[Progress on study of factors influencing the prognosis and complications of surgery for discoid meniscus injury in children].

The discoid meniscus is a common congenital meniscal malformation that is prevalent mainly in Asians and often occurs in the lateral discoid meniscus. Patients with asymptomatic discoid meniscus are usually treated by conservative methods such as observation and injury avoidance, while patients with symptoms and tears need to be treated surgically. Arthroscopic saucerization combined with partial meniscectomy and meniscus repair is the most common surgical approach., and early to mid-term reports are good. The prognostic factors are the patient's age at surgery、follow-up time and type of surgery. Some patients experience complications such as prolonged postoperative knee pain, early osteoarthritis, retears and Osteochondritis dissecans. The incidence of prolonged postoperative knee pain was higher and the incidence of Osteochondritis dissecans was the lowest. Retears of the lateral meniscus is the main reason for reoperation.

Biomechanical Study of Minimally Invasive Nonfusion Surgery for Treatment of Disc Herniation Associated with Adjacent Segment Disease: A Finite Element Analysis.

OBJECTIVE: We explored the biomechanical changes of 2 conventional minimally invasive nonfusion surgical methods for treating disc herniation in adjacent segment disease using 3-dimensional finite element analysis. METHODS: A model comprising L3 to the sacrum was validated and used to establish an L4-L5 fusion model, and an adjacent segment disease (ASD) model was developed by modifying the material properties of the intervertebral discs. The ASD model was used to simulate 2 conventional minimally invasive nonfusion surgical methods, which resulted in the creation of 2 postoperative models (M1 and M2). The range of motion and the equivalent stress for each model were recorded under 6 different working conditions. The data are descriptive and were analyzed comparatively under a normal load. RESULTS: Compared with the ASD group, the range of motion of the adjacent segment in the M1 and M2 groups remained unaffected. However, significant Von-Mises stress changes were found in the annulus fibrosus and nucleus pulposus (NP), especially during extension, ipsilateral bending, and rotation. Stress in the NP also shifted toward the surgical incision in the annulus fibrosus during these movements. The maximum Von-Mises stress in the NP of the cephalic segment increased more than did that of the caudal segment. CONCLUSIONS: Minimal nonfusion surgery for ASD might not affect adjacent segment stability significantly. Nonetheless, it can lead to segmental degeneration deterioration and postoperative recurrence. The cephalic segment is affected more than the caudal segment. Therefore, consideration of disc degeneration and appropriate selection of surgical methods for ASD are crucial.

Sodium houttuyfonate protects against cardiac injury by regulating cardiac energy metabolism in diabetic rats.

Diabetic cardiomyopathy is a diabetic complication with complicated pathophysiological changes and pathogenesis and difficult treatment. Sodium houttuyfonate is the adduct of sodium bisulfite and houttuynin, the main volatile component in Houttuynia cordata Thunb, possesses a variety of activities including multiple interventions on inhibiting ventricular remodeling. The study aims to explore effect of sodium houttuyfonate on diabetic myocardial injury and its underlying mechanisms. The diabetes model was established by intraperitoneal injection of streptozotocin at a dose of 85 mg/kg. By intragastric administration for 26 days, sodium houttuyfonate (50 and 100 mg/kg/d) reversed the abnormal serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, improved the abnormal levels of serum aspartate aminotransferase and brain natriuretic peptide, reduced electrocardiogram P-R and QRS interval extension, accelerated the heart rate, decreased serum malondialdehyde content, up-regulated the myocardial energy metabolism including elevated the contents of ATP, ADP, total adenine nucleotides and phosphocreatine in myocardium, decreased AMP/ATP ratio, elevated myocardial Ca2+-Mg2+-ATPase activity, and down-regulated the mRNA expressions of AMP protein activation kinase α2 (AMPK-α2) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). In a conclusion, these results suggest that sodium houttuyfonate can improve cardiac energy metabolism disorder caused by diabetes by increasing cardiac Ca2+-Mg2+-ATPase activity and regulating AMPK signaling pathway, and then attenuates cardiac injury caused by hyperglycemia. In addition, sodium houttuyfonate also has the effects of anti-oxidation and improving abnormal levels of blood lipid.

[Transcriptome Analysis of Chronic Myelogenous Leukemia Cell Line with Imatinib Resistance].

