Objective:Drug-loaded mucoadhesive silk fibroin(SF)microneedle patch can overcome the limitations of low bioavailability and significant pain associated with traditional treatment methods,such as topical application o...Objective:Drug-loaded mucoadhesive silk fibroin(SF)microneedle patch can overcome the limitations of low bioavailability and significant pain associated with traditional treatment methods,such as topical application or injection of triamcinolone for oral submucous fibrosis(OSF).However,these systems release the drug too quickly,failing to meet the clinical requirements.This study aims to construct a mucoadhesive SF microneedle patch pre-assembled with silk fibroin nanospheres(SFN)and explore its ability to sustain the release of triamcinolone in the treatment of OSF.Methods:SFN was pre-assembled via precipitation reaction and characterized by scanning electron microscope(SEM)for the morphology.The particle size andζ-potential were measured by dynamic light scattering(DLS).Triamcinolone was loaded onto SFN using a diffusional post-loading method.The effective loading of triamcinolone was confirmed using Fourier-transform infrared spectroscopy(FTIR).The concentration of unloaded triamcinolone was quantified by high-performance liquid chromatography.Drug encapsulation efficiency and loading capacity of SFN were then calculated to determine the optimal amount of drug loading.The SFN suspension was pre-mixed with SF solution to prepare the microneedle under-layer.The microneedle morphology was observed by SEM.Compression mechanical tests were performed to evaluate the fracture force of microneedles at different nanosphere contents(5%,10%,and 20%),determining the optimal pre-mixing ratio.Ex-vivo mouse oral mucosa permeation studies were performed to ascertain the insertion depth of the microneedles via histological sections.The adhesive top layer was synthesized using SF and tannic acid,with FTIR confirming its successful synthesis.Its viscoelasticity was characterized by a rheometer,and differential scanning calorimetry analyzed thermal properties.Tensile tests evaluated the interfacial bonding strength between the adhesive layer and microneedle base to ensure no detachment during use.Adhesion to wet oral mucosal tissues was tested and compared to commercial oral patches.Under the optimized conditions,the double-layered mucoadhesive microneedle patch with pre-assembled nanospheres was prepared.Its cell compatibility was evaluated by cell counting kit-8(CCK-8),live/dead staining,and phalloidin staining after co culturing with fibroblasts.The drug release experiment was conducted to demonstrate its sustained release efficacy.Results:SFN(mean diameter 46.25 nm)was successfully prepared.The maximum drug encapsulation efficiency was(63.88±1.09)%(corresponding loading capacity of SFN was(27.41±3.06)%when the weight ratio of triamcinolone/SFN was 0.5.The corporation of SFN did not affect microneedle morphology.The mechanical properties of microneedles decreased with increasing nanosphere amount.Only the fracture force of the group with 5%SFN[(0.07±0.01)N/needle]exceeded the minimum force required for mucosal penetration,thus selected as the optimal pre-mixing ratio.Histological sections confirmed that the SFN microneedles could penetrate the epithelial layer and deliver drugs to OSF affected areas.Adhesion strength between the microneedle base and top layer was(94.8±6.89)kPa,confirming strong bonding with no detachment during use.The wet adhesive strength of the double-layered mucoadhesive microneedle patch[(41.28±7.43)kPa]was significantly enhanced compared to commercial oral patches(4.5 kPa,P<0.01).CCK-8 and live/dead staining results confirmed no significant cytotoxicity.Drug release experiment showed the double-layered mucoadhesive microneedle patch with pre-assembled SFN enabled sustained release time of triamcinolone from 4 days to 14 days.Conclusion:Pre-assembling nanospheres in mucoadhesive SF microneedle patches can extend triamcinolone release time,meeting clinical requirements for sustained drug delivery.展开更多
Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human or...Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human oral mucosafibroblasts(hOMF)were induced with transforming growth factor beta1(TGF-β1)and intervened with Pue.Expressions offibrosis-related markers were analyzed by Western blot and IF staining.Cell viability was characterized by the CCK-8 assay.Expressions of miR-30 family members were quantified by qRT-PCR.The correlation betweenfibroblast activation protein(FAP)and miR-30 family expression was evaluated by the Pearson correlation coefficient.Bioinformatics prediction and dual-luciferase reporter assay were employed to verify the regulation between FAP and miR-30b-5p.The specific mechanism of Pue on OSF was explored through the promotion or inhibition of miR-30b-5p.Results:After induction by TGF-β1,hOMF showed upregulated Collagen I,Collagen III,and FAP expressions,while miR-30 family expression was downregulated with miR-30b-5p being the most significant.Pue intervention inhibited the excessive proliferation of TGF-β1-induced hOMF,downregulated FAP,collagen type 3(COL3A1),collagen type 1(COL1A1),matrix metalloproteinase 1(MMP1),and matrix metalloproteinase 3(MMP3)expressions,and restored miR-30 family expression.Bioinformatics prediction and dual-luciferase reporter assay revealed that miR-30b-5p selectively inhibited FAP expression.Mechanistically,miR-30b-5p mimic suppressed the excessive proliferation of TGF-β1-induced hOMF and declinedfibrosis levels.Pue intervention significantly reversed the promotion of TGF-β1-induced OSF by miR-30b-5p inhibition.Conclusion:Pue mediated miR-30b-5p targeting FAP against OSF,which provided a theoretical basis for the pathogenesis research and Pue application in OSF.展开更多
