Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle.

Glioblastoma multiforme (GBM) has remained one of the most lethal and challenging cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in irinotecan can induce toxicities that outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM.

Who is who in oral cancer?

Great attention has been attached to explore the association between oral bacteria and oral cancer. Recently, four common inhabitants of oral cavity, Porphyromonas gingivalis, Fusobacterium nucleatum, Treponema denticola and Streptococcus anginosus, have been identified as potential etiologic bacterial agents for oral carcinogenesis. They might promote the oncogenesis and progression of oral cancer by induction of chronic inflammation, enhancement of migration and invasiveness, inhibition of cell apoptosis, augment of cell proliferation, suppression of immune system and production of carcinogenic substances. Thus, this review will focus on the possible mechanisms of these oral bacteria contributing to occurrence and development of oral cancer, and the potential clinical implications of utilizing oral bacteria on the diagnosis, prevention and treatment of oral cancer will be discussed.

Multiple Treatment Meta-Analysis of Intra-Articular Injection for Temporomandibular Osteoarthritis.

PURPOSE: The purpose of the present study was to compare the efficacy of intra-articular injections of different agents for temporomandibular osteoarthritis (TMJOA) using a network meta-analysis. MATERIALS AND METHODS: A comprehensive search strategy was performed in multiple English and Chinese language electronic databases. Randomized controlled trials comparing the effect of intra-articular injections of different agents to treat TMJOA were included in accordance with the inclusion and exclusion criteria. The bias of risk in each study was assessed, with data extraction performed independently by 2 reviewers. The primary outcomes included pain intensity and maximal mouth opening. RESULTS: A total of 11 trials were included in the present study, and 10 different agents (ie, hyaluronic acid, dexamethasone, prednisolone, betamethasone, betamethasone plus hyaluronic acid, morphine, tramadol, platelet-derived growth factor [PDGF], placebo, arthrocentesis alone) administered using intra-articular injections were assessed. The evidence from the direct comparisons showed that arthrocentesis plus sodium hyaluronate resulted in significantly better pain relief outcomes compared with arthrocentesis alone. Also, the visual analog scale score was further reduced to 1.27 by PDGF injection after arthrocentesis (arthrocentesis plus PDGF) compared with arthrocentesis alone. Morphine and tramadol had a high probability of being the best treatment for pain control, with PDGF ranked third. When considering pain relief, arthrocentesis plus sodium hyaluronate resulted in a better outcome than arthrocentesis alone, and arthrocentesis plus PDGF was better than arthrocentesis plus placebo. PDGF injections had the greatest probability of being the best treatment for improving joint opening, followed by sodium hyaluronate. CONCLUSIONS: Tramadol, morphine, and PDGF injections after arthrocentesis were effective in the treatment of TMJOA with excellent effects in reducing pain and improving joint opening. Hyaluronic acid injections were effective for improving the maximal mouth opening of patients with TMJOA in the short-term. The combination of a corticosteroid and hyaluronic acid injection reduced the symptoms of TMJOA more than corticosteroid injections alone, but not of hyaluronic acid alone.

Is There a Difference in Intra-Articular Injections of Corticosteroids, Hyaluronate, or Placebo for Temporomandibular Osteoarthritis?

PURPOSE: Corticosteroids are widely used for treatment of temporomandibular joint (TMJ) osteoarthritis (OA). This study investigated the effects of corticosteroids on TMJOA compared with placebo or hyaluronate. MATERIALS AND METHODS: The authors designed and implemented a systematic review and meta-analysis to compare the effects of intra-articular injection of corticosteroid, hyaluronate, or placebo for patients with TMJOA. The authors searched related randomized controlled studies electronically in multiple English- and Chinese-language electronic databases. The predictor variable was intra-articular injection with corticosteroid, hyaluronate, or placebo. Primary outcome variables were pain intensity and maximal mouth opening. Other variables included success rate and adverse events. Meta-analyses were performed with Rev Man 5.3. RESULTS: Eight studies met the inclusion criteria. Meta-analysis showed that corticosteroid injections after arthrocentesis were superior to placebo in relieving pain as assessed with the visual analog scale (mean difference [MD], -0.74; 95% confidence interval [CI], -1.34 to -0.13; P = .02; I2 = 0%) in the long-term, but was inferior in increasing maximal mouth opening (MD, -2.06; 95% CI, -2.76 to -1.36; P < .00001; I2 = 28%). Although corticosteroid and hyaluronate injections without arthrocentesis decreased pain and improved maximal mouth opening, the corticosteroid group had a significantly lower success rate (odds ratio = 0.41; 95% CI, 0.17-1.00; P = .05; I2 = 0%) than the hyaluronate group in the short term. CONCLUSION: Corticosteroid injections after arthrocentesis are recommended for patients with TMJOA to relieve joint pain rather than increase maximal mouth opening. Corticosteroid and hyaluronate have marked effectiveness on TMJOA; however, hyaluronate might be the better alternative to some extent.