OBJECTIVE: To investigate the regulation of chronic myelogenous leukemia （CML） imatinib resistant genes, in order to improve the therapeutic effect of CML imatinib resistant patients. METHODS: The human CML cell line K562 and imatinib-resistant K562 cells (K562/G01) were collected, and transcriptome of the cells were achieved by RNA-seq. The sequencing data were analyzed by using standard procedures. RESULTS: Compared with K562 cells, 464 genes were significantly changed in K562/G01 cells, including 163 up-regulated and 301 down-regulated genes. The GO function annotation analysis and KEGG pathway analysis results showed that the differentially expressed genes were mainly involved in biological processes such as oxidative phosphorylation, localization to protein organelle, ribonucleoprotein complex biogenesis and so on. Gene Set Enrichment Analysis (GSEA) plots showed that 5 gene-sets were up-regulated in K562/G01 significantly, including the pathway of TGF-beta, mTOR and CML. CONCLUSION: CML imatinib resistance is associated with oxidative phosphorylation, during which the pathway of TGF-beta and mTOR are significantly up-regulated.

Identification of pimavanserin tartrate as a potent Ca2+-calcineurin-NFAT pathway inhibitor for glioblastoma therapy.

Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor, and 95% of patients die within 2 years after diagnosis. In this study, aiming to overcome chemoresistance to the first-line drug temozolomide (TMZ), we carried out research to discover a novel alternative drug targeting the oncogenic NFAT signaling pathway for GBM therapy. To accelerate the drug's clinical application, we took advantage of a drug repurposing strategy to identify novel NFAT signaling pathway inhibitors. After screening a set of 93 FDA-approved drugs with simple structures, we identified pimavanserin tartrate (PIM), an effective 5-HT2A receptor inverse agonist used for the treatment of Parkinson's disease-associated psychiatric symptoms, as having the most potent inhibitory activity against the NFAT signaling pathway. Further study revealed that PIM suppressed STIM1 puncta formation to inhibit store-operated calcium entry (SOCE) and subsequent NFAT activity. In cellula, PIM significantly suppressed the proliferation, migration, division, and motility of U87 glioblastoma cells, induced G1/S phase arrest and promoted apoptosis. In vivo, the growth of subcutaneous and orthotopic glioblastoma xenografts was markedly suppressed by PIM. Unbiased omics studies revealed the novel molecular mechanism of PIM's antitumor activity, which included suppression of the ATR/CDK2/E2F axis, MYC, and AuroraA/B signaling. Interestingly, the genes upregulated by PIM were largely associated with cholesterol homeostasis, which may contribute to PIM's side effects and should be given more attention. Our study identified store-operated calcium channels as novel targets of PIM and was the first to systematically highlight the therapeutic potential of pimavanserin tartrate for glioblastoma.

SLC38A4 functions as a tumour suppressor in hepatocellular carcinoma through modulating Wnt/ß-catenin/MYC/HMGCS2 axis.

BACKGROUND: Many molecular alterations are shared by embryonic liver development and hepatocellular carcinoma (HCC). Identifying the common molecular events would provide a novel prognostic biomarker and therapeutic target for HCC. METHODS: Expression levels and clinical relevancies of SLC38A4 and HMGCS2 were investigated by qRT-PCR, western blot, TCGA and GEO datasets. The biological roles of SLC38A4 were investigated by functional assays. The downstream signalling pathway of SLC38A4 was investigated by qRT-PCR, western blot, immunofluorescence, luciferase reporter assay, TCGA and GEO datasets. RESULTS: SLC38A4 silencing was identified as an oncofetal molecular event. DNA hypermethylation contributed to the downregulations of Slc38a4/SLC38A4 in the foetal liver and HCC. Low expression of SLC38A4 was associated with poor prognosis of HCC patients. Functional assays demonstrated that SLC38A4 depletion promoted HCC cellular proliferation, stemness and migration, and inhibited HCC cellular apoptosis in vitro, and further repressed HCC tumorigenesis in vivo. HMGCS2 was identified as a critical downstream target of SLC38A4. SLC38A4 increased HMGCS2 expression via upregulating AXIN1 and repressing Wnt/ß-catenin/MYC axis. Functional rescue assays showed that HMGCS2 overexpression reversed the oncogenic roles of SLC38A4 depletion in HCC. CONCLUSIONS: SLC38A4 downregulation was identified as a novel oncofetal event, and SLC38A4 was identified as a novel tumour suppressor in HCC.