AIM To investigate the intestinal segment-specific effects of diabetes and insulin replacement on the density of different subpopulations of submucous neurons. METHODS Ten weeks after the onset of type 1 diabetes samp...AIM To investigate the intestinal segment-specific effects of diabetes and insulin replacement on the density of different subpopulations of submucous neurons. METHODS Ten weeks after the onset of type 1 diabetes samples were taken from the duodenum, ileum and colon of streptozotocin-induce diabetic, insulin-treated diabetic and sex-and age-matched control rats. Whole-mount preparations of submucous plexus were prepared from the different gut segments for quantitative fluorescent immunohistochemistry. The following double-immunostainings were performed: neuronal nitric oxide synthase(n NOS) and Hu C/D, heme oxygenase(HO) 1 and peripherin, as well as HO2 and peripherin. The density of n NOS-, HO1-and HO2-immunoreactive(IR) neurons was determined as a percentage of the total number of submucous neurons. RESULTS The total number of submucous neurons and the proportion of n NOS-, HO1-and HO2-IR subpopulations were not affected in the duodenal ganglia of control, diabetic and insulin-treated rats. While the total neuronal number did not change in either the ileum or the colon, the density of nitrergic neurons exhibited a 2-and 3-fold increase in the diabetic ileum and colon, respectively, which was further enhanced after insulin replacement. The presence of HO1-and HO2-IR submucous neurons was robust in the colon of controls(38.4%-50.8%), whereas it was significantly lower in the small intestinal segments(0.0%-4.2%, P < 0.0001). Under pathophysiological conditions the only alteration detected was an increase in the ileum and a decrease in the colon of the proportion of HO-IR neurons in insulin-treated diabetic animals. CONCLUSION Diabetes and immediate insulin replacement induce the most pronounced region-specific alterations of n NOS-, HO1-and HO2-IR submucous neuronal density in the distal parts of the gut.展开更多
To analyze the clinical symptoms and signs in cases of oral submucous fibrosis which has transformed into squamous cell carcinoma, twenty-nine patients with squamous cell carcinoma correlated with oral submucous fibro...To analyze the clinical symptoms and signs in cases of oral submucous fibrosis which has transformed into squamous cell carcinoma, twenty-nine patients with squamous cell carcinoma correlated with oral submucous fibrosis, leukoplakia, lichen planus were taken biopsy for positive diagnosis. The clinical and pathological diagnosis of oral submucous fibrosis depended on clinical and pathological diagnostic standards. The oral submucous fibrosis involving different portions and size in the mouth was observed and recorded. The portions of oral cancer, clinical findings and symptoms, cancerous size, the conditions of the local lymphatic nodes and of oral submucous fibrosis correlated with squamous cell carcinoma in the mouth, oral leukoplakia, lichen planus were also observed and recorded. In twenty-nine patients with oral squamous cell carcinoma, duration from oral submucous fibrosis transformed into oral cancer ranged from 2 to 15 years with an average year of 6.69. The serious degrees of oral submucous fibrosis in the patients with oral cancer were that the moderately advanced stage was found in 3 cases (10.34%) and the advanced stage was found in 26 cases (89.65%). The cancerous portion was that the buccal mucosa was found in 9 cases (31.03%);the tongue was found in 14 cases (48.27%);the other portion was found in the rest 6 cases (20.68%). Among the twenty-nine patients twenty-three patients with squamous cell carcinoma were associated with leukoplakia (79.31%), five patients were associated with lichen planus (17.24%). Twenty-seven patients (93.1%) had habits of betel quid chewing, smoked cigarette and drank alcohol, the rest two patients had habits of betel quid chewing and cigarette smoking. The present study demonstrates that oral submucous fibrosis is a real precancerous lesion and may transform into squamous cell carcinoma in the mouth.展开更多
Objective:To explore the clinical efficacy of Danshen injection in combined with local injection of triamcinolone acetonide in the treatment of oral submucous fibrosis (OSF) and the effect on serum TGF-β1 and IL-6.Me...Objective:To explore the clinical efficacy of Danshen injection in combined with local injection of triamcinolone acetonide in the treatment of oral submucous fibrosis (OSF) and the effect on serum TGF-β1 and IL-6.Methods:A total of 70 patients with OSF who were admitted in our hospital from October, 2015 to October, 2016 were included in the study and randomized into the observation group and the control group (n=35). The patients in the control group were given multipoint injection of triamcinolone acetonide (40 mg/time) in the basal region of oral mucosal regions. On this basis, the patients in the observation group were given additional Danshen injection (4 mL/time), 1 time/week, for 12 times. VAS was used for evaluation. The oral mucosa lesion area and mouth opening were measured. The morning fasting peripheral venous blood before and after treatment in the two groups was collected. The blood rheometer was used to detect the whole blood viscosity [high shear (HS), moderate shear (MS), and low shear (LS)], plasma viscosity (PV), and fibrinogen (FIB). ELISA was used to detect the serum TGF-β1 and IL-6 levels.Results: VAS score in the observation group was significantly reduced (P<0.05), mucosal lesion area was significantly less than that in the control group (P<0.05), and mouth opening was significantly greater than that in the control group (P<0.05). LS, MS, PV, and FIB after treatment in the observation group were significantly reduced when compared with before treatment (P<0.05), while LS, MS, HS, PV, and FIB after treatment in the control group were not significantly changed (P>0.05). TGF-β1 and IL-6 levels after treatment in the observation group were significantly lower than those in the control group (P<0.05).Conclusions: Danshen injection in combined with local injection of triamcinolone acetonide in the treatment of OSF can effectively reduce the serum TGF-β1 and IL-6 levels, inhibit the connective tissue fibrosis, and improve the pain, oral mucosal lesion area, and mouth opening, with a satisfactory clinical effect.展开更多
The morphometric analysis of the spinous cell in 16 specimens of oral submucous fibrosis (OSF) was made by using interactive image analysis system (IBAS-II). 19 parameters of the size and shape were chosen, and compar...The morphometric analysis of the spinous cell in 16 specimens of oral submucous fibrosis (OSF) was made by using interactive image analysis system (IBAS-II). 19 parameters of the size and shape were chosen, and compared with normal mucosa, leukoplakia, dysplasia and carcinoma. The results indicated that the cell dimensions (area, perimeter, all kinds of diameter) and nuclear cytoplasmic ratio in OSF were between normal mucosa and dysplasia as well as carcinoma. The former showed a progressive decrease (P<0.01), and the latter showed a progressive increase (P<0.01). The dimensions of the nuclei did not show considerable differences among the groups (P>0.05). A series of discriminant functions had been developed with stepwise discriminant analysis, the agreement ratio for OSF was 93.75%. The decrease of cell area and the increase of nuclear cytoplasmic ratio could reflect a malignant progress. The cell morphometric model could discriminate OSF well from other groups, suggesting that the change of the epith展开更多