Paresthesia in dentistry: The ignored neurotoxicity of local anesthetics.

Local anesthetics are frequently used by dentists to relieve localized discomfort of the patient and improve treatment conditions. The risk of paresthesia after local anesthesia is frequently encountered in dental clinics. The neurotoxicity of local anesthetics is a disregarded factor in paresthesia. The review summarizes the types of common local anesthetics, incidence and influencing factors of paresthesia after local anesthesia, and systematically describes the neurotoxicity mechanisms of dental local anesthetic. Innovative strategies may be developed to lessen the neurotoxicity and prevent paresthesia following local anesthesia with the support of a substantial understanding of paresthesia and neurotoxicity.

Transcriptomic dissection of termite gut microbiota following entomopathogenic fungal infection.

Termites are social insects that live in the soil or in decaying wood, where exposure to pathogens should be common. However, these pathogens rarely cause mortality in established colonies. In addition to social immunity, the gut symbionts of termites are expected to assist in protecting their hosts, though the specific contributions are unclear. In this study, we examined this hypothesis in Odontotermes formosanus, a fungus-growing termite in the family Termitidae, by 1) disrupting its gut microbiota with the antibiotic kanamycin, 2) challenging O. formosanus with the entomopathogenic fungus Metarhizium robertsii, and finally 3) sequencing the resultant gut transcriptomes. As a result, 142531 transcripts and 73608 unigenes were obtained, and unigenes were annotated following NR, NT, KO, Swiss-Prot, PFAM, GO, and KOG databases. Among them, a total of 3,814 differentially expressed genes (DEGs) were identified between M. robertsii infected termites with or without antibiotics treatment. Given the lack of annotated genes in O. formosanus transcriptomes, we examined the expression profiles of the top 20 most significantly differentially expressed genes using qRT-PCR. Several of these genes, including APOA2, Calpain-5, and Hsp70, were downregulated in termites exposed to both antibiotics and pathogen but upregulated in those exposed only to the pathogen, suggesting that gut microbiota might buffer/facilitate their hosts against infection by finetuning physiological and biochemical processes, including innate immunity, protein folding, and ATP synthesis. Overall, our combined results imply that stabilization of gut microbiota can assist termites in maintaining physiological and biochemical homeostasis when foreign pathogenic fungi invade.

Carcinosarcoma of the deep lobe of the parotid gland in the parapharyngeal region: A case report.

BACKGROUND: Salivary carcinosarcoma is an extremely rare tumor containing both malignant epithelial and mesenchymal constituents. This article reports a rare case of carcinosarcoma with salivary duct carcinoma and osteosarcoma as the tumor components. The clinicopathological characteristics, treatment, and prognosis are discussed in conjunction with the literature. CASE SUMMARY: A 48-year-old man presented with a complaint of a mass in the right parotid region. Osteosarcoma was first considered for assessment by fine-needle aspiration cytology. Physical examination revealed a mass measuring approximately 4 cm × 3.5 cm × 3 cm. The mass, the whole lobe of the right parotid gland, and the right mandible were completely removed during surgery. Postoperative histopathology confirmed carcinosarcoma of the salivary gland. CONCLUSION: A definite diagnosis of salivary gland carcinosarcoma can only be obtained after complete surgical resection.

Primordial odontogenic tumour: a case report.

Odontogenic primary tumor is a rare benign odontogenic tumor in the maxillofacial area. A case of odontogenic primary basal tumor is reported. The clinicopathological features and treatment principles are discussed in the literature.

A Classification-Guided Segmentation Algorithm Based on Deep Learning for Epithelium Segmentation in Histopathological Images of Radicular Cysts.

