Use of free flaps with supermicrosurgery for oncological reconstruction of the maxillofacial region.

Supermicrosurgery involves the dissection and anastomosis of vessels<0.8 mm in diameter with minimal donor site morbidity. This study evaluated the feasibility and outcomes of free flaps using supermicrosurgery to repair oncological defects in the maxillofacial region. Forty-two patients were treated with supermicrosurgery to repair oncological defects in the maxillofacial region between December 2015 and February 2021. The supermicrosurgery technique was used for different types of free flap, including 24 superficial circumflex iliac artery perforator flaps, seven anterolateral thigh flaps, three peroneal artery perforator flaps, five medial femoral condyle osteo-adipofascial flaps, and three profunda artery perforator flaps. An artery-to-artery approach was used in 38 patients; venous grafts for anastomosis were used in four patients to resolve an arterial discrepancy. Forty-one flaps (97.6%) survived. Thirty-six patients (85.7%) healed without any complications; three flaps required revision surgery including one lost, one demonstrated wound dehiscence, and two demonstrated wound infection. Supermicrosurgery is a useful complement to conventional microsurgery in head and neck reconstruction.

[Efficacy and prognostic analysis of 125I brathytherapy combined with chemotherapy for pediatric parameningeal rhabdomyosarcoma].

Objective: To analyze the efficacy and prognostic factors in children with parameningeal rhabdomyosarcoma (PMRMS) treated by 125I brachytherapy combined with chemotherapy. Methods: A retrospective analysis of the clinical data of 33 pediatric patients treated with 125I brachytherapy combined with chemotherapy in Peking University Stomatological Hospital from July 2013 to October 2018 was carried out to analyze the efficacy and prognostic factors. Results: Among the 33 patients, 19 were males and 14 were females; the median age was 4 years old (1-12 years old). There were 17 cases with embryonic type, 9 cases with alveolar type, and 7 with undifferentiated type; 26 cases with original PMRMS, and 7 cases with recurrent PMRMS. The tumors occurred in subtemporal-mastoid area in 15 patients, while nasopalatine-paranasal area in 6 cases, and parapharyngeal-submandibular area in 12 cases. There were 28 patients in IRS Ⅲ, and 5 patients in IRS Ⅳ. As for the risk level, 28 cases were in the middle-risk group and 5 cases in the high-risk group. The median follow-up time was 52 months. The 1, 3, and 5-year local control rates were 87.9%, 58.6%, and 49.9%, and the 1, 3, and 5-year survival rates were 93.8%, 60.5%, and 47.5%, respectively. The 5-year local control rate and 5-year survival rate of 12 patients with the tumor in the parapharyngeal-submandibular area were 91.7% and 100%, respectively. The 5-year local control rate and 5-year survival rate of the 6 patients with tumor in the nasopalatine-paranasal area were both 83.3%. The 3-year local control rate and 3-year survival rate of the 15 patients with tumor in the subtemporal-mastoid area were 17.5% and 21.4%. The multivariate survival analysis using Cox proportional risk regression model showed that the tumor located in the subtemporal-mastoid area was an independent risk factor affecting the 5-year overall survival rate (HR=38.40, 95%CI: 4.87-302.52, P=0.001). Within 3 months after 125I seed implantation, the incidence of acute radiotherapy adverse reactions in all patients was 84.8% (28/33). Twenty-one patients (63.6%) had a grade 1 acute radiotherapy reaction, and 7 cases (21.2%) had a grade 2 acute radiotherapy reaction. No acute radiotherapy adverse reactions of grade 3 or 4 occurred. Three months after 125I seed implantation, the adverse reactions were significantly alleviated, and no adverse reactions of grade 3 or above such as skin ulcer or salivary gland fibrosis occurred, and no serious cranio-maxillofacial deformities occurred. Conclusions: 125I seed brachytherapy combined with chemotherapy has a definite clinical effect in the treatment of children with parameningeal rhabdomyosarcoma. The prognosis of rhabdomyosarcoma in the parapharyngeal-submandibular area and nasopalatine-paranasal area is better than that in the subtemporal-mastoid area.

Venous superdrainage using superficial circumflex iliac vein in deep circumflex iliac artery perforator flap with iliac crest for oromandibular reconstruction.