AIM: To investigate the effect of Ginkgo biloba extract on the enteric neurons in the small intestine of diabetic rats. METHODS: Fifteen Wistar rats were divided into three groups: control group (C), diabetic group (D...AIM: To investigate the effect of Ginkgo biloba extract on the enteric neurons in the small intestine of diabetic rats. METHODS: Fifteen Wistar rats were divided into three groups: control group (C), diabetic group (D) and diabetic-treated (DT) daily with EGb 761 extract (50 mg/kg body weight) for 120 d. The enteric neurons were identified by the myosin-V immunohistochemical technique. The neuronal density and the cell body area were also analyzed. RESULTS: There was a significant decrease in the neuronal population (myenteric plexus P = 0.0351; submucous plexus P = 0.0217) in both plexuses of the jejunum in group D when compared to group C. With regard to the ileum, there was a significant decrease (P = 0.0117) only in the myenteric plexus. The DT group showed preservation of the neuronal population in the jejunum submucous plexus and in the myenteric plexus in the ileum. The cell body area in group D increased significantly (P = 0.0001) in the myenteric plexus of both segments studied as well as in the ileum submucosal plexus, when compared to C. The treatment reduced (P = 0.0001) the cell body area of the submucosal neurons of both segments and the jejunum myenteric neurons. CONCLUSION: The purified Ginkgo biloba extract has a neuroprotective effect on the jejunum submucous plexus and the myenteric plexus of the ileum of diabetic rats.展开更多
Objective: To develop a BALB/c mouse model of oral submucous fibrosis(OSF)induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes.Methods: BALB/c mice were randomly assigned to either ...Objective: To develop a BALB/c mouse model of oral submucous fibrosis(OSF)induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes.Methods: BALB/c mice were randomly assigned to either the control(distilled water) or experimental group(arecoline)(n = 40). Eight mice from each group were sacrificed every 4 weeks since 8 weeks post treatment. Changes in histopathologic features, levels of collagen type Ⅰ and collagen type Ⅲ, and angiogenesis were measured.Results: In the 8th week, epithelium atrophy, collagen cumulation and micrangium pathologic changes in the lamina propria were observed in the oral mucosa. In the 20th week, hyaline degeneration of the connective tissues was observed on the tongue and palate mucosa. The angiogenesis and collagen type Ⅰ changed significantly as the diseases advanced(P < 0.05); however, collagen type Ⅲ was not statistically different.Conclusions: An OSF model involving mice can be rapidly induced by drinking a highdose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type Ⅰ.展开更多
Quality of life(QoL) is a vital and often required health outcome measure that is relevant to patient care. A healthy oral cavity enables person to perform daily activities without any limitations. However, any distur...Quality of life(QoL) is a vital and often required health outcome measure that is relevant to patient care. A healthy oral cavity enables person to perform daily activities without any limitations. However, any disturbance may result in impaired QoL. The oral health-remains an essential element of people's health and well-being. In recent years, the tradition of clinical practice and research has been changed by incorporating QoL assessment, as it helps in assessment of patients' needs and monitoring treatment responses. Oral potentially malignant disorders(OPMDs) are a group of chronic disorders including oral leukoplakia(OL), oral lichen planus and oral submucous fibrosis(OSF). It is evident that patients with OPMDs experience significant health-related symptoms, functional limitations and psycho-social impairment, compromising their Qo L. Moreover, the worsening of Qo L has been associated with advanced stages of OPMDs. Despite of increasing number of OPMD cases in recent decades, limited literature is available regarding QoL in this population. Although, there is higher prevalence of habit-related OPMDs, particularly OSF and OL in Southern Asian countries, only a few studies have been performed in these populations. Moreover, these studies administered generic Qo L instruments, which offer less sensitivity to clinical changes. However, condition-specific instruments are more sensitive and allows better measurement of QoL. As the impacts of different conditions on OHRQoL may vary, the development and validation of a QoL instrument specific to each clinical entity of OPMDs is currently needed.展开更多
Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibros...Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaquelike, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary.The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used.展开更多
BACKGROUND Congenital palate perforation is extremely rare. There is controversy about its exact etiology and appropriate management. Here, a case of congenital palatal perforation is reported. The diagnosis and treat...BACKGROUND Congenital palate perforation is extremely rare. There is controversy about its exact etiology and appropriate management. Here, a case of congenital palatal perforation is reported. The diagnosis and treatment of the disease are summarized.CASE SUMMARY A full-term neonate boy was referred for oral and craniomaxillofacial surgery with a finding of a hole in the palate at birth. The operation was postponed after pediatric consultation because of the patient’s poor nutrition and underweight for his age. At the age of 10 mo, the patient underwent modified von Langenbeck palatoplasty. He was followed for four years after surgery without any signs of re-rupture. His speech was satisfactory.CONCLUSION Considering the anatomy and etiology, congenital palate perforation can be classified as isolated or associated with submucous cleft palate, and the treatment procedure should be altered accordingly.展开更多
