Lichen planus pemphigoides induced by anti-PD-1 antibody: A case only involved in oral mucosa with excellent topical treatment efficiency.

Lichen planus pemphigoides (LPP) is a rare autoimmune subepidermal disease that can occur in patients receiving immune checkpoint inhibitors. Its clinical manifestations are combined with the characteristics of lichen planus with bullous pemphigoid that can occur on either skin or oral mucosa. It should be noted that oral LPP is very rare. Here, we report a novel case of oral LPP induced by an anti-PD-1 agent. The patient presented with typical clinical features in oral mucosa, and the diagnosis was based on histopathology and immunological studies. Given that the patient was receiving an anti-PD-1 agent, topical therapy was chosen, and a nice therapeutic effect was obtained. No significant recurrence was observed after a 2-year follow-up. A good and stable therapeutic effect achieved by rapid and local symptomatic medication suggests that accurate and sensitive diagnosis is necessary.

Ionizing radiation-induced "zombie" carcinoma-associated fibroblasts with suppressed pro-radioresistance on OSCC cells.

OBJECTIVES: This study was to investigate the effect of ionizing radiation (IR) on oral carcinoma-associated fibroblasts (CAFs) and to further explore subsequent effects of IR-induced "zombie" CAFs on oral squamous cell carcinoma (OSCC) cells. MATERIALS AND METHODS: Three primary CAFs and one primary normal-associated fibroblasts (NAFs) were separated from human OSCC and normal oral mucosa tissues, identified by immunocytochemistry. Cells were exposed to IR by X-ray irradiator under different doses. The DNA damage, proliferation, and migration of irradiated CAFs were, respectively, detected by immunofluorescence and wound healing assay, while senescence was detected by ß-galactosidase staining. Finally, the effect of irradiated CAFs on biological behavior and radioresistance of Cal-27 cells were determined via assays mentioned above. RESULTS: Oral CAFs were sensitive to IR with DNA damage increasing and proliferation decreasing. 18 Gy IR could not kill oral CAFs but induce them to "zombies," with arrested proliferation, increased senescence, and reduced migration. "Zombie" CAFs (zCAFs) could enhance proliferation, migration, and invasion of Cal-27 cells, and show suppressed pro-radioresistance by reducing DNA damage and facilitating survival. CONCLUSIONS: IR-induced zCAFs could continuously promote radioresistance of OSCC cells though being suppressed, suggesting the potential promoting effect on tumor relapse post-radiotherapy that needed further exploring.

Significant efficacy of short-course, low-concentration betamethasone mouthwash therapy for severe erosive oral lichen planus: a randomized controlled trial.

OBJECTIVES: To evaluate the short-term efficacy of low-concentration betamethasone mouthwash for severe erosive oral lichen planus (EOLP). MATERIALS AND METHOD: In this randomized, investigator-blind, positive-controlled trial, OLP patients with erosive lesions received betamethasone mouthwash (0.137 mg/mL) or dexamethasone mouthwash (0.181 mg/mL) three times daily for 2 or 4 weeks and were followed up for 3 months to observe recurrence. The primary outcome was the week-2 reduction in erosive area. RESULTS: Fifty-seven participants were randomized to betamethasone (n = 29) and dexamethasone (n = 28). At week 2, participants using betamethasone (n = 28) experienced a greater reduction in erosive area than gargling with dexamethasone (n = 26). Similarly, secondary outcomes, including the healing proportion of erosions, reduced pain level, reduction in atrophic area, Thongprasom score, and recurrence interval, showed the superiority of betamethasone. At week 4, betamethasone (n = 7) was not superior to dexamethasone (n = 15) in further reducing lesional area and pain level. No serious adverse events were documented. CONCLUSIONS: The 0.137 mg/mL compound betamethasone mouthwash exhibited significant efficacy in rapidly enhancing erosion healing within 2 weeks and extending the recurrence interval with a good safety profile. CLINICAL RELEVANCE: This study proved the significant efficacy of short-course 0.137 mg/mL betamethasone mouthwash therapy for treating erosion and pain, providing a novel topical agent for patients with severe EOLP. TRIAL REGISTRATION: This study was prospectively registered at the International Clinical Trials Registry Platform ( ChiCTR1800016507 ) on 5 June 2018.

[Research Progress in the Application of Terahertz Spectroscopy and Imaging Technology in Stomatology].