Evolution of blood lipids and risk factors of dyslipidemia among people living with human immunodeficiency virus who had received first-line antiretroviral regimens for 3 years in Shenzhen.

BACKGROUND: Lipid abnormalities are prevalent among people living with human immunodeficiency virus (HIV) (PLWH) and contribute to increasing risk of cardiovascular events. This study aims to investigate the incidence of dyslipidemia and its risk factors in PLWH after receiving different first-line free antiretroviral regimens. METHODS: PLWH who sought care at the Third People's Hospital of Shenzhen from January 2014 to December 2018 were included, and the baseline characteristics and clinical data during the follow-up were collected, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The risk factors of dyslipidemia after antiretroviral therapy were analyzed with the generalized estimating equation model. RESULTS: Among the 7623 PLWH included, the mean levels of TC, HDL-C and LDL-C were 4.23 ±â€Š0.85 mmol/L, 1.27 ±â€Š0.29 mmol/L and 2.54 ±â€Š0.65 mmol/L, respectively, and the median TG was 1.17 (IQR: 0.85-1.68) mmol/L. Compared with that in PLWH receiving tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + ritonavir-boosted lopinavir (LPV/r), zidovudine (AZT) + 3TC + efavirenz (EFV), and AZT + 3TC + LPV/r, the incidence of dyslipidemia was lower in PLWH receiving TDF + 3TC + EFV. In multivariate analysis, we found that the risks of elevations of TG, TC, and LDL-C were higher with TDF + 3TC + LPV/r (TG: odds ratio [OR] = 2.82, 95% confidence interval [CI]: 2.55-3.11, P < 0.001; TC: OR = 1.24, 95% CI: 1.14-1.35, P < 0.001; LDL: OR = 1.06, 95% CI: 1.00-1.12, P = 0.041), AZT + 3TC + EFV (TG: OR = 1.41, 95% CI: 1.28-1.55, P < 0.001; TC: OR = 1.43, 95% CI: 1.31-1.56, P < 0.001; LDL: OR = 1.18, 95% CI: 1.12-1.25, P < 0.001), and AZT + 3TC + LPV/r (TG: OR = 3.08, 95% CI: 2.65-3.59, P < 0.001; TC: OR = 2.40, 95% CI: 1.96-2.94, P < 0.001; LDL: OR = 1.52, 95% CI: 1.37-1.69, P < 0.001) than with TDF + 3TC + EFV, while treatment with TDF + 3TC + LPV/r was less likely to restore HDL-C levels compared with TDF + 3TC + EFV (OR = 0.95, 95% CI: 0.92-0.97, P < 0.001). In addition to antiretroviral regimens, antiretroviral therapy duration, older age, overweight, obesity and other traditional factors were also important risk factors for dyslipidemia. CONCLUSION: The incidence of dyslipidemia varies with different antiretroviral regimens, with TDF + 3TC + EFV having lower risk for dyslipidemia than the other first-line free antiretroviral regimens in China.

[Application of percutaneous pie-crusting deep medial collateral ligament release for posterior horn surgery of medial meniscus].

OBJECTIVE: To explore clinical and radiographic effects of percutaneous pie-crusting deep medial collateral ligament release in patients with posterior horn tear of medial meniscus combined with tight medial compartment. METHODS: From January 2012 to December 2016, 35 patients with medial meniscus posterior horn injury were treated with percutaneous pie crusting deep medial collateral ligament release technique, including 21 males and 14 females, aged from 21 to 55 years old with an average of (39.1±6.5) years old. Degree of meniscus extrusion were recorded before and 24 months after operation. The knee valgus stress test was performed to evaluate stability of medial collateral ligament, and compared difference between healthy and affected side. Lysholm and IKDC functional scores were compared before and 24 months after operation. RESULTS: All patients were followed up from 27 to 60 months with an average of (36.7±6.8) months. All patients were underwent operation, the wound healed well without complications. Operative time ranged from 0.5 to 1.2 h with an average of (0.8±0.4) h. Nineteen patients were performed partial meniscectomy, 16 patients were performed repair suture. Convex of meniscus before operation was (1.5±0.7) mm, and (1.7±0.4) mm after operation;had no statistical difference(P>0.05). Lysholm score was improved from 53.4±8.8 before operation to 91.5±4.6 at 24 months after operation;IKDC score was increased from 50.7±9.2 before operation to 90.6±3.9 at 24 months after operation;there was statistically significant (P<0.05). Valgus stress test was performed on 0 ° and 30 ° position of knee flexion in affected side and compared with ipsilateral side, all patients showed negative. CONCLUSION: For patients with medial meniscus tear of posterior horn combined with tight medial compartment, percutaneous pie-crusting deep medial collateralligament release could improve medial compartment space, and Knee valgus instability and meniscus extrusion are not affected.

