[Establishment and validation of a nomogram model for evaluating the metastasis of lymph nodes posterior to the right recurrent laryngeal nerve in papillary thyroid carcinoma].

Objective: To explore the related factors of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in papillary thyroid carcinoma (PTC) and establish a nomogram model for evaluating LN-prRLN metastasis. Methods: The clinical data of patients with PTC who underwent surgery in the Department of Thyroid Surgery of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were retrospectively analyzed. Multivariate logistic regression was used to analyze the related factors of LN-prRLN metastasis and construct a nomogram model for evaluating LN-prRLN metastasis. Meanwhile, the data of 120 patients from January to June 2022 were also collected for external verification. Results: A total of 466 patients with PTC were enrolled, including 106 males and 360 females, and aged 44 (33, 53) years. There were 280 cases in the training group and 186 cases in the internal validation group, respectively. Multivariate logistic regression analysis showed that age (OR=0.966, 95%CI: 0.938-0.996, P=0.027), tumor size (OR=1.048, 95%CI: 1.001-1.098, P=0.043), multifocality (OR=2.459, 95%CI: 1.268-4.767, P=0.008), right central lymph node metastasis reported by ultrasound (OR=3.099, 95%CI: 1.255-7.651, P=0.014), extrathyroid extension (OR=3.561, 95%CI: 1.255-10.102, P=0.017) and serum thyroglobulin level (OR=1.010, 95%CI: 1.001-1.018, P=0.032) were related factors for LN-prRLN metastasis. The area under the curve (AUC) values of receiver operating characteristic (ROC) curves of the training group, internal validation group and external validation group were 0.765 (95%CI: 0.691-0.840), 0.747 (95%CI: 0.657-0.837) and 0.754 (95%CI: 0.639-0.869), respectively. Conclusion: Dissection of the LN-prRLN is recommended for young PTC patients with large tumor size, multifocality, right central lymph node metastasis reported by ultrasound, extrathyroid extension and high serum thyroglobulin level.

[Investigation and analysis of airborne allergenic pollen in 4 districts and 5 counties of Hohhot City].

Objective: To investigate the species, concentration and seasonal trends of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. Methods: The Department of allergy, Beijing Shijitan Hospital Affiliated to Capital Medical University conducted a cross-sectional study about monitoring the airborne allergenic pollen from August 1, 2021 to July 31, 2022 by the gravitational method in 4 districts and 5 counties of Hohhot City, which include Yuquan District, Xincheng District, Huimin District, Saihan District, Tuoketuo County, Helingeer County, Tumotezuoqi County, Wuchuan County and Qingshuihe County. Daily pollens were counted and identified by optical microscopy, and the data were analyzed. Results: The airborne allergenic pollen was collected every month all year round in 4 districts and 5 counties of Hohhot city. Through the whole year of the total quantity of pollens ranged from 24 850 to 50 154 grains per 1 000 mm2 and two peaks of pollen concentration in air were observed,which happened in spring (from March to May) and in summer and autumn (from July to September). In spring, the main pollens were tree pollens, which principally distributed in Populus pollen (18.29%), Ulmus pollen (8.36%), Pinus pollen (6.20%), Cupressaceae pollen (5.23%), Betulaceae pollen (2.73%), Salix pollen (1.80%) and Quercus pollen (1.16%). In summer and autumn, the main pollens were weed pollens, which mainly included Artemisia pollen (42.73%), Chenopodiaceae pollen or Amaranthaceae pollen (7.46%), Poaceae pollen (2.26%), Humulus pollen or Cannabis pollen (0.60%). Conclusion: There were two peaks of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. In the spring peak of pollen, the main airborne pollens were tree pollens. In the summer and autumn peak of pollen, the main airborne pollens were weed pollens. The Artemisia pollen was the most major airborne pollen in this area.

Exosomes Derived from Endothelial Cells Inhibit Neointimal Hyperplasia Induced by Carotid Artery Injury in Rats via ROS-NLRP3 Inflammasome Pathway.