BACKGROUND Vaginal myomectomy is the most common form of radical treatment for prolapsed submucosal leiomyoma and is typically performed under general anesthesia.However,an alternative treatment approach is needed for...BACKGROUND Vaginal myomectomy is the most common form of radical treatment for prolapsed submucosal leiomyoma and is typically performed under general anesthesia.However,an alternative treatment approach is needed for patients who cannot tolerate general anesthesia.We describe a case with such a patient who was successfully treated via a minimally invasive method under local anesthesia.CASE SUMMARY A 46-year-old female suffered from abnormal uterine bleeding,severe anemia,and a reduced quality of life attributed to a massive prolapsed submucosal leiomyoma.She could not tolerate general anesthesia due to a congenital thoracic malformation and cardiopulmonary insufficiency.A new individualized combined treatment,consisting uterine artery embolization(UAE),percutaneous microwave ablation(PMWA)of the pedicle and the endometrium,and transvaginal removal of the leiomyoma by twisting,was performed.The lesion was completely removed successfully under local anesthesia without any major complications.The postoperative follow-up showed complete symptom relief and a significant improvement in the quality of life.CONCLUSION UAE combined with PMWA can be performed under local anesthesia and is a promising alternative treatment for patients who cannot tolerate general anesthesia.展开更多
Objective:To explore the effects of Huoxue Huayu detoxification method on the levels of GSK-3βandβ-catenin in OSF patients and its mechanism.Methods:A total of 120 patients with oral submucosal fibrosis(OSF)treated ...Objective:To explore the effects of Huoxue Huayu detoxification method on the levels of GSK-3βandβ-catenin in OSF patients and its mechanism.Methods:A total of 120 patients with oral submucosal fibrosis(OSF)treated in our hospital from May 2018 to December 2019 were selected and divided into routine treatment group and Huoxue Huayu detoxification group of 60 cases according to the lottery method.The routine treatment group was treated with triamcinolone acetonide injection,and the Huoxue Huayu detoxification group was treated with Huoxue Huayu detoxification.The lesion area,mouth opening degree,SFRP1 level in gingival crevicular fluid and saliva,TCM symptom score,TGF-β1,IL-6,GSK-3β,β-catenin expression and clinical effect were observed in the two groups.Results:After treatment,the lesion area of oral mucosa in the Huoxue Huayu detoxification group was smaller than that in the routine treatment group(P<0.05),and the mouth opening degree in the Huoxue Huayu detoxification group was larger than that in the routine treatment group(P<0.05);After treatment,the level of SFRP1 in gingival crevicular fluid and saliva and clinical effect in the Huoxue Huayu detoxification group were higher than those in the routine treatment group(P<0.05);the TCM syndrome score,TGF-β1,IL-6,GSK-3β,β-catenin expression in the Huoxue Huayu detoxification group were lower than those in the routine treatment group(P<0.05).Conclusion:By acting on Wnt/β-catenin signaling pathway,Huoxue Huayu detoxification method can regulate the expression of TGF-β1,IL-6,GSK-3β,β-catenin,improve the clinical symptoms of patients with oral submucous fibrosis,alleviate the body inflammation,alleviate the pain,with remarkable effect.展开更多
Oral submucosal fibrosis(OSF)is a chronic,progressive and insidious oral mucosal disease.Its development is highly associated with areca chewing and eventually evolves into oral squamous cell carcinoma(OSCC),which is ...Oral submucosal fibrosis(OSF)is a chronic,progressive and insidious oral mucosal disease.Its development is highly associated with areca chewing and eventually evolves into oral squamous cell carcinoma(OSCC),which is currently recognized as a precancerous state by the International Center for Research on Cancer(IARC).Due to the extremely complex carcinogenesis process of OSF,the carcinogenesis mechanism is not clear,and most scholars believe that the disease is the result of multiple factors.Therefore,this paper mainly summarized the latest research on the molecular mechanism of OSF canceration,aiming at understanding the law of OSF canceration and providing theoretical reference for early detection,diagnosis and treatment of OSF canceration.展开更多
Many lesions of the oral region are treated with surgical methods such as curettage and resection. Chemotherapy and radiation therapy with or without surgical intervention can be used as an adjunct in some cases. Intr...Many lesions of the oral region are treated with surgical methods such as curettage and resection. Chemotherapy and radiation therapy with or without surgical intervention can be used as an adjunct in some cases. Intralesional steroid injection is a conservative procedure which is already used in various regions of the body andjoints. This technique is used also for a number of mouth and jaw lesions. Localized langerhans cell histiocytosis, central giant cell granuloma, oral submucous fibrosis, oral lichen planus, lichen sclerosus of the oral mucosa, lymphatic malformations and orofacial granulomatosis can be considered among these diseases. The purpose of this review is to investigate the effects of intralesional steroid injections in the treatment of oral diseases.展开更多
There are some surgeries after which a temporary cover for raw wounds is required to ensure healing.Some of those circumstances are loss of tissue due to burns,trauma,amputation,chronic ulcer,leprosy,and skin graft si...There are some surgeries after which a temporary cover for raw wounds is required to ensure healing.Some of those circumstances are loss of tissue due to burns,trauma,amputation,chronic ulcer,leprosy,and skin graft sites.Although the body initiates regeneration mechanisms,however the time taken for complete healing of wounds is unpredictable.Also,there is a tendency for long standing wounds to undergo infection and scarring.Oral mucosa is no exception to scarring and infection of wounds and there has always been a search for new materials that can be used for coverage of oral defects.Xenogenous collagen is one such grafting material.Over the years collagen implant solutions for a number of clinical applications include general surgery,burn surgery,neurosurgery,plastic and reconstructive surgery,oral surgery,and peripheral nerve and tendon surgery.This paper aims to focus on collagen as an effective option of wound closure in plastic and reconstructive surgery of the head and neck,especially after loss of soft tissue following resection of oral malignancies.展开更多
基金supported by the National Key Research and Development Program(2022YFC2402900)the Key Research and Development Program of Hainan Province(ZDYF2024SHFZ128)the Science and Technology Innovation Program of Hunan Province(2022RC1213),China.
