低频电磁场对大鼠主动脉平滑肌细胞基质金属蛋白酶的影响

目的 观察不同磁场强度及作用时间的低频电磁场（LFEMF）对培养的大鼠主动脉血管平滑肌细胞（VSMC）表达基质金属蛋白酶-2（MMP-2）的影响。方法 用含10％小牛血清的DMEM培养液体外培养大鼠主动脉VSMC，随机分为对照组、LFEMF不同磁场强度（20，40，60mT）及时间（10，20，30min）干预组，运用MMP-2活性酶图分析法结合光密度扫描分析，观察LFEMF对VSMC的MMP-2表达的影响。结果 不同磁场强度组均明显抑制MMP-2的活性，且具有剂量依赖性，但抑制作用不随时间延长而变化，不具有时间依赖性。结论 适当强度和作用时间的LFEMF抑制VSMC的MMP-2活性的表达，磁场对经皮腔内冠状动脉成形术（PTCA）及支架植入术后的再狭窄（RS）可能具有防治作用。     

Mid to Distal Small Bowel Resection with the Preservation of the Terminal Ileum Improves Glucose Homeostasis in Diabetic Rats by Activating the Hindgut-Dependent Mechanism

Background

The aim of this study was to develop a novel surgical model to test the “hindgut hypothesis” and thereby study the role of the gut in glucose homeostasis and the mechanism of action of bariatric surgery.

Method

Sprague-Dawley rats were given a high-fat and high-sugar diet and treated with 25 mg/kg streptozotocin (STZ). The fat-sugar-fed/STZ-treated rats were randomized into mid to distal small bowel resection with the preservation of the terminal ileum (DBRPI) and sham operation (which had a formal celiotomy with bowel manipulation only) groups. Rats were observed for 12 weeks after the operation. The main outcome measures were weight, food intake, non-fasting glucose, an oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), the levels of fasting and glucose-induced insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), serum bile acids, and lipid profile.

Result

The DBRPI and sham groups exhibited no difference in weight and food intake after surgery. When compared to the sham controls, the DBRPI group displayed an improvement in non-fasting glucose, oral glucose tolerance, and insulin tolerance at 4 and 12 weeks postresection. DBRPI elicited an increased serum insulin, PYY and GLP-1 levels at 12 weeks postoperation; furthermore, DBRPI resulted in higher serum levels of triglyceride, total bile acids, total bilirubin, and direct bilirubin levels and lower free fatty acid level at 12 weeks.

Conclusions

This study provides strong evidences for the key role of hindgut in the amelioration of diabetes after bariatric surgery. Moreover, these findings confirm that DBRPI is a simple and effective surgical model for testing the “hindgut hypothesis” and focused study of biliary enterohepatic recycling in the context of bariatric operations.     

Coronary sinus cannulation with a steerable catheter during biventricular device implantation

Objectives. To determine whether a steerable catheter with electrogram guidance (CS-assist group) could facilitate access to the coronary sinus (CS) during cardiac resynchronization therapy (CRT) implantation. Design. Consecutive patients who underwent CRT implantation were recruited prospectively into the CS-assist group (n = 81) and compared with those using conventional techniques without an electrogram guidance (conventional group, n = 101). Results. The CS cannulation success rate was clearly greater in the CS-assist group (100%) than that in the conventional group (95%, p < 0.05), with significantly shorter mean procedure time (52.6 ± 20.6 min vs. 73.2 ± 40.9 min, p < 0.01) and fluoroscopy time (3.6 ± 3.2 min vs. 14.2 ± 20.4 min, p < 0.01). In the five CS cannulation failure cases, mean procedure time (144.0 ± 37.0 min) and fluoroscopy time (57.8 ± 24.8 min) were significantly longer than those in the other patients (61.2 ± 32.3 and 8.2 ± 13.6 min, respectively, n = 177, both p < 0.01). Conclusions. Using the steerable catheter with real-time electrogram guidance, location of and access to the CS is more rapid and successful, which may improve the success of the CRT implantation and may give significant time savings.     

