[Clinicopathological analysis of 105 patients with fibrous dysplasia of cranio-maxillofacial region].

OBJECTIVE: To compare the clinicopathologic features and prognosis of the different types of fibrous dysplasia (FD) of cranio-maxillofacial region, so as to provide a new reference for clinicians to treat these patients and make prognostic judgement. METHODS: Clinical records, radiographic data and pathological information of 105 patients diagnosed with FD or McCune-Albright syndrome (MAS) at the Department of Oral Pathology, Peking University Hospital of Stomatology from January 2013 to December 2020 were collected. The patients were divided into 4 groups: monostotic FDs, polyostotic FDs, MAS and a specific type called craniofacial fibrous dysplasia (CFD) limited in the craniofacial region. The clinicopathological characteristics, treatment and follow-up data of each type were analyzed. RESULTS: Of all the 105 patients, 46 were males and 59 were females, with a male-to-female ratio of 1 ∶1.3. The onset age ranged from 0 to 56 years and the median age was 12 years. On the basis of different involvement conditions, 4 types were divided. The most common type was monostotic FDs (43 cases, 40.95%), including maxilla (29 cases), mandibular (12 cases) and zygoma (2 cases). 32 cases (30.48%) were diagnosed with polyostotic FDs, 7 cases (6.67%) were MAS, and 23 cases (21.90%) were CFDs confirmed by computed tomography (CT) analysis. CFD was clearly distinct from other types of FD, such as the patient gender and the serum alkaline phosphatase level in peripheral blood before operative surgery. The pathologic findings of various types FD were quite similar, whilst the predominant fibrous tissue hyperplasia could be observed in polyostotic FDs and MAS types. CONCLUSION: The clinicopathologic features of FD in the cranio-maxillofacial region are different from the FD lesions in other parts of the body. The clinicopathological features of CFD are significantly different from those of monostotic and polyostotic FDs in the cranio-maxillofacial region. Therefore, the clinicians should pay attention to distinguish CFD in clinic, imaging and pathology aspects, so as to further clarify its features in clinic management and prognosis.

[Detection of SMO gene mutations in odontogenic keratocyst].

Objective: To detect the SMO mutations in odontogenic keratocyst (OKC) and to explore the mechanism behind. Methods: Patients with OKC who received treatment in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology,Peking University, from September 2012 to June 2017 were enrolled. OKC samples from 10 patients diagnosed as naevoid basal cell carcinoma syndrome (NBCCS)-related OKC (4 females and 6 males) and 20 patients diagnosed as sporadic OKC (7 females and 13 males) were collected. Genomic DNAs were extracted from fibrous capsules and epithelial lining respectively. SMO mutations were detected and analyzed by Sanger sequencing. Results: Three SMO mutations were found in one NBCCS-associated OKC who carrying c.2081C>G (p.P694R) mutation) and two sporadic OKC who carrying c.907C>T (p.L303F) mutation and c.1247_1248delinsAA (p.G416E), respectively), among which the first two mutations were novel mutations that had not been reported before. Besides, two mutations in sporadic OKC were not paired with PTCH1 mutations. Conclusions: In addition to PTCH1 gene mutations, SMO gene mutations also exist in OKC which might be related to the development of OKC.

[Clinicopathological analysis of 844 cases of odontogenic keratocysts].

