Modeling human gastric cancers in immunocompetent mice

Gastric cancer(GC)is a major cause of cancer-related mortality worldwide.GC is determined by multiple(epi)genetic and environmental factors;can occur at distinct anatomic positions of the stomach;and displays high heterogeneity,with different cellular origins and diverse histological and molecular features.This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics.In the past decade,great progress has been made in the study of GC,particularly in molecular subtyping,investigation of the immune microenvironment,and defining the evolutionary path and dynamics.Preclinical mouse models,particularly immunocompetent models that mimic the cellular and molecular features of human GC,in combination with organoid culture and clinical studies,have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion,and the development of novel therapeutic strategies.Herein,we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models,emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.

Obstructive Tumor of the Palate in the Old Person: A Case Report

Introduction: Pleomorphic adenoma or mixed salivary gland tumor is a heterogeneous benign tumor of the salivary glands. The most common site is the parotid gland. Its extra-parotid locations, particularly in the accessory salivary glands, are rarer. We report a case of a pleomorphic adenoma of the posterior palate which posed management problems. Observation: This is an 85-year-old patient who consulted for a tumor of the posterior palate that had been evolving for 3 years. The examination revealed a globular tumor of the posterior palate extending beyond the midline by approximately 7 cm in long axis, shooting towards the oropharynx and hindering breathing, speech and eating, indicating a life-saving tracheotomy. A CT scan of the facial area revealed a well-circumscribed tumor at the expense of the soft palate, with multiple sites of bone lysis. The biopsy performed was in favor of a pleomorphic adenoma. The patient underwent total surgical excision of a huge tumor on the palate. The aftermath of the operation was marked by a loosening of the sutures with an oronasal fistula requiring the creation of an obturator plate due to the patient’s refusal to have another operation. Conclusion: Large pleomorphic adenoma of the posterior palate is a rare entity that can cause respiratory problems and surgical difficulties. His prognosis is generally good.

Research Progress on the Application of Nanomaterials in the Treatment of Oral Cancer

Oral cancer is a complex pathological process caused by a combination of exogenous factors represented by oncoviruses and endogenous factors represented by immune damage,individual DNA damage,and repair.Targeted treatment for oral cancer is based on the perspective of molecular genetics,which can not only reduce toxicity and increase efficacy,but also improve the quality of life of patients.This is the bottleneck that clinical oral cancer treatment needs to break through the most.Nanomaterials can exhibit a unique large molecular surface area,with relatively high surface reactivity and multiple surface active centers,resulting in strong adsorption capacity in molecular metabolism.There is a certain foundation in its application in the field of biology,but it has good tumor cytotoxicity and inhibition of proliferation in the treatment of oral cancer.This study reviews the application of nanomaterials in tumor prevention,treatment,and other fields,providing new ideas for the future treatment of this disease.

Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects

Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of P.gingivalis in IR remain unclear.In the present study,clinical samples were analysed to determine the statistical correlation between P.gingivalis and IR occurrence.Through culturing of hepatocytes,myocytes,and adipocytes,and feeding mice P.gingivalis orally,the functional correlation between P.gingivalis and IR occurrence was further studied both in vitro and in vivo.Clinical data suggested that the amount of P.gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score.In vitro studies suggested that coculture with P.gingivalis decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and adipocytes.Mice fed P.gingivalis tended to undergo IR.P.gingivalis was detectable in the liver,skeletal muscle,and adipose tissue of experimental mice.The distribution sites of gingipain coincided with the downregulation of INSR.Gingipain proteolysed the functional insulin-binding region of INSR.Coculture with P.gingivalis significantly decreased the INSR–insulin binding ability.Knocking out gingipain from P.gingivalis alleviated the negative effects of P.gingivalis on IR in vivo.Taken together,these findings indicate that distantly migrated P.gingivalis may directly proteolytically degrade INSR through gingipain,thereby leading to IR.The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

Split Hand/Foot Malformation about Two Family Cases

Split hand/foot malformation (SHFM), formerly known as ectrodactyly is a rare congénital anomaly, its incidence varies from 1/8.500 to 1/25.000 live birth. It mainly affects the development of the limbs, its clinical variability is standard, can present as an isolated feature or as a syndrome associated with other congenital anomalies. Our objective was to present the two cases of SHFM, and to review the literature on the clinical aspects and discuss a probable origin. The father went to school and is a driver because the malformations concerned only the fingers, were less severe, and did not prevent the realization of certain simple gestures of the daily life. On the other hand, the malformations of the fingers of the newborn were severe and the absence of the thumbs compromised the later prehension function. Also the association of a microglossia and a cleft palate contributed to a weight loss that justified hospitalization. The clinical presentation of split hands and feet is variable and the prognosis depends on the type of anomaly. Familial cases suggest a probable genetic origin. Genetic testing is necessary to establish genetic counseling.