This study attempted to investigate whether exosomes derived from rat endothelial cells (EC-Exo) attenuate intimal hyperplasia after balloon injury using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence staining, Evans blue staining, and Western blotting. The results indicated that EC-Exo inhibited intimal hyperplasia in the carotid artery after balloon injury, promoted re-endothelialization, and reduced vascular inflammation and ROS-NLRP3-mediated cell pyroptosis. Thus, EC-Exo can inhibit neointimal hyperplasia after carotid artery injury in rats presumably by inhibiting the ROS-NLRP3 inflammasome and phenotypic transformation of vascular smooth muscle cells.

[The clinical value of further accurate staging of pT2 gastric cancer based on the depth of invasion].

Objective: To investigate the clinical value of pT2 gastric cancer staging pT2a and pT2b according to the depth of muscularis propria invasion in evaluating the prognosis of gastric cancer. Methods: According to the 8th edition of TNM staging system for gastric cancer proposed by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), patients with gastric cancer who underwent radical surgery in the Fourth Hospital of Hebei Medical University from January 1, 2008 to January 1, 2015 were selected and divided into pT2a and pT2b stage group according to the depth of tumor invasion. The 5-year overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Results: The median follow-up time of 1 411 patients with postoperative pathological pT2 stage was 68.8 months, and 1 347 patients (95.46%) received complete follow-up data. The 5-year OS rate was 65.85%, and the 5-year DFS rate was 67.83 %. The 5-year OS rate and 5-year DFS rate of 709 pT2a patients were 72.50% and 73.91%, respectively. The 5-year OS rate and 5-year DFS rate of 638 pT2b patients were 58.46% and 61.13%, respectively, significantly different from those of the pT2a group (P<0.001). Hierarchical analysis was performed according to N staging. The 5-year OS rates of pT2aN0M0 (274 cases), pT2aN1M0 (192 cases), pT2aN2M0 (147 cases), pT2aN3aM0 (59 cases) and pT2aN3bM0 (37 cases) were 83.58 %, 72.40 %, 68.71 %, 54.24 % and 35.12 %, respectively. The 5-year DFS rates were 84.67 %, 77.08 %, 67.35 %, 54.24 % and 35.14 %, respectively. In the pT2b group, the 5-year OS rates of pT2bN0M0 (209 cases), pT2bN1M0 (166 cases), pT2bN2M0 (127 cases), pT2bN3aM0 (78 cases) and pT2bN3bM0 (58 cases) were 76.08%, 62.05%, 56.69%, 37.18% and 17.24%, respectively, and the 5-year DFS rates were 80.86%, 69.28%, 54.33%, 35.90% and 15.52%, respectively. Under the same N stage, the OS rates of patients in the pT2a group were better than those in the pT2b group (P values were 0.023, 0.034, 0.034, 0.043 and 0.018, respectively). When the N stage was N0 and N1, there was no significant difference in the 5-year DFS rate between the pT2a group and the pT2b group (P values were 0.199 and 0.090, respectively). When the N stages were N2, N3a and N3b, the difference between the pT2a stage group and the pT2b stage group was statistically significant (P values were 0.027, 0.022 and 0.025, respectively). Conclusions: In the 8th edition of AJCC/UICC gastric cancer staging system, pT2 stage can be divided into pT2a stage (invasion of superficial muscularis) and pT2b stage (invasion of deep muscularis) according to the infiltration depth of muscularis propria. There are significant differences in prognosis between the two groups. Combined with the number of lymph node metastasis, the prognosis of patients with pT2 gastric cancer can be more accurately evaluated.

[The effect of cancer nodules on survival prognosis of gastric cancer patients].