EZH2, a Potential Regulator of Dental Pulp Inflammation and Regeneration

Introduction

Dental pulp has limited capability to regenerate, which happens in the early stage of pulpitis. An ambiguous relationship exists; inflammation may impair or support pulp regeneration. Epigenetics, which is involved in cell proliferation and inflammation, could regulate human dental pulp cell (HDPCs) regeneration. The aim of this study was to determine the role of the epigenetic mark, enhancer of zeste homolog 2 (EZH2), in the inflammation, proliferation, and regeneration of dental pulp. We used trimethylated histone H3 lysine 27(H3K27me3) and its lysine demethylase 6B (KDM6B) to monitor functional effects of altered EZH2 levels.

Methods

We detected epigenetic marks (EZH2, H3K27me3, and KDM6B) in pulp tissue by immunohistochemistry and immunofluorescence. EZH2 levels in HDPCs in inflammatory responses or differentiation were analyzed by quantitative polymerase chain reaction and Western blot. Quantitative polymerase chain reaction was used to assess the effects of EZH2 inhibition on interleukins in HDPCs upon tumor necrosis factor alpha stimulation. Cell proliferation was tested by cell counting kit-8, cell cycle, and apoptosis analysis. HDPC differentiation was investigated by quantitative polymerase chain reaction, alkaline phosphatase activity, and oil red O staining.

Results

EZH2 and H3K27me3 were decreased, whereas KDM6B was increased in infected pulp tissue and cells, which were similar to HDPC differentiation. EZH2 inhibition suppressed IL-1b, IL-6, and IL-8 messenger RNA (mRNA) in HDPCs upon inflammatory stimuli and impeded HDPC proliferation by decreasing cell number, arresting cell cycle, and increasing apoptosis. Suppressed EZH2 impaired adipogenesis, peroxisome proliferator-activated receptor r (PPAR-r), and CCAAT-enhancer binding protein a (CEBP/a) mRNA in adipogenic induction while enhancing alkaline phosphatase activity, Osx, and bone sialoprotein (BSP) mRNA in mineralization induction of HDPCs.

Conclusions

EZH2 inhibited HDPC osteogenic differentiation while enhancing inflammatory response and proliferation, suggesting its role in pulp inflammation, proliferation, and regeneration.     

High-level β1-integrin expression in a subpopulation of highly tumorigenic oral cancer cells

Objectives

The β1 integrin (CD29) is a putative marker for cancerous epithelial stem cells. Cancer stem cells are essential to drive tumor growth, recurrence, and metastasis. We investigated the role of β1-integrin expression in the development of malignant phenotypes of oral squamous cell carcinoma (OSCC).

Materials and methods

Immunostaining was used to analyze the expression levels of β1 integrins in different types of cell colonies and tumor spheres. The results of cell viability and migration assays with and without siRNA knockdown of β1-integrin expression were compared. Cells expressing β1 integrins were evaluated for their tumorigenicity in mice. The expression of β1 integrins in human specimens of oral cancers at different clinical stages was semiquantified based on immunohistochemical staining of the β1-integrin protein.

Results

The expression level of β1 integrins in Meng-1 oral epidermoid carcinoma cells (OECM-1) cells was significantly higher in holoclonal colonies and tumor spheres compared to control cells. The knockdown of β1-integrin expression in OECM-1 cells reduced cell proliferation, migration, and tumor sphere formation. Beta-1 integrin (+) cells were more tumorigenic in the mouse xenograft model than β1 integrin (?) cells. In the human specimens, the expression level of the β1-integrin protein positively correlated with the clinical stage.

Conclusion

The expression of β1 integrin in OECM-1 cells is involved in the development of malignant phenotypes of OSCC.

Clinical relevance

Inhibitors for β1-integrin signaling may be suitable to become target-specific therapies for OSCC.     