Ophthalmologic Repercussions of Orbital Fractures

Orbital fractures refer to all continuity solutions involving the wall of the orbit. They are responsible for serious complications, particularly ophthalmological. Objective: To identify the epidemiological, anatomical and clinical aspects as well as the possible ocular complications of orbital fractures in the Gbêkê region. Methods: Prospective study from July 1, 2020, to October 31, 2020, i.e., a duration of 4 months. It took place in the ophthalmology department of the University Hospital of Bouaké. Patients with orbital fractures with ocular repercussions received during the study period were included. Results: Out of 27 cases of orbital floor fracture received, 20 had ocular complications, i.e., a prevalence of 74.07%. The average age was 32 years with extremes of 18 and 48 years. The male gender predominated with 80%, i.e. a sex ratio of 4. Subconjunctival hemorrhage was the most frequent reason for consultation (70%). The etiology was dominated by road traffic accidents (85%). The average consultation time was 24 hours. 80% of the patients had a distance visual acuity (DVA) between 3/10 and 10/10.) Diplopia was observed in 60% of patients. Blow out fracture (70%) was the most prominent orbital lesion. At the paraclinical level, 80% of the patients had performed a CT scan of the orbit. Evisceration was the predominant ophthalmologic surgical management (4 patients). At the bone level, reconstruction of the orbital floor with a polydioxanone plate (PDS) was performed in 50% of patients. Conclusion: The risk of ocular injury in orbital fractures is frequent because of the close relationship between the orbit and the eyeball.

Circulating micro RNAs as diagnostic and prognostic tools for hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is an aggressive malignancy and the second leading cause of cancerrelated deaths worldwide. Conventional biomarkers exhibit poor performance in the surveillance,diagnosis,and prognosis of HCC. Micro RNAs(mi RNAs) are a class of evolutionarily conserved small non-coding RNAs that are involved in the regulation of gene expression and protein translation,and they play critical roles in cell growth,differentiation,and the development of various types of cancers,including HCC. Recent evidence revealed the role of mi RNAs as potential novel and ideal biomarkers for HCC. mi RNAs are released to extracellular spaces,and they are extremely stable in bodily fluids,including serum or plasma,where they are packaged into various microparticles or associated with RNA-binding proteins. Numerous studies have demonstrated that circulating mi RNAs have potential applications as minimally invasive biomarkers for HCC diagnosis and prognosis. The present review highlights current understanding of mi RNA biogenesis and the origins and types of circulating mi RNAs. We summarize recent progress in the use of circulating mi RNAs as diagnostic and prognostic biomarkers for HCC. We also discuss the challenges and perspectives of the clinical utility of circulating mi RNAs in HCC.

The Association between Lower Incisal Inclination and Morphology of the Supporting Alveolar Bone—A Cone-Beam CT Study

Aim To investigate the relationship between the positioning of the lower central incisor and physical morphology of the surrounding alveolar bone. Methodology Thirty-eight patients （18 males, 20 females）, with mean age of 13.4 years, were included in this study. As part of orthodontic treatment planning the patients were required to take dental Cone-beam CT （CBCT） covering the region of lower incisors, the sur- rounding alveolar bone and the mandibular symphysis. The cephalometric parameters were designed and measured to indicate the inclination of lower central incisor and physical morphology of the adjacent alveolar bone. Computer-aided descriptive statistical analysis was performed using SPSS 15.0 software package for Windows. A correlation analysis and a linear regression analysis between the incisor inclination and the alveolar bone morphology were performed. Results Significant positive correlations were found between the lower central incisor inclination and the morphological contour of the alveolar bone （P〈0.05）. The lower central incisor root apex was closer to the lingual alveolar crest when it was buccally inclined. Conclusion The morphology of the alveolar bone may be affected by incisal inclination.