Ankle distraction arthroplasty for the treatment of severe ankle arthritis: Case report, technical note, and literature review.

RATIONALE: Widely applied in the treatment of severe ankle arthritis (AA), ankle distraction arthroplasty (ADA) can avoid not only the ankle range of motion loss but also ankle fusion. However, the clinical outcomes of ADA for severe AA are poorly understood. This study aims to present our clinical outcomes of severe AA treated by ADA. PATIENT CONCERNS: A 53-year-old man suffered right ankle sprain 10 years ago, endured right ankle pain and limited movement for 6 years. DIAGNOSIS: The patient was diagnosed as severe AA. INTERVENTIONS: He received ankle distraction arthroplasty. No adjuvant procedures were performed. The visual analog scale (VAS), the American Orthopaedic Foot and Ankle Society (AOFAS) score, the short-form (SF)-36 physical component summary (PCS) score and ankle activity score (AAS) were recorded to access the clinical outcomes pre- and postoperatively. Moreover, ankle joint space distance was evaluated on weight-bearing radiographs. OUTCOMES: The patient derived effective pain relief and restored a satisfactory range of movement. There was a 13-month follow-up period after frame removal. The AOFAS score improved from 56 preoperatively to 71 postoperatively. The VAS score decreased from 6 prior to surgery to 1 after surgery. The SF-36 PCS was 47.2 and 71.8 pre- and postoperative, respectively. The AAS scores were improved from 3.4 preoperatively to 7.3 postoperatively. LESSONS: ADA is reliable to achieve pain relief, functional recovery, and serve AA resolution. Besides, it is an alternative to ankle arthrodesis or total ankle arthroplasty in selected patients with severe AA.

[Arthroscopic pullout suture repair of posterior root tear of the medial meniscus via the double tibial tunnels].

OBJECTIVE: To evaluate the surgical technique and clinical effect of arthroscopic pullout suture repair of posterior root tear of the medial meniscus via the double tibial tunnels. METHODS: From May 2014 to May 2017, 22 patients with posterior root tear of medial meniscus were treated by pullout suture repair via the double tibial tunnels, including 8 males and 14 females, aged 34 to 53 years old, with a mean of averaged(45.7±4.7) years old. The patients were followed up for 12 to 24 months, with a mean of (16.4±5.2) months. RESULTS: The Lysholm score of knee joint before operation was 61.8±4.3, IKDC score before operation was 59.9±2.9, Lysholm score at the latest follow-up was 89.1±3.0, and IKDC score was 89.0±2.5. The difference was statistically significant. CONCLUSIONS: Arthroscopic pullout suture repair via the double tibial tunnelsis an effective treatment for symptomatic posterior root tear of medial meniscus, and it can significantly improve the knee functional outcome.

[Ultrasound-guided suprascapular nerve block combined with acupuncture for the treatment of calcified tendinitis of rotator cuff].

OBJECTIVE: To explore the method and effect of ultrasound-guided suprascapular nerve block combined with acupuncture in the treatment of calcified tendinitis of rotator cuff. METHODS: From January 2015 to December 2017, total 30 patients with calcified tendinitis, including 23 cases of supraspinatus tendon, 5 cases of infraspinatus tendon and 2 cases of subscapular tendon, were treated with ultrasound-guided suprascapular nerve block combined with acupuncture. There were 7 males and 23 females, ranging in age from 36 to 71 years old, with an average of 51.6 years old. There were 17 cases on the right and 13 cases on the left. VAS pain score, Constant-murley score, UCLA score and X-ray examination were used to evaluate the clinical results before and after surgery. RESULTS: The mean follow-up was 14.3 months (6 to 30 months). The preoperative VAS score was 3.82±1.13, Constant-Murley score was 36.91±7.95 and UCLA score was 11.35±2.17. The final follow-up scores were 1.32±1.06, 90.61±2.89 and 33.22±1.51, respectively. The final follow-up scores were improved significantly(P<0.05). CONCLUSIONS: Conservative treatment of calcified rotator cuff tendinitis is ineffective. Suprascapular nerve block guided by ultrasound combined with acupuncture has a good therapeutic effect. It is a minimally invasive, economic, safe and effective method, which is worth promoting.

