibroblasts during wound repair, which results in pathological scars. We hypothesised that oxymatrine may promote hypertrophic scar repair by inhibiting fibroblast autophagy. In vitro studies showed that inhibition of autophagy by oxymatrine decreased viability and collagen metabolism, and increased apoptosis of human scar fibroblasts (HSFs). In vivo studies showed that inhibition of autophagy by oxymatrine promoted scar repair, resulting in a significantly improved final outcome of the hypertrophic scars, a smaller scar area, decreased epidermal and dermal thickness, and a significant downregulation of CK10, P63, collagen I, α-SMA, and TGF-ß1. In summary, oxymatrine promoted hypertrophic scar repair by decreasing HSF viability and collagen, and inducing apoptosis via autophagy inhibition. This study provides a new perspective on the mechanism of hypertrophic burn scar formation, as well as key scientific data for the application of the phytochemical oxymatrine as a new method for the prevention and treatment of hypertrophic scars.

Exogenous pyruvate represses histone gene expression and inhibits cancer cell proliferation via the NAMPT-NAD+-SIRT1 pathway.

Pyruvate is a glycolytic metabolite used for energy production and macromolecule biosynthesis. However, little is known about its functions in tumorigenesis. Here, we report that exogenous pyruvate inhibits the proliferation of different types of cancer cells. This inhibitory effect of pyruvate on cell growth is primarily attributed to its function as a signal molecule to repress histone gene expression, which leads to less compact chromatin and misregulation of genome-wide gene expression. Pyruvate represses histone gene expression by inducing the expression of NAD+ biosynthesis enzyme, nicotinamide phosphoribosyltransferase (NAMPT) via myocyte enhancer factor 2C (MEF2C), which then increases NAD+ levels and activates the histone deacetylase activity of SIRT1. Chromatin immunoprecipitation analysis indicates that pyruvate enhances SIRT1 binding at histone gene promoters where it reduces histone acetylation. Although pyruvate delays cell entry into S phase, pyruvate represses histone gene expression independent of cell cycle progression. Moreover, we find that administration of pyruvate reduces histone expression and retards tumor growth in xenograft mice without significant side effects. Using tissues from cervical and lung cancer patients, we find intracellular pyruvate concentrations inversely correlate with histone protein levels. Together, we uncover a previously unknown function of pyruvate in regulating histone gene expression and cancer cell proliferation.

Japanese Encephalitis Virus Induces Apoptosis and Encephalitis by Activating the PERK Pathway.

Accumulated evidence demonstrates that Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) has been reported to induce apoptosis under acute or prolonged ER stress. However, the precise role of PERK in JEV-induced apoptosis and encephalitis remains unknown. Here, we report that JEV infection activates the PERK-ATF4-CHOP apoptosis pathway both in vitro and in vivo PERK activation also promotes the formation of stress granule, which in turn represses JEV-induced apoptosis. However, PERK inhibitor reduces apoptosis, indicating that JEV-activated PERK predominantly induces apoptosis via the PERK-ATF4-CHOP apoptosis pathway. Among JEV proteins that have been reported to induce ER stress, only JEV NS4B can induce PERK activation. PERK has been reported to form an active molecule by dimerization. The coimmunoprecipitation assay shows that NS4B interacts with PERK. Moreover, glycerol gradient centrifugation shows that NS4B induces PERK dimerization. Both the LIG-FHA and the LIG-WD40 domains within NS4B are required to induce PERK dimerization, suggesting that JEV NS4B pulls two PERK molecules together by simultaneously interacting with them via different motifs. PERK deactivation reduces brain cell damage and encephalitis during JEV infection. Furthermore, expression of JEV NS4B is sufficient to induce encephalitis via PERK in mice, indicating that JEV activates PERK primarily via its NS4B to cause encephalitis. Taken together, our findings provide a novel insight into JEV-caused encephalitis.IMPORTANCE Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) has been reported to induce apoptosis under acute or prolonged ER stress. However, whether the PERK pathway of ER stress response plays important roles in JEV-induced apoptosis and encephalitis remains unknown. Here, we found that JEV infection activates ER stress sensor PERK in neuronal cells and mouse brains. PERK activation induces apoptosis via the PERK-ATF4-CHOP apoptosis pathway upon JEV infection. Among the JEV proteins prM, E, NS1, NS2A, NS2B, and NS4B, only NS4B activates PERK. Moreover, activated PERK participates in apoptosis and encephalitis induced by JEV and NS4B. These findings provide a novel therapeutic approach for JEV-caused encephalitis.

