Hepatocyte-specific knockout of HIF-2α cannot alleviate carbon tetrachloride-induced liver fibrosis in mice.

Background: The effects of hypoxia inducible factor-2α (HIF-2α) deficiency on liver fibrosis have not been demonstrated in a fibrosis model induced by carbon tetrachloride (CCl4). We aimed to examine whether hepatocyte-specific HIF-2α deletion could ameliorate CCl4-induced liver fibrosis in mice. Methods: Hepatocyte-specific HIF-2α knockout mice were created using an albumin promoter-driven Cre recombinase. HIF-2α knockout (KO) mice and floxed control wild-type (WT) mice were fed a normal diet (ND) and received either twice weekly intraperitoneal injections of CCl4 solution (CCl4 dissolved in olive oil) or the corresponding amount of olive oil for 8 weeks. The indicators of liver function, glucose and lipid metabolism, and liver histology were compared among the different groups. Results: Hepatocyte-specific HIF-2α knockout had no effect on the growth, liver function, glucose or lipid metabolism in mice. CCl4-treated KO and WT mice had a similar pattern of injury and inflammatory cell infiltration in the liver. Quantification of Masson staining, α-smooth muscle actin (α-SMA) immunohistochemistry, and the hydroxyproline (HYP) content revealed similar liver fibrosis levels between KO and WT mice injected intraperitoneally with CCl4. Immunohistochemistry analysis suggested that HIF-2α was mainly expressed in the portal area and hepatic sinusoids but not in hepatocytes. Bioinformatics analyses further indicated that HIF-2α expression was neither liver specific nor hepatocyte specific, and the effect of HIF-2α in hepatocytes on liver fibrosis may not be as important as that in liver sinuses. Conclusions: Hepatocyte HIF-2α expression may not be a key factor in the initiation of liver fibrogenesis, and hepatocyte-specific deletion of HIF-2α may not be the ideal therapeutic strategy for liver fibrosis.

Optimisation of Selective Laser Melted Ti6Al4V Functionally Graded Lattice Structures Accounting for Structural Safety.

This paper presents a new framework for lightweight optimisation of functionally graded lattice structures (FGLSs) with a particular focus on enhancing and guaranteeing structural safety through three main contributions. Firstly, a design strategy of adding fillets to the joints of body-centred cubic (BCC) type lattice cells was proposed to improve the effective yield stress of the lattices. Secondly, effective properties of lattice metamaterials were experimentally characterised by conducting quasi-static uniaxial compression tests on selective laser melted specimens of both Ti6Al4V BCC and filleted BCC (BCC-F) lattices with different relative densities. Thirdly, a yield stress constraint for optimising FGLSs was developed based on surrogate models quantifying the relationships between the relative density and the effective properties of BCC and BCC-F lattices developed using experimental results assisted by numerical homogenisation. This framework was tested with two case studies. Results showed that structural safety with respect to avoiding yield failure of the optimised FGLSs can be ensured and the introduction of fillets can effectively improve the strength-to-weight ratio of the optimised FGLSs composed of BCC type lattices. The BCC-F FGLS achieved 14.5% improvement in weight reduction compared with BCC FGLS for the Messerschmitt-Bölkow-Blohm beam optimisation case study.

Evaluation of [18F]F-TZ3108 for PET Imaging of Metabolic-Associated Fatty Liver Disease.