Terahertz waves, the electromagnetic waves in the range of 0.1 to 10 THz, has the advantages of being damage-free, causing no ionizing radiation injury, and being capable of recognizing the fingerprint spectrum of molecular characteristics, thus holding encouraging prospects for wide applications in the field of biomedicine. Terahertz spectrum can be used to identify and characterize biological structures of different levels, from biomolecules such as proteins to cells and tissues, through the spectral signals and/or restored images of the samples. Herein, we summarized the current stomatogical application of and research progress in terahertz spectroscopy and imaging in dentistry, reported the latest research findings, strengths and limitations from three perspectives, tooth anatomical structure, the extent of caries progression, and oral soft tissue, and suggested possible directions for future exploration.

A case of Melkersson-Rosenthal syndrome with endocrine disorders: Extraordinary efficiency of hydroxychloroquine and mechanism hypothesis.

BACKGROUND AND PURPOSE: Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disease. In addition to the traditional clinical triad, there is also a diversity of clinical signs, and it may be related to other systemic diseases. METHODS: In the present study, we report a case of MRS with endocrine disorders that exhibits extraordinary therapeutic efficiency by using hydroxychloroquine (HCQ), explore whether there is an internal connection between MRS and endocrine disorders, and discuss the mechanism of the therapeutic efficiency of using HCQ. The hypothesis proposed for the first time is that MRS may essentially be a systemic granulomatous disease. RESULTS: The physical examination revealed orofacial swelling and fissured tongue. The histopathologic examination showed epithelioid granulomas. Combined with the other examination, this case was diagnosed as incomplete MRS. HCQ and local drugs were introduced. The patient achieved clinical recovery and psychological cure by the 18-week follow-up, and the 1-year follow-up found no reactivation of MRS. Moreover, the levels of cortisol and adrenocorticotropic were within normal ranges. CONCLUSIONS: After the drug therapy was targeted at granuloma, not only did all of the symptoms related to MRS disappear, but the endocrine system also returned to normal. It is speculated that the endocrine disorder in this patient may be related to MRS. We further propose the first-time hypothesis that MRS may essentially be a systemic granulomatous disease. It provides a new medication method with high-level efficiency.

Tacrolimus 0.03% ointment treatment in exfoliative cheilitis: A randomised controlled clinical trial and monitoring blood concentration.

BACKGROUND: Tacrolimus has been used to treat various inflammatory skin diseases, but its safety for topical application on the oral mucosa is unknown. Exfoliative cheilitis (EC) is a chronic inflammatory disorder of the lips characterised by repeated scaling; it is difficult to manage. The aim of this study was to assess the efficacy and safety of tacrolimus 0.03% ointment as a topical treatment in patients with EC. METHODS: In this randomised controlled clinical trial, 40 patients with EC were randomly assigned to receive either tacrolimus 0.03% ointment (experimental group, n = 20) or triamcinolone acetonide 0.1% cream (control group, n = 20) treatment for a 3-week period. Medication was administered in 3, 2 and 1 daily doses during the first, second and third weeks, respectively. The patients with complete healing were followed up for 3 months. The clinical outcomes were measured, including the scores regarding signs (scale, dryness, rhagades and swelling) and symptoms (rough, dry, pain, pruritus and burning sensation) at every visit. Blood concentrations of tacrolimus were assessed. RESULTS: After the 3-week treatment, healing rates of scale in the experimental and control groups were 65% and 10%, respectively (P = .018). Improvement in all signs and two symptoms (rough, pruritus) was much greater in the experimental group (P < .05). The 3-month recurrence rate was higher in the control group (P = .029). Tacrolimus blood concentrations were in the safe range (< 5 ng/mL). CONCLUSION: Topical tacrolimus 0.03% ointment has good short-term efficacy and safety for treating EC.

The hypothesis of tumor-associated macrophages mediating semi-phagocytosis of cancer cells in distant metastasis.

Tweetable abstract Tumor-associated macrophages might promote the distant metastasis of tumor cells by semi-phagocytosis. The authors propose that this newly discovered process occurs in tumor-associated macrophages and may lead to a novel approach for blocking cancer metastasis.

Fundamental and Clinical Applications of Materials Based on Cancer-Associated Fibroblasts in Cancers.

Cancer stromal cells play a role in promoting tumor relapse and therapeutic resistance. Therefore, the current treatment paradigms for cancers are usually insufficient to eradicate cancer cells, and anti-cancer therapeutic strategies targeting stromal cells have been developed. Cancer-associated fibroblasts (CAFs) are perpetually activated fibroblasts in the tumor stroma. CAFs are the most abundant and highly heterogeneous stromal cells, and they are critically involved in cancer occurrence and progression. These effects are due to their various roles in the remodeling of the extracellular matrix, maintenance of cancer stemness, modulation of tumor metabolism, and promotion of therapy resistance. Recently, biomaterials and nanomaterials based on CAFs have been increasingly developed to perform gene or protein expression analysis, three-dimensional (3D) co-cultivation, and targeted drug delivery in cancer treatment. In this review, we systematically summarize the current research to fully understand the relevant materials and their functional diversity in CAFs, and we highlight the potential clinical applications of CAFs-oriented biomaterials and nanomaterials in anti-cancer therapy.