OBJECTIVE: To investigate the clinicopathologic features and prognostic factors in odontogenic keratocyst (OKC), and to provide new reference for clinic treatment and management of these patients. METHODS: Clinicopathological data of 844 cases initially diagnosed as or associated with OKC at Department of Oral Pathology, Peking University Hospital of Stomatology from 2000 to 2018 were collected. The cases were divided into 4 groups: sporadic OKCs (intraosseous, cystic lesion irrelevant to nevoid basal cell carcinoma syndrome), syndromic OKCs, solid OKCs and peripheral OKCs. The patients were follow-up for 6 to 216 months and the factors that might relate to recurrence were analyzed. RESULTS: There were 805 cases (95.4%) of sporadic OKCs, 32 cases (3.8%) of syndromic OKCs, 3 cases of solid OKCs and 4 cases of peripheral OKCs. The main age of sporadic OKCs was 36.03 years with the peak at the second and third decades. Ratio of male and female was 1.27:1. The predilection site was the molar and ramus area of mandibular (56.2%). In the study, 428 cases (71.2%) were unilocular in radiography while 28.8% were multilocular. The recurrent rate of enucleation with the follow-up was 20.1% (118/588) while most of them occurred in 1-3 years after surgery. The recurrent rate of multilocular patients (39.0%) was significantly higher than that of the unilocular. Enucleation after marsupialization (43 cases) or enucleation only (545 cases) showed no difference in recurrence (P>0.05). The syndromic OKCs was younger (main 20.97) and preferred to be multiple compared with sporadic OKCs (30/32, 93.7%). The predilection site was also molar and ramus area of mandibular (41.7%). Age and gender distribution of multiple cases had no significant difference with those in sporadic OKCs. More daughter cysts and epithelial islands were seen (56.3% and 17.9%). Furthermore, the recurrent rate was significantly higher than that of the sporadic OKCs (13/29, 44.9%). But there was no evidence of recurrent-related factors. The age of solid and peripheral OKCs, averaged at 45.00 and 65.75 years, were older than others. Four of peripheral OKCs showed no recurrence after enucleation. CONCLUSION: The recurrence rate of sporadic OKCs after enucleation is 20.1%. The multilocular lesions prefer to be recurrent. There is no significant difference of recurrence with enucleation only or enucleation after marsupialization. Compared with sporadic OKCs, the syndromic patients are younger and easier to be multiple. It tends to be recurrent frequently and rapidly. There are no related factors about recurrence of syndromic patients. The clinicians should considerate comprehensively and make an individual management of therapy and follow-up. Solid and peripheral OKCs are rare and older.

[Method and experience of lymph node examination after gastrectomy with D2 lymphadenectomy for gastric cancer].

The insufficiency of the examined number of lymph nodes after surgery for gastric cancer may undermine the stage of lymph node metastasis, which would have a significant impact on prognostic evaluation and strategy formulation of adjuvant therapy. Under the premise of standard D2 lymphadenectomy, the number of harvested lymph nodes is mainly dependent on the procedures of lymph node examination. Since 2013, our center has set up a special lymph node examination team. In the same year, the average number of harvested lymph nodes in each sample was 46, which was significantly higher than before (average 18 nodes/case in 2004-2012). After continuous quality improvement and regular quality control in 2014, average number of retrieved lymph nodes was 64 per specimen. Therefore, this paper summarizes the methods and experience of lymph node examination in gastric cancer specimens of general surgery in Southern Hospital. The overall construction of the lymph node examination team of gastric cancer in our center mainly includes three parts: establishment of a specialized lymph node examination team, effective standard operating procedures (SOP), and long-term and sustained quality control. The specialized lymph node examination team consists of postgraduate students who are not involved in surgery but have been trained by surgeons. Standard procedures include theoretical reserve of gastric anatomy, surgical observation to correspond to specimens in vitro and in vivo, and standardized specimen processing procedures. Long-term and sustained quality control requires periodic report of lymph node examination data and continuous feedback optimization of the process. Intraoperative lymph node tracing navigation and specimen lymph node intensification are carried out with nanocarbon and indocyanine green dye staining, and then lymph nodes are harvested based on the traditional methods, which can improve the examination rate of lymph nodes, especially for small lymph nodes. Research on lymph node tracing methods, requires multidisciplinary cooperation in particular, will become a hot topic.

Association between interleukin-21 gene polymorphisms (rs12508721) and HBV-related hepatocellular carcinoma.