PURPOSE: Sigma-1 receptor (Sig-1R), a chaperone that resides at the mitochondrion-associated endoplasmic reticulum (ER) membrane, is an ER stress biomarker. It is thought that ER stress plays a critical role in the progression of metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate a positron emission tomography (PET) tracer [18F]F-TZ3108 targeting Sig-1R for MAFLD. PROCEDURES: The mouse model of MAFLD was established by feeding high-fat diet (HFD) for 12 weeks. Dynamic (0-60 min) PET/CT scans were performed after intravenous injection of 2-deoxy-2[18F]fluoro-D-glucose ([18F]-FDG) and [18F]F-TZ3108. Tracer kinetic modeling was performed for quantification of the PET/CT imaging of the liver. Post-PET biodistribution, the liver tissue western blotting (WB), and immunofluorescence (IF) were performed to compare the expression of Sig-1R levels in the organs harvested from both MAFLD and age-matched control mice. RESULTS: The micro PET/CT imaging revealed a significantly decreased uptake of [18F]F-TZ3108 in the livers of the MAFLD group compared to the healthy controls, while the uptake of [18F]-FDG in the livers was not significantly different between the two groups. Based on the tracer kinetic modeling, the binding disassociate rate (k4) for [18F]F-TZ3108 was significantly increased in MAFLD group compared to healthy controls. The volume distribution (VT), and the non-displacement binding potential (BPND) revealed significantly decrease in MAFLD compared to healthy controls respectively. The post-PET biodistribution (%ID/g) of [18F]F-TZ3108 in the livers of MAFLD mice was significantly reduced nearly twofold than that in the livers of control mice. WB and IF experiments further confirmed the reduction of Sig-1R expression in the MAFLD group. CONCLUSIONS: The expression of Sig-1R in the liver, measured by the PET tracer, [18F]F-TZ3108, was significantly decreased in mouse model of MAFLD. The [18F]F-TZ3108 PET/CT imaging may provide a novel means of visualization for ER stress in MAFLD or other diseases in vivo.

Development and validation of a novel 3-gene prognostic model for pancreatic adenocarcinoma based on ferroptosis-related genes.

BACKGROUND: Molecular markers play an important role in predicting clinical outcomes in pancreatic adenocarcinoma (PAAD) patients. Analysis of the ferroptosis-related genes may provide novel potential targets for the prognosis and treatment of PAAD. METHODS: RNA-sequence and clinical data of PAAD was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The PAAD samples were clustered by a non-negative matrix factorization (NMF) algorithm. The differentially expressed genes (DEGs) between different subtypes were used by "limma_3.42.2" package. The R software package clusterProfiler was used for functional enrichment analysis. Then, a multivariate Cox proportional and LASSO regression were used to develop a ferroptosis-related gene signature for pancreatic adenocarcinoma. A nomogram and corrected curves were constructed. Finally, the expression and function of these signature genes were explored by qRT-PCR, immunohistochemistry (IHC) and proliferation, migration and invasion assays. RESULTS: The 173 samples were divided into 3 categories (C1, C2, and C3) and a 3-gene signature model (ALOX5, ALOX12, and CISD1) was constructed. The prognostic model showed good independent prognostic ability in PAAD. In the GSE62452 external validation set, the molecular model also showed good risk prediction. KM-curve analysis showed that there were significant differences between the high and low-risk groups, samples with a high-risk score had a worse prognosis. The predictive efficiency of the 3-gene signature-based nomogram was significantly better than that of traditional clinical features. For comparison with other models, that our model, with a reasonable number of genes, yields a more effective result. The results obtained with qPCR and IHC assays showed that ALOX5 was highly expressed, whether ALOX12 and CISD1 were expressed at low levels in tissue samples. Finally, function assays results suggested that ALOX5 may be an oncogene and ALOX12 and CISD1 may be tumor suppressor genes. CONCLUSIONS: We present a novel prognostic molecular model for PAAD based on ferroptosis-related genes, which serves as a potentially effective tool for prognostic differentiation in pancreatic cancer patients.

Position of Coracoid Button Predicts Loss of Reduction in Acromioclavicular Joint Dislocation Patients Treated With the Suture-Button.

BACKGROUND: Loss of reduction is the most common complication after acromioclavicular (AC) joint dislocation treated with the suture-button. Some predictors of it are known, but finding new predictors is an ongoing process. In this study, we evaluate the importance of the position of the coracoid button. MATERIALS AND METHODS: Between April 2010 and February 2017, 186 patients with AC joint dislocation were identified. All patients were managed with the same surgical technique and postoperative protocol. The position of the coracoid button was determined immediately after surgery by anterior-posterior views of the operated shoulder and was classified as medial (Group A, 42 cases), central (Group B, 85 cases) and lateral (Group C, 59 cases) positions. The main outcome measurement was loss of reduction. The main analysis was the association between the coracoid button position and loss of reduction. RESULTS: No significant difference was found in the baseline characteristics among 3 groups. During follow-up, there were 15 cases (35.7%) developing loss of reduction in Group A, 5 cases (5.9%) in Group B and 26 cases (44.1%) in Group C. The rate of loss of reduction in Groups A and C were higher than that in Group B (p < .05). Moreover, there was no significant difference in the rate of reduction loss between lateral and medial positions of the coracoid buttons (p > .05). CONCLUSION: Our results indicated that both lateral and medial positions of the coracoid buttons could predict loss of reduction in AC joint dislocation patients treated with the suture-button.