Membrane disruptive antimicrobial potential of NK-lysin from yellow catfish (Pelteobagrus fulvidraco).

NK-lysins, a type of broad-spectrum antimicrobial peptide (AMP), act as an essential effector of innate defense against microbial attack in higher vertebrates and so in fish. The present study delineates the structural and functional characterization of NK-lysin from yellow catfish (Pelteobagrus fulvidrac) (Pelteobagrus fulvidraco). PfNK-lysin encodes a 153-residue peptide, which displays the hallmark features of other known NK-lysins with the ordered array of six well-conserved cysteine residues and five-exon/four-intron structure. It was found to be ubiquitous in tissues, being detected most abundantly in gill and head kidney. In vivo exposure to stimuli (LPS, PolyI:C, and Edwardsiella ictaluri) induced PfNK-lysin expression in head kidney and spleen. Synthetic PfNK-lysin-derived peptide exhibited in vitro bactericidal potency against both Gram-positive and Gram-negative bacteria, with the highest inhibitory effect on pathogen Edwardsiella ictaluri. Fluorescence microscopy and scanning electron microscopy further confirmed its capacity to cause damage to the bacterial plasma membrane. Taken together, these data suggest that PfNK-lysin might participate in antimicrobial defense of yellow catfish by membrane-disruptive action.

MiR-26b-3p regulates osteoblast differentiation via targeting estrogen receptor α.

BACKGROUND: Understanding of the molecular mechanisms of miRNAs involved in osteoblast differentiation is important for the treatment of bone-related diseases. METHODS: MC3T3-E1 cells were induced to osteogenic differentiation by culturing with bone morphogenetic protein 2 (BMP2). After transfected with miR-26b-3p mimics or inhibitors, the osteogenic differentiation of MC3T3-E1 cells was detected by ALP and ARS staining. Cell viability was analyzed by MTT. The expressions of miR-26b-3p and osteogenic related markers and signaling were examined by qPCR and western blot. Direct binding of miR-26b-3p and ER-α were determined by dual luciferase assay. RESULTS: miR-26b-3p was significantly down-regulated during osteoblast differentiation. Overexpression of miR-26b-3p inhibited osteoblast differentiation, while inhibition of miR-26b-3p enhanced osteoblast differentiation. Further studies demonstrated miR-26b-3p inhibited the expression of estrogen receptor α (ER-α) by directly targeting to the CDS region of ER-α mRNA. Overexpression of ER-α rescued the suppression effects of miR-26b-3p on osteoblast differentiation, while knockdown of ER-α reversed the upregulation of osteoblast differentiation induced by knockdown of miR-26b-3p. CONCLUSION: Our study demonstrates that miR-26b-3p suppresses osteoblast differentiation of MC3T3-E1 cells via directly targeting ER-α.

Walnut oil promotes healing of wounds and skin defects in rats via regulating the NF-kB pathway.

