Correlation between serum laminin levels and prognosis of acute myocardial infarction.

Background: Acute myocardial infarction (AMI) is a critical cardiovascular disease (CVD). Laminin (LN) is involved in the process of myocardial fibrosis and ventricular remodeling observed in AMI; however, there are currently no studies on the correlation between LN and AMI prognosis. Purpose: To explore the predictive value of serum LN levels for major adverse cardiovascular events (MACE) in patients, 6 months after an acute myocardial infarction. Methods: A total of 202 AMI patients who were hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Nantong University between December 2019 and December 2020 were included. The observation endpoint was the occurrence of MACE. Univariate and multivariate logistic analyses were used to evaluate the relationships between the variables and endpoint. The predictive value of LN for MACE in AMI patients was assessed using receiver operating characteristic (ROC) analysis. Results: A total of 47 patients developed MACE. Univariate logistic analysis showed that smoking, emergency percutaneous coronary intervention (EPCI), age, cardiac troponin I (c-TNI) levels, N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels, and LN levels were associated with the occurrence of MACE (p < 0.05). Multivariate logistic analysis showed that LN was an independent predictor of MACE (odds ratio [OR] = 1.021, 95%CI: 1.014-1.032, p < 0.001). According to the ROC curve, LN can be used as an effective predictor of MACE (AUC = 0.856, 95%CI: 0.794-0.918, p < 0.001). According to the cutoff value, LN>58.80 ng/ml (sensitivity = 83.00%, specificity = 76.80%) or LN>74.15 ng/ml (sensitivity = 76.6%, specificity = 83.2%) indicate a poor prognosis for AMI. Different cut-off values are selected according to the need for higher sensitivity or specificity in clinical applications. Conclusions: LN may be a predictor of MACE following AMI in patients and could be utilized as a novel substitute marker for the prevention and treatment of AMI.

Applying Lean Six Sigma to Reduce the Incidence of Unplanned Surgery Cancellation at a Large Comprehensive Tertiary Hospital in China.

Unplanned surgery cancellation (USC) was an important quality management issue in the course of medical care for surgical patients, which caused inappropriate use of hospital resources and had negative impacts on quality and safety. This study used Lean Six Sigma to reduce the incidence of USC. Following the Lean Six Sigma DMAIC (Define, Measure, Analyze, Improve, and Control) process, the main factors influencing the USC were identified, such as the time of informing patient admission, the time of submitting operation notice, and the management of test report follow-up. A series of measures were implemented including improving the health education content of virtual bed patients, standardizing the way of communication between the Admission Management Center and the patients, improving the timing of anesthesia evaluation, optimizing the process of operation notice with an information system, and implementing the regulations of virtual bed management. The incidence of USC reduced from 10.21% in Jan. 2016 to 3.8% in Dec. 2016, and the Z-score increased from 1.25 to 1.68, which improved patient safety and demonstrated that Lean Six Sigma was an effective method to solve cross-department issues in hospital.

[Progress in diagnosis and therapy of thoracic outlet syndrome].

Thoracic outlet syndrome(TOS) are constellation of symptoms caused by compression of the neurovascular bundle including the brachial plexus, the subclavian artery and the subclavian vein at the thoracic outlet region. It includes neurogenic TOS, venus TOS, arterial TOS, and neurogenic TOS is the most common type. TOS has varied manifestations and lack of confirmatory testing, therefore, the diagnosis should be conbination with thorough history, physical examination and associated supplementary examinations. Conservative and surgical treatment can be choosed for TOS and the outcomes are generally good. Conservative management is the initial treatment strategy for neurogenic TOS. In cases of symptomatic vascular TOS and neurovascular TOS, which has been failed by conservative treatment, surgery should be considered more promptly.

Corrigendum: Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast cancer cells and osteoclasts.

This corrects the article DOI: 10.1038/srep19074.

Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast caner cells and osteoclasts.

Bone is the most common site of distant relapse in breast cancer, leading to severe complications which dramatically affect the patients' quality of life. It is believed that the crosstalk between metastatic breast cancer cells and osteoclasts is critical for breast cancer-induced osteolysis. In this study, the effects of dihydroartemisinin (DHA) on osteoclast formation, bone resorption, osteoblast differentiation and mineralization were initially assessed in vitro, followed by further investigation in a titanium-particle-induced osteolysis model in vivo. Based on the proved inhibitory effect of DHA on osteolysis, DHA was further applied to MDA-MB-231 breast cancer-induced mouse osteolysis model, with the underlying molecular mechanisms further investigated. Here, we verified for the first time that DHA suppressed osteoclast differentiation, F-actin ring formation and bone resorption through suppressing AKT/SRC pathways, leading to the preventive effect of DHA on titanium-particle-induced osteolysis without affecting osteoblast function. More importantly, we demonstrated that DHA inhibited breast tumor-induced osteolysis through inhibiting the proliferation, migration and invasion of MDA-MB-231 cells via modulating AKT signaling pathway. In conclusion, DHA effectively inhibited osteoclastogenesis and prevented breast cancer-induced osteolysis.