Egr1 Knockdown Combined with an ACE Inhibitor Ameliorates Diabetic Kidney Disease in Mice: Blockade of Compensatory Renin Increase.

BACKGROUND: Increased compensatory intrarenal renin diminishes the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in the treatment of diabetic kidney disease (DKD). Early growth response-1 (Egr1) is a crucial transcriptional factor in the progress of DKD and is a potential transcription factor of intrarenal renin according to bioinformatic analysis. However, whether inhibition of Egr1 can suppress compensatory renin increase in DKD is unclear. METHODS: We generated a high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mouse model. The mice were treated with either enalapril (an ACEI) or enalapril combined with a shEgr1 plasmid, and age-matched DKD mice were used as controls. Urine microalbumin, urinary renin and kidney TGF-ß1 were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) and Masson staining were used to determine renal pathological changes. Egr1, renin, TNF-α, and FN were measured by real-time quantitative PCR, Western blot, and immunohistochemistry. The SV40-MES13 murine mesangial cell line was transfected with pENTER-Egr1 plasmid and siEgr1. RESULTS: Our results showed that enalapril increased the renin level of urinary and renal in DKD mice, while shEgr1 attenuated this effect. In addition, enalapril treatment reduced the levels of urinary microalbumin, TNF-α, TGF-ß1 and FN, and alleviated the pathological changes, while shEgr1 strengthened these effects. The protein and mRNA expression of renin in the SV40 MES13 cells was upregulated and downregulated following overexpression and silence of Egr1, respectively. CONCLUSION: Silence of Egr1 could alleviate renal injury in DKD by downregulating intrarenal renin.

Detection of dorsal screw penetration during volar plating of the distal radius fractures: A comparison of different fluoroscopic views and screw sizes.

OBJECTIVE: The objective of this study was to compare different screw lengths combined with different fluoroscopic views to detect intraoperative dorsal screw penetration in distal radius fractures treated with volar locked plating. MATERIAL AND METHODS: From April 2014 to October 2018, one hundred and eighty patients were included. We divided the patients into four groups. Intraoperative AP and lateral views were taken and sizes of the screws were chosen based on actual measurement (Group A, 45 patients). AP, lateral and tangential views were taken and sizes of the screws were also chosen based on actual measurement (Group B, 45 patients). Intraoperative AP and lateral views were taken and the selected screws were 2mm shorter than actual measurement (Group C, 45 patients). AP, lateral and tangential views were taken and the selected screws were 2mm shorter than actual measurement (Group D, 45 patients). Prominent screws were changed intraoperatively according to each view. A computed tomography (CT) was taken postoperatively to identify residual prominent screws. RESULTS: The number of dorsally prominent screws exceeding 1mm was 6 of 301 in Group A (2.0%), 15 of 290 (5.2%) in Group B, 2 of 289 in Group C (0.7%), and 2 of 282 (0.7%) in Group D. All these prominent screws (25 screws) were exchanged for shorter screws during surgery. Group A and Group B had significant difference in detecting intraoperative dorsal screw penetration (p<0.05). Group C and Group D had no significant difference in detecting intraoperative dorsal screw penetration (p>0.05). Postoperative CT identified 12 additional prominent screws with≥1mm dorsal penetration in Group A, 2 screws in Group B, 1 screw in Group C and 0 screw in Group B respectively. Significant difference was found between Group A and Group B of CT results (p<0.05) while no statistical difference was found between Group C and Group D of CT results (p>0.05). DISCUSSIONS: Tangential view helped identify screw penetration. If tangential view was not available intraoperatively, screw penetration could also be avoided by downsizing the distal locking screw by 2mm shorter than actual measurement.