Objective: To explore the relationship between cancer nodules and clinicopathological characteristics of gastric cancer, and analyze its impact on survival prognosis of gastric cancer patients. Methods: A retrospective analysis of 2 386 patients with gastric cancer who underwent radical surgery from January 1, 2012 to January 1, 2015 in the Third Surgery Department of the Fourth Hospital of Hebei Medical University was performed. The relationship between cancer nodules and clinicopathological characteristics of gastric cancer and its impact on survival prognosis of gastric cancer patients were analyzed. Results: Among the 2 386 patients, there were 459 cases (19.24%) with cancer nodules, and 1 927 cases (80.76%) without cancer nodules. Logistic multivariate analysis showed that pT staging (P=0.036), pN staging (P=0.024), pTNM staging (P=0.032), Borrmann classification (P=0.008), vascular tumor thrombus (P=0.001) were independent risk factors for cancer nodules. The complete follow-up date of 2 273 cases (95.26%) of 2 386 patients with gastric cancer were obtained. A total of 1 259 patients relapsed and 1 152 died during the follow-up period. The 5-years overall survival (OS) rate was 49.32%, and the 5-years disease-free survival (DFS) rate was 44.61%. Among them, the 5-years OS rate and DFS rate of those with cancer nodules were 26.76% and 24.94%, while the 5-years OS rate and DFS rate of those without cancer nodules were 54.75% and 49.34%, respectively (P<0.001). Patients with positive cancer nodules were divided into 3 groups according to the number of cancer nodules: 1 (115 cases), 2 to 3 (202 cases), and more than 4 (124 cases). The 5-years OS rates of 3 groups were 41.74%, 30.69% and 10.48%, respectively (P<0.001). The 5-years DFS rates were 40.00%, 28.22% and 9.68%, respectively (P<0.001). Cox multivariate analysis showed that histological type (P=0.004), pT staging (P=0.007), pN staging (P=0.004), pTNM staging (P=0.002), vascular tumor thrombus (P=0.034), cancer nodules (P=0.005) and the number of cancer nodules (P=0.001) were independent risk factors for the prognosis of gastric cancer patients, and postoperative adjuvant chemotherapy (P=0.043) was a protective factor for the prognosis of gastric cancer patients. Conclusion: Cancer nodules are closely related to the tumor stage and prognosis of gastric cancer patients. The number of cancerous nodules is an independent risk factor for the prognosis of gastric cancer patients.

Upregulation of LINC00504 is associated with aggressive progression and poor prognosis in non-small cell lung cancer.

OBJECTIVE: Long noncoding RNA LINC00504 (LINC00504) has been demonstrated to be dysregulated in several tumors. However, its function in tumor progression remains largely unclear. The goal of our present study was to determine the expressions of LINC00504 in non-small cell lung cancer (NSCLC) and its clinical associations. PATIENTS AND METHODS: The expressions of LINC00504 were detected in 181 pairs of NSCLC specimens and adjacent normal tissues using qRT-PCR assays. Chi-square tests were applied to analyze the associations of LINC00504 expressions with various clinicopathological parameters of NSCLC specimens. The possible associations between LINC00504 expressions and overall survival were investigated using Kaplan-Meier assays. Univariate and multivariate assays were performed to further determine the prognostic value of LINC00504 levels in NSCLC patients. RESULTS: We showed that LINC00504 expressions were distinctly decreased in clinical NSCLC specimens compared to adjacent non-tumor specimens (p < 0.01). High LINC00504 expressions were strongly associated with TNM stage (p = 0.038) and lymph node status (p = 0.010). In addition, Kaplan-Meier analysis indicated that NSCLC patients with high LINC00504 expression tend to have shorter overall survival (p = 0.0036). More importantly, the results of multivariate analysis indicated LINC00504 as an independent prognostic marker (p = 0.0028). CONCLUSIONS: These findings revealed that LINC00504 might act as a prognostic biomarker for NSCLC patients.

[Application of laparoscopic exploration combined with abdominal exfoliative cytology in the diagnosis and treatment of locally advanced gastric cancer].