文摘Objective:Drug-loaded mucoadhesive silk fibroin(SF)microneedle patch can overcome the limitations of low bioavailability and significant pain associated with traditional treatment methods,such as topical application or injection of triamcinolone for oral submucous fibrosis(OSF).However,these systems release the drug too quickly,failing to meet the clinical requirements.This study aims to construct a mucoadhesive SF microneedle patch pre-assembled with silk fibroin nanospheres(SFN)and explore its ability to sustain the release of triamcinolone in the treatment of OSF.Methods:SFN was pre-assembled via precipitation reaction and characterized by scanning electron microscope(SEM)for the morphology.The particle size andζ-potential were measured by dynamic light scattering(DLS).Triamcinolone was loaded onto SFN using a diffusional post-loading method.The effective loading of triamcinolone was confirmed using Fourier-transform infrared spectroscopy(FTIR).The concentration of unloaded triamcinolone was quantified by high-performance liquid chromatography.Drug encapsulation efficiency and loading capacity of SFN were then calculated to determine the optimal amount of drug loading.The SFN suspension was pre-mixed with SF solution to prepare the microneedle under-layer.The microneedle morphology was observed by SEM.Compression mechanical tests were performed to evaluate the fracture force of microneedles at different nanosphere contents(5%,10%,and 20%),determining the optimal pre-mixing ratio.Ex-vivo mouse oral mucosa permeation studies were performed to ascertain the insertion depth of the microneedles via histological sections.The adhesive top layer was synthesized using SF and tannic acid,with FTIR confirming its successful synthesis.Its viscoelasticity was characterized by a rheometer,and differential scanning calorimetry analyzed thermal properties.Tensile tests evaluated the interfacial bonding strength between the adhesive layer and microneedle base to ensure no detachment during use.Adhesion to wet oral mucosal tissues was tested and compared to commercial oral patches.Under the optimized conditions,the double-layered mucoadhesive microneedle patch with pre-assembled nanospheres was prepared.Its cell compatibility was evaluated by cell counting kit-8(CCK-8),live/dead staining,and phalloidin staining after co culturing with fibroblasts.The drug release experiment was conducted to demonstrate its sustained release efficacy.Results:SFN(mean diameter 46.25 nm)was successfully prepared.The maximum drug encapsulation efficiency was(63.88±1.09)%(corresponding loading capacity of SFN was(27.41±3.06)%when the weight ratio of triamcinolone/SFN was 0.5.The corporation of SFN did not affect microneedle morphology.The mechanical properties of microneedles decreased with increasing nanosphere amount.Only the fracture force of the group with 5%SFN[(0.07±0.01)N/needle]exceeded the minimum force required for mucosal penetration,thus selected as the optimal pre-mixing ratio.Histological sections confirmed that the SFN microneedles could penetrate the epithelial layer and deliver drugs to OSF affected areas.Adhesion strength between the microneedle base and top layer was(94.8±6.89)kPa,confirming strong bonding with no detachment during use.The wet adhesive strength of the double-layered mucoadhesive microneedle patch[(41.28±7.43)kPa]was significantly enhanced compared to commercial oral patches(4.5 kPa,P<0.01).CCK-8 and live/dead staining results confirmed no significant cytotoxicity.Drug release experiment showed the double-layered mucoadhesive microneedle patch with pre-assembled SFN enabled sustained release time of triamcinolone from 4 days to 14 days.Conclusion:Pre-assembling nanospheres in mucoadhesive SF microneedle patches can extend triamcinolone release time,meeting clinical requirements for sustained drug delivery.
基金This work was supported by the National Natural Science Foundation of China(Nos.81874496,82374530)the Clinical Medical Technology Innovation Guide Project of Hunan Province(No.2020SK53206)+3 种基金the Natural Science Foundation of Hunan Province(No.2021JJ70062)the Changsha Natural Science Foundation Project(No.kq2014019)the Health Special Fund Research Project of Hunan Province(No.B2020-07)the Clinical Pharmaceutical Research Fund of Hunan Medical Association(No.B202012).
文摘Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human oral mucosafibroblasts(hOMF)were induced with transforming growth factor beta1(TGF-β1)and intervened with Pue.Expressions offibrosis-related markers were analyzed by Western blot and IF staining.Cell viability was characterized by the CCK-8 assay.Expressions of miR-30 family members were quantified by qRT-PCR.The correlation betweenfibroblast activation protein(FAP)and miR-30 family expression was evaluated by the Pearson correlation coefficient.Bioinformatics prediction and dual-luciferase reporter assay were employed to verify the regulation between FAP and miR-30b-5p.The specific mechanism of Pue on OSF was explored through the promotion or inhibition of miR-30b-5p.Results:After induction by TGF-β1,hOMF showed upregulated Collagen I,Collagen III,and FAP expressions,while miR-30 family expression was downregulated with miR-30b-5p being the most significant.Pue intervention inhibited the excessive proliferation of TGF-β1-induced hOMF,downregulated FAP,collagen type 3(COL3A1),collagen type 1(COL1A1),matrix metalloproteinase 1(MMP1),and matrix metalloproteinase 3(MMP3)expressions,and restored miR-30 family expression.Bioinformatics prediction and dual-luciferase reporter assay revealed that miR-30b-5p selectively inhibited FAP expression.Mechanistically,miR-30b-5p mimic suppressed the excessive proliferation of TGF-β1-induced hOMF and declinedfibrosis levels.Pue intervention significantly reversed the promotion of TGF-β1-induced OSF by miR-30b-5p inhibition.Conclusion:Pue mediated miR-30b-5p targeting FAP against OSF,which provided a theoretical basis for the pathogenesis research and Pue application in OSF.