Projection of the Most Anterior Line of the Spinal Canal on Lateral Radiograph: An Anatomic Study for Percutaneous Kyphoplasty and Percutaneous Vertebroplasty.

ABSTRACTPurpose: To measure the projection of the most anterior line of the spinal canal on lateral radiographs of the vertebra (C3-L5) and evaluate the efficacy of the safety line (SL) in preventing intraspinal cement leakage in percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP). Materials and Methods: Fifteen adult dry-bone spine specimens were analyzed. The projection of the SL was viewed on lateral radiographs. The distance between the SL and the posterior vertebral body line (PVBL) was measured. Two groups of patients were treated by PKP, and cement injection was stopped either before the PBVL (group 1) or before the SL (group 2) under lateral fluoroscopy. The rate of cement leakage was compared between the two groups. Results: The largest distance between the SL and PVBL was at L1 (5.22 ± 0.62 mm). From L1 to L5, the distance decreased progressively to 1.05 ± 0.64 mm. Similar variation was also observed from L1 to T1 (0.19 ± 0.18 mm). The postoperative computed tomography scan was more sensitive and accurate in detecting intraspinal leakage than radiography in group 1 (p = 0.000); however, there was no significant difference in sensitivity or accuracy between methods in group 2 (p = 0.063). The rate of intraspinal cement leakage was significantly higher in group 1 than group 2 (p = 0.000). Conclusions: The operator should frequently check to ensure that cement injection has stopped upon reaching the SL. Surgeons may benefit from this quantitative anatomical study of PKP and PVP.

Recognizable type of pituitary, heart, kidney and skeletal dysplasia mostly caused by SEMA3A mutation: A case report.

BACKGROUND: The SEMA3A gene, which is located at 7q21.11, is involved in hypothalamic neuron migration, heart development, kidney development, and skeleton metabolism. Mutation of the SEMA3A gene is associated with Kallmann syndrome 16 with or without a normal sense of smell. In addition, two case reports showed that mutation of the SEMA3A gene could cause short stature, low gonadotropin, hypogonadism, thoracic deformity, a high scapula, rib and lower limb deformity, facial deformity (long face, epicanthic folds, backwards ears), and arterial malformation. CASE SUMMARY: We reported the case of a 26-year-old Chinese man who was admitted because of short stature. Physical examination showed that he had many abnormal symptoms, including a short neck, facial moles, knee valgus, transverse palm, continuous grade 5/6 murmurs in the pulmonary auscultation area, no whiskers, or pubic hair, no Adam's apple, short penis and cryptorchidism. Radiological examination showed pituitary, gonad, heart, kidney and skeletal dysplasia. The laboratory tests revealed low growth hormone, luteinizing hormone, follicle-stimulating hormone, testosterone and estrogen. Clinical whole-exome detection showed that our patient, unlike previously reported patients, has a new SEMA3A gene mutation (c.950A>G). Now, his height has increased by 3 cm. In addition, he has a good appetite and reduced subcutaneous fat over 3 mo of recombinant human growth hormone injections therapy. Unfortunately, he refuses further treatment about gonad. CONCLUSION: Patients who come to a hospital because of their short stature must undergo gene detection if they have other simultaneous abnormal phenotypes.

Inhibition of EZH2 ameliorates cartilage endplate degeneration and attenuates the progression of intervertebral disc degeneration via demethylation of Sox-9.

BACKGROUND: Cartilaginous endplate (CEP) degeneration is considered as one of the major causes of intervertebral disc degeneration (IVDD) which causes low back pain. Recent studies have proved that epigenetic alteration is involved in a variety of diseases. This work explored the role of histone methyltransferase enhancer of zeste homologue 2 (EZH2) in CEP degeneration, as well as its underlying epigenetic mechanisms, and confirmed the effect of EZH2 knockdown on delaying IVDD development. METHODS: Western blotting, immunofluorescence staining, and ChIP assay were applied to demonstrate the molecular mechanism of EZH2 in CEP tissue. The therapeutic potential of EZH2 was investigated using puncture-induced rat models. FINDINGS: The EZH2 expression was upregulated in human and rat CEP tissue. It was also found that the overexpression of EZH2 suppressed the expression of Collagen II, aggrecan and Sox-9, and promoted the expression of ADTAMTS5 and MMP13 in rat endplate chondrocytes (EPCs), which could be reversed by EZH2 silencing. The correlation between EZH2 and Sox-9 was further explored, while overexpression of Sox-9 could reverse the effect of EZH2 in rat EPCs. Moreover, inhibition of EZH2 upregulated the level of Sox-9 by demethylating H3K27me3 at Sox-9 promoter sites, revealing the regulatory mechanism of EZH2 on Sox-9. Meanwhile, puncture-induced rat models showed that EZH2 knockdown exerted a protective effect on CEP and disc degeneration. INTERPRETATION: This study reveals that EZH2 inhibition is a promising strategy for mitigating the symptoms and progression of IVDD. FUNDING: This study was funded by the Natural Science Foundation of Zhejiang Province (Y16H060034). Authors declare that the funders had no involvement in the study design, data analysis and interpretation of the results.