Cage migration after transforaminal lumbar interbody fusion and factors related to it.

OBJECTIVE: To review and analyze cage migration and related risk factors in patients who have undergone transforaminal lumbar interbody fusion (TLIF). METHODS: A retrospective study was conducted to review the complications of cage migration in 512 patients who had undergone a TLIF procedure from January 2010 to June 2011 in five spinal centers. In all, 263 men and 249 women with a mean age of 54.7 years were included. All patients were followed up at 3, 6 and 12 months after the procedure. The clinical outcomes were evaluated by visual analogue scores, the Oswestry disability index, plain radiography and three-dimensional CT scanning to analyze the incidence of, and risk factors related to, cage migration. RESULTS: Cage migration was found in 6 of the 512 patients (1.17%). Significant differences were found between all pairs of centers. Different shapes and sizes of cages had different incidences of migration. Analysis showed that rectangular-shaped cages had a significantly greater incidence of cage migration (3.11%, 5/161) than did kidney-shaped cages (0.28%, 1/351; P < 0.05). Small cages had a tendency to more frequent post-operative cage migration (5.13%, 4/78) than did large cages (0.46%, 2/434; P < 0.05). Double segment TLIF cages migrated more frequently (5.75%, 5/87) than did mono-segment cages (0.24%, 1/425; P < 0.05)). Furthermore, when the adjacent endplates were of linear type, the cages migrated much more frequently (3.50%) than when they were of concave-concave type (0.27%; P < 0.05). CONCLUSION: Cage size, shape, number of fused segments and adjacent endplate shape might be risk factors for cage migration in addition to surgical technique, disc height and bone mineral density.

The invention of an iliosacral screw fixation guide and its preliminary clinical application.

OBJECTIVE: To introduce an iliosacral screw fixation guide and evaluate its efficacy in fixation of sacroiliac joint fracture-dislocations. METHODS: Between January 2011 and May 2011, eight patients (five men, three women) with sacroiliac joint fracture-dislocation underwent percutaneous iliosacral screw fixation with the assistance of this minimally invasive guide and under CT guidance. The patients, aged from 26 to 56 years (mean 32 years), had vertically unstable pelvic fractures. Before surgery, six patients who had displacement of >2 cm in their sacroiliac joints underwent skeletal traction on the femoral condyle. The inserted sites were marked out on the affected side of their buttocks after the best screw trajectory had been determined under CT control. The gear that controls the direction of the minimally invasive guide was adjusted according to the inserting angle determined by CT scans. A K-wire was inserted into the sacroiliac joint along the pilot sleeve of the guide, and a hollow screw (diameter 7.3 mm) was implanted into the sacroiliac joint along the K-wire. RESULTS: All eight operations were successful on the first attempt. The operations lasted from 10 to 20 minutes (mean 14 minutes). Immediate CT scans confirmed that all the screws had been placed in the desired positions, none had penetrated the bones and the configuration of the sacroiliac joints had been satisfactorily restored and firmly fixed. No patient experienced numbness or radiating pain in the lower limbs during surgery. There were no postoperative vascular or neurological complications. CONCLUSION: The minimally invasive guide can eliminate discrepancies resulting from the surgeon's own sensory input when inserting screws under the guidance of CT, making percutaneous iliosacral screw fixation more accurate, safe and simple.

[Comparative study of two operation methods on complicated fractures of the distal radius and ulna].

OBJECTIVE: To compare the differences between external fixator and volar T-shaped plate in the treatment of complicated fractures of the distal radius and ulna, and evaluate the appropriate operation method for the fractures. METHODS: From July 2005 to July 2007, forty-eight cases of complicated fractures of the distal radius and ulna were treated with operation. There were 21 males and 9 females in the internal fixator group, ranged from 22 to 52 years old (with an average of 38.4 +/- 1.5 years). There were 10 mals and 8 femals in the external fixator group,ranged from 25 to 56 years old (with an average of 40.5 +/- 2.3 years). The X-ray films were measured to acquire radial length, palmar tilt and radial inclination after operations. The functional evaluation were scored with a modified Gartland and Werley's (GW) scoring system at 6 and 12 months after operation. RESULTS: The patients were followed up for 12 to 18 months with an average of 14.2 months. The radial length was (8.82 +/- 0.55) mm, palmar tilt (9.23 +/- 0.86) degrees, radial inclination (19.66 +/- 1.38) degrees in the internal fixator group, while those were (8.25 +/- 0.36) mm, (8.56 +/- 0.72) degrees, (18.82 +/- 1.42) degrees in the external fixator group. The film parameter of internal fixator group was better than the external fixator group, but with no statistical significance (P > 0.05). In the internal fixator group, 16 cases obtained excellent, 7 good, 5 fair, 2 poor, while in the external fixator group, 4 cases obtained excellent, 2 good, 8 fair, 4 poor in 6 months. The GW scores of internal fixator group were lower than that of the external fixator group (P < 0.05). At 12 months after surgery, in the internal fixator group, 17 cases obtained excellent, 7 good, 5 fair, 1 poor; while in the external fixator group, 5 cases obtained excellent, 9 good, 2 fair, 2 poor. The GW score was similar between the two groups (P > 0.05). CONCLUSION: The volar T-shaped plate fixation may offer effective stability,the short-term outcome is better than the external fixator group,and there are relatively fewer complications. But the treatment outcome of the two operation methods are similar for the long time follow up.