Leukocyte-Poor Platelet-Rich Plasma-Derived Growth Factors Enhance Human Fibroblast Proliferation In Vitro.

BACKGROUND: Leukocyte-poor platelet-rich plasma (LP-PRP) from peripheral blood is currently used as a concentrated source of growth factors to stimulate repair at sites of soft tissue injury. Fibroblasts are primary mediators of wound healing. Thus, we aimed to assess the positive effect of LP-PRP on human fibroblast proliferation in vitro. METHODS: LP-PRP was prepared from 49 donors. The fibroblasts were seeded, and at 24 hours after seeding, 1 × 107/10 µL LP-PRP was added once to each well. The cells were harvested 10 times during study period at our planned points, and we examined cell proliferation using the water-soluble tetrazolium salt-1 assay. We collected the supernatants and measured the amount of growth factors such as platelet-derived growth factor (PDGF)-AB/BB, insulin-like growth factor-1 (IGF-1), transforming growth factor-ß1 (TGF-ß1), and vascular endothelial growth factor (VEGF), which are known to be involved in wound healing processes, by multiplex assay. RESULTS: Human fibroblasts treated with LP-PRP showed a significant increase in proliferation when compared to untreated controls (p < 0.001 at days 4, 6, and 8). Multiplex cytokine assays revealed various secretion patterns. PDGF-AB/BB appeared at early time points and peaked before fibroblast proliferation. IGF-1 and TGF-ß1 secretion gradually increased and peaked on days 4 and 6 post-treatment. The early VEGF concentration was lower than the concentration of other growth factors but increased along with cell proliferation. CONCLUSIONS: Platelets in LP-PRP release growth factors such as PDGF, IGF-1, TGF-ß1 and VEGF, and these growth factors have a promoting effect for human fibroblast proliferation, one of the important mediators of wound healing. These results suggest that growth factors derived from LP-PRP enhance the proliferation of human fibroblast.

Enhanced Tendon-to-Bone Healing of Chronic Rotator Cuff Tears by Bone Marrow Aspirate Concentrate in a Rabbit Model.

BACKGROUND: To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. METHODS: In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. RESULTS: The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. CONCLUSIONS: Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications.

Functional and Radiographic Outcomes After Arthroscopic Transosseous Suture Repair of Medium Sized Rotator Cuff Tears.

PURPOSE: To evaluate the functional and anatomical outcomes after arthroscopic transosseous suture (TOS) repair of 2 to 4 cm sized rotator cuff tears and to identify preoperative factors influencing repair failure. METHODS: From May 2013 to August 2014, patients with symptomatic 2 to 4 cm full-thickness tears underwent arthroscopic TOS repair, and those who could be followed up for a minimum of 2 years were included in this retrospective study. Functional and anatomical outcomes were analyzed up to 2 years postoperatively. Factors affecting cuff repair failure were evaluated, using both univariate and multivariate analyses. RESULTS: Twenty-seven patients were included. On preoperative magnetic resonance imaging data, the mean anteroposterior dimension tear size was 27.0 ± 3.3 mm and mean retraction was 30.7 ± 3.1 mm. Anatomic failure (Sugaya III, IV, and V) rate was 33% with arthroscopic TOS repair; however, significant improvements were found regardless of cuff healing. Mean American Shoulder and Elbow Surgeons score (range, 0-100) improved from 48.8 ± 16.6 preoperatively to 80.1 ± 11.1 postoperatively (P < .001), mean Constant score (range, 0-100) improved from 54.5 ± 11.8 to 73.7 ± 8.5 (P < .001), and mean pain visual analog scale score (range, 0-10) improved from 3.9 ± 1.7 to 2.0 ± 1.1 (P < .001). These changes reached each minimal clinically important difference previously reported. Greater tear size in anteroposterior dimension (P = .034), decreased acromiohumeral distance (P = .022), and higher fatty infiltration of supraspinatus (P = .011) were independent preoperative factors associated with repair failure. Twelve patients (44%) experienced intraoperative bone laceration. CONCLUSIONS: Arthroscopic TOS repair was a reliable technique for patients with 2 to 4 cm size rotator cuff tear. Preoperative factors associated with cuff repair failure were greater tear size in anteroposterior dimension, decreased acromiohumeral distance, and higher fatty infiltration of supraspinatus. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

CTGF secreted by mesenchymal-like hepatocellular carcinoma cells plays a role in the polarization of macrophages in hepatocellular carcinoma progression.