Factors associated with the decision for operative versus conservative treatment of displaced distal radius fractures in the elderly.

BACKGROUND: The treatment of senile distal radius fractures had not been clearly defined. The objective of this study was to identify the factors associated with the decision for operative treatment of displaced distal radius fractures in patients aged over 55 years. METHODS: Data of 318 patients with displaced distal radius fractures were collected on patient-, fracture- and surgeon-related characteristics that were plausibly related to the decision for operation. Mean comparisons or chi-squared test were used for univariate analysis of the above-mentioned factors, and then multiple logistic regression was used to identify factors associated with the decision for operation. RESULTS: Univariate analysis showed that age, osteoporosis, Charlson score, associated orthopaedic injuries requiring surgery, Orthopaedic Trauma Association (AO) and Fernandez classification, radial height, volar tilt, volar/dorsal comminution, ulnar variance, intra-articular displacement/step-off, associated distal radioulnar joint instability or radiocarpal joint dislocation and subspecialty of treating surgeons had statistically significant association with operative intervention. In the multivariate analysis, the predictors of operative intervention were younger patient age (P = 0.028), associated orthopaedic injuries requiring surgery (P = 0.020), higher AO classification (P = 0.037), higher Fernandez classification (P = 0.041), radial shortening >5 mm (P = 0.020), volar tilt > -10° (P = 0.020), volar/dorsal comminution (P = 0.020), ulnar variance >5 mm (P = 0.023), intra-articular displacement/step-off >2 mm (P = 0.004), associated distal radioulnar joint instability or radiocarpal joint dislocation (P = 0.047) and treatment by an upper extremity specialist (P = 0.038). CONCLUSION: The decision for surgery was predominantly influenced by the characteristics and severity of the fracture. Patients' age and treatment by an upper extremity specialist were also significant factors associated with a higher likelihood of operative intervention.

Minimally invasive procedure of acute acromioclavicular joint dislocation: one suture-button device versus two suture-button devices.

The purpose of this study was to assess the clinical results of patients treated with either one suture-button device or two suture-button devices for acute acromioclavicular (AC) joint dislocations. Eighty patients were randomized to operative stabilization either by one suture-button device (OSB, 40) or by two suture-button devices (TSB, 40). Postoperative complications, the Constant, VAS and SST scores, patient subjective satisfaction result were reviewed. The total incidence of complications was similar in both groups (16/40 vs. 17/40, P =0 .820). There were no significant differences in the length of hospitalization, the Constant, VAS and SST scores, and the ability to return to previous work between the two groups. However, the patients of TSB group had longer incision length, more blood loss, more operative and radiation time and more hospitalization costs (P < 0.01). The radiological evaluation showed no significant difference in the CC distance between the two groups (P = 0.557). Our results indicated that one suture-button device could achieve the same good radiological and clinical results as two suture-button devices did.

Analysis of risk factors for loss of reduction after acromioclavicular joint dislocation treated with the suture-button.