The deep circumflex iliac artery perforator flap with iliac crest (DCIAPF) is considered a favourable single-flap option for oromandibular reconstruction. The aim of this study was to evaluate the effectiveness of venous superdrainage using the superficial circumflex iliac vein (SCIV) in the DCIAPF for oromandibular reconstruction. The data of 22 patients (12 female, 10 male) aged 10-76 years (median 53 years) who underwent simultaneous oromandibular reconstruction with a DCIAPF were reviewed retrospectively. Eleven patients received the DCIAPF with SCIV for superdrainage (group A) and another 11 patients received the conventional single-pedicled DCIAPF flap (group B). No flap loss occurred in either group. Venous congestion due to relative venous insufficiency was significantly more frequent in group B (P=0.045). There was no significant difference in the incidence of partial flap necrosis and wound dehiscence, or in the total operation time between the two groups. Superdrainage using the SCIV has the potential to reduce the incidence of venous congestion due to relative venous insufficiency in DCIAPF used for oromandibular reconstruction.

Recurrent adamantinoma of the mandible.

Adamantinoma is an extremely rare tumour originating from bone that can be divided into classical and osteofibrous dysplasia (OFD)-like adamantinoma. This low-grade malignancy almost exclusively occurs in long bones, and only few cases of mandibular adamantinoma have been reported. Here, we report the case of a 30-year-old female with a 2-year history of right mandible tenderness. Radiological examinations showed a lytic lesion involving the right mandible without a well-defined margin. Biopsy confirmed the diagnosis of adamantinoma. She underwent a segmental mandibulectomy and reconstruction with a fibula flap. The definitive diagnosis was OFD-like adamantinoma. However, the tumour recurred after 5 years. The residual mandible and fibula flap were widely involved. A total mandibulectomy was performed. Five years later, there is no evidence of recurrence or metastasis. We recommend that adamantinoma be treated by radical resection with clear margins, and long-term surveillance is necessary due to the likely high local recurrence rate and the potential for late tumour metastasis.

Comparison of outcomes using radiotherapy or brachytherapy after resection of primary adenoid cystic carcinoma in oral and maxillofacial regions.

We wished to investigate the outcome of surgery combined with external-beam radiotherapy (EBRT) or brachytherapy (125I seeds) for the treatment of primary adenoid cystic carcinoma (ACC) of the oral and maxillofacial region. Data of patients with primary ACC were reviewed retrospectively. Patients were divided into EBRT and brachytherapy groups. Wide tumor excision was done to achieve negative margins. Standard radiotherapy in the EBRT group was 60 Gy. A treatment-planning system was used to create implantation plans with a prescribed dose of 60-120 Gy and 125I seeds were implanted postoperatively. Kaplan-Meier method and log-rank tests were used to analyze local control and survival. The median duration of followup was 66.1 and 46.8 months for the EBRT group and brachytherapy group, respectively. There was no significant difference in local control, control of metastasis to regional lymph nodes, or control of distant metastasis between the two groups. There was no significant difference in overall survival, disease-specific survival, or disease-free survival in the two groups at 3 years and 5 years. The prevalence of complications in the brachytherapy group was lower than that in the EBRT group. Both methods elicited good treatment effects, but the prevalence of adverse events was lower in the brachytherapy group.

Anti-IFNAR treatment does not reverse neuropsychiatric disease in MRL/lpr lupus mice.

OBJECTIVE: Many systemic lupus erythematosus patients display a type I interferon (IFN) signature, and IFNα levels positively correlate with disease severity. Previous studies blocking the type I IFN pathway systemically in lupus models showed some beneficial effects. However, its effects on neuropsychiatric manifestations have yet to be carefully assessed, even though IFNα has been associated with induction of depression. Our aim was to investigate whether disrupting the type I IFN pathway would attenuate the development of murine neuropsychiatric lupus. METHODS: Female MRL/lpr mice were administered an antitype I IFN receptor (IFNAR) antibody or a control antibody intraperitoneally three times weekly for 12 weeks starting at age 4-5 weeks. Behavior was assessed during and at the end of the treatment schedule. RESULTS: No significant differences were seen between the anti-IFNAR- and control-treated mice when assessing for depression-like behavior or cognitive dysfunction, although anti-IFNAR antibody-treated mice displayed significant decreases in levels of IFN-stimulated genes. Anti-IFNAR treatment also did not significantly improve brain histology, cellular infiltration, or blood-brain barrier integrity. CONCLUSIONS: Surprisingly, our results showed no improvement in neuropsychiatric disease and suggest that the role of IFNAR signaling in the pathogenesis of neuropsychiatric lupus continues to need to be carefully assessed.