基金Supported by the Hungarian Scientific Research Fund,OTKA grant,No.PD 108309(Nikolett Bódi)by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences(Mária Bagyánszki)by the Stipendium Hungaricum Scholarship,No.2015-SH-500041,Tempus Public Foundation(Lalitha Chandrakumar)
文摘AIM To investigate the intestinal segment-specific effects of diabetes and insulin replacement on the density of different subpopulations of submucous neurons. METHODS Ten weeks after the onset of type 1 diabetes samples were taken from the duodenum, ileum and colon of streptozotocin-induce diabetic, insulin-treated diabetic and sex-and age-matched control rats. Whole-mount preparations of submucous plexus were prepared from the different gut segments for quantitative fluorescent immunohistochemistry. The following double-immunostainings were performed: neuronal nitric oxide synthase(n NOS) and Hu C/D, heme oxygenase(HO) 1 and peripherin, as well as HO2 and peripherin. The density of n NOS-, HO1-and HO2-immunoreactive(IR) neurons was determined as a percentage of the total number of submucous neurons. RESULTS The total number of submucous neurons and the proportion of n NOS-, HO1-and HO2-IR subpopulations were not affected in the duodenal ganglia of control, diabetic and insulin-treated rats. While the total neuronal number did not change in either the ileum or the colon, the density of nitrergic neurons exhibited a 2-and 3-fold increase in the diabetic ileum and colon, respectively, which was further enhanced after insulin replacement. The presence of HO1-and HO2-IR submucous neurons was robust in the colon of controls(38.4%-50.8%), whereas it was significantly lower in the small intestinal segments(0.0%-4.2%, P < 0.0001). Under pathophysiological conditions the only alteration detected was an increase in the ileum and a decrease in the colon of the proportion of HO-IR neurons in insulin-treated diabetic animals. CONCLUSION Diabetes and immediate insulin replacement induce the most pronounced region-specific alterations of n NOS-, HO1-and HO2-IR submucous neuronal density in the distal parts of the gut.
文摘To analyze the clinical symptoms and signs in cases of oral submucous fibrosis which has transformed into squamous cell carcinoma, twenty-nine patients with squamous cell carcinoma correlated with oral submucous fibrosis, leukoplakia, lichen planus were taken biopsy for positive diagnosis. The clinical and pathological diagnosis of oral submucous fibrosis depended on clinical and pathological diagnostic standards. The oral submucous fibrosis involving different portions and size in the mouth was observed and recorded. The portions of oral cancer, clinical findings and symptoms, cancerous size, the conditions of the local lymphatic nodes and of oral submucous fibrosis correlated with squamous cell carcinoma in the mouth, oral leukoplakia, lichen planus were also observed and recorded. In twenty-nine patients with oral squamous cell carcinoma, duration from oral submucous fibrosis transformed into oral cancer ranged from 2 to 15 years with an average year of 6.69. The serious degrees of oral submucous fibrosis in the patients with oral cancer were that the moderately advanced stage was found in 3 cases (10.34%) and the advanced stage was found in 26 cases (89.65%). The cancerous portion was that the buccal mucosa was found in 9 cases (31.03%);the tongue was found in 14 cases (48.27%);the other portion was found in the rest 6 cases (20.68%). Among the twenty-nine patients twenty-three patients with squamous cell carcinoma were associated with leukoplakia (79.31%), five patients were associated with lichen planus (17.24%). Twenty-seven patients (93.1%) had habits of betel quid chewing, smoked cigarette and drank alcohol, the rest two patients had habits of betel quid chewing and cigarette smoking. The present study demonstrates that oral submucous fibrosis is a real precancerous lesion and may transform into squamous cell carcinoma in the mouth.
文摘Objective:To explore the clinical efficacy of Danshen injection in combined with local injection of triamcinolone acetonide in the treatment of oral submucous fibrosis (OSF) and the effect on serum TGF-β1 and IL-6.Methods:A total of 70 patients with OSF who were admitted in our hospital from October, 2015 to October, 2016 were included in the study and randomized into the observation group and the control group (n=35). The patients in the control group were given multipoint injection of triamcinolone acetonide (40 mg/time) in the basal region of oral mucosal regions. On this basis, the patients in the observation group were given additional Danshen injection (4 mL/time), 1 time/week, for 12 times. VAS was used for evaluation. The oral mucosa lesion area and mouth opening were measured. The morning fasting peripheral venous blood before and after treatment in the two groups was collected. The blood rheometer was used to detect the whole blood viscosity [high shear (HS), moderate shear (MS), and low shear (LS)], plasma viscosity (PV), and fibrinogen (FIB). ELISA was used to detect the serum TGF-β1 and IL-6 levels.Results: VAS score in the observation group was significantly reduced (P<0.05), mucosal lesion area was significantly less than that in the control group (P<0.05), and mouth opening was significantly greater than that in the control group (P<0.05). LS, MS, PV, and FIB after treatment in the observation group were significantly reduced when compared with before treatment (P<0.05), while LS, MS, HS, PV, and FIB after treatment in the control group were not significantly changed (P>0.05). TGF-β1 and IL-6 levels after treatment in the observation group were significantly lower than those in the control group (P<0.05).Conclusions: Danshen injection in combined with local injection of triamcinolone acetonide in the treatment of OSF can effectively reduce the serum TGF-β1 and IL-6 levels, inhibit the connective tissue fibrosis, and improve the pain, oral mucosal lesion area, and mouth opening, with a satisfactory clinical effect.