The effects of walnut oil on wound healing and skin injury repair was observed in Sprague-Dawley (SD) rats, and mechanism of action was investigated. Normal SD rats were divided into an experimental group and a control group. Each group was observed at4 time points (day [D]3, D7, D14, and D21). In both groups, a skin wound was created on the back of the rats, with the spine as the central axis. In the experimental group, the wound was covered with walnut oil, and then bandaged and fixed with sterile gauze. In the control group, the wound was bandaged with vaseline gauze. At each corresponding time point, the wound area and wound healing time of each rat were examined. Epithelial cells of the wound tissues were observed using haematoxylin and eosin staining and immunohistochemical analysis,and the numbers of inflammatory cells and capillaries were counted. A western blot method was used to detect the expression of nuclear factor (NF)-κB and epidermal growth factor (EGF) in the wound tissues of both groups. Meanwhile, enzyme-linked immunosorbent analysis (ELISA) was used to detect the expression of transforming growth factor (TGF)-ß1 and matrix metalloproteinase (MMP)-1 in rat sera. A total of 48 SD rats completed the experiment. Healing time of residual wounds in the experimental group was 10.0±3.5 days, which was significantly shorter than that in the control group (18.0±6.0 days) (p<0.05). The wound healing rates in the experimental group were 54.14 % (D3) and 91.2 3% (D7), whereas those in the control group were 22.12% (D3) and 54.84% (D7 (p<0.05).Histological examinations revealed no epithelial cells on D3, D7, D14, and D21 in both the experimental and control groups. However, the number of inflammatory cells decreased significantly and the number of capillaries increased significantly in the experimental group compared to control (p<0.05). NF-κB expression was significantly lower, EGF expression significantly higher in the in the experimental group. Conversely, ELISA showed a significant increase in the expression of TGF-ß1 and MMP-1 in rat sera in the experimental group. So we conclude that walnut oil has significant effects in promoting the healing of skin defect wounds in SD rats.

Loading rutin on surfaces by the layer-by-layer assembly technique to improve the oxidation resistance and osteogenesis of titanium implants in osteoporotic rats.

The purpose of this study was to construct a rutin-controlled release system on the surface of Ti substrates and investigate its effects on osteogenesis and osseointegration on the surface of implants. The base layer, polyethylenimine (PEI), was immobilised on a titanium substrate. Then, hyaluronic acid (HA)/chitosan (CS)-rutin (RT) multilayer films were assembled on the PEI using layer-by-layer (LBL) assembly technology. We used scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and contact angle measurements to examine all Ti samples. The drug release test of rutin was also carried out to detect the slow-release performance. The osteogenic abilities of the samples were evaluated by experiments on an osteoporosis rat model and MC3T3-E1 cells. The results (SEM, FTIR and contact angle measurements) all confirmed that the PEI substrate layer and HA/CS-RT multilayer film were effectively immobilised on titanium. The drug release test revealed that a rutin controlled release mechanism had been successfully established. Furthermore, thein vitrodata revealed that osteoblasts on the coated titanium matrix had greater adhesion, proliferation, and differentiation capacity than the osteoblasts on the pure titanium surface. When MC3T3-E1 cells were exposed to H2O2-induced oxidative stressin vitro, cell-based tests revealed great tolerance and increased osteogenic potential on HA/CS-RT substrates. We also found that the HA/CS-RT coating significantly increased the new bone mass around the implant. The LBL-deposited HA/CS-RT multilayer coating on the titanium base surface established an excellent rutin-controlled release system, which significantly improved osseointegration and promoted osteogenesis under oxidative stress conditions, suggesting a new implant therapy strategy for patients with osteoporosis.

Glc7/PP1 dephosphorylates histone H3T11 to regulate autophagy and telomere silencing in response to nutrient availability.