Resveratrol alleviates osteoporosis through improving the osteogenic differentiation of bone marrow mesenchymal stem cells.

OBJECTIVE: To investigate the protective effect of Resveratrol (RES) on TNF-α-induced inhibition of osteogenic differentiation, thus alleviating the progression of osteoporosis (OP). MATERIALS AND METHODS: OP model in rats was first conducted by performing ovariectomy (OVX). Rats were randomly divided into sham group, OVX group, and RES+OVX group. Body weight of each rat was regularly recorded every week. Bone mineral density (BMD) of rat femoral metaphysis was measured by micro-CT. Changes in radial degrees and loads of rat femora were examined through three-point bending experiments. Relative levels of OCN and Runx2 in each group were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Alkaline phosphatase (ALP) activity and calcification ability were assessed through ALP staining and alizarin red staining, respectively. Bone mesenchymal stem cells (BMSCs) were extracted from healthy rats and divided into control group, Tumor necrosis factor-α (TNF-α) group, RES group, and TNF-α+RES group based on different treatments. Relative levels of OCN and Runx2, ALP activity, and calcification ability in each group were detected in the same way. Finally, protein levels of NF-κB and ß-catenin in BMSCs were determined. RESULTS: Rats in each group gained body weight during the experimental period, especially those in OVX group and RES+OVX group. No significant difference in the body weight was found between OVX group and RES+OVX group. BMD in rat femora of RES+OVX group was higher than in OVX group but lower than sham group. Elastic/max radial degree and elastic/max load of femora were markedly reduced in OVX group compared to RES+OVX group. Relative levels of OCN and Runx2, ALP activity and calcification ability decreased in OVX group relative to sham group, which were partially reversed by RES treatment. After osteogenic differentiation in BMSCs induced with TNF-α, viability and calcification ability were markedly reduced and were upregulated by RES treatment. Moreover, RES treatment enhanced the downregulated levels of OCN and Runx2 in BMSCs undergoing TNF-α induction. Upregulated protein levels of nuclear factor kappa-B (NF-κB) and ß-catenin in TNF-α-induced BMSCs were downregulated by RES treatment. CONCLUSIONS: The inhibited osteogenic differentiation of BMSCs undergoing TNF-α induction is improved by resveratrol treatment, which contributes to alleviate the progression of osteoporosis.

[Study of surgery combined with 125I brachytherapy for adenoid cystic carcinoma of oral and maxillofacial region].

OBJECTIVE: To retrospectively analyze the results of treatment outcome by surgery combined with 125I brachytherapy and correlative factors of adenoid cystic carcinoma (ACC). METHODS: In the study, 75 patients with primary ACC of oral and maxillofacial region were treated by surgery combined with 125I seeds brachytherapy. Radical resection or subtotal resection was applied for the tumor. The brachytherapy treatment planning system was used to create implant plans with the prescribed dose of 60 Gy to 120 Gy. The 125I seeds were implanted intraoperatively or postoperatively. The regular follow-up was required. The Kaplan-Meier method was used to assess the tumor control rate and the patients' survival rates. Meanwhile, the Cox regression analysis was used to find out the prognostic factors. RESULTS: Local control rates at the end of 3 and 5 years were as follows: T1-T2, 92.2% and 82.0%; T3-T4, 82.6% and 82.6%; and overall, 90.0% and 78.8%. The disease-free survival rates were 74.9% and 54.3%, respectively. The overall survival rates for all the patients were 86.0% and 79.6%, respectively at the end of 3 and 5 years and were 91.3% and 91.3% for T1-T2 patients vs. 73.9% and 59.7% for T3-T4 patients. Distant metastasis-free survival rates at the end of 3 and 5 years were 84.4% and 76.7%, respectively. The distant metastasis-free survival rates at the end of 3 and 5 years were 83.4% and 79.6% with T1-T2 lesion compared with 86.0% and 67.8% with T3-T4 lesion. According to the COX univariate analysis and multivariate analysis, the risk of local recurrence would be raised by the age. Tumor stage and tumor site were the prognostic factors of the overall survival rates. CONCLUSION: 125I brachytherapy conducted as an adjuvant therapy postoperatively of ACC of oral and maxillofacial region can acquire satisfactory localregional control, distant metastasis-free survival, disease-free survival and overall survival. Tumors are prone to recur on the older patients. Patients having advanced tumor stage or tumor located in the nasal cavity or sinuses will suffer lower survival rates.