Reconstruction of palatomaxillary defects following cancer ablation with temporalis muscle flap in medically compromised patients: a 15-year single institutional experience

Objectives

Successful reconstruction of palatomaxillary defects following cancer ablation represents a formidable challenge for surgeons to achieve consistently favorable outcomes. The purpose of this article is to present our experience in oncologic palatomaxillary repair with temporalis muscle flap (TMF) for medically compromised patients who are not ideal candidates for microvascular reconstruction at a Chinese tertiary referral hospital over a 15-year period (1998–2012).

Method

A retrospective chart review was performed to identify patients with compromised medical conditions who underwent oncologic palatomaxillary reconstruction using TMF. Patients’ demographics, clinicopathological variables, and surgical techniques were presented. Postoperative functional and aesthetic outcomes were assessed by measurements and patients self-evaluations.

Results

Sixty-nine TMFs were successfully harvested and used for immediate oncologic palatomaxillary reconstruction in 67 patients (31 males and 36 females, mean age 60.4 years) with diverse primary malignancies. These patients’ co-morbidities included systemic diseases, preoperative chemotherapy/radiotherapy, and elder over 65 years which precluded the ideal utility of free flaps. Fifty-one patients remained alive without disease, while nine had recurrences/metastases and seven died during the follow-up (0.5–10.4 years, mean 3.7 years). All flaps survived with only partial necroses in four cases. Complications and donor-site morbidities were minimal with five transient facial paralysis and four mild diplopia and enophthalmos. Unrestricted diet and mouth opening, intelligible speech, and satisfactory temporal aesthetics were obtained in most patients.

Conclusion

The TMF is a reliable, versatile, and alternative option for oncologic palatomaxillary reconstruction with satisfactory functional and aesthetic outcomes and minimal complications, especially when appropriately selected for those medically compromised patients.     

头帽-肌激动器一下唇挡矫治器治疗安氏Ⅱ错（牙合）的临床研究

目的：研究头帽一肌激动器一下唇挡矫治器治疗生长发育期安氏Ⅱ类1分类错（牙合）对骨骼、牙齿和软组织的影响。方法：选择20例安氏Ⅱ类1分类患者,随机分两组分别采用头帽一肌激动器一下唇挡矫治器和头帽一肌激动器～进行治疗,常规拍摄治疗前后的头颅侧位片进行分析,对结果进行T检验。结果：Pg／OLP显著增加,Si--LiPg明显减少。结论：头帽一肌激动器一下唇挡矫治器组能更好的刺激下颌的发育,明显改善患者侧貌。     

放射性颌骨坏死的术式选择及疗效评价

目的：探讨经济有效的治疗放射性颌骨坏死（RONJ）的手术方式。方法77例RONJ根据颌骨坏死的范围、软组织条件选择不同治疗方式。方案1：骨坏死范围局限,牙龈及周围软组织无明显炎症的采用局部刮治或方块切除术;方案2：骨坏死范围较大、周围软组织炎症明显和（或）伴有明显纤维化的病例在控制炎症后,扩大切除同时行血管化游离复合组织瓣修复。结果21例采用方案1,其中15例一期愈合、6例行二次刮治或方块切除;56例采用方案2,其中软组织条件较好的30例,22例一期愈合,5例延期愈合,3例发生骨组织瓣血管危象,经探查和再吻合后1例正常愈合,2例仍发生组织瓣坏死;软组织炎症明显或伴有局部组织明显纤维化26例中,7例出现骨组织瓣血管危象,探查和再吻合后5例正常,2例出现骨坏死,9例一期愈合,15例局部出现不同程度软组织感染坏死,延期愈合。结论局限性放射性颌骨坏死可采用刮治或方块切除;骨坏死范围较大、软组织条件较好的采用血管化游离组织瓣进行修复;软组织纤维化明显的失败率较高,临床使用时应综合多方因素考虑。     