How cells adapt their gene expression to nutritional changes remains poorly understood. Histone H3T11 is phosphorylated by pyruvate kinase to repress gene transcription. Here, we identify the protein phosphatase 1 (PP1), Glc7 as the enzyme that specifically dephosphorylates H3T11. We also characterize two novel Glc7-containing complexes and reveal their roles in regulating gene expression upon glucose starvation. Specifically, the Glc7-Sen1 complex dephosphorylates H3T11 to activate the transcription of autophagy-related genes. The Glc7-Rif1-Rap1 complex dephosphorylates H3T11 to derepress the transcription of telomere-proximal genes. Upon glucose starvation, Glc7 expression is up-regulated and more Glc7 translocates into the nucleus to dephosphorylate H3T11, leading to induction of autophagy and derepressed transcription of telomere-proximal genes. Furthermore, the functions of PP1/Glc7 and the two Glc7-containing complexes are conserved in mammals to regulate autophagy and telomere structure. Collectively, our results reveal a novel mechanism that regulate gene expression and chromatin structure in response to glucose availability.

Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence.

Vascular endothelial cells (ECs) senescence correlates with the increase of cardiovascular diseases in ageing population. Although ECs rely on glycolysis for energy production, little is known about the role of glycolysis in ECs senescence. Here, we report a critical role for glycolysis-derived serine biosynthesis in preventing ECs senescence. During senescence, the expression of serine biosynthetic enzyme PHGDH is significantly reduced due to decreased transcription of the activating transcription factor ATF4, which leads to reduction of intracellular serine. PHGDH prevents premature senescence primarily by enhancing the stability and activity of pyruvate kinase M2 (PKM2). Mechanistically, PHGDH interacts with PKM2, which prevents PCAF-catalyzed PKM2 K305 acetylation and subsequent degradation by autophagy. In addition, PHGDH facilitates p300-catalyzed PKM2 K433 acetylation, which promotes PKM2 nuclear translocation and stimulates its activity to phosphorylate H3T11 and regulate the transcription of senescence-associated genes. Vascular endothelium-targeted expression of PHGDH and PKM2 ameliorates ageing in mice. Our findings reveal that enhancing serine biosynthesis could become a therapy to promote healthy ageing.

Walnut ointment promotes full-thickness burning wound healing: role of linoleic acid.

PURPOSE: To investigate the active ingredients of walnut ointment (WO) and its mechanism in repairing wounds. METHODS: The ingredients of WO were detected by gas chromatography-mass spectrometry. The effect of linoleic acid (LA) was tested by in vitro Alamar Blue (AB) reagent. Image J software, histological and immunohistochemical analysis were used to confirm the healing effect of LA in the porcine skin model. The animals were euthanized after the experiment by injection of pentobarbital sodium. RESULTS: LA, 24% in WO, promotes keratinocytes and fibroblasts proliferation, which were 50.09% and 15.07% respectively higher than control (p < 0.05). The healing rate of the LA group (96.02% ± 2%, 98.58% ± 0.78%) was higher than the saline group (82.11% ± 3.37%, 88.72% ± 1.73%) at week 3 and week 4 (p < 0.05). The epidermal thickness of the LA was 0.16 ± 0.04 mm greater and the expression of the P63 and CK10 proteins was stronger in the LA group than the control (p < 0.05). CONCLUSIONS: LA, which is the main components in WO can promote full-thickness burning wounds (FBWs) by stimulating cell proliferation and differentiation.

Interplay Between Glucose Metabolism and Chromatin Modifications in Cancer.

Cancer cells reprogram glucose metabolism to meet their malignant proliferation needs and survival under a variety of stress conditions. The prominent metabolic reprogram is aerobic glycolysis, which can help cells accumulate precursors for biosynthesis of macromolecules. In addition to glycolysis, recent studies show that gluconeogenesis and TCA cycle play important roles in tumorigenesis. Here, we provide a comprehensive review about the role of glycolysis, gluconeogenesis, and TCA cycle in tumorigenesis with an emphasis on revealing the novel functions of the relevant enzymes and metabolites. These functions include regulation of cell metabolism, gene expression, cell apoptosis and autophagy. We also summarize the effect of glucose metabolism on chromatin modifications and how this relationship leads to cancer development. Understanding the link between cancer cell metabolism and chromatin modifications will help develop more effective cancer treatments.