Interleukin-21 (IL-21), as a multifunctional cytokine, plays an important role in many diseases, such as cancer, inflammatory and autoimmune diseases. We aimed to investigate the relationship between polymorphisms of IL-21 gene and susceptibility of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in a Chinese population. Studied subjects were divided into three groups: 100 patients with HBV-related HCC, 115 patients with chronic HBV infection and 127 healthy controls. Genomic DNA was isolated from peripheral blood, and the polymerase chain reaction-ligase detection reaction (PCR-LDR) method was used to genotype the SNPs (rs2221903, rs907715 and rs12508721) within IL-21 gene. Our results showed that IL-21 polymorphisms were associated with the risk of HCC and chronic HBV infection when compared with healthy controls. The rs2221903A/G AG genotype was associated with a higher risk of chronic HBV infection when compared with healthy controls [AG versus AA + GG, P = 0.036, OR = 1.898, 95%CI = 1.038-3.471]. The rs12508721C/T TT genotype was related with a lower risk of chronic HBV infection and HBV-related HCC than in healthy controls [TT versus CT + CC, P = 0.026, OR = 0.451, 95%CI = 0.221-0.920; P = 0.049, OR = 0.482, 95%CI = 0.231-1.005]. No significant difference in the genotype and allele distrubutions of rs907715G/A SNP was observed in the HBV-related HCC group, chronic HBV-infected group and the healthy control group when compared to each other. Our findings suggest that the rs12508721T/C and rs2221903A/G polymorphisms of IL-21 gene are associated with the susceptibility of HBV-related HCC and chronic HBV infection. The genetic variant may in fact cause protection against the HBV-related HCC. However, the function in these SNPs of IL-21 gene needs to clarify the mechanisms involved in the pathogenesis of HBV-related HCC further.

Lack of association between EPHX1 polymorphism and esophageal cancer risk: evidence from meta-analysis.

The microsomal epoxide hydrolase 1 (EPHX1) Tyr113His and His139Arg polymorphisms have been reported to be associated with esophageal cancer (EC) risk, yet the results of these previous results have been inconsistent or controversial. The objective of this study was to explore whether the EPHX1 Tyr113His and His139Arg polymorphisms confer risk to EC. The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database until May 2013. The association between the EPHX1 Tyr113His and His139Arg polymorphisms and EC risk was pooled by odds ratios (ORs) together with their 95% confidence intervals (95%CIs). A total of eight case-control studies with 1163 EC patients and 1868 controls (seven studies for both Tyr113His and His139Arg polymorphisms, one study only for Tyr113His polymorphism) were eventually identified. We found no association between EPHX1 Tyr113His and His139Arg polymorphisms and EC risk in overall population (For Tyr113His: His vs. Tyr: OR = 1.05, 95%CI = 0.95-1.15, P = 0.379; His/His vs. Tyr/Tyr: OR = 1.04, 95%CI = 0.88-1.22, P = 0.208; His/Tyr vs. Tyr/Tyr: OR = 0.96, 95%CI = 0.80-1.15, P = 0.577; His/His vs. His/Tyr + Tyr/Tyr: OR = 1.10, 95%CI = 0.96-1.26, P = 0.164; His/His + His/Tyr vs. Tyr/Tyr: OR = 1.01, 95%CI = 0.90-1.12, P = 0.543. For His139Arg: Arg vs. His: OR = 1.04, 95%CI = 0.94-1.14, P = 0.465; Arg/Arg vs. His/His: OR = 1.06, 95%CI = 0.91-1.24, P = 0.470; Arg/His vs. His/His: OR = 1.03, 95%CI = 0.91-1.16, P = 0.673; Arg/Arg vs. Arg/His + His/His: OR = 1.04, 95%CI = 0.85-1.27, P = 0.708; Arg/Arg + Arg/His vs. His/His: OR = 1.02, 95%CI = 0.93-1.13, P = 0.617). In subgroup analysis based on ethnicity, significant association has been found in neither EPHX1 Tyr113His nor His139Arg polymorphism. The current meta-analysis suggests no evidence of association between the EPHX1 polymorphism and EC risk.

Fibroblasts isolated from a keratocystic odontogenic tumor promote osteoclastogenesis in vitro via interaction with epithelial cells.