[Simulation of dose distribution in bone medium of 125I photon emitting source with Monte Carlo method].

OBJECTIVE: To present a theoretical analysis of how the presence of bone in interstitial brachytherapy affects dose rate distributions with MCNP4C Monte Carlo code and to prepare for the next clinical study on the dose distribution of interstitial brachytherapy in head and neck neoplasm. METHODS: Type 6711,125I brachytherapy source was simulated with MCNP4C Monte Carlo code whose cross section library was DLC-200. The dose distribution along the transverse axis in water and dose constant were compared with the American Association of Physicists in Medicine (AAPM) TG43UI update dosimetry formalism and current literature. The validated computer code was then applied to simple homogeneous bone tissue model to determine the affected different bone tissue had on dose distribution from 125I interstitial implant. RESULTS: 125I brachytherapy source simulated with MCNP4C Monte Carlo code met the requirements of TG43UI report. Dose rate constant, 0.977 78 cGy/(h×U), was in agreement within 1.32% compared with the recommended value of TG43UI. There was a good agreement between TG43UI about the dosimetric parameters at distances of 1 to 10 cm along the transverse axis of the 125I source established by MCNP4C and current published data. And the dose distribution of 125I photon emitting source in different bone tissue was calculated. Dose-deposition capacity of photons was in decreasing order: cortical bone, spongy bone, cartilage, yellow bone marrow, red bone marrow in the same medium depth. Photons deposited significantly in traversal axis among the phantom material of cortical bone and sponge bone relevant to the dose to water. In the medium depth of 0.01 cm, 0.1 cm, and 1 cm, the dose in the cortical bone was 12.90 times, 9.72 times, and 0.30 times of water respectively. CONCLUSION: This study build a 125I source model with MCNP4C Monte Carlo code, which is validated, and could be used in subsequent study. Dose distribution of photons in different bone medium is not the same as water, and its main energy deposits in bone medium surface, so we should consider the effect of bone medium when we design the target area adjacent to the bone tissue in 125I sources implantation plan.

Iodine-125 brachytherapy alone for advanced primary parotid gland carcinoma.

This study aimed to evaluate the efficacy of iodine-125 (125I) brachytherapy alone for the treatment of advanced parotid gland carcinoma and to identify predictors of tumour control and patient survival. Primary parotid gland carcinoma patients (n=23) treated with 125I brachytherapy alone between 1 October 2005 and 31 July 2013 at Peking University Stomatology Hospital were enrolled in this retrospective study. All had clinical stage IV disease. The prescribed dose was 60-160Gy. The local control rate, survival rate, and predictors of the prognosis were evaluated. Adverse events related to treatment were also noted. The average follow-up time was 29 months (range 9-74 months). Among the 23 patients, six had local failure and 11 died during the follow-up period. The 1-, 3-, and 5-year overall survival rates were 87.0%, 55.4%, and 47.5%, respectively. The 1-, 3-, and 5-year progression-free survival rates were 73.9%, 47.0%, and 39.2%, respectively. The 1-, 3-, and 5-year local control rates were 82.1%, 73.9%, and 73.9%, respectively. Age and distant metastasis were independent predictors of survival, while the preoperative duration of the disease was an independent predictor of local control. The use of 125I seed brachytherapy alone for the treatment of primary parotid gland carcinoma can provide good short-term results without causing any severe side effects.

The application of individual virtual nostalgic game design to the evaluation of cognitive function.

The aim of this study was to develop a task set based on personalized material for nostalgic experience, which could detect cognitive ability via a virtual experience system combined with Kinect somatosensory interactive operation applications without the user wearing any accessory input device. Fifty-nine subjects participated in the experiment. The receiver operating characteristic curve of the game system was statistically analyzed for determining the best cutoff-point in the cognitive function assessment. Correlation analysis and regression analysis were used to explore the correlations between the results and the clinical cognitive assessment scales. According to the MoCA scores, the results showed that the accuracy of the system was 86.4% in evaluating mild cognitive impairment. The system seems feasible and was strongly correlated with clinical cognitive assessment scales. We anticipate that daily use of our system could keep track of changes of cognitive function of the elderly in home life.

[Clinical application of 125I radioactive seeds brachytherapy in the treatment of the pediatric soft tissue sarcoma in head and neck].