Anti-proteolytic capacity and bonding durability of proanthocyanidin-biomodified demineralized dentin matrix

Our previous studies showed that biomodification of demineralized dentin collagen with proanthocyanidin（PA） for a clinically practical duration improves the mechanical properties of the dentin matrix and the immediate resin–dentin bond strength. The present study sought to evaluate the ability of PA biomodification to reduce collagenase-induced biodegradation of demineralized dentin matrix and dentin/adhesive interfaces in a clinically relevant manner. The effects of collagenolytic and gelatinolytic activity on PA-biomodified demineralized dentin matrix were analysed by hydroxyproline assay and gelatin zymography. Then, resin-/dentin-bonded specimens were prepared and challenged with bacterial collagenases. Dentin treated with 2% chlorhexidine and untreated dentin were used as a positive and negative control, respectively. Collagen biodegradation, the microtensile bond strengths of bonded specimens and the micromorphologies of the fractured interfaces were assessed. The results revealed that both collagenolytic and gelatinolytic activity on demineralized dentin were notably inhibited in the PA-biomodified groups, irrespective of PA concentration and biomodification duration. When challenged with exogenous collagenases, PA-biomodified bonded specimens exhibited significantly less biodegradation and maintained higher bond strengths than the untreated control. These results suggest that PA biomodification was effective at inhibiting proteolytic activity on demineralized dentin matrix and at stabilizing the adhesive/dentin interface against enzymatic degradation, is a new concept that has the potential to improve bonding durability.

Development and application of rapid rehabilitation system for reconstruction of maxillofacial soft-tissue defects related to war and traumatic injuries

Background: Maxillofacial war injuries usually cause severe facial organ defects and deformities, handicapping the patient's daily activities, even result in a tendency to commit suicide. The application of maxillofacial prosthesis is an alternative to surgery in functional–aesthetic facial reconstruction. Computer aided design and computer aided manufacturing has opened up a new approach to the fabrication of maxillofacial prosthesis. An intelligentized rapid simulative design and manufacture system for prosthesis was developed to facilitate the prosthesis fabrication procedure.Methods: Maxillofacial prosthesis rapid simulation design and rapid fabrication system consists of three components: digital impression, intelligentized prosthesis designing, and rapid manufacturing. The patients' maxillofacial digital impressions were taken with Structured-light 3D scanner; and then the 3D model of prostheses and their negative molds could be designed in specific software; finally, with the resin molds fabricated by rapid prototyping machine, the prostheses could be produced directly and quickly.Results: Fifteen patients of maxillofacial defect caused by traumatic injuries received prosthesis rehabilitation provided by the established system. The contour of the prostheses coordinated properly with the appearance of the patients, and the uniform-thickness border sealed well to adjacent tissues. All the patients were satisfied with their prostheses.Conclusions: The rapid simulative rehabilitation system of maxillofacial defects has been approaching completion. It could provide advanced technological reservation for the Army in the issue of maxillofacial defect rehabilitation.

Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities

Along with the development of new materials, advanced medical imaging and surgical techniques, osseointegrated dental implants are considered a successful and constantly evolving treatment modality for the replacement of missing teeth in patients with complete or partial edentulism. The importance of restoring the peripheral neural feedback pathway and thus repairing the lack of periodontal rnechanoreceptors after tooth extraction has been highlighted in the literature. Nevertheless, regenerating the nerve fibers and reconstructing the neural feedback pathways around osseointegrated implants remain a challenge. Recent studies have provided evidence that platelet-rich plasma （PRP） therapy is a promising treatment for musculoskeletal injuries. Because of its high biological safety, convenience and usability, PRP therapy has gradually gained popularity in the clinical field Although much remains to be learned, the growth factors from PRP might play key roles in peripheral nerve repair mechanisms. This review presents known growth factors contributing to the biological efficacy of PRP and illustrates basic and （pre-）clinical evidence regarding the use of PRP and its relevant products in peripheral nerve regeneration. In addition, the potential of local application of PRP for structural and functional recovery of iniured peripheral nerves around dental implants is discussed.

Visualization analysis of research frontiers and trends in nerve regeneration and osseoperception in the repair of tooth loss

This study analyzed 85 articles indexed by the Web of Science concerning nerve regeneration and osseoperception during tooth loss repair. Using the Web of Science database and Citespace Ⅲ software, a document co-citation network map was drawn by document co-citation analysis and word frequency analysis methods. Combined with emergent node secondary literature retrieval, subject headings with apparent changing word frequency trends were retrieved so as to identify research frontiers and development trends. Research frontiers and hotspots for neuronal calcium sensor protein were quantitatively explored to forecast future research developments in nerve regeneration and osseoperception during repair of tooth loss.