Objective: To explore the clinical significance of laparoscopic exploration combined with abdominal exfoliative cytology in the diagnosis and treatment of patients with locally advanced gastric cancer. Methods: Inclusion criteria: (1) cancer confirmed by gastroscopy and pathology without preoperative anti-tumor treatment; (2) no distant metastases found in preoperative imaging examinations; (3) patients without surgical contraindications and being tolerant to surgery; (4) patients were willing to undergo laparoscopic exploration and abdominal exfoliative cytology examination, and signed informed consent. A retrospective cohort study method was used to collect and analyze the clinicopathological data of 225 patients with advanced gastric cancer based on the above inclusion criteria from a prospective, multicenter, open, randomized controlled phase III clinical trial (registration No. NCT01516944) conducted between February 2012 and December 2018 in The Fourth Hospital of Hebei Medical University, including 162 males and 63 females with age ranged from 23 to 78 years old. Forty-five patients (20.0%) were classified as Borrmann type I to II, and 180 (80.0%) were classified as type III to IV. All the patients underwent laparoscopy and peritoneal lavage cytology under general anesthesia. Laparoscopic exploration sequence: left and right diaphragm→liver and spleen→parietal peritoneum→pelvic cavity→greater omentum, small intestine, mesentery→transverse colon mesentery →stomach. Contents of exploration: (1) with or without ascites; (2) whether metastatic lesions existed in the peritoneum, mesentery, omentum and Douglas pouch; (3) whether metastasis existed on the liver surface; (4) whether the gastric lymph nodes were swollen; (5) whether infiltration occurred on the gastric serosa surface; (6) whether gastric wall was stiff. The left and right subphrenic, the abdominal and pelvic peritoneum, and the mesentery were rinsed with 500 ml of sterilized normal saline. Position of the reverse Trendelenburg was used in the Douglas pouch. The peritoneal lavage fluid under the liver and spleen fossa was collected. Cytological examination was carried out for exfoliative tumor cells. Evaluation criteria: (1) peritoneal metastasis (P): P0 meant no peritoneal metastasis, P1 meant peritoneal metastasis; (2) free peritoneal cancer cells (CY): CY0 meant no cancer cells in peritoneal lavage fluid cytology, CY1 meant cancer cells in peritoneal lavage fluid cytology. The results of patients undergoing laparoscopic exploration combined with abdominal exfoliative cytology, treatment options and prognosis were analyzed. Kaplan-Meier method was used to calculate the survival rate and a survival curve was drawn. Log-rank test was used for survival analysis. Results: After laparoscopic exploration in 225 patients, clinical staging was corrected in 68 (30.2%) patients, of whom 7 (3.1%) downstaged and 61 (27.1%) increased in staging. Of 164 patients evaluated as P0CY0 after the first laparoscopy and peritoneal cytology examination, 126 underwent radical D2 surgery, and the other 38 patients were found to have later local lesions or extensive fusion of local lymph nodes, so then received neoadjuvant chemotherapy. Twenty-nine patients evaluated as P1CY0 or P1CY1 and 32 patients as P0CY1 underwent intraperitoneal hyperthermic chemotherapy+conversion therapy, and then a second laparoscopic exploration was performed to determine the treatment plan. In total, the original treatment regimens were changed after laparoscopic exploration in 99(44.0%) cases. The follow-up period ended in January 2019. The overall 2-year survival rate of 225 patients was 64.0%. As for those who were evaluated as P0CY0, P0CY1 and P1CY0-1 after the first laparoscopic exploration, the 2-year overall survival rate was 70.7%, 65.6% and 24.1%, respectively (P=0.002). The stratified analysis showed that among 180 patients with stage III tumor, after laparoscopic exploration combined with abdominal exfoliative cytology, 125 patients were found to be P0CY0, 28 were P0CY1, and 27 were P1CY0-1, whose 2-year overall survival rates were 70.4%, 64.3%, and 29.6% respectively, and the difference among these 3 groups was statistically significant (P=0.009). Conclusion: Laparoscopic exploration combined with abdominal exfoliative cytology in patients with locally advanced gastric cancer has important clinical guiding significance in improving accurate staging, treatment options and prognosis evaluation, and can avoid non-therapeutic open-close abdominal surgery.

Enhanced expression of circular RNA hsa_circ_000984 promotes cells proliferation and metastasis in non-small cell lung cancer by modulating Wnt/ß-catenin pathway.

