Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

Objective:To investigate regional distribution and clinicopathological features of Epstein-Barr virus associated gastric cancer (EBVaGC).Methods:Epstein-Barr virus encoded RNA (EBER)was detected in 4 081 cases of gastric adenocarcinoma in Cancer Hospital, Chinese Academy of Medical Sciences by using in situ hybridization. EBVaGCs were identified and their proportions in different provinces, autonomous regions and municipalities were compared. The correlation between EBVaGC and clinicopathological features was also analyzed.Results:A total of 3.0% (123/4 081) patients with gastric adenocarcinoma are EBVaGCs. Among the areas with cases more than 90, the highest proportion of EBVaGC was found in Jilin province, accounting for 7.6%, and then followed by 5.4% in Liaoning province, 4.1% in Anhui province, 3.9% in Beijing, 3.7% in Inner Mongolia Autonomous Region, 3.4% in Shanxi province, 3.0% in Heilongjiang province, 2.1% in Shandong province, 1.6% in Hebei province, and no EBVaGC was found in Henan province. EBVaGC proportions are significantly different in these provinces, autonomous regions and municipalities ( P<0.05). Multivariate analysis of logistic regression revealed that gender ( OR=2.231, 95% CI: 1.290~3.858), WHO classification ( OR=2.338, 95% CI: 2.051~2.664) and N stage ( OR=0.420, 95% CI: 0.284~0.621) were independent impact factors for EBVaGC. The proportion of EBVaGC was higher in males, gastric carcinomas accompanied with lymphoid stroma and patients without lymph node metastasis. Conclusions:The proportion of EBVaGC in gastric adenocarcinoma displays area distribution disparity in China. The gender, WHO classification and N stage are closely associated with EBVaGC.

Objective:To investigate regional distribution and clinicopathological features of Epstein-Barr virus associated gastric cancer (EBVaGC).Methods:Epstein-Barr virus encoded RNA (EBER)was detected in 4 081 cases of gastric adenocarcinoma in Cancer Hospital, Chinese Academy of Medical Sciences by using in situ hybridization. EBVaGCs were identified and their proportions in different provinces, autonomous regions and municipalities were compared. The correlation between EBVaGC and clinicopathological features was also analyzed.Results:A total of 3.0% (123/4 081) patients with gastric adenocarcinoma are EBVaGCs. Among the areas with cases more than 90, the highest proportion of EBVaGC was found in Jilin province, accounting for 7.6%, and then followed by 5.4% in Liaoning province, 4.1% in Anhui province, 3.9% in Beijing, 3.7% in Inner Mongolia Autonomous Region, 3.4% in Shanxi province, 3.0% in Heilongjiang province, 2.1% in Shandong province, 1.6% in Hebei province, and no EBVaGC was found in Henan province. EBVaGC proportions are significantly different in these provinces, autonomous regions and municipalities ( P<0.05). Multivariate analysis of logistic regression revealed that gender ( OR=2.231, 95% CI: 1.290~3.858), WHO classification ( OR=2.338, 95% CI: 2.051~2.664) and N stage ( OR=0.420, 95% CI: 0.284~0.621) were independent impact factors for EBVaGC. The proportion of EBVaGC was higher in males, gastric carcinomas accompanied with lymphoid stroma and patients without lymph node metastasis. Conclusions:The proportion of EBVaGC in gastric adenocarcinoma displays area distribution disparity in China. The gender, WHO classification and N stage are closely associated with EBVaGC.

OBJECTIVETo observe the effects of electroacupuncture(EA) at different acupoints for fasting blood glucose(FBG) and oral glucose tolerance in type 2 diabetes rats so as to verify the glucose-lowering effects of EA.

METHODSTotal 100 SD male rats were seen as experimental objects,among which 13 were randomly assigned into a blank group. Other rats were fed with high fat and high sugar diet combined with intraperitoneal injection of small dose streptozotocin (STZ) to establish type 2 diabetes model. Sixty diabetic rats were randomly assigned into a model group,a Weiwanxiashu group,a Xinshu group,a Shenshu group and a Housanli group,12 cases in each one. Combined with the improved diet habits and routines,EA (2 Hz and 2 mA) was used at "Weiwanxiashu" (EX-B 3),"Xinshu" (BL 15),"Shenshu" (BL 23) and "Housanli" (ST 36) in the corresponding groups,6 times a week for 4 weeks. There was no treatment in the blank group and in the model group. The observation indexes were the FBG on the 7th,14th,21st,and 28th day of intervention,the instant glucose-lowering effect on the 21st day during treatment,and the area under the curve of oral glucose tolerance test (OGTT) after intervention. Also,the glucose regulation condition was observed.

RESULTSType 2 diabetes model could be established by high fat and high sugar diet combined with intraperitoneal injection of small dose STZ. Glucose decreased apparently at the end of the 1st week or the 2nd week compared with that before treatment in the Weiwanxiashu,Xinshu and Shenshu groups(<0.05,<0.01). The instant FBG of the Weiwanxiashu and Xinshu groups was obviously lower than that of the model and Housanli groups at the end of the 3rd week(all<0.01). The area under the curve of OGTT of the Weiwanxiashu group was apparently smaller than that of the model group (<0.05),and the results of the index in the other groups were not significantly different from that of the model group(all>0.05).

CONCLUSIONSLow frequency EA at "Weiwanxiashu"(EX-B 3),"Xinshu"(BL 15) and "Shenshu"(BL 23) can reduce glucose with different onset times,effects,and durations. And "Weiwanxiashu"(EX-B 3) is more effective.

Objective To investigate the arteries supplying the temporalis. Methods Ten cadavers were examined after embalming with a fluid containing 10% formaldehyde. For detailed examination of the supplying arteries of the temporalis, a mixture of latex and barium sulfate in a ratio of 1∶1 was injected into both carotid arteries of 10 fresh cadavers. The skin and soft tissue were removed from the temporal and lateral regions of the head, and the superficial temporal artery was dissected. As soon as the origin of the medial temporal artery was identified, the zygomatic arch was cut and lifted. The maxillary artery with its branches of the infratemporal region was carefully dissected. After identification of all vessels of the infratemporal region, the temporalis was removed, and then radiographic examination of the injected arteries was performed using 2.5 mA and 40 kV. The injected arteries were clearly identified on the radiographic images, and the area supplied by each artery was determined. Planimetric evaluation of these areas was performed. Results In all specimens, three arteries supplying the temporalis were identified: the anterior deep temporal artery that supplied the anterior part between 11 % and 25% of the temporalis with a mean of 17%, the posterior deep temporal artery that supplied the central part of 27% to 50% of the lateral aspect of the temporalis, with a mean of 38% and a branch of the superficial temporal artery, the medial temporal artery, which supplied the posterior part and in 25% the posterior and the upper part of the temporalis, resulting in 30% to 58% of the muscle's lateral aspect, with a mean of 45%. Conclusion According to a detailed description of the arterial supply of the temporalis, two different pedicled flaps using the anterior or central part of the temporalis can be selectively used for reconstructive surgery.