On the road to smart biomaterials for bone research: definitions, concepts, advances, and outlook

The demand for biomaterials that promote the repair,replacement,or restoration of hard and soft tissues continues to grow as the population ages.Traditionally,smart biomaterials have been thought as those that respond to stimuli.However,the continuous evolution of the field warrants a fresh look at the concept of smartness of biomaterials.This review presents a redefinition of the term“Smart Biomaterial”and discusses recent advances in and applications of smart biomaterials for hard tissue restoration and regeneration.To clarify the use of the term“smart biomaterials”,we propose four degrees of smartness according to the level of interaction of the biomaterials with the bio-environment and the biological/cellular responses they elicit,defining these materials as inert,active,responsive,and autonomous.Then,we present an up-to-date survey of applications of smart biomaterials for hard tissues,based on the materials’responses(external and internal stimuli)and their use as immune-modulatory biomaterials.Finally,we discuss the limitations and obstacles to the translation from basic research(bench)to clinical utilization that is required for the development of clinically relevant applications of these technologies.

Deposition of stain resistance coating by non-thermal plasma brush application to dental whitening

A non-thermal plasma brush is employed to deposit stain-resistant SiO2-like coatings on resin composite fillings and bovine teeth.With post-treating by plasma,the hardness of the coating increases from H to 8H and the water contact angle decreases from 98.8° to 61.7°.The Fourier transform infrared spectroscopy (FTIR) results show that,after plasma post-treating,the Si-O-Si and Si-OH bonds of the coating increase.Scanning electron microscope (SEM) images show the coatings to be uniform,without cracks.The coatings present outstanding performance in a stain resistance test both on resin composite and bovine teeth.Being easy to handle and less time consuming than traditional methods,with a body-friendly temperature and material,this plasma brush provides a promising in-situ coating method on patient teeth in dental clinics.

Hyalinizing clear cell carcinoma-a rare entity in the oral cavity: A case report

BACKGROUND Hyalinizing clear cell carcinoma(HCCC)is an uncommon tumor that originates in the salivary glands.This neoplasia constitutes less than 1%of minor salivary gland tumors.CASE SUMMARY A 67-year-old female visited the maxillofacial surgery department owing to a smooth,slightly yellowish protruding mass on the left side of the floor of the mouth,at the level of the molars;the tumor mass had a soft consistency on palpation and did not adhere to deep planes.The microscopical analysis of the excisional biopsy showed that the lesion was composed of sheets and cords of clear cells separated by thick eosinophilic bands of hyaline collagen.Normal glandular tissue was absent,periodic acid-Schiff with and without diastase stains,and immunohistochemical reactions were performed to confirm the diagnosis.This is the second case reported in the literature of HCCC arising in the floor of the mouth.CONCLUSION HCCC is a rare salivary gland tumor that has not been studied extensively.Its diagnosis is usually challenging,because clinically,it can be confused with a benign neoplasm.

Immunomodulatory effects and mechanisms of distraction osteogenesis

Distraction osteogenesis(DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.

Alendronate disturbs femoral growth due to changes during immunolocalization of transforming growth factor-β1 and bone morphogenetic protein-2 in epiphyseal plate

BACKGROUND The epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone.Despite the abovementioned atractive reasons for alendronate’s use,few data on the effect of alendronate during epiphyseal growth exist.AIM Verify the effect of alendronate on the growth epiphyseal plate,and compare its effect with the size of the femur during the double-staining of the immunolocalization of transforming growth factor-β1(TGF-β1)and bone morphogenetic protein-2(BMP2)in endochondral ossifing in specimens that have received alendronate.METHODS Forty newborn rats were randomly divided into two groups:a control group(were given applications of 1 mg/kg physiologic saline)and a group that received Alendronate(a dose of 2.5 mg/kg).These groups were then divided into two subgroups for euthanasia in two and 12 d of life.After euthanasia,the femurs were removed,and the femoral bones were measured linearly between the apex of the greater trochanter until the lower intercondylar midlle face to verify the probable bone growth between 3 and 12 d in control and alednroanto treated rats.Posteriorly,the surgical pieces were also sent to the histopathology laboratory to produce histological slides.The obtained slides were stained with hematoxylin and eosin to measure each of the cartilage zones in endochondral development.and other slides were immunohistochemically tested for anti-TGF-β1 and BMP-2 antibodies to investigate the immunolocalization of these proteins in the epiphyseal plaque area.RESULTS On the third day,some diferences between the control group and specimens treated with alendronate were verified.Macroscopiccaly,we found similarities in size between the femoral bones when we compared the control group with the specimens that received alendronate.On the 12^th day,the bone size of the mice receiving the drug was significantly smaller than those of the control group.These results coincide with changes in the TGF-β1 and BMP-2 expression.In the specimens that received alendronate,the TGF-β1 was expressed in some sites of trabecular bone that was neoformed,peripherally to the bone marrow area.The BMP-2 was also positive in proliferative chondrocytes and hypertrofic chondrocytes.On the 12^th day,all layers of chondrocytes exhibited positivity for BMP-2 in the specimens that received alendronate.In the interface between the trabecular bone and cartilage,an area of disorganized bone deposition was evident.Neoformed bone also appeared to be different at 12 d.In the control group,BMP-2 was positive in an intense area of bone trabeculae,whereas the alendronate-treated group showed TGF-β1 positive trabeculae and a greater bone area.CONCLUSION Alendronate alters the immunolocalization of TGF-β1 and BMP-2 simultaneously,a condition that changes the usual histological aspects of the cartilage zone and impairs epiphysis growth and femur growth.