M2 macrophages play critical roles in the progression of hepatocellular carcinoma (HCC), and they are associated with poor outcomes. TGF-ß-induced epithelial-mesenchymal transition (EMT) has been shown to be critically important to cancer cell dissemination in HCC. However, the relationship between stromal-like HCC cells and M2 macrophages formation is not clear. Here, we interrogated the molecular link between mesenchymal-like HCC cells and the formation of M2 macrophages. We demonstrated that mesenchymal-like HCC cells secrete connective tissue growth factor (CTGF) to polarized macrophages. Reciprocally, Chemokine ligand 18 (CCL18) from M2 macrophages promotes HCC progression. Furthermore, CTGF and CCL18 were increased significantly in HCC compared to adjacent normal liver tissues. In summary, our study discovered a positive feedback loop between CTGF and CCL18 in HCC metastasis. Targeting CTGF or CCL18 might provide beneficial effects for the clinical treatment of HCC.

The MBNL3 splicing factor promotes hepatocellular carcinoma by increasing PXN expression through the alternative splicing of lncRNA-PXN-AS1.

Understanding the roles of splicing factors and splicing events during tumorigenesis would open new avenues for targeted therapies. Here we identify an oncofetal splicing factor, MBNL3, which promotes tumorigenesis and indicates poor prognosis of hepatocellular carcinoma patients. MBNL3 knockdown almost completely abolishes hepatocellular carcinoma tumorigenesis. Transcriptomic analysis revealed that MBNL3 induces lncRNA-PXN-AS1 exon 4 inclusion. The transcript lacking exon 4 binds to coding sequences of PXN mRNA, causes dissociation of translation elongation factors from PXN mRNA, and thereby inhibits PXN mRNA translation. In contrast, the transcript containing exon 4 preferentially binds to the 3' untranslated region of PXN mRNA, protects PXN mRNA from microRNA-24-AGO2 complex-induced degradation, and thereby increases PXN expression. Through inducing exon 4 inclusion, MBNL3 upregulates PXN, which mediates the pro-tumorigenic roles of MBNL3. Collectively, these data demonstrate detailed mechanistic links between an oncofetal splicing factor, a splicing event and tumorigenesis, and establish splicing factors and splicing events as potential therapeutic targets.

An alternative POLDIP3 transcript promotes hepatocellular carcinoma progression.

Alternative splicing plays critical roles in many pathophysiological processes and splicing dysregulation is a hallmark of cancer. The different isoforms may have significantly different effects on cancers. POLDIP3 is a target of ribosomal protein S6 kinase 1, and regulates DNA replication and mRNA translation. In this study, we measured the expression of an alternative POLDIP3 transcript (POLDIP3-ß), which lacks exon 3 and 29 amine acids, in clinical hepatocellular carcinoma (HCC) tissues. The roles of POLDIP3-ß on HCC cell proliferation, apoptosis, and migration were assessed by Glo cell viability assays, Ethynyl deoxyuridine incorporation assays, colony formation assays, TUNEL assays, Annexin V-propidium iodide staining and flow cytometry, transwell assays, wound healing assays, and in vivo xenograft growth. Our results showed that POLDIP3-ß was significantly upregulated in HCC tissues compared with paired adjacent noncancerous hepatic tissues. In vitro and in vivo functional experiments results demonstrated that overexpression of POLDIP3-ß drastically increased HCC cell proliferation, inhibited HCC cell apoptosis, enhanced HCC cell migration, and promoted xenograft growth. While the effects of normal POLDIP3, which contains exon 3, were much weaker. In conclusion, our study demonstrated that an alternative transcript of POLDIP3 is upregulated and functions as a critical oncogene in HCC. Selectively targeting this isoform of POLDIP3 would be a promising therapeutic strategy for HCC.

Extraction of Fenugreek (Trigonella foenum-graceum L.) Seed Oil Using Subcritical Butane: Characterization and Process Optimization.