OBJECTIVE: In recent years, several circular RNAs (circRNAs) have been identified to play important roles in human cancers. However, the exact effects and molecular mechanisms of circRNAs in non-small cell lung cancer (NSCLC) progression are still unknown. In this study, we aimed to investigate the effect of circular hsa_circ_000984 on NSCLC. PATIENTS AND METHODS: Quantitative real-time PCR was performed to detect the expression levels of hsa_circ_000984 in NSCLC tissues and cell lines. The associations between the expression of hsa_circ_000984 and clinicopathological parameters and patients' survival were analyzed. The cell growth was detected by CCK-8 assay and colony formation assay. Cell migration and invasion assays were used to study the changes in cell migration and invasion capacity. Western blot was performed to analyze the possible relationship between hsa_circ_000984 and the genes downstream of the Wnt/ß-catenin pathway. RESULTS: We found that hsa_circ_000984 was highly expressed in NSCLC tissues and cell lines and correlated with advanced TNM stage and lymph nodes metastasis. The clinical assays indicated that patients with high hsa_circ_000984 expression had shorter overall survival and disease-free survival. The functional investigations showed that the knockdown of hsa_circ_000984 suppressed NSCLC cells proliferation, migration, invasion, and EMT. Moreover, hsa_circ_000984 displayed its oncogenic roles by modulating the activation of Wnt/ß-catenin pathway, which was demonstrated by measuring the expression levels of, ß-catenin, c-myc, and cyclin D1. CONCLUSIONS: Our findings may facilitate a better understanding of hsa_circ_000984, and it might be a potential prognostic biomarker and treatment target for NSCLC patients.

N1-guanyl-1,7-diaminoheptane enhances the chemosensitivity of NSCLC cells to cetuximab through inhibition of eukaryotic translation initiation factor 5A2 activation.

OBJECTIVE: N1-guanyl-1, 7-diaminoheptane (GC7), an inhibitor of deoxyhypusine synthase has been shown to exhibit significant anti-cancer activity. However, the biological role of eukaryotic translation initiation factor 5A2 activation (EIF5A2) and GC7 on drug resistance in non-small cell lung cancer (NSCLC) has not been investigated. In this study, we aimed to investigate the therapeutic effect of GC7 combined with cetuximab in NSCLC therapy. MATERIALS AND METHODS: The current study used cell viability assays, EdU incorporation assays, and western blot to detect that the GC7 exhibited synergistic cytotoxicity with cetuximab in NSCLC. RESULTS: CCK-8 assays showed that combined treatment with GC7 and cetuximab significantly inhibited the viabilities in three NSCLC cell lines. In addition, EdU incorporation assays also indicated that GC7 co-treatment remarkably enhanced the cetuximab sensitivity in NSCLC cells. Nevertheless, down-regulation of EIF5A2 diminished the regulatory role of GC7 in cetuximab cytotoxicity. Western blot showed that transfection of EIF5A2 siRNA significantly suppressed the protein expression of EIF5A2 in NSCLC cells. CONCLUSIONS: These findings demonstrate that combined treatment with GC7 could enhance cetuximab sensitivity by inhibiting EIF5A2 in NSCLC cells, implying the potential clinical application of GC7 in cetuximab-based chemotherapy for NSCLC patients.

Analysis of pulmonary microvasculature changes after photodynamic therapy delivered to distant sites.

Photodynamic therapy (PDT) can exert local damage by direct tumor cytotoxicity, by disruption of the microvasculature or by a combination of these effects. Although systemic effects after PDT of small tissue areas (< 1% total body surface area) are unlikely, treatment of larger areas may result in an accumulated effect leading to toxicity. Several investigators have described animal death after high dose PDT to tumors on the hind limb of animals and hypothesized that a toxic shock syndrome caused by vasoactive agents released after PDT is responsible. Because one of the most vulnerable organs to toxic shock injury is the lung, we studied the systemic effects of local PDT to this organ by intravital microscopy using a pulmonary window chamber. The PDT treatment conditions (25 mg/kg Photofrin, 24 h, 150 J/cm2 630 nm, maximum area 6.28 cm2) were chosen that produce systemic toxicity and lethality in rats. Adhesion of leukocytes in the lung was monitored in vivo using anti-CD-13-labeled microspheres. The progression of pulmonary edema was assessed by monitoring the leakage of rhodamine-labeled albumin and by wet-to-dry lung weight ratios. Although an increased leukocyte adherence was observed and a significant number of animals died after the extensive PDT treatment, no biologically significant lung edema could be demonstrated. These data indicate that lung edema and acute respiratory distress syndrome is not the cause of death in these animals and that the toxicity is related to other mechanisms including circulatory shock after extensive muscle damage.