Upregulation of human leukocyte antigen-G expression and its clinical significance in ductal breast cancer.

Human leukocyte antigen(HLA)-G could inhibit functions of immune cells and induce regulatory T cells (Treg) and could be involved in antitumor immune responses. In the current study, HLA-G expression in 58 primary breast cancer lesions was analyzed with immunohistochemistry. Plasma soluble HLA-G was detected with enzyme-linked immunosorbent assay in 92 breast cancer patients and in 70 normal healthy donors. The proportion of CD4(+)CD25(+)FoxP3(+) Treg was analyzed with flow cytometry in 64 breast cancer patients and 23 normal controls. HLA-G expression was observed in 70.7% (41/58) of breast cancer lesions. Lesion HLA-G expression was more frequently observed in advanced disease stage (I/II vs III/IV, p = 0.044) and tumor grade (I/II vs III/IV, p = 0.021). sHLA-G was dramatically increased in patients when compared with normal controls (median 82.19 vs 9.65 U/ml, p < 0.001); The area under the receiver operating characteristic (ROC) curve for sHLA-G was 0.953 (95% confidence interval [CI] = 0.926-0.981, p < 0.001). However, sHLA-G was irrelevant to the disease stage and tumor grade. Moreover, CD4(+)CD25(+)FoxP3(+) Treg are markedly increased in the breast cancer patients compared with normal controls (4.46+/-1.36% vs 2.67+/-1.45%, p < 0.001), and the increased frequency of Treg was strongly correlated to sHLA-G levels (R = 0.582, p = 0.001). Our findings indicated that HLA-G could play critical roles in the progression of breast cancer, and plasma sHLA-G levels might be a useful preoperative biomarker for diagnosis.

Genetically engineered mesenchymal stem cells: The ongoing research for bone tissue engineering.

Bone grafting is crucial in the surgical treatment of bone defects and nonunion fractures. Autogenous bone, allogenous bone, and biomaterial scaffold are three main sources of bone grafts. The biomaterial scaffold, both natural and synthetic, is widely accessible but weak in osteogenic potential. One approach to solve this problem is cell-based bone tissue engineering (BTE), established by growing living osteogenic cells on scaffold in vitro to build up its osteoinducitive capability. Mesenchymal stem cell (MSC) is suitable for use in cell-based BTE, but it remains a considerable challenge to induce MSCs to form solely bone and while preventing MSCs from differentiating into fats, muscles, and possibly neural elements in vivo. Recently, there is a drastic rise in use of genetically engineered MSCs, which can secrete growth factors or alter the transcription level, leading to osteoblast lineage commitment, bone formation, fracture repair, and spinal fusion. In this article, we reviewed the literatures regarding applications of genetically engineered MSCs in BTE. We addressed the currently applicable genes and candidate genes for MSCs modification, transduction efficiency and safety issues of the transfect vectors, and administration routes, and we briefly described in vivo tracking and potential clinical application of the genetically modified MSCs in BTE.

Osteoblastogenic effects of dexamethasone through upregulation of TAZ expression in rat mesenchymal stem cells.

Transcriptional coactivator with PDZ-binding motif (TAZ), a beta-catenin-like molecule, drives mesenchymal stem cell (MSC) to differentiate into osteoblast lineage through co-activation of Runx2-dependent gene transcription and repression of peroxisome proliferator-activated receptorgamma (PPARgamma)-dependent gene transcription. Dexamethasone (DEX), a synthetic and widely used glucocorticoid, affects osteogenesis. However, the signaling pathway by which DEX affects osteoblastic differentiation remains obscure. In this study, we found that DEX at the concentration of 10(-8)M enhanced calcium deposition, TAZ, bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP) expression during osteoblastic differentiation. RU486, an antagonist of glucocorticoid receptor, blocked the improvement of TAZ expression while MSCs were treated with 10(-8)M DEX. Moreover, higher concentration (10(-7)M) of DEX robustly suppressed TAZ and ALP expression in MSCs. These findings suggest that TAZ is not only involved in the signal pathway of BMP-2-induced osteoblastic differentiation, but also involved in the signaling pathway of DEX-induced osteoblastic differentiation, supporting the notion that TAZ is a convergence point of two signaling pathways, BMP-2 signaling pathway and Wnt-beta-catenin signaling pathway.