In histopathological analysis of radicular cysts (RCs), lesions in epithelium can provide pathologists with rich information on pathologic degree, which is helpful to determine the type of periapical lesions and make precise treatment planning. Automatic segmentation and localization of epithelium from whole slide images (WSIs) can assist pathologists to complete pathological diagnosis more quickly. However, the class imbalance problem caused by the small proportion of fragmented epithelium in RCs imposes challenge on the typical automatic one-stage segmentation method. In this paper, we proposed a classification-guided segmentation algorithm (CGSA) for accurate segmentation. Our method was a two-stage model, including a classification network for region of interest (ROI) location and a segmentation network guided by classification. The classification stage eliminated most irrelevant areas and alleviated the class imbalance problem faced by the segmentation model. The results of 5-fold cross validation demonstrated that CGSA outperformed the one-stage segmentation method which was lacking in prior epithelium localization information. The epithelium segmentation achieved an overall Dice's coefficient of 0.722, and intersection over union (IoU) of 0.593, which improved by 5.5% and 5.9% respectively compared with the one-stage segmentation method using UNet.Clinical Relevance- This work presents a framework for automatic epithelium segmentation in histopathological images of RCs. It can be applied to make up for the shortcomings of manual annotation which is labor-intensive, time-consuming and objective.

[Mandibular Langerhans cell histiocytosis: a case report].

Langerhans cell histiocytosis is commonly found in cranial bones and rarely found in the mandible. This article presents a case of mandibular Langerhans cell histiocytosis and discusses its pathogeny, clinical features, diagnosis, and treatment.

[Improvement program on pretreatment of acid decalcified tissue in hematoxylin-eosin staining].

OBJECTIVE: To explore the treatment conditions of acid decalcified specimens and improve the poor quality of sections and unclear structure of hematoxylin-eosin (HE) staining caused by the change in pH in tooth and hard tissue after acid decalcification. METHODS: A total of 20 cases of oral pathological specimens that contain hard tissues were decalcified and treated with routine treatment, concentrated ammonia water immersion treatment, and saturated lithium carbonate solution immersion treatment. The quality and HE staining effects of hard tissue sections treated with different methods were compared. RESULTS: Compared with routine treatment, lithium carbonate saturated solution treatment showed complete sections. Hematoxylin is strongly stained, the nucleus is clear, and the cytoplasm is bright. CONCLUSIONS: Soaking acid decalcified specimens in lithium carbonate saturated solution before embedding in dehydration can neutralize the acidic environment of the tissue. The quality of sections and HE staining effect are improved and are suitable for the pretreatment of acid decalcified tissue samples of oral pathology.

Maxillofacial injuries caused by the 2008 Wenchuan earthquake in China.

PURPOSE: To describe the pattern of maxillofacial injuries sustained by survivors of the 2008 Wenchuan earthquake in the West China Hospital of Stomatology from May 12 to June 23, 2008. PATIENTS AND METHODS: Cross-sectional data were analyzed using hospital-based records of earthquake survivors admitted to the West China Hospital of Stomatology. A self-designed form to record information about variables such as the gender and age of the survivors and type of location of soft and hard tissue injuries was used. RESULTS: The age of earthquake survivors of maxillofacial injuries ranged from 4 to 84 years. Fractures and soft tissue injuries were the most common of all injuries in the maxillofacial region, constituting 40.7% and 38.9%, respectively. Thirteen patients (11.5%) had dental injuries and 9 (8.0%) also had other organ injuries. CONCLUSION: During the Wenchuan earthquake, the incidence of maxillofacial injuries in survivors was relatively low compared with injury in other organs. However, because most injuries were maxillofacial fractures and facial soft tissue damage, special attention was paid to maxillofacial injury when planning and providing emergency treatment. The effective management of earthquake injuries and those caused by other types of disaster requires a multidisciplinary approach, and maxillofacial surgeons should form an integral part of this multidisciplinary team.

The maintenance of an oral epithelial barrier.

Oral epithelial barrier consists of closely controlled structure of the stratified squamous epithelium, which is the gateway to human bodies and encounters a huge burden of microbial, airborne and dietary antigens, as well as masticatory damage. Once this barrier is destroyed, it will trigger bone loss, tissue damage and microbial dysbiosis and lead to diseases, such as periodontitis, oral mucosal diseases and oral cancer. Recently, increasing evidences showed that different factors including microorganism, saliva, proteins and immune components have been considered to play a critical role in the disruption of oral epithelial barrier. Herein, we discussed mechanisms governing the maintenance of oral epithelial barrier. Besides, the role of oral epithelial barrier failure in oral carcinogenesis will also be talked about.

Porphyromonas gingivalis Promotes 4-Nitroquinoline-1-Oxide-Induced Oral Carcinogenesis With an Alteration of Fatty Acid Metabolism.