Research on hemodynamics of cerebral arteriovenous malformation by Doppler ultrasound.

Combined extracranial and transcranial Doppler (TCD) instruments were used to study the hemodynamics of 20 patients with cerebral arteriovenous malformation (AVM) proved angiographically. It was discovered that the flow velocities in AVM-feeding arteries and their proximal arteries were increased; the increase of flow velocities in feeding arteries close to AVM was more remarkable than that in feeding-arteries proximal to extracranial internal carotid artery far from AVM; pulsating indexes of AVM-feeding arteries were decreased; increase of flow velocities in AVM-feeding arteries was related to the decrease of pulsating index; the flow velocities of nontapering feeding arteries were faster than those of tapering arteries; the greater the size of AVM, the faster the velocity in feeding artery; and the flow velocities and pulsating indexes of AVM-feeding arteries were gradually recovered to normal 3-5 weeks after resection of AVM. It is believed that increase of flow velocity in AVM-feeding artery is associated with distention and decreased resistance of flow in AVM-feeding artery. TCD combined with CT scans are helpful to the diagnosis of AVM. Combination of TCD and cerebral angiography (CAG) to evaluate comprehensively the preoperative hemodynamics of AVM and to monitor postoperative changes is helpful to detecting cerebral steal due to steal leakage in circle of Willis and preventing the hazardous postoperative complications caused by pressure breakthrough of normal perfusion.

[Further experience in the diagnosis and treatment of sphenoidal ridge meningioma].

72 cases with sphenoidal ridge meningioma operated on in recent 12 years in our department were reported. In the microsurgical group and non-microsurgical group, the rate of total removal of medial tumors was 65% and 20% respectively (P < 0.01); lateral tumors was 100% and 77% respectively (P > 0.05); the mortality was 6.7% and 11.9% respectively (P > 0.05); the rate of neurological impaired was 33.3% and 64.3% respectively (P < 0.001); good rate of following up for a long time was 87.5% and 16.7% in medial group respectively (P < 0.05); 66.7% and 75% in lateral group respectively (P > 0.05). It is believed that application of CT and angiography and microsurgical technique is helpful to the diagnosis and treatment of sphenoidal ridge meningioma.

BMP-2 and titanium particles synergistically activate osteoclast formation.

A previous study showed that BMP-2 (bone morphogenetic protein-2) and wear debris can separately support osteoclast formation induced by the receptor activator of NF-κB ligand (RANKL). However, the effect of BMP-2 on wear debris-induced osteoclast formation is unclear. In this study, we show that neither titanium particles nor BMP-2 can induce osteoclast formation in RAW 264.7 mouse leukemic monocyte macrophage cells but that BMP-2 synergizes with titanium particles to enhance osteoclast formation in the presence of RANKL, and that at a low concentration, BMP-2 has an optimal effect to stimulate the size and number of multinuclear osteoclasts, expression of osteoclast genes, and resorption area. Our data also clarify that the effects caused by the increase in BMP-2 on phosphorylated SMAD levels such as c-Fos expression increased throughout the early stages of osteoclastogenesis. BMP-2 and titanium particles stimulate the expression of p-JNK, p-P38, p-IkB, and P50 compared with the titanium group. These data suggested that BMP-2 may be a crucial factor in titanium particle-mediated osteoclast formation.

Adenovirus-mediated siRNA targeting TNF-α and overexpression of bone morphogenetic protein-2 promotes early osteoblast differentiation on a cell model of Ti particle-induced inflammatory response in vitro.