文摘The morphometric analysis of the spinous cell in 16 specimens of oral submucous fibrosis (OSF) was made by using interactive image analysis system (IBAS-II). 19 parameters of the size and shape were chosen, and compared with normal mucosa, leukoplakia, dysplasia and carcinoma. The results indicated that the cell dimensions (area, perimeter, all kinds of diameter) and nuclear cytoplasmic ratio in OSF were between normal mucosa and dysplasia as well as carcinoma. The former showed a progressive decrease (P<0.01), and the latter showed a progressive increase (P<0.01). The dimensions of the nuclei did not show considerable differences among the groups (P>0.05). A series of discriminant functions had been developed with stepwise discriminant analysis, the agreement ratio for OSF was 93.75%. The decrease of cell area and the increase of nuclear cytoplasmic ratio could reflect a malignant progress. The cell morphometric model could discriminate OSF well from other groups, suggesting that the change of the epith
文摘AIM: To investigate the effect of Ginkgo biloba extract on the enteric neurons in the small intestine of diabetic rats. METHODS: Fifteen Wistar rats were divided into three groups: control group (C), diabetic group (D) and diabetic-treated (DT) daily with EGb 761 extract (50 mg/kg body weight) for 120 d. The enteric neurons were identified by the myosin-V immunohistochemical technique. The neuronal density and the cell body area were also analyzed. RESULTS: There was a significant decrease in the neuronal population (myenteric plexus P = 0.0351; submucous plexus P = 0.0217) in both plexuses of the jejunum in group D when compared to group C. With regard to the ileum, there was a significant decrease (P = 0.0117) only in the myenteric plexus. The DT group showed preservation of the neuronal population in the jejunum submucous plexus and in the myenteric plexus in the ileum. The cell body area in group D increased significantly (P = 0.0001) in the myenteric plexus of both segments studied as well as in the ileum submucosal plexus, when compared to C. The treatment reduced (P = 0.0001) the cell body area of the submucosal neurons of both segments and the jejunum myenteric neurons. CONCLUSION: The purified Ginkgo biloba extract has a neuroprotective effect on the jejunum submucous plexus and the myenteric plexus of the ileum of diabetic rats.
基金supported by grants from the National Natural Science Foundation of China(Grant No.81460105)the National Natural Science Foundation of China(Grant No.81360407)+1 种基金the National Natural Science Foundation of Hainan Province(Grant No.2058321)Foundation of Health Department of Hainan Province(Grant No.14A210189)
文摘Objective: To develop a BALB/c mouse model of oral submucous fibrosis(OSF)induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes.Methods: BALB/c mice were randomly assigned to either the control(distilled water) or experimental group(arecoline)(n = 40). Eight mice from each group were sacrificed every 4 weeks since 8 weeks post treatment. Changes in histopathologic features, levels of collagen type Ⅰ and collagen type Ⅲ, and angiogenesis were measured.Results: In the 8th week, epithelium atrophy, collagen cumulation and micrangium pathologic changes in the lamina propria were observed in the oral mucosa. In the 20th week, hyaline degeneration of the connective tissues was observed on the tongue and palate mucosa. The angiogenesis and collagen type Ⅰ changed significantly as the diseases advanced(P < 0.05); however, collagen type Ⅲ was not statistically different.Conclusions: An OSF model involving mice can be rapidly induced by drinking a highdose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type Ⅰ.
文摘Quality of life(QoL) is a vital and often required health outcome measure that is relevant to patient care. A healthy oral cavity enables person to perform daily activities without any limitations. However, any disturbance may result in impaired QoL. The oral health-remains an essential element of people's health and well-being. In recent years, the tradition of clinical practice and research has been changed by incorporating QoL assessment, as it helps in assessment of patients' needs and monitoring treatment responses. Oral potentially malignant disorders(OPMDs) are a group of chronic disorders including oral leukoplakia(OL), oral lichen planus and oral submucous fibrosis(OSF). It is evident that patients with OPMDs experience significant health-related symptoms, functional limitations and psycho-social impairment, compromising their Qo L. Moreover, the worsening of Qo L has been associated with advanced stages of OPMDs. Despite of increasing number of OPMD cases in recent decades, limited literature is available regarding QoL in this population. Although, there is higher prevalence of habit-related OPMDs, particularly OSF and OL in Southern Asian countries, only a few studies have been performed in these populations. Moreover, these studies administered generic Qo L instruments, which offer less sensitivity to clinical changes. However, condition-specific instruments are more sensitive and allows better measurement of QoL. As the impacts of different conditions on OHRQoL may vary, the development and validation of a QoL instrument specific to each clinical entity of OPMDs is currently needed.
文摘Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaquelike, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary.The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used.
基金Supported by Shanghai Science and Technology Commission Project,No.17410710500,No.19441906000,No.YG2015MS02,No.PW2016E-1,and No.JYJX03201810
文摘BACKGROUND Congenital palate perforation is extremely rare. There is controversy about its exact etiology and appropriate management. Here, a case of congenital palatal perforation is reported. The diagnosis and treatment of the disease are summarized.CASE SUMMARY A full-term neonate boy was referred for oral and craniomaxillofacial surgery with a finding of a hole in the palate at birth. The operation was postponed after pediatric consultation because of the patient’s poor nutrition and underweight for his age. At the age of 10 mo, the patient underwent modified von Langenbeck palatoplasty. He was followed for four years after surgery without any signs of re-rupture. His speech was satisfactory.CONCLUSION Considering the anatomy and etiology, congenital palate perforation can be classified as isolated or associated with submucous cleft palate, and the treatment procedure should be altered accordingly.