OBJECTIVES: Investigate the role of the epithelial-mesenchymal interaction of keratocystic odontogenic tumor (KCOT) in influencing osteoclastogenesis. MATERIALS AND METHODS: Fibroblasts isolated from KCOT fibrous capsule and normal gingival mucosa were, respectively, co-cultured with human immortalized oral epithelial cells (HIOECs), and the supernatant was collected to make conditioned medium, in which the osteoclastogenesis of osteoclast precursor cell line Raw 264.7 was observed. Genes related to bone resorption (RANKL, OPG, COX-2, and M-CSF) were analyzed by real-time PCR. Antibodies against human sRANKL and inhibitor of COX-2: NS398 were added to conditioned medium to investigate the inhibitory effect on osteoclastogenesis. RESULTS: Compared with co-cultured gingival fibroblasts and HIOECs (GE-CM), the conditioned medium from co-cultured KCOT fibroblasts and HIOECs (KE-CM) induced more osteoclast-like cell formation and increased NFATC1 mRNA in Raw264.7 cells (P < 0.05). Co-cultured KCOT fibroblasts (KF) and HIOECs, respectively, expressed more COX-2 mRNA than the co-cultured gingival fibroblasts (GF) and HIOECs (P < 0.05). While the ratio of RANKL/OPG in HIOECs co-cultured with KF was also significantly higher than that co-cultured with GF (P < 0.05). The anti-human sRANKL antibody in KE-CM inhibited osteoclastogenesis of Raw264.7 cells; however, NS398 displayed little inhibition. CONCLUSION: An interesting phenomenon of osteoclastogenic effect of KE-CM in vitro was investigated, which suggested an indispensable role of epithelial-mesenchymal interaction of KCOT in its bone destruction. It could be at least partly attributed to the up-regulated ratio of RANKL/OPG in epithelium induced by KCOT fibroblasts, the aggressiveness of tumor as result of epithelial-mesenchymal interaction deserves exploration further.

Fibroblasts regulate variable aggressiveness of syndromic keratocystic and non-syndromic odontogenic tumors.

UNLABELLED: Keratocystic odontogenic tumors (KCOTs) are jaw lesions that can be either sporadic or associated with nevoid basal cell carcinoma syndrome, which typically occurs as multiple, aggressive lesions that can lead to large areas of bone destruction and resorption and cause major impairment and even jaw fracture. To clarify the role of fibroblasts in the aggressivness of syndromic (S-) as compared with non-syndromic (NS-) KCOTs, we assessed fibroblasts derived from 16 S- and NS-KCOTs for differences in cell proliferation, multilineage differentiation potential, alkaline phosphatase activity, and osteoclastogenic potential. S-KCOT fibroblasts had proliferative and osteoclastogenic capacity higher than those from NS-KCOTs, as evidenced by higher numbers of tartrate-resistant acid-phosphatase-positive multinuclear cells, expression of cyclooxygenase 2, and ratio of receptor activator of nuclear factor-kappa B ligand to osteoprotegerin. The osteogenic potential was higher for S- than for NS-KCOT fibroblasts and was associated with lower mRNA expression of runt-related transcription factor 2, collagen type I α1, osteocalcin, and osteopontin as well as reduced alkaline phosphatase activity. These results suggest that the distinct characteristics of fibroblasts in KCOTs are responsible for the greater aggressiveness observed in the syndromic subtype. ABBREVIATIONS: AP, alkaline phosphatase; CK, cytokeratin; COL1A1, collagen type I α1; COX-2, cyclooxygenase-2; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-1α, interleukin 1α; KCOT, keratocystic odontogenic tumor; NBCCS, nevoid basal cell carcinoma syndrome; NS-KCOT, non-syndrome-associated KCOT; OCN, osteocalcin; OPG, osteoprotegerin; OPN, osteopontin; RANKL, receptor activator of nuclear factor-kappa B ligand; Runx2, runt-related transcription factor 2; S-KCOT, syndrome-associated KCOT; TAF, tumor-associated fibroblast; and TRAP, tartrate-resistant acid phosphatase.

Development of an antioxidant system after early weaning in piglets.