[Comparative study on curative effect of minimally invasive locking plate for the treatment of intra-articular calcaneal fractures via sinus tarsi approach].

OBJECTIVE: To compare clinical efficacy of minimally invasive locking plate and anatomic locking plate in treating intra-articular calcaneal fractures via sinus tarsi approach. METHODS: A retrospective analysis was conducted of 48 patients with intra-articular calcaneal fractures treated with surgery via sinus tarsi approach from July 2016 to June 2017. According to differernt methods of internal fixation, the patients were divided into minimally invasive locking plate group and anatomic locking plate group. In minimally invasive locking plate group, there were 14 males and 10 females, aged from 27 to 46 years old with an average age of (38.70±5.58) years old, 18 patients were typeⅡand 6 patients were type Ⅲ according to Sanders classification. In anatomic locking plate group, there were 17 males and 7 females, aged from 26 to 46 years old with an average age of (37.10±6.44) years old, 16 patients were typeⅡ and 8 patients were type Ⅲ according to Sanders classification. Operative time, visual analogue scale (VAS), postoperative complications between two groups were compared, and Böhler angle, Gissane angal, calcaneal width and height were recorded and compared between two groups at 1 week after operation and final follow up. The functional effect was assessed according to Maryland foot function score at final follow up. RESULTS: All patients were followed up for (14.10±1.94) months (ranged 12 to 18 months). All patients were obtained bone union from 8 to 16 weeks with an average of (10.60±2.25) weeks. Operation time, VAS score and complication rate in minimally invasive locking plate group were (69.50±7.51) min, (2.80±1.07) and 2 cases respectively, and (77.50±7.15) min, (3.80±1.09) and 8 cases in anatomic locking plate group respectively, there were statistical difference between two groups (P<0.05). However, there were no statistically differences in Maryland foot function score, Böhler angle, Gissane angle, calcaneal width and height at 1 week after opertaion and final follow-up between two groups (P>0.05). CONCLUSION: Compare with anatomic locking plate, minimally invasive locking plate via sinus tarsi approach for Sanders typeⅡ and Ⅲ intra-articular calcaneal fractures could obtain similar reliable fixation and functional recovery with more simple operation, shorter operative time, lighter postoperative pain and less complications.

Investigating the effects of walnut ointment on non-healing burn wounds.

Effective treatments for non-healing burn wounds are an unmet need for 95% of burn sufferers. Approaches currently available to treat non-healing burn wounds are not satisfactory due to undesirable side-effects or expense. The anti-oxidation and antibacterial activities of walnuts are recommended for treating chronic diseases. Walnut ointment has been developed and successfully applied to treat non-healing burn wounds in our hospital for decades. We report herein a detailed retrospective case review examining patients' response to the walnut ointment. The walnut ointment has shortened healing time of non-healing burn wounds and improved clinical outcomes. In order to investigate the mechanism of action, walnut ointment has been applied on wounds of porcine full-thickness burn wound models. Histological and immunohistochemical analysis indicated our walnut ointment supports wound healing through promoting keratinocyte proliferation and differentiation. Taken together, we recommend the walnut ointment offers an effective and economical treatment for patients presenting with non-healing burn wounds.

The SESAME complex regulates cell senescence through the generation of acetyl-CoA.