Objective: To investigate the clinical application and preliminary results of 125I radioactive seeds brachytherapy in the comprehensive treatment of the pediatric soft tissue sarcoma in head and neck. Methods: A total of 24 pediatric patients with soft tissue sarcoma in head and neck were treated at Peking University School of Stomatology from April 2012 to July 2015. The data was collected and analyzed through statistical methods, which included the pathological type, gender, age, tumor location, volume, treatment and the clinical results after the application of 125I radioactive seeds brachytherapy. Results: Among the 24 patients, there were 18 patients of rhabdomyosarcoma, 2 Ewing's sarcoma, 2 fibrosarcoma, 1 synovial sarcoma and 1 malignant fibrous histiocytoma. After a follow-up of 9-48 months, 1 case of temporal rhabdomyosarcoma was observed to have a progression to the the lateral cranial base at the time of 12 months, 2 cases realized local control and systemic progression, the rest were completely relieved, and there was no recurrence during the follow-up period.The Kaplan-Meier survival analysis showed that the 1-year and 3-year local control rate were both 94.1%, the 1-year and 3-year event-free survival rate were 87.4% and 77.7%. Conclusion: The preliminary results indicate that 125I radioactive seeds brachytherapy play a very important role in the improvement of the local control rate and survival quality of the pediatric soft tissue sarcoma patient in head and neck, and it's a minimally invasive treatment with the advantage of accuracy andsmall side effects.

Chemical removal of necrotic periodontal ligament on delayed replanted teeth by sodium hypochlorite: morphological analysis and microhardness indentation test of cementum.

AIM: To compare the efficacy of sodium hypochlorite (NaOCl) used at different concentrations and working times for removing necrotic periodontal ligament (PDL) from delayed replanted teeth and to observe the effects of NaOCl on surface structure and microhardness of cementum. METHODOLOGY: A total of 88 healthy premolars with a single root extracted for orthodontic purposes were selected and kept dry at room temperature for 1 h. The teeth were divided into 11 groups: group 1 (control): roots were untreated; group 2: necrotic PDL was removed with gauze; groups 3-11: teeth were immersed in NaOCl at different concentrations (1, 2.5 and 5.25%) and for different working times (5, 10 and 15 min). The specimens in each group were inspected separately for cementum integrity and the presence of PDL remnants by histomorphometric analysis, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Another 14 healthy premolars with roots divided into two pieces were selected for Vickers microhardness indentation tests before and after NaOCl treatment. The data were analysed statistically using Wilcoxon signed-rank test of two-related samples (P = 0.05). RESULTS: In teeth treated with 1% NaOCl for 15 min or 5.25% NaOCl for 5 min, the cementum remained morphologically intact without cracks, and PDL remnants were absent. In the 1% NaOCl for 15 min group, the microstructure of cementum was arranged more regularly, as observed ×8000 magnification by SEM. Teeth in each of the other groups displayed cementum damage and/or the presence of PDL remnants. Microhardness tests revealed that treatment with 1% NaOCl for 15 min or 5.25% NaOCl for 5 min significantly decreased microhardness of root cementum (P < 0.05). CONCLUSIONS: Use of either 1% NaOCl for 15 min or 5.25% NaOCl for 5 min was effective at removing necrotic PDL from the delayed replanted teeth whilst having a minimal influence on cementum integrity. However, 1% NaOCl for 15 min was less damaging to cementum.

Brachytherapy for recurrent malignant tumours of the parotid gland.

To find out if brachytherapy with radioactive seeds was effective in patients with recurrent malignant tumours of the parotid gland we retrospectively studied 64 such patients, 24 of whom were treated with implantation of radioactive seeds alone, and 40 of whom had their recurrent tumours resected followed by implantation of radioactive seeds. Patients were followed up for a mean of 50 months (range 4 months to 12 years). The local control rate was 76.6%, and overall survival 79.7%. Of the 24 patients treated with brachytherapy alone, 22 achieved a complete response (91.7%). At 1, 3, and 5 years the local control rates were 81.5%, 67.2%, and 53.8%, respectively, and the overall survival 82.7%, 70%, and 61.2%, respectively. In the 40 patients whose tumours were resected before brachytherapy, the local control rates at 1, 3, and 5 years were 87.5%, 82.4%, and 78.6%, respectively, and the overall survival was 97.5%, 86.5%, and 86.5%, respectively. Sex, age, histopathological grade, size of tumour, history of radiotherapy, time of recurrence and method of treatment were not shown to have a significant effect on local control, but method of treatment had a significant impact on overall survival (p=0.008). We conclude that treatment of recurrent malignant tumours of the parotid efficacy can be successfully treated with brachytherapy with radioactive seeds, either alone or combined with resection.