The objective of this experiment was to investigate oxidative injury and the development of an antioxidant system after early weaning in piglets. A total of 40 piglets (Landrace× Large White, weaned at 14 d after birth) were randomly slaughtered 0 (w0d), 1 (w1d), 3 (w3d), 5 (w5d), or 7 d (w7d; n = 8) after weaning. Concentrations of malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and protein carbonyl and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase were measured in plasma. Gene expressions of antioxidant enzymes were determined by quantitative reverse transcription PCR analysis. The mediation of transcription factor 65 (p65) and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways by oxidative stress was determined by Western blot analysis. Results showed that the plasma MDA level was significantly higher at 3 d (P < 0.05) and that the protein carbonyl level increased at 1, 3, and 5 d (P < 0.05) compared with w0d. In addition, early weaning suppressed the plasma activity of SOD at 1 d (P < 0.05) and reduced the GSH-Px activity at 3 d (P < 0.05). The expression results in the jejunum indicate that the genes related to antioxidant enzymes were downregulated (P < 0.05) at 3 and 5 d after weaning. Uncoupling protein 2 (Ucp2), which is considered to be a feedback regulation on reactive oxygen species generation, tended to decrease in the ileum (P < 0.05) after weaning. Tumor protein 53 (p53), which regulates reactive oxygen species generation, was enhanced (P < 0.05) in the jejunum after weaning. Meanwhile, early weaning suppressed p65 (at 3, 5, and 7 d; P < 0.05) and Nrf2 (at 5 and 7 d; P < 0.05) signals in the jejunum, which might feedback-regulate antioxidant gene expression and promote the development of the antioxidant system. Therefore, we speculate that weaning disrupted oxidative balance and caused oxidative injury in piglets, and this imbalance can recover with the development of an antioxidant system via feedback regulation.

The growth and osteoclastogenic effects of fibroblasts isolated from keratocystic odontogenic tumor.

OBJECTIVES: To investigate the growth characteristics and effects on osteoclastogenesis in fibroblasts isolated from keratocystic odontogenic tumor (KCOT) fibrous capsule. MATERIALS AND METHODS: Fibroblasts isolated from KCOT fibrous capsule and normal gingival mucosa were cultured in vitro. Their colony-forming units and proliferative activity were investigated, and the osteoclastogenic effects were also observed by a co-culture system with osteoclast precursor cell line Raw264.7. The mRNA of several genes related to bone resorption (IL-6, VEGF, COX-2, and M-CSF) was analyzed by real-time PCR. RESULTS: Keratocystic odontogenic tumor fibroblasts developed fewer CFU and had longer population doubling time than gingival fibroblasts (P < 0.05). In contrast to gingival fibroblasts, KCOT fibroblasts expressed less IL-6, COX-2, and M-CSF (P < 0.05); however, the Raw264.7 co-cultured with KCOT fibroblasts developed more osteoclast-like cells and expressed higher level of nfatc1 than that co-cultured with gingival fibroblasts. Increased COX-2 expression and VEGF expression were detected in KCOT fibroblasts and Raw264.7 co-culture system (P < 0.05). CONCLUSION: Although KCOT fibroblasts showed lower level of cell proliferation than gingival fibroblasts, higher osteoclastogenic ability was detected when co-cultured with Raw264.7. These results suggest that the cell-cell interaction in the co-culture system, possibly by increasing COX-2 and VEGF expression, may be responsible for the increased osteoclastogenic effects of KCOT fibroblasts.

Effect of dietary arginine and N-carbamoylglutamate supplementation on reproduction and gene expression of eNOS, VEGFA and PlGF1 in placenta in late pregnancy of sows.

The objectives of this study were to investigate the potential mechanisms of dietary arginine (Arg) and N-carbamoylglutamate (NCG) supplementation on reproductive performance of sows. Twenty-seven crossbred (Landrace×Large White) sows with similar body weight and parity at day (90±1) of gestation were assigned randomly into 3 groups (n=9) control group, Arg group, NCG group, and fed with the following diets: a control diet, and the control diet supplemented with 1.0% Arg or 0.1% NCG. Litter size was recorded. Blood samples were obtained for biochemical analyses. Placenta chorioallantoic membrane tissue collected immediately after birth to preserve in RNA stabilizer for mRNA analysis of endothelial nitric oxide synthase (eNOS), endothelial growth factor a (VEGFA) and placenta growth factor 1 (PlGF1) by real time-PCR. The results showed that compared with the control group, the average birth weight of all piglets born alive were 16.2% and 14.3% higher in the Arg and NCG groups (P<0.05), respectively; plasma VEGFA was higher in the Arg group (P<0.05). The expression of VEGFA in the allantochorion tissue of the NCG-supplemented group was higher (P<0.01), and tended to be higher in the Arg-supplemented group (0.05

Effects of oral supplementation with glutamate or combination of glutamate and N-carbamylglutamate on intestinal mucosa morphology and epithelium cell proliferation in weanling piglets.