Therapeutic Evaluation of Recurrent Aphthous Ulcer with Integrated Traditional Chinese Medicine and Western Medicine

Objective: To observe the curative effects of Yiqing granule and Zhibai Dihuang pill combined with Oralpolin gel on recurrent aphthous ulcer. Methods: 150 patients with mild recurrent aphthous ulcer were classified as excessive internal heat type and deficiency internal heat type by traditional Chinese medicine theory. Then, they were randomly divided into the positive control group (thalidomide group), the trial group (Yiqing granule group/Zhibai Dihuang pill group), and the negative control group (topical medication group). All the patients in every group used Oralpolin gel. Additionally, the patients in the positive control group took thalidomide tablets orally and those in the trial group orally took proprietary Chinese medicine (Yiqing granule/Zhibai Dihuang pill). The treatment lasted for 4 weeks. The curative effects were all evaluated according to the “RAU Efficacy Evaluation Trial Standard” which was formulated by the Professional Committee of Mucosal Diseases of Chinese Stomatological Association. Results: Of all the 150 patients involved in this medical experiment, 146 cases finished it, including 66 ones in the trial group, 36 ones in the positive control group, and 44 ones in the negative control group. The total drop-out rate was 2.7%. For the excessive internal heat type, the effective rates in the thalidomide group, the Yiqing granule group and the local medication group were 91.7%, 52.6% and 52.9% respectively in order. For the deficiency internal heat type, the effective rates in the thalidomide group, the Zhibai Dihuang pill group and the local medication group were 87.5%, 71.4% and 40% respectively in order. The clinical efficacy of the Zhibai Dihuang pill group was better than that of the local medication group and similar to that of the thalidomide group (P Conclusion: Zhibai Dihuang pill is significantly effective in the treatment for mild recurrent aphthous ulcer of deficiency internal heat type without severe adverse reactions.

Effect of low-level laser therapy on tooth-related pain and somatosensory function evoked by orthodontic treatment

Low-level laser therapy(LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals(12–33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group(LG) or a placebo group(PG)(1:1). The LG received LLLT(810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm–2) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale(NRS) of pain, pressure pain thresholds(PPTs), cold detection thresholds(CDTs), warmth detection thresholds(WDTs), cold pain thresholds(CPTs), and heat pain thresholds(HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance(ANOVA). The NRS pain scores were significantly lower in the LG group(P = 0.01). The CDTs,CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG(P < 0.033). The parameters tested also showed significantly less sensitivity on the nontreatment side of the LG compared to that of the PG(P < 0.043). There were no differences between the groups for any quantitative sensory testing(QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment.Further clinical applications are suggested.

Oral graft vs host disease:An immune system disorder in hematopoietic cell transplantation

Graft vs host disease(GVHD) is a complication of patients who are treated by hematopoietic cell transplantation.National Institutes of Health in 2005 by Working Group on Diagnosis and Staging Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD(cGVHD) established 2 principal categories of oral GVHD, acute and chronic. The oral mucosa may be the first site of manifestation of the disease. Clinical diagnosis needs to be confirmed by a biopsy of oral mucosa and minor salivary glands. Microscopic results have played a major role in the diagnosis and management of acute and chronic oral GVHD. Development of second malignancies is the greatest risk of oral cGVHD patients, mostly regarding squamous cell carcinoma. The focus of oral GVHD therapy is to improve symptoms and maintain oral function. The aim of this review article is to update the information on the oral GVHD in its clinical, microscopic features and their complications.