Nineteen polymorphic microsatellite markers developed for Trachinotus ovatus.

To evaluate the population genetic diversity of the ovate pompano, we isolated and characterized 19 microsatellite markers using a (CA)13-enriched genomic library. Polymorphism was assessed in 30 individuals from a single population collected from the Daya Bay Aquaculture Center, Guangdong, China. The number of alleles per locus ranged from 2 to 18 with an average of 7.8. The observed and expected heterozygosities varied from 0.2667 to 1.000 and from 0.3960 to 0.9435, respectively. Sixteen of 19 loci conformed to Hardy-Weinberg equilibrium, and no significant linkage disequilibrium was detected between any locus pairs. Our study supplies candidate microsatellite markers that can be useful for studying the population genetic structure of ovate pompano.

Submental cutaneous sinus tract of mandibular second molar origin.

AIM: To report a case in which a submental cutaneous sinus tract resulted from apical periodontitis associated with a mandibular second molar. SUMMARY: A 53-year-old man presented with a chronic cutaneous sinus tract in the submental region, which had previously been misdiagnosed as a thyroglossal fistula. The origin of the sinus tract was shown by sinus tract angiography to be the left mandibular second molar (tooth 37), which had apical periodontitis. The sinus tract healed after extraction of the tooth and partial excision of the lesion from an extraoral approach. Histological examination confirmed that the tract was lined with granulation tissue and not with epithelial tissue. A submental sinus tract drainage pathway was observed. Prompt dental evaluation, especially of all mandibular teeth, should be considered when assessing cases of submental cutaneous sinus tracts. KEY LEARNING POINTS: An odontogenic origin should be part of the differential diagnosis for orofacial skin lesions. Cutaneous sinus tracts of mandibular molar origin are complex and thus a comprehensive examination should be stressed. It is necessary to examine all mandibular teeth in cases of odontogenic submental cutaneous sinus tracts. Sinus tract angiography can be used to identify the sinus tract pathway and to confirm the associated teeth. The treatment of an odontogenic cutaneous sinus tract requires the elimination of the source of infection.

125I brachytherapy alone for recurrent or locally advanced adenoid cystic carcinoma of the oral and maxillofacial region.

BACKGROUND AND PURPOSE: This retrospective study was to evaluate the local control and survival of (125)I brachytherapy for recurrent and/or locally advanced adenoid cystic carcinoma (ACC) of the oral and maxillofacial region. PATIENTS AND METHODS: A total of 38 patients with recurrent and/or locally advanced ACC of the oral and maxillofacial region received (125)I brachytherapy alone from 2001-2010. Twenty-nine were recurrent cases following previous surgery and radiation therapy. The other 9 cases involved primary tumors. Overall, 12 tumors were located in the major salivary glands, 12 in the minor salivary glands, and 14 in the paranasal region, the nasal cavity or the skull base. The prescribed dose was 100-160 Gy. RESULTS: Patients were followed for 12-122 months (median 51 months). The 2-, 5-, and 10-year local tumor control rates were 86.3, 59, and 31.5 %, respectively. The 2-, 5-, and 10-year overall survival rates were 92.1, 65 and 34.1 %, respectively. Tumors > 6 cm had significantly lower local control and survival rates. No severe complications were observed during follow-up. CONCLUSION: (125)I brachytherapy is a feasible and effective modality for the treatment of locally advanced unresectable or recurrent ACC.

Enhanced secretion of IFN-gamma by activated Th1 cells occurs via reverse signaling through TNF-related activation-induced cytokine.