Wear particles are phagocytosed by macrophages and other inflammatory cells, resulting in cellular activation and release of proinflammatory factors, which cause periprosthetic osteolysis and subsequent aseptic loosening, the most common causes of total joint arthroplasty failure. During this pathological process, tumor necrosis factor-alpha (TNF-α) plays an important role in wear-particle-induced osteolysis. In this study, recombination adenovirus (Ad) vectors carrying both target genes [TNF-α small interfering RNA (TNF-α-siRNA) and bone morphogenetic protein 2 (BMP-2)] were synthesized and transfected into RAW264.7 macrophages and pro-osteoblastic MC3T3-E1 cells, respectively. The target gene BMP-2, expressed on pro-osteoblastic MC3T3-E1 cells and silenced by the TNF-α gene on cells, was treated with titanium (Ti) particles that were assessed by real-time PCR and Western blot. We showed that recombinant adenovirus (Ad-siTNFα-BMP-2) can induce osteoblast differentiation when treated with conditioned medium (CM) containing RAW264.7 macrophages challenged with a combination of Ti particles and Ad-siTNFα-BMP-2 (Ti-ad CM) assessed by alkaline phosphatase activity. The receptor activator of nuclear factor-κB ligand was downregulated in pro-osteoblastic MC3T3-E1 cells treated with Ti-ad CM in comparison with conditioned medium of RAW264.7 macrophages challenged with Ti particles (Ti CM). We suggest that Ad-siTNFα-BMP-2 induced osteoblast differentiation and inhibited osteoclastogenesis on a cell model of a Ti particle-induced inflammatory response, which may provide a novel approach for the treatment of periprosthetic osteolysis.

BMP-2 and titanium particles synergistically activate osteoclast formation

A previous study showed that BMP-2 (bone morphogenetic protein-2) and wear debris can separately support osteoclast formation induced by the receptor activator of NF-κB ligand (RANKL). However, the effect of BMP-2 on wear debris-induced osteoclast formation is unclear. In this study, we show that neither titanium particles nor BMP-2 can induce osteoclast formation in RAW 264.7 mouse leukemic monocyte macrophage cells but that BMP-2 synergizes with titanium particles to enhance osteoclast formation in the presence of RANKL, and that at a low concentration, BMP-2 has an optimal effect to stimulate the size and number of multinuclear osteoclasts, expression of osteoclast genes, and resorption area. Our data also clarify that the effects caused by the increase in BMP-2 on phosphorylated SMAD levels such as c-Fos expression increased throughout the early stages of osteoclastogenesis. BMP-2 and titanium particles stimulate the expression of p-JNK, p-P38, p-IkB, and P50 compared with the titanium group. These data suggested that BMP-2 may be a crucial factor in titanium particle-mediated osteoclast formation.

Traumatic carotid cavernous fistula concomitant with pseudoaneurysm in the sphenoid sinus.

SUMMARY: This study was designed to elucidate the generating mechanism, diagnosis and treatment of traumatic carotid cavernous fistula (tCCF) concomitant with pseudoaneurysm in the sphenoid sinus. Six cases of tCCF concomitant with pseudoaneurysm in the sphenoid sinus were analyzed in this study. Clinical history, neurological examination, CT and MRI scans, pre- and postembolization cerebral angiograms and follow-up data were included. All patients presented with massive epistaxis and symptoms of tCCF. The pseudoaneurysms and fistulas were occluded with detachable balloons, and preservation of the parent artery in two cases. One patient also had indirect carotid cavernous fistula (CCF) on the contralateral side embolized by transfacial vein approach with microcoils. Complete symptom resolution was achieved in all cases, without procedure related complications. During the follow-up period all patients returned to work. Falling from a high speed motorcycle without wearing a helmet may be one of the main causes of this disease. The site of impact during the accident mostly localizes in the frontal and lateral of the orbit. Intracavernous sinus hypertension of tCCF combining with fracture of the lateral wall of the sphenoid may lead to the formation of a pseudoaneurysm in the sphenoid sinus. MRI scan is very helpful in the diagnosis of this disease before the patient receives angiography. Detachable balloon occlusion of the pseudoaneurysm and fistula is a safe and efficient treatment.