Acetyl-CoA is a central node in carbon metabolism and plays critical roles in regulatory and biosynthetic processes. The acetyl-CoA synthetase Acs2, which catalyses acetyl-CoA production from acetate, is an integral subunit of the serine-responsive SAM-containing metabolic enzyme (SESAME) complex, but the precise function of Acs2 within the SESAME complex remains unclear. Here, using budding yeast, we show that Acs2 within the SESAME complex is required for the regulation of telomere silencing and cellular senescence. Mechanistically, the SESAME complex interacts with the histone acetyltransferase SAS protein complex to promote histone H4K16 acetylation (H4K16ac) enrichment and the occupancy of bromodomain-containing protein, Bdf1, at subtelomeric regions. This interaction maintains telomere silencing by antagonizing the spreading of Sir2 along the telomeres, which is enhanced by acetate. Consequently, dissociation of Sir2 from telomeres by acetate leads to compromised telomere silencing and accelerated chronological ageing. In human endothelial cells, ACSS2, the ortholog of yeast Acs2, also interacts with H4K16 acetyltransferase hMOF and are required for acetate to increase H4K16ac, reduce telomere silencing and induce cell senescence. Altogether, our results reveal a conserved mechanism to connect cell metabolism with telomere silencing and cellular senescence.

[Effects of Jiangu granule containing serum on the cyclins in rat's osteoblast at G1 phase].

OBJECTIVE: To investigate the effects of Jiangu granule containing serum (JGG-serum) on the cyclins in rat's osteoblast at G1 phase. METHODS: Osteoblasts isolated by enzymatic digestion from SD rats were cultured and intervened with JGG-serum or normal saline (as control) respectively. Cell generation cycle was detected by flow cytometry, and expressions of Cyclin D1, cyclin-dependent kinase 4 (CDK4), oncogene protein (P21) in the osteoblast were detected dynamically using immuno-cytochemical and RT-PCR technique. RESULTS: As compared with the control, the cell generation cycle and cell proliferation were proceeding quicker in the JGG-serum (20%) intervention group; with higher protein and mRNA expressions of Cyclin D1 and CDK4, as well as much lowered expressions of P21 in nuclei of osteoblast detected at all time points (24 h, 48 h and 72 h after treatment, P < 0.05 or P < 0.01). CONCLUSION: JGG-serum can adjust the G1 phase cyclins in osteoblast cultured in vitro, increase the mRNA and protein expressions of Cyclin D1 and CDK4, and inhibit P21 expression, so as to accelerate the proliferation of osteoblast.

[Case-control study on minimally invasive surgery and conventional open plating for displaced midshaft clavicular fracture based on 3D-print].

OBJECTIVE: To compare clinical effect of minimally invasive surgery and conventional open plating for acute displaced midshaft clavicle fracture based on 3D-print. METHODS: From July 2016 and December 2016, 40 patients with acute displaced midshaft clavicle fractures were retrospectively analyzed. The patients were divided into 3D minimally invasive surgery group (group A) and conventional open plating group (group B) according to different surgical incisions and whether to use 3D printing. In group A, including 11 males and 9 female, aged from 19 to 57 years old with an average of(37.2±9.3)years old; type 2A2 were 4 patients, type 2B1 were 9 patients and type 2B2 were 7 patients according to Robinson classification. In group B, including 13 males and 7 female, aged from 17 to 54 years old with an average of(35.1±9.5) years old; type 2A2 were 5 patients, type 2B1 were 8 patients and type 2B2 were 7 patients according to Robinson classification. Operative time, blood loss, length of incision, fracture healing time, complications were observed and compared between two groups, DASH score and Constant score of shoulder joint were evaluated at 12 months after operation. RESULTS: Forty patients were followed up from 12 to 18 months with an average of(15.1±2.0) months. All fractures were healed, healing time in group A ranged from 12 to 18 months with an average of (14.3±1.7) months, in group B ranged from 11 to 18 months with an average of (14.4±1.9) months, while there was no statistical differences between two groups(P>0.05). No differences in blood loss between two groups(P>0.05). Operative time, length of incision in group A was less than that of group B (P<0.05). There were no significant differences in DASH score and Constant score at 12 months between two groups(P>0.05). One patient in group A occurred complication, and 6 patients in group B occurred compilations, and has statistical differences between two groups(P<0.05). CONCLUSIONS: Minimally invasive technique based on 3D-print could resolve some difficulties of minimally invasive surgery effectively and achieve fracture healing and functional recovery similar to traditional open reduction with more beautiful incision, less complication, shorter operation time.