To evaluate the effects of glutamate (Glu) or combination of Glu and N-carbamylglutamate (NCG) on intestinal mucosa morphology and epithelium cell proliferation, 18 piglets weaned at 21 d (BW 5.56 ± 0.51 kg) were grouped into 3 treatments and fed one of the following diets for 20 d: a standard diet (SD), SD+Glu(1%), or SD+Glu(1%)+NCG(0.05%). All the piglets were killed for intestinal mucosa collection, and real-time PCR was used to detect mRNA abundance of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and ß-catenin. The results showed that compared with the control group, adding Glu or Glu+NCG to the diet resulted in a higher villus height and mucosal thickness (P < 0.05) in the jejunum. However, the villus height/crypt depth ratio was unaltered. The RT-PCR results showed that Glu+NCG significantly increased PCNA mRNA abundance in both jejunum and ileum (P < 0.05), while they also significantly increased ß-catenin and VEGF mRNA abundance in ileum (P < 0.05). Only Glu increased PCNA mRNA abundance in the jejunum (P < 0.05) and ß-catenin mRNA in the jejunum (P < 0.05). These results indicated that oral supply of Glu improved intestinal mucosa morphology, and combined Glu and NCG may have favorable effects on intestinal epithelium cell proliferation than Glu alone.

Differences in collagen fibres in the capsule walls of parakeratinized and orthokeratinized odontogenic cysts.

Epithelial-mesenchymal interactions are thought to play an important role in the pathogenesis of odontogenic lesions. Keratocystic odontogenic tumour (KCOT) is a benign cystic neoplasm with a characteristic parakeratinized epithelial lining, which differs histologically and behaviourally from the so-called orthokeratinized odontogenic cyst (OOC). The purpose of this study was to investigate the differences in collagen fibres within the fibrous tissue walls of KCOT and OOC. Formalin-fixed paraffin-embedded tissue samples from 15 cases of KCOT and 15 cases of OOC were collected. Paraffin sections were stained with picrosirius red and observed under a standard light microscope using optical polarization. Unicystic ameloblastoma (UA, 15 cases) and subcutaneous epidermoid cysts (EC, 15 cases) were included in the study for comparative purposes. Significant difference was detected between the polarization colours in the fibrous tissue walls of KCOT and OOC (P<0.05), whilst no significant differences were found between KCOT and UA and between OOC and EC (P>0.05). The stromal collagen fibres of KCOT were different from those of OOC, but similar to those of UA, which suggests that the stroma of KOCT may play an important role in determining the neoplastic behaviour of the lesion through epithelial-mesenchymal interaction.

The odontogenic keratocyst: a cyst, or a cystic neoplasm?

The odontogenic keratocyst (OKC, currently designated by the World Health Organization as a keratocystic odontogenic tumor) is a locally aggressive, cystic jaw lesion with a putative high growth potential and a propensity for recurrence. Although it is generally agreed that some features of OKCs are those of a neoplasia, notably the relatively high proliferative rate of epithelial cells, controversies over the behavior and management of OKCs still exist. This article is intended to review this intriguing entity and to summarize the findings of recent studies related to the nature of OKCs and their clinical and therapeutic implications. Recent advances in genetic and molecular research, i.e., PTCH1 mutations and involvement of the Hedgehog signaling pathway, have led to increased knowledge of OKC pathogenesis which hints at potential new treatment options, although the question of whether the OKC is a cyst or a cystic neoplasm is yet to be answered with certainty. Since some advocate a more conservative treatment for OKCs, notably marsupialization and decompression, future treatment strategies may focus on molecular approaches and eventually reduce or eliminate the need for aggressive surgeries.