In this study, the subcritical butane extraction process of fenugreek seed oil was optimized using response surface methodology with a Box-Behnken design. The optimum conditions for extracted oil from fenugreek seed was as follows: extraction temperature of 43.24 °C , extraction time of 32.80 min, and particle size of 0.26 mm. No significant differences were found between the experimental and predicted values. The physical and chemical properties of the oil showed that the oil could be used as edible oil. Fatty acid composition of oils obtained by subcritical butane under the optimum conditions and by accelerated solvent extraction showed negligible difference. The oils were rich in linoleic acid (42.71%-42.80%), linolenic acid (26.03%-26.15%), and oleic acid (14.24%-14.40%). The results revealed that the proposed method was feasible, and this essay shows the way to exploit fenugreek seeds by subcritical butane extraction under the scope of edible oils.

Effects of a Single-Dose Interscalene Block on Pain and Stress Biomarkers in Patients Undergoing Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

PURPOSE: To compare the effects of a single-dose interscalene block and general anesthesia (SISB/GA) with the effects of GA only in the early postoperative period after arthroscopic rotator cuff repair by evaluating subjective pain visual analog scale scores and objective pain-related stress biomarkers. METHODS: Patients refractory to conservative treatment of the affected shoulder were enrolled in this prospective, randomized endpoint study. Patients diagnosed with a rotator cuff tear (1-4 cm) based on magnetic resonance imaging were included. Exclusion criteria were small (<1 cm) and massive (>4 cm) rotator cuff tears. Thirty-one patients each were randomized into the SISB/GA and GA treatment groups. Preoperative pain scores were measured at 6:00 AM on the day of surgery, measured again at 1 and 6 hours postoperatively, and then every 6 hours until 3 days postoperatively. Blood sampling was performed to evaluate the stress biomarkers insulin, dehydroepiandrosterone sulfate, and fibrinogen preoperatively at 6:00 AM on the day of surgery and postoperatively at 18, 42, and 66 hours (6:00 AM on postoperative days 1-3). RESULTS: Pain scores were significantly decreased in the SISB/GA group (2.50 ± 0.94) versus the GA group (3.82 ± 1.31) on the day of surgery (P < .001), and especially at 6 hours postoperatively (SISB/GA: 2.42 ± 1.43; GA: 4.23 ± 2.17; P < .001). Insulin was decreased significantly in the SISB/GA group (10.55 ± 7.92 µU/mL) versus the GA group (20.39 ± 25.60 µU/mL) at 42 hours postoperatively (P = .048). There was no significant change in dehydroepiandrosterone sulfate or fibrinogen over time (P > .05). CONCLUSIONS: After arthroscopic rotator cuff repair, an SISB effectively relieved pain on the day of surgery without any complications. In addition, insulin levels were significantly reduced at 42 hours postoperatively. LEVEL OF EVIDENCE: Level I, prospective randomized controlled trial.

Use of a real-size 3D-printed model as a preoperative and intraoperative tool for minimally invasive plating of comminuted midshaft clavicle fractures.

BACKGROUND: Open reduction and plate fixation is the standard operative treatment for displaced midshaft clavicle fracture. However, sometimes it is difficult to achieve anatomic reduction by open reduction technique in cases with comminution. METHODS: We describe a novel technique using a real-size three dimensionally (3D)-printed clavicle model as a preoperative and intraoperative tool for minimally invasive plating of displaced comminuted midshaft clavicle fractures. A computed tomography (CT) scan is taken of both clavicles in patients with a unilateral displaced comminuted midshaft clavicle fracture. Both clavicles are 3D printed into a real-size clavicle model. Using the mirror imaging technique, the uninjured side clavicle is 3D printed into the opposite side model to produce a suitable replica of the fractured side clavicle pre-injury. RESULTS: The 3D-printed fractured clavicle model allows the surgeon to observe and manipulate accurate anatomical replicas of the fractured bone to assist in fracture reduction prior to surgery. The 3D-printed uninjured clavicle model can be utilized as a template to select the anatomically precontoured locking plate which best fits the model. The plate can be inserted through a small incision and fixed with locking screws without exposing the fracture site. Seven comminuted clavicle fractures treated with this technique achieved good bone union. CONCLUSIONS: This technique can be used for a unilateral displaced comminuted midshaft clavicle fracture when it is difficult to achieve anatomic reduction by open reduction technique. Level of evidence V.