[Clinical application of the reconstruction of prevertebral fascia in cervical vertebrae anterior approach].

OBJECTIVE: To evaluate the preventive effect of the reconstruction of prevertebral fascia on the complication of cervical vertebrae anterior approach. METHODS: One hundred and seventy-six patients with cervical vertebrae anterior approach were divided into two groups by throwing coins, coins for the positive, patients entered the group A, coins for the negative, patients entered the group B. Eighty-seven cases of group B were treated with cervical vertebrae anterior decompression, bone grafting and internal fixation with plate and screws. In other 89 cases of group A, prevertebral fascia were covered on the surface of the plate and screws as experiment group. The patients were followed up after three weeks, three months and 12 months. The incidence of the dysphagia was as observation indicator and was statistically analyzed. RESULTS: The followed-up period was 3 weeks, 3 months and 12 months after operation. The incidence of the dysphagia of group A was respectively 25.8%, 9.0%, 5.6%; the incidence of the dysphagia of group B was respectively 25.3%, 20.6%, 14.9%. The dysphagia in the experiment group was lower than that in contrast group, 3 months and 12 months after operation (3 months P = 0.030, 12 months P = 0.049 < 0.05). CONCLUSION: The reconstruction of prevertebral fascia is an effective method to avoid the dysphagia of cervical vertebrae anterior approach.

Staphylococcal enterotoxin C injection in combination with ascorbic acid promotes the differentiation of bone marrow-derived mesenchymal stem cells into osteoblasts in vitro.

Staphylococcal enterotoxin C injection is established as a clinical therapy for delayed healing or disunion of bone fractures. In the present study, the effects of staphylococcal enterotoxin C injection in combination with ascorbic acid (SEC-AA) on the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) and their influences on the mineralization of osteoblasts were investigated. SEC-AA treatment induced increased levels of alkaline phosphatase activity in MSCs and increased numbers of alizarin red-stained calcified nodules, indicating enhanced differentiation of MSCs into osteoblasts. The findings demonstrated that SEC-AA promoted the differentiation of MSCs into osteoblasts and accelerated the cytopoiesis of osteoblasts. Our data provide a cytological model for bone fracture therapy aimed at shortening the time required for healing and improving the clinical outcome, and also provide a theoretical basis for inducible differentiation of MSCs, mineralization of osteoblasts and reconstruction of bone tissues.

The kringle 1 domain of hepatocyte growth factor has antiangiogenic and antitumor cell effects on hepatocellular carcinoma.

The kringle 1 domain of human hepatocyte growth factor (HGFK1) was previously shown to inhibit bovine aortic endothelial cell proliferation, suggesting that it might be an antiangiogenic molecule. Here, we evaluated the in vivo efficacy of a recombinant adenoassociated virus carrying HGFK1 (rAAV-HGFK1) for the treatment of hepatocellular carcinoma (HCC) in a rat orthotopic HCC model and explored its molecular mechanisms in vitro in both endothelial and tumor cells. We first showed that rAAV-HGFK1 treatment significantly prolonged the survival time of rats transplanted with tumor cells. Treatment with rAAV-HGFK1 inhibited tumor growth, decreased tumor microvessel density, and completely prevented intrahepatic, lung, and peritoneal metastasis in this in vivo model. In vitro, rAAV-HGFK1 exhibited both antiangiogenic and antitumor cell effects, inhibiting the proliferation of both murine microvascular endothelial cells (MEC) and tumor cells, and inducing apoptosis and G(0)-G(1) phase arrest in these cells. To our surprise, rAAV-HGFK1 did not act through the hepatocyte growth factor/hepatocyte growth factor receptor pathway. Instead, it worked mainly through epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) signaling, with more minor contributions from vascular endothelial growth factor/vascular endothelial growth factor receptor and beta fibroblast growth factor (bFGF)/beta fibroblast growth factor receptor (bFGFR) signaling. In both MECs and tumor cells, rAAV-HGFK1 acted through two pathways downstream of EGFR, namely inhibition of extracellular signal-regulated kinase activation and stimulation of p38 mitogen-activated protein kinase/c-Jun-NH(2)-kinase activation. These results suggest for the first time that HGFK1 exerts both antiangiogenic and antitumor cell activities mainly through EGF/EGFR signaling, and may thus be considered as a novel therapeutic strategy for the treatment of HCC.