BACKGROUND: The most commonly reported complication after acromioclavicular (AC) joint dislocation treated with the Suture-button is loss of reduction. Loss of reduction is a major factor influencing the patient's joint function and subjective satisfaction. The objective of this study is to analyze the risk factors causing loss of reduction after AC joint dislocation treated with the Suture-button. METHODS: One hundred and thirty patients with AC joint dislocation who were surgically treated the Suture-button in our hospital from February 2009 to February 2015, were recorded their age, sex, BMI, time from injury to surgery, Rockwood's classification, with or without osteoporosis, double or triple button technique, position of the clavicle tunnel, tunnel diameter, coracoid button position, alignment of the button, acromioclavicular ligament repair or not, different methods of postoperative limb immobilization, and so on. Mean comparisons or chi-square test was used for univariate analysis of the above factors, and then multivariate logistic regression analysis was performed to predict risk factors. RESULTS: Reduction was lost in 23.1% of the patients. Univariate analysis showed that button alignment, double or triple button technique, coracoid button position, position of the clavicle tunnel, acromioclavicular ligament repair or not and osteoporosis had statistically significant association with loss of reduction for AC joint (P = 0.031, 0.034, 0.000, 0.042, 0.047 and 0.000 respectively). Multivariate logistic regression analysis demonstrated that osteoporosis (P = 0.003), position of the clavicle tunnel (P = 0.032) and coracoid button position (P < 0.001) were the risk factors that significantly associated with the loss of reduction after AC joint dislocation treated with the Suture-button. CONCLUSIONS: Clavicle tunnel location using relative ratio method, accurate placement of button plate under coracoid process (inside or outside deviation <20°), various reinforcement operations for patients with osteoporosis are important factors in preventing loss of reduction.

Acute acromioclavicular joint dislocation treated with tightrope : Mini-open versus percutaneous stabilization.

The purpose of this study was to compare prospecti- vely the radiographic and clinical results of patients treated with tightrope through either mini-open or percutaneous stabilization for acute AC joint injuries. Eighty patients were included in this study and were randomly divided into two groups. Group A included 40 injuries treated with mini-open repair. Group B consisted of 40 injuries treated with percutaneous stabilization. Demographic and clinical data were comparable between the two groups before surgery (P>0.05). Peri-operative data, complications and clinical outcomes between the two groups were compared. The average follow-up time of Group A, was 26.5±4.3 months and Group B, was 25.2±5.6 months (P>0.05). The mean operative time was 63.2±9.6 minutes and 45.6±7.1 minutes, and the mean incision length was 6.0±1.5 cm and 4.0±0.8 cm, respectively. The operative time and incision length were significantly longer in Group A (both P<0.05). However, the radiological assessment revealed no significant difference in the coracoclavicular (CC) distance between the two groups (P>0.05). The rate of loss of reduction in the Group A was similar to that in Group B (6/40 vs. 5/40, P>0.05). Both methods were efficient methods for acute AC joint dislocation. However, percutaneous fixation had the advantages of a shorter surgical time and smaller incision length.

Early Growth Response 1 (Egr1) Is a Transcriptional Activator of NOX4 in Oxidative Stress of Diabetic Kidney Disease.

BACKGROUND: NADPH oxidase 4 (NOX4) plays a major role in renal oxidative stress of diabetic kidney disease (DKD). NOX4 was significantly increased in Egr1-expressing fibroblasts, but the relationship between Egr1 and NOX4 in DKD is unclear. METHODS: For the evaluation of the potential relationship between Egr1 and NOX4, both were detected in HFD/STZ-induced mice and HK-2 cells treated with TGF-ß1. Then, changes in NOX4 expression were detected in HK-2 cells and mice with overexpression and knockdown of Egr1. The direct relationship between Egr1 and NOX4 was explored via chromatin immunoprecipitation (ChIP). RESULTS: We found increased levels of Egr1, NOX4, and α-SMA in the kidney cortices of diabetic mice and in TGF-ß1-treated HK-2 cells. Overexpression or silencing of Egr1 in HK-2 cells could upregulate or downregulate NOX4 and α-SMA. ChIP assays revealed that TGF-ß1 induced Egr1 to bind to the NOX4 promoter. Finally, Egr1 overexpression or knockdown in diabetic mice could upregulate or downregulate the expression of NOX4 and ROS, and α-SMA was also changed. CONCLUSION: Our study provides strong evidence that Egr1 is a transcriptional activator of NOX4 in oxidative stress of DKD. Egr1 contributes to DKD by enhancing EMT, in part by targeting NOX4.