基金Supported by Science and Technology Commission of Shanghai Municipality,China,No.19DZ2251100Shanghai Municipal Health Commission,China,No.SHSLCZDZK 03502National Natural Science Foundation of China,No.81725008.
文摘BACKGROUND Vaginal myomectomy is the most common form of radical treatment for prolapsed submucosal leiomyoma and is typically performed under general anesthesia.However,an alternative treatment approach is needed for patients who cannot tolerate general anesthesia.We describe a case with such a patient who was successfully treated via a minimally invasive method under local anesthesia.CASE SUMMARY A 46-year-old female suffered from abnormal uterine bleeding,severe anemia,and a reduced quality of life attributed to a massive prolapsed submucosal leiomyoma.She could not tolerate general anesthesia due to a congenital thoracic malformation and cardiopulmonary insufficiency.A new individualized combined treatment,consisting uterine artery embolization(UAE),percutaneous microwave ablation(PMWA)of the pedicle and the endometrium,and transvaginal removal of the leiomyoma by twisting,was performed.The lesion was completely removed successfully under local anesthesia without any major complications.The postoperative follow-up showed complete symptom relief and a significant improvement in the quality of life.CONCLUSION UAE combined with PMWA can be performed under local anesthesia and is a promising alternative treatment for patients who cannot tolerate general anesthesia.
基金National natural science foundation of China(No.81874496)Project of Hunan administration of traditional Chinese medicine(No.201808)Hunan education department project(No.18C0408)。
文摘Objective:To explore the effects of Huoxue Huayu detoxification method on the levels of GSK-3βandβ-catenin in OSF patients and its mechanism.Methods:A total of 120 patients with oral submucosal fibrosis(OSF)treated in our hospital from May 2018 to December 2019 were selected and divided into routine treatment group and Huoxue Huayu detoxification group of 60 cases according to the lottery method.The routine treatment group was treated with triamcinolone acetonide injection,and the Huoxue Huayu detoxification group was treated with Huoxue Huayu detoxification.The lesion area,mouth opening degree,SFRP1 level in gingival crevicular fluid and saliva,TCM symptom score,TGF-β1,IL-6,GSK-3β,β-catenin expression and clinical effect were observed in the two groups.Results:After treatment,the lesion area of oral mucosa in the Huoxue Huayu detoxification group was smaller than that in the routine treatment group(P<0.05),and the mouth opening degree in the Huoxue Huayu detoxification group was larger than that in the routine treatment group(P<0.05);After treatment,the level of SFRP1 in gingival crevicular fluid and saliva and clinical effect in the Huoxue Huayu detoxification group were higher than those in the routine treatment group(P<0.05);the TCM syndrome score,TGF-β1,IL-6,GSK-3β,β-catenin expression in the Huoxue Huayu detoxification group were lower than those in the routine treatment group(P<0.05).Conclusion:By acting on Wnt/β-catenin signaling pathway,Huoxue Huayu detoxification method can regulate the expression of TGF-β1,IL-6,GSK-3β,β-catenin,improve the clinical symptoms of patients with oral submucous fibrosis,alleviate the body inflammation,alleviate the pain,with remarkable effect.
基金National Natural Science Foundation of China(No.81960199)Major Science and Technology Plan and Key R&D Plan Project of Hainan Province(No.ZDYF2021SHFZ114)Hainan Provincial Department of Health Project(No.22A200001)。
文摘Oral submucosal fibrosis(OSF)is a chronic,progressive and insidious oral mucosal disease.Its development is highly associated with areca chewing and eventually evolves into oral squamous cell carcinoma(OSCC),which is currently recognized as a precancerous state by the International Center for Research on Cancer(IARC).Due to the extremely complex carcinogenesis process of OSF,the carcinogenesis mechanism is not clear,and most scholars believe that the disease is the result of multiple factors.Therefore,this paper mainly summarized the latest research on the molecular mechanism of OSF canceration,aiming at understanding the law of OSF canceration and providing theoretical reference for early detection,diagnosis and treatment of OSF canceration.
文摘Many lesions of the oral region are treated with surgical methods such as curettage and resection. Chemotherapy and radiation therapy with or without surgical intervention can be used as an adjunct in some cases. Intralesional steroid injection is a conservative procedure which is already used in various regions of the body andjoints. This technique is used also for a number of mouth and jaw lesions. Localized langerhans cell histiocytosis, central giant cell granuloma, oral submucous fibrosis, oral lichen planus, lichen sclerosus of the oral mucosa, lymphatic malformations and orofacial granulomatosis can be considered among these diseases. The purpose of this review is to investigate the effects of intralesional steroid injections in the treatment of oral diseases.
文摘There are some surgeries after which a temporary cover for raw wounds is required to ensure healing.Some of those circumstances are loss of tissue due to burns,trauma,amputation,chronic ulcer,leprosy,and skin graft sites.Although the body initiates regeneration mechanisms,however the time taken for complete healing of wounds is unpredictable.Also,there is a tendency for long standing wounds to undergo infection and scarring.Oral mucosa is no exception to scarring and infection of wounds and there has always been a search for new materials that can be used for coverage of oral defects.Xenogenous collagen is one such grafting material.Over the years collagen implant solutions for a number of clinical applications include general surgery,burn surgery,neurosurgery,plastic and reconstructive surgery,oral surgery,and peripheral nerve and tendon surgery.This paper aims to focus on collagen as an effective option of wound closure in plastic and reconstructive surgery of the head and neck,especially after loss of soft tissue following resection of oral malignancies.