Glycolysis regulates gene expression by promoting the crosstalk between H3K4 trimethylation and H3K14 acetylation in Saccharomyces cerevisiae.

Cells need to coordinate gene expression with their metabolic states to maintain cell homeostasis and growth. However, how cells transduce nutrient availability to appropriate gene expression response via histone modifications remains largely unknown. Here, we report that glucose specifically induces histone H3K4 trimethylation (H3K4me3), an evolutionarily conserved histone covalent modification associated with active gene transcription, and that glycolytic enzymes and metabolites are required for this induction. Although glycolysis supplies S-adenosylmethionine for histone methyltransferase Set1 to catalyze H3K4me3, glucose induces H3K4me3 primarily by inhibiting histone demethylase Jhd2-catalyzed H3K4 demethylation. Glycolysis provides acetyl-CoA to stimulate histone acetyltransferase Gcn5 to acetylate H3K14, which then inhibits the binding of Jhd2 to chromatin to increase H3K4me3. By repressing Jhd2-mediated H3K4 demethylation, glycolytic enzymes regulate gene expression and cell survival during chronological aging. Thus, our results elucidate how cells reprogram their gene expression programs in response to glucose availability via histone modifications.

Comparison of post-operative numbness and patient satisfaction using minimally invasive plate osteosynthesis or open plating for acute displaced clavicular shaft fractures.

BACKGROUND: Anterior chest wall numbness after plate fixation of clavicular shaft fractures is a common complication. This is usually related to damage of the branches of the supraclavicular nerve in conventional open plating. We investigated whether the use of minimally invasive plate osteosynthesis could reduce the incidence of post-operative numbness and improve patients' satisfaction compared to open plating. METHODS: Between August 2012 and October 2015, 73 patients with acute clavicle shaft fracture (Robinson classification 2A2-2B2) were treated with plate fixation at our institution. Thirty-eight patients underwent minimally invasive plate osteosynthesis (MIPO), and the other 35 patients received conventional open reduction and internal fixation (ORIF). The incidence of anterior chest wall numbness, numbness area, and patient satisfaction were evaluated at 2 weeks, 3 months and 1 year after the operation by questionnaires. Shoulder joint function was evaluated using the Constant-Murley score and the Disability of the Arm, Shoulder and Hand (DASH) score, and pain was measured using a Visual Analogue Scale (VAS). RESULTS: The patients in the MIPO group had a lower incidence and smaller area of anterior chest wall numbness than the ORIF group at each follow-up interval. The patients who underwent MIPO reported higher satisfaction with the operation. There was no significant difference in the Constant-Murley score, DASH score and VAS of the 2 groups at 1-year follow-up. CONCLUSION: The MIPO technique for clavicle shaft fractures is an effective way to reduce post-operative numbness and improve patients' satisfaction compare to conventional open plating. Surgeons could consider using this technique as an alternative procedure to prevent iatrogenic supraclavicular nerve damage and subsequent anterior chest wall numbness.

Reciprocal Regulation of Metabolic Reprogramming and Epigenetic Modifications in Cancer.

Cancer cells reprogram their metabolism to meet their demands for survival and proliferation. The metabolic plasticity of tumor cells help them adjust to changes in the availability and utilization of nutrients in the microenvironment. Recent studies revealed that many metabolites and metabolic enzymes have non-metabolic functions contributing to tumorigenesis. One major function is regulating epigenetic modifications to facilitate appropriate responses to environmental cues. Accumulating evidence showed that epigenetic modifications could in turn alter metabolism in tumors. Although a comprehensive understanding of the reciprocal connection between metabolic and epigenetic rewiring in cancer is lacking, some conceptual advances have been made. Understanding the link between metabolism and epigenetic modifications in cancer cells will shed lights on the development of more effective cancer therapies.