Inhibitions of vascular endothelial growth factor expression and foam cell formation by EGb 761, a special extract of Ginkgo biloba, in oxidatively modified low-density lipoprotein-induced human THP-1 monocytes cells.

It has been reported that oxidatively modified low-density lipoprotein (Ox-LDL) involvement with vascular endothelial growth factor (VEGF) and foam cell formation play an important role in atherosclerosis (AS). Protective effects of Ginkgo biloba extract (EGb 761) have been identified for some cardiovascular and neurological disorders. The aim of this study was to investigate whether Ox-LDL regulates VEGF expression in human THP-1 monocytes, as well as the effect of EGb 761 on VEGF expression and the formation of foam cells. After exposure to Ox-LDL alone or in combination with EGb 761 for up to 48h, cell viability was measured using the MTT assay. VEGF protein content in the supernatant was analyzed by enzyme-linked immunosorbent assay (ELISA). VEGF mRNA was determined by real-time PCR. To determine the effect of EGb 761 on foam cell formation, an Ox-LDL-induced foam cell model was used. Ox-LDL inhibited the growth of THP-1 cells and EGb 761 increased the cell survival rate. Ox-LDL markedly increased VEGF expression in THP-1 cells in a time- and concentration-dependent manner, which was significantly suppressed by EGb 761. EGb 761 also inhibited monocyte/macrophage-derived foam cell formation. These results suggest that Ox-LDL is involved in the development of human AS through VEGF induction in monocytes, and that EGb 761 prevents in vitro atherogenesis, probably via downregulation of VEGF expression in monocytes and inhibition of monocyte/macrophage-derived foam cell formation. The findings suggest a mechanism for the in vivo anti-AS effect of EGb 761 and support its potential clinical use in AS.

Soft-tissue osteoma in the pterygomandibular space: report of a rare case.

Osteoma is a slow-growing, benign and uncommon neoplasm located primarily in the region of the maxillofacial skeleton. An extraskeletal soft-tissue osteoma is exceedingly rare. Here, we report a case of soft-tissue osteoma occurring in the pterygomandibular space in a 66-year-old woman. The patient complained of a hard mass superior to the left posterior teeth. Clinical examination did not reveal any extraoral swelling, facial asymmetry or difficulty in mouth opening, and the regional lymph nodes were non-palpable. CT images revealed well-circumscribed dense, radiopaque masses located between the left side of the maxilla and the lateral plate of the left pterygoid process and the left ramus of the mandible. Intraoperatively, the masses were completely surrounded by soft tissues with no attachment to the bone. Histological examination indicated the diagnosis of cancellous osteoma.

PTCH1 and SMO gene alterations in keratocystic odontogenic tumors.

UNLABELLED: Keratocystic odontogenic tumors (KCOTs, previously known as odontogenic keratocysts) are aggressive jaw lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (NBCCS). Mutations in the PTCH1 (PTCH) gene are responsible for NBCCS and are related in tumors associated with this syndrome. Mutations in the SMO gene have been identified in basal cell carcinoma and in medulloblastoma, both of which are features of NBCCS. To clarify the role of PTCH1 and SMO in KCOTs, we undertook mutational analysis of PTCH1 and SMO in 20 sporadic and 10 NBCCS-associated KCOTs, and for SMO, 20 additional cases of KCOTs with known PTCH1 status were also included. Eleven novel (1 of which occurred twice) and 5 known PTCH1 mutations were identified. However, no pathogenic mutation was detected in SMO. Our findings suggest that mutations are rare in SMO, but frequent in PTCH1 in sporadic and NBCCS-associated KCOTs. ABBREVIATIONS: NBCCS, nevoid basal cell carcinoma syndrome; KCOTs, keratocystic odontogenic tumors; BCCs, basal cell carcinomas.

Intravitreal steroids for macular edema in diabetes.