Microbiota has been widely considered to play a critical role in human carcinogenesis. Human papilloma virus, hepatitis B and C virus, and Helicobacter pylori are implicated in the pathogenesis of cancer of uterine cervix, liver, and stomach, respectively. However, whether Porphyromonas gingivalis (P. gingivalis), a common Gram negative oral bacteria, is associated with oral carcinogenesis still remains unclear and its underlying mechanism needs to be addressed. Here, we established a combined experimental system of 4NQO-induced oral carcinoma model and chronic periodontitis model and investigated the effects of P. gingivalis infection on oral carcinogenesis and fatty acid metabolism during oral carcinogenesis. The data showed that in this animal model, P. gingivalis infection induced mice periodontitis, increased the tongue lesion size and multiplicity of each mouse and promoted oral cancer development. P. gingivalis treatment significantly increased the level of free fatty acids and altered the fatty acid profile in tongue tissues and the serum of mice. And P. gingivalis induced the formation of fatty liver of the mice. Besides, immunohistochemical analysis and qRT-PCR showed that the expression of fatty-acid synthase and acetyl-CoA carboxylase 1 were increased in the tongue and liver tissues of 4NQO-treated mice infected with P. gingivalis. These results showed that P. gingivalis promoted oral carcinogenesis and aggravated disturbance of fatty acid metabolism, indicating a close association among P. gingivalis, lipid metabolic and oral carcinogenesis.

[Effect of Radix scutellariae on the growth and form of Porphyromanus endodontics in vitro].

OBJECTIVE: To provide scientific evidence for underpinning the use of Radix Scutellariae in the treatment of pulp and periapical diseases. METHODS: Using minute amount serial dilution test, this study assessed the minimal inhibitory concentration of Radix Scutellariae extreact against Porphyromanus Endodontics. The forms of Porphyromanus endodontics treated with Radix Scutellariae extract at different concentrations were observed by use of SEM. RESULTS: The MIC of Radix Scutellariae extract was determined to be 1 mg/ml. Radix Scutellariae changed the forms of Porphyromanus endodontics, making them become bigger, longer and crumbled. CONCLUSION: Radix Scutellariae could inhibit the growth of Porphyromanus Endodontics.

[Ossifying fibromyxoid tumor in the mandible: a case report].

Ossifying fibromyxoid tumor is an uncommon neoplasm with uncertain histogenesis. This tumor is usually characterized by a small, painless mass in the subcutaneous tissue or limb muscles. In this case, an ossifying fibromyxoid tumor of the mandible was reported, and relevant literature was reviewed.

Regulation of plasminogen activator activity and expression by cyclic mechanical stress in rat mandibular condylar chondrocytes.

To investigate the mechanism of cartilage degradation induced by overloading in the temporomandibular joint (TMJ), the effect of cyclic mechanical compressive stress on the activity of plasminogen activator (PA) and the expression of the predominant components of the PA system were analyzed in cultured mandibular condylar chondrocytes (MCCs) in rats. MCCs were exposed to cyclic mechanical compressive stress (2000, 4000 and 6000 µ strain) at 0.5 Hz by a four­point bending system. The activity of PA was determined by hydrolysis of the chromogenic substrate H­D-Val-Leu-Lys­pNA (S­2251). The mRNA and protein expression levels of urokinase­type PA (uPA), tissue­type PA (tPA), uPA receptor (uPAR) and PA inhibitor 1 (PAI­1) were detected by qPCR and western blot analysis, respectively. Cyclic mechanical stress at 4000 and 6000 µ strain induced the expression of uPA, tPA and uPAR, and increased the activity of PA. Furthermore, cyclic mechanical stress at 6000 µ strain also inhibited the expression of PAI­1. Analysis of pericellular proteolytic activity demonstrated that PA functioned as the active enzyme in excessive mechanical stress responsiveness (e.g., 4000 and 6000 µ strain) largely via uPAR, not PAI­1. Cyclic mechanical stress at 2000 µ strain induced the expression of tPA and PAI­1; however, it did not change the activity of PA. These results suggested that the mechanical induction of uPA, tPA and uPAR upregulated PA activity, which may provide a proteolytic environment of extracellular matrix components and subsequently contribute to the cartilage degradation in TMJ osteoarthritis.

Maxillofacial space infection experience in West China: a retrospective study of 212 cases.