Effects of sevoflurane on NF-кB and TNF-α expression in renal ischemia-reperfusion diabetic rats.

BACKGROUND: Ischemia-reperfusion (I/R) injury is the main reason of acute renal failure. However, inflammatory response and cell apoptosis are important mechanisms implicated in I/R injury. Recent studies indicated that nuclear factor kappa B (NF-кB) and tumor necrosis factor α (TNF-α) are both involved in these mechanisms. Sevoflurane reduces NF-кB and TNF-α expression in rats' heart and decreases their renal I/R injury. However, few studies are available regarding the effect of sevoflurane on kidney of diabetic rats. Therefore, the aim of this study was to evaluate sevoflurane effect on NF-кB and TNF-α expression in diabetic rats to decrease renal I/R injury. METHODS: Male Sprague-Dawley rats were divided into five groups: Group A, non-diabetic rats underwent sham operation; Group B, non-diabetic rats with renal I/R injury; Group C, diabetic rats underwent sham operation; Group D, diabetic rats with renal I/R injury; Group E, diabetic rats with renal I/R injury after sevoflurane pretreatment. Rats of Group E were exposed to 2.5% sevoflurane for 30 min. After 24 h, creatinine (Cr), blood urea nitrogen (BUN), renal cell apoptosis, and NF-кB and TNF-α expression in kidney were assessed. RESULTS: Renal cell apoptosis, NF-кB, and TNF-α expression were significantly higher in diabetic rats with renal I/R injury group compared to diabetic rats that underwent sham operation (P < 0.01). These changes were significantly reduced by sevoflurane (P < 0.01). CONCLUSION: Sevoflurane exerted a protective effect against renal injury by lowering the expression of NF-кB and TNF-α in renal I/R diabetic rats.

Management of pin tract infection in pediatric supracondylar humerus fractures: a comparative study of three methods.

The objective of this study was to prospectively compare the incidence of pin tract infection in pediatric supracondylar humerus fractures managed with pin care daily or every other day or weekly. We hypothesized that there were some differences between these three methods. From June 2012 to May 2015, 135 children with supracondylar humerus fractures were randomized to postoperative pin care by cleaning pin tracts daily (group A, 45 cases) or cleaning every 2 days (group B, 45 cases) or cleaning weekly (group C, 45 cases). The three groups were comparable with respect to age, gender, affected side, body mass index (BMI), fracture type, injury to surgery time, number of intraoperative percutaneous pinning, and follow-up time. We collected data on pin retention time, union time, and pin tract infection. The average follow-up time of group A was 4.5 ± 1.3 and 4.2 ± 1.6 months in group B and 4.3 ± 1.4 months in group C. The patient demographics and intraoperative variables of three groups were comparable. No significant difference between these three groups was found in union time and pin fixation time. Of the 135 children, 48 (35.6%) cases had pin tract infection. Grade I infections (Checketts-Otterburns classification) occurred around 28.9% of 270 pin and grade II around 6.7%. We found no differences between three groups as regards frequency and severity of pin tract infections (both P > 0.05). However, complain of pain was more frequent in group A than other two groups (P < 0.05). CONCLUSIONS: All of the three methods were effective for the management of pin site infection in pediatric supracondylar humerus fractures. However, excessive frequent care as well as pin care daily had the disadvantages of child's fear and parental anxiety. What is Known: • Pin site infection is a common complication after fracture fixation and bone lengthening using percutaneous pins or wires. • Closed reduction and percutaneous K-wires fixation are the mainstay of treatment in pediatric supracondylar humeral fractures. What is New: • All of the three methods were effective for the management of pin site infection. • Excessive frequent care as well as pin care daily has the disadvantages of child's fear and parental anxiety.

Astragaloside IV attenuates free fatty acid-induced ER stress and lipid accumulation in hepatocytes via AMPK activation.

Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is not completely understood, the increased influx of free fatty acids (FFAs) into the liver and the FFA-induced hepatic endoplasmic reticulum (ER) stress are two crucial pathogenic processes in the initiation and development of NAFLD. In this study we investigated the effects of astragaloside IV (AS-IV), a bioactive compound purified from Astragali Radix, on FFA-induced lipid accumulation in hepatocytes and elucidated the underlying mechanisms. Human HepG2 cells and primary murine hepatocytes were exposed to FFAs (1 mmol/L, oleate/palmitate, 2:1 ratio) with or without AS-IV for 24 h. Exposure to FFAs induced marked lipid accumulation in hepatocytes, whereas co-treatment with AS-IV (100 µg/mL) significantly attenuated this phenomenon. Notably, AS-IV (50-200 µg/mL) concentration-dependently enhanced the phosphorylation of AMPK, acetyl-CoA carboxylase (ACC) and SREBP-1c, inhibited the accumulation and nuclear translocation of mature SREBP-1 and subsequently decreased the mRNA levels of lipogenic genes including acc1, fas and scd1. AS-IV treatment also concentration-dependently attenuated FFA-induced hepatic ER stress evidenced by the reduction of the key markers, GRP78, CHOP and p-PERK. Pretreated the cells with the AMPK inhibitor compound C (20 µmol/L) greatly diminished these beneficial effects of AS-IV. Our results demonstrate that AS-IV attenuates FFA-induced ER stress and lipid accumulation in an AMPK-dependent manner in hepatocytes, which supports its use as promising therapeutics for hepatic steatosis.

The outcomes of pediatric femoral shaft fractures treated surgically by different types of orthopedists.

BACKGROUND: The objective of this study was to compare the outcomes of pediatric femoral shaft fractures treated with titanium elastic nail (TEN) by pediatric orthopedists and non-pediatric orthopedists. METHODS: From May 2006 to June 2014, 88 children with femoral shaft fractures were randomized to operative stabilization either by pediatric orthopedists (Group A, 44 cases) or by non-pediatric orthopedists (Group B, 44 cases). Demographic data and clinical characteristics (age, sex, weight, fracture side and type, cause of injury, associated injuries and interval from injury to surgery) were comparable between the two groups before surgery. Peri-operative data, clinical and functional outcomes between the two groups were recorded. RESULTS: The mean follow-up period was 20.9±4.5months for Group A and 20.0±3.6months for Group B (P=0.356). There was no significant difference in the time to union, length of hospitalization, full weight-bearing time and TEN scores between the two groups (P=0.785, P=0.835, P=0.803, P=0.940, respectively). However, the mean operating time and radiation time was longer in Group B than in Group A (P=0.001 and P=0.047, respectively). Also, there was a trend for patients of Group B to have a higher rate of open reduction (P=0.047). When comparing the total complications, no significant difference existed between the groups (P=0.978). CONCLUSIONS: This study indicated that both pediatric and non-pediatric orthopedists provided satisfactory clinical and functional results in treating these common injuries.

Comparison of 3 Minimally Invasive Methods for Distal Tibia Fractures.

This study compared the results of external fixation combined with limited open reduction and internal fixation (EF + LORIF), minimally invasive percutaneous plate osteosynthesis (MIPPO), and intramedullary nailing (IMN) for distal tibia fractures. A total of 84 patients with distal tibia shaft fractures were randomized to operative stabilization using EF + LORIF (28 cases), MIPPO (28 cases), or IMN (28 cases). The 3 groups were comparable with respect to patient demographics. Data were collected on operative time and radiation time, union time, complications, time of recovery to work, secondary operations, and measured joint function using the American Orthopaedic Foot and Ankle Society (AOFAS) score. There was no significant difference in time to union, incidence of union status, time of recovery to work, and AOFAS scores among the 3 groups (P>.05). Mean operative time and radiation time in the MIPPO group were longer than those in the IMN or EF + LORIF groups (P<.05). Wound complications after MIPPO were more common compared with IMN or EF + LORIF (P<.05). Anterior knee pain occurred frequently after IMN (32.1%), and irritation symptoms were encountered more frequently after MIPPO (46.4%). Although EF + LORIF was associated with fewer secondary procedures vs MIPPO or IMN, it was related with more pin-tract infections (14.3%). Findings indicated that EF + LORIF, MIPPO, and IMN all achieved similar good functional results. However, EF + LORIF had some advantages over MIPPO and IMN in reducing operative and radiation times, postoperative complications, and reoperation rate. [Orthopedics. 2016; 39(4):e627-e633.].