BACKGROUND: Macular edema is secondary to leakage from diseased retinal capillaries and is an important cause of poor central visual acuity in patients with diabetic retinopathy. OBJECTIVES: This review evaluated the effectiveness and safety of intraocular steroids in treating diabetic macular edema (DME). SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE in June 2007, reference lists, Science Citation Index and conference proceedings. SELECTION CRITERIA: We included randomized clinical trials (RCTs) evaluating any form of intravitreal steroids for treating DME. DATA COLLECTION AND ANALYSIS: Two authors independently assessed eligibility, methodological quality and extracted data. We performed meta-analyses when appropriate. MAIN RESULTS: Seven studies, involving 632 DME eyes were included. Four examined the effectiveness of intravitreal triamcinolone acetate injection (IVTA), three examined intravitreal steroids implantation (fluocinolone acetonide implant (FAI) or dexamethasone drug delivery system (DDS)). Two trials were at low risk of bias, one was at median risk of bias, two were at high risk of bias and the remaining two were at unclear risk of bias. The preponderance of data suggest a beneficial effect from IVTA. Comparing IVTA with controls, the mean difference in visual acuity was -0.15 LogMAR (95% CI -0.21 to -0.09) at 3 months (based on three trials), -0.23 LogMAR (95% CI -0.33 to -0.13) at 6 months (two trials), -0.29 LogMAR (95% CI -0.47 to -0.11) at 9 months (one trial), and -0.11 LogMAR (95% CI -0.20 to -0.03) at 24 months (one trial), all in favor of IVTA. The relative risk (RR) for one or more lines improvement in visual acuity was 2.85 (95% CI 1.59 to 5.10) at 3 months (two trials), 1.25 (95% CI 0.66 to 2.38) at 6 months (one trial), and 2.17 (95% CI 1.15 to 4.11) at 24 months (one trial), all in favor of IVTA. We did not find evidence for three or more lines improvement in visual acuity. The mean difference in retinal thickness was -131.97 um (95% CI -169.08 to -94.86) at 3 months (two trials), -135.00 um (95% CI -194.50 to -75.50) at 6 months (one trial), -133.00 um (95% CI -199.86 to -66.14) at 9 months (one trial), and -59.00 um (95% CI -103.50 to -14.50) at 24 months (one trial), all in favor of IVTA. The RR for at least one grade macular edema resolution was 5.15 (95% CI 2.23 to 11.88) at 3 months in favor of IVTA (one trial). Two trials reported improved clinical outcome when FAI was compared to standard of care. Beneficial effect was also observed in one dexamethasone DDS trial. Increased intraocular pressure and cataract formation were side effects requiring monitoring and management. AUTHORS' CONCLUSIONS: RCTs included in this review suggest that steroids placed inside the eye by either intravitreal injection or surgical implantation may improve visual outcomes in eyes with persistent or refractory DME. Since the studies in our report focused on chronic or refractory DME, the question arises whether intravitreal steroids therapy could be of value in other stages of DME, especially the earlier stages either as standalone therapy or in combination with other therapies, such as laser photocoagulation.

PTCH germline mutations in Chinese nevoid basal cell carcinoma syndrome patients.

OBJECTIVES: PTCH, the human homologue of the Drosophila segment polarity gene, patched, has been identified as the gene responsible for nevoid basal cell carcinoma syndrome. The aim of this study was to investigate PTCH gene mutation in Chinese patients with nevoid basal cell carcinoma syndrome. MATERIALS AND METHODS: DNA was isolated from both odontogenic keratocyst tissue and peripheral blood of five patients with syndrome and one patient with only multiple odontogenic keratocysts, and mutational analysis of the PTCH gene performed by direct sequencing after amplification of all 23 exons by polymerase chain reaction (PCR). RESULTS: A previously reported germline mutation (c.2619C>A) was identified in two familial cases involving the mother and the daughter, with the mother also carrying a novel somatic mutation (c.361_362insGAGC). Three novel germline PTCH mutations (c.1338_1339insGCG, c.331delG and c.1939A>T) were detected in three unrelated patients with syndrome. The patient with multiple odontogenic keratocysts who failed to fulfill the diagnostic criteria of the syndrome also carried a novel germline mutation (c.317T>G). CONCLUSION: The frequent germline PTCH mutations detected in our series provide further evidence for the crucial role of PTCH in the pathogenesis of nevoid basal cell carcinoma syndrome in Chinese.