OBJECTIVES: Our objectives were to analyze the clinical features of maxillofacial space infection (MSI) patients admitted to the West China Hospital of Stomatology over a five-year period, and to identify potential risk factors associated with life-threatening complications. METHODS: A retrospective medical chart review was performed and the sociodemographic and clinical characteristics of patients with MSI were evaluated. RESULTS: A total of 212 patients were enrolled in this study, including 125 males (59.0%) and 87 females (41.0%), with an age range of 1-88 years (median 47.5 years). The most common cause of MSI was odontogenic infection (56.1%). The submandibular space was the space most commonly involved in both single space and multiple space infections (37.5% and 29.1%, respectively). One hundred and two patients (48.1%) self-medicated before admission, and the time from onset of symptoms until presentation was longer in those who self-medicated compared with those who did not (p=0.028). Fifty-seven patients (26.9%) had life-threatening complications and six died (2.8%). In multivariate analysis, age, self-medication, admission temperature, respiratory difficulty, and underlying diseases were found to be risk factors for life-threatening complications. The most common occupation of the patients was farmer (54.7%). Among the farmers, 72.4% had an odontogenic etiology; however, 91.7% of the farmers with odontogenic space infections had not undergone dental treatment before admission. CONCLUSIONS: Our experience suggests that the management of MSI should be more aggressive when the above risk factors are present, in order to avoid life-threatening complications. In addition, considering the poor medical conditions in the rural areas of West China, standard dental care and services should be provided in the future to replace self-medication.

Analysis of 46 maxillofacial fracture victims in the 2008 Wenchuan, China earthquake.

PURPOSE: At 14:28 hours on May 12, 2008, a massive earthquake wracked most areas of Sichuan, China, causing catastrophic human loss. The aim of this study was to delineate the characteristics of victims with maxillofacial fractures in this disaster. PATIENTS AND METHODS: A descriptive analysis was conducted based on the medical records of earthquake maxillofacial injuries casualties transferred to West China Hospital of Stomatology, Sichuan University, after the earthquake. Data regarding demographic details, psychological status, patterns, anatomic sites, etiology, concomitant injuries, and management of earthquake maxillofacial fractures were evaluated. RESULTS: A total of 46 maxillofacial fracture patients' records of 28 (60.9%) males and 18 (39.1%) females were included in this study, with peak incidence (32.6%) in the elderly age group (older than 50 years). The most common etiology of earthquake maxillofacial fractures was building collapse (71.7%). The mandible (65.2%) was the most frequent site of the maxillofacial fracture, followed by the zygomatic complex (21.7%) and maxilla (13.0%). The most prevalent of maxillofacial fracture pattern was multiple and/or comminuted fractures (56.5%), which accounted for 72.7% (24/33) in building collapse injury group. There were 9 (19.6%) patients with significant concomitant injuries and the most common site of concomitant injuries was the head (4 cases) and extremity (4 cases). Four (8.7%) patients' maxillofacial fractures were treated conservatively, 16 (34.8%) underwent closed reduction and fixation, and 26 (56.5%) underwent open reduction and rigid internal fixation (RIF). Apart from 3 patients (6.5%) who showed infection, all patients with facial fractures achieved successful bony union with an acceptable occlusion and facial form. Additionally, it is noteworthy that all patients in our study presented the symptoms of posttraumatic stress disorder (PTSD). CONCLUSION: There is a variation of mechanism of injuries, age group, severity, patterns, concomitant injuries, and management of earthquake maxillofacial fractures. Knowledge of these characteristics provides useful strategies for patient care and prevention of further complications. A multidisciplinary and coordinated approach is important for optimum stabilization and ongoing treatment of victims of building collapse injury. The high percentage of PTSD confirms that psychologists should form an integral part of this multidisciplinary team.

[The effect of Redix Scutellariae on butyrate of Porphyromonas endodontalis in vitro].

OBJECTIVE: To study the effect of Radix Scutellariae on the growth, metabolism of Porphyromonas endodontalis (P.e), as a preparation for studying the mechanism of Radix Scutellariae in treating pulp and periapical diseases. METHODS: P.e was chosen as the experimental bacteria. Radix Scutellariae was extracted by means of reflux with 80% ethanol. The value of MIC of Radix Scutellariae was measured by minute amount serial dilusion test, and the production of butyrate was measured by high liquid chromatograph(HPLC). RESULTS: Radix Scutellariae could inhibit the growth of P.e, of which the MIC was 100 mg/L. Following the increase in concentration of Radix Scutellariae, the amount of butyrate decreased to (3.527 +/- 0.009) mg/L, (3.048 +/- 0.005) mg/L, (2.490 +/- 0.011) mg/L, (2.209 +/- 0.016) mg/L, respectively (P < 0.05). CONCLUSION: Radix Scutellariae could inhibit the growth and metabolism of P.e and might be an effective agent in treating pulp and periapical diseases.