Exact solution for a metapopulation version of Schelling’s model

In 1971, Schelling introduced a model in which families move if they have too many neighbors of the opposite type. In this paper, we will consider a metapopulation version of the model in which a city is divided into N neighborhoods, each of which has L houses. There are ρNL red families and ρNL blue families for some ρ < 1/2. Families are happy if there are ≤ρ_cL families of the opposite type in their neighborhood and unhappy otherwise. Each family moves to each vacant house at rates that depend on their happiness at their current location and that of their destination. Our main result is that if neighborhoods are large, then there are critical values ρ_b < ρ_d < ρ_c, so that for ρ < ρ_b, the two types are distributed randomly in equilibrium. When ρ > ρ_b, a new segregated equilibrium appears; for ρ_b < ρ < ρ_d, there is bistability, but when ρ increases past ρ_d the random state is no longer stable. When ρ_c is small enough, the random state will again be the stationary distribution when ρ is close to 1/2. If so, this is preceded by a region of bistability.In 1971, Schelling (1) introduced one of the first agent-based models in the social sciences. Families of two types inhabit cells in a finite square, with 25–30% of the squares vacant. Each family has a neighborhood that consists of a 5 × 5 square centered at their location. Schelling used a number of different rules for picking the next family to move, but the most sensible seems to be that we pick a family at random on each step. If the fraction of neighbors of the opposite type is too large, then they move to the closest location that satisfies their constraints. Schelling simulated this and many other variants of this model (using dice and checkers) to argue that if people have a preference for living with those of their own color, the movements of individual families invariably led to complete segregation (2).As Clark and Fossett (3) explain “The Schelling model was mostly of theoretical interest and was rarely cited until a significant debate about the extent and explanations of residential segregation in US urban areas was engaged in the 1980s and 1990s. To that point, most social scientists offered an explanation that invoked housing discrimination, principally by whites.” At this point Schelling’s article has been cited more than 800 times. For a sampling of results from the social sciences literature, see Fossett’s lengthy survey (4) or other more recent treatments (5–7). About 10 y ago, physicists discovered this model and analyzed a number of variants of it using techniques of statistical mechanics (8–14). However, to our knowledge, the only rigorous work is ref. 15, which studies the 1D model in which the threshold for happiness is ρ_c = 0.5 and two unhappy families within distance w swap places at rate 1.Here, we will consider a metapopulation version of Schelling’s model in which there are N neighborhoods that have L houses, but we ignore spatial structure within the neighborhoods and their physical locations. We do this to make the model analytically tractable, but these assumptions are reasonable from a modeling point of view. Many cities in the United States are divided into neighborhoods that have their own identities. In Durham, these neighborhoods have names like Duke Park, Trinity Park, Watts-Hillendale, Duke Forest, Hope Valley, Colony Park, etc. They are often separated by busy roads and have identities that are reinforced by e-mail newsgroups that allow people to easily communicate with everyone in their neighborhood. Because of this, it is the overall composition of the neighborhood that is important not just the people who live next door. In addition, when a family decides to move they can easily relocate anywhere in the city.Families, which we suppose are indivisible units, come in two types that we call red and blue. There are ρNL of each type, leaving (1 − 2ρ)NL empty houses. This formulation was inspired by Grauwin et al. (16), who studied segregation in a model with one type of individual whose happiness is given by a piecewise linear unimodal function of the density of occupied sites in their neighborhood. To define the rules of movement, we introduce the threshold level ρ_c such that a neighborhood is happy for a certain type of agent if the fraction of agents of the opposite type is ≤ρ_c. For each family and empty house, movements occur at rates that depend on the state of the source and destination houses:where q, r < 1, and ϵ are small, e.g., 0.1 or smaller. Because there are O(NL) vacant houses, dividing the rates by NL makes each family moves at a rate O(1). Because ϵ is small, happy families are very reluctant to move to a neighborhood in which they would be unhappy, whereas unhappy families move at rate 1 to neighborhoods that will make them happy. As we will see later, the equilibrium distribution does not depend on the values of the rates q and r for transitions that do not change a family’s happiness. We do not have an intuitive explanation for this result.