Growing evidence has demonstrated that members of TNF superfamily transduce signals after engagement with their receptors. TNF-related activation-induced cytokine (TRANCE), a member of TNF superfamily, is preferentially expressed on the surface of activated CD4(+) Th1 cells. The soluble receptor activator of NF-kappaB (RANK).Fc fusion protein suppresses IFN-gamma secretion by activated Th1 cells, but does not affect IL-4 secretion by Th2 cells. The suppressive effect on IFN-gamma secretion is observed when Th1 cells are activated by APCs, but not by immobilized anti-TCR beta mAb. In contrast, immobilized RANK.Fc fusion protein augments IFN-gamma secretion by Th1 cells, indicating the occurrence of reverse signaling through TRANCE during T cell/APC interaction. The enhanced secretion of IFN-gamma mediated via TRANCE correlates with the activation of p38 mitogen-activated protein kinase and is blocked by SB203580, a p38 mitogen-activated protein kinase-specific inhibitor. Thus, in addition to its role in activating dendritic cells by binding to the receptor RANK, TRANCE itself can signal the augmentation of IFN-gamma secretion via a p38-dependent pathway, and this provides yet another example of reverse signaling by a member of TNF superfamily.

Coumarins and antiplatelet constituents from the root bark of Zanthoxylum schinifolium.

Further study on the chloroform-soluble portion of the root bark of Zanthoxylum schinifolium led to the isolation of eight new coumarins: methylschinilenol (1), hydroxyepoxycollinin I (2), 8-methoxyanisocoumarin H (3), hydroxyschininallylol (4), hydroxyepoxycollinin II (5), schinitrienin (6), schininallylone (7), and isoschinilenol (8), along with twenty-six known compounds including fourteen coumarins, and nine alkaloids. The structural elucidation was determined by spectroscopic data. Among the isolates, terpenyl-coumarins and furoquinolines were the active constituents with antiplatelet aggregation in vitro and collinin (10) showed significant anti-HBC DNA replication activity.

Opposing functional effects of cyclic GMP and cyclic AMP may act through protein phosphorylation in rabbit cardiac myocytes.

1. We tested the hypothesis that the negative functional effects of cyclic GMP (cGMP) oppose the positive effects of cyclic AMP (cAMP) in cardiac myocytes through interaction at the level of their respective protein kinases. 2. Cell shortening was studied using a video-edge detector. The O2 consumption of a suspension of rabbit ventricular myocytes was measured using O2 electrodes. Protein phosphorylation was measured autoradiographically following SDS-PAGE. Data were collected with: (1) 8-bromo-cGMP (8-Br-cGMP) 10(-7) or 10(-5) M; (2) 8-bromo-cAMP (8-Br-cAMP) 10(-7) or 10(-5) M; (3) 8-Br-cAMP 10(-5) M followed by 8-Br-cGMP 10(-7) or 10(-5) M; (4) 8-Br-cGMP 10(-5) M followed by 8-Br-cAMP 10(-7) or 10(-5) M; (5) 8-Br-cGMP 10(-7) or 10(-5) M followed by KT 5720 (cAMP-dependent protein kinase inhibitor) or KT 5823 (cGMP-dependent protein kinase inhibitor) 10(-6) M; and (6) 8-Br-cAMP 10(-7) or 10(-5) M followed by KT 5720 or KT 5823 10(-6) M. 3. 8-Br-cGMP 10(-5) M decreased percent shortening (Pcs) from 6.3+/-0.6 to 3.6+/-0.4% and rate of shortening (Rs) from 66.7+/-4.4 to 41.8+/-4.2 microm s(-1). 8-Br-cAMP 10(-5) M increased Pcs (from 3.7+/-0.2 to 4.8+/-0.2) and Rs (from 50.0+/-3.0 to 60.0+/-3.1). With 8-Br-cAMP 10(-5) M, 8-Br-cGMP 10(-5) M decreased Pcs and Rs less. The positive functional effects of 8-Br-cAMP 10(-7) or 10(-5) M were also diminished with 8-Br-cGMP 10(-5) M. Following 8-Br-cGMP 10(-7) or 10(-5) M, KT 5720 10(-6) M further decreased Pcs to 2.5+/-0.3 and Rs to 30.0+/-4.1. KT 5823 10(-6) M returned Pcs to 4.7+/-0.4 and Rs to 61.3+/-5.3. Following 8-Br-cAMP 10(-7) or 10(-5) M, KT 5720 decreased the elevated Pcs and Rs significantly and KT 5823 10(-6) M further increased these parameters. 4. cGMP and cAMP phosphorylated the same five protein bands. With KT 5720 or KT 5823, all of the bands were lighter at the same concentration of 8-Br-cAMP and 8-Br-cGMP. 5. We conclude that, in rabbit ventricular myocytes, the opposing functional effects of cGMP and cAMP are related to the interaction at the level of their respective protein kinases.