A personalized computational model predicts cancer risk level of oral potentially malignant disorders and its web application for promotion of non-invasive screening.

BACKGROUND: Despite their high accuracy to recognize oral potentially malignant disorders (OPMDs) with cancer risk, non-invasive oral assays are poor in discerning whether the risk is high or low. However, it is critical to identify the risk levels, since high-risk patients need active intervention, while low-risk ones simply need to be follow-up. This study aimed at developing a personalized computational model to predict cancer risk level of OPMDs and explore its potential web application in OPMDs screening. METHODS: Each enrolled patient was subjected to the following procedure: personal information collection, non-invasive oral examination, oral tissue biopsy and histopathological analysis, treatment, and follow-up. Patients were randomly divided into a training set (N = 159) and a test set (N = 107). Random forest was used to establish classification models. A baseline model (model-B) and a personalized model (model-P) were created. The former used the non-invasive scores only, while the latter was incremented with appropriate personal features. RESULTS: We compared the respective performance of cancer risk level prediction by model-B, model-P, and clinical experts. Our data suggested that all three have a similar level of specificity around 90%. In contrast, the sensitivity of model-P is beyond 80% and superior to the other two. The improvement of sensitivity by model-P reduced the misclassification of high-risk patients as low-risk ones. We deployed model-P in web.opmd-risk.com, which can be freely and conveniently accessed. CONCLUSION: We have proposed a novel machine-learning model for precise and cost-effective OPMDs screening, which integrates clinical examinations, machine learning, and information technology.

Graft interposition for preventing Frey's syndrome in patients undergoing parotidectomy.

BACKGROUND: Frey's syndrome is characterised by transient flushing and sometimes facial sweating in the area of the auriculotemporal nerve. It most commonly occurs after parotidectomy, but other causes may include submandibular gland surgery, mandibular condylar fracture, obstetric (forceps) trauma, sympathectomy and metabolic disease. Although the pathophysiology of Frey's syndrome remains controversial, the generally accepted hypothesis is that it occurs as the result of injury to the auriculotemporal nerve.There is currently no clear evidence to establish the efficacy and safety of the different methods used for the treatment of Frey's syndrome, therefore the prevention of this symptom during surgery is important. The main method used for prevention is the interposition of a graft between the skin flap and the parotid bed during surgery. Biomaterials, allograft or autograft can be used for this purpose. OBJECTIVES: To evaluate the effects and safety of biomaterial, allograft or autograft interposition for the prevention of Frey's syndrome in patients undergoing parotidectomy, and to identify its effect on prevention and delayed occurrence. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Cochrane Register of Controlled Trials (CENTRAL; 2019, Issue 2); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 5 February 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in patients with parotid disease (including tumours, inflammation, trauma etc.) undergoing parotidectomy with a minimal follow-up period of six months. We planned to include trials with interventions including biomaterial, allograft or autograft interposition alone or in combination with other surgical techniques. We included trials that compared any graft interposition and no graft interposition, or different graft interpositions. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcome measures were incidence rate of Frey's syndrome assessed clinically (Minor's starch-iodine test) and other complications (postoperative infection, subjective painful or restricted cervical movement, scar spread, rejection of the graft, complications related to the donor site such as accessory nerve injury and haematoma). Our secondary outcome measures were incidence rate of Frey's syndrome assessed by participants (by questionnaire) and sweating area assessed by Minor's starch-iodine test. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included three RCTs (124 participants), two of which we assessed as at high risk of bias and one at unclear risk of bias. All studies were hospital-based and recruited participants undergoing superficial parotidectomy. Most participants were diagnosed with benign lesions of the parotid gland. Participants were followed up for more than six months. The studies evaluated the two comparisons shown below:Sternocleidomastoid muscle flap versus no flapTwo studies assessed this comparison. Both assessed the effects of the sternocleidomastoid muscle flap procedure on the incidence rate of Frey's syndrome assessed clinically but neither showed a significant difference between groups (risk ratio (RR) 0.08, 95% confidence interval (CI) 0.00 to 1.23; 24 participants and RR 1.23, 95% CI 0.88 to 1.73; 36 participants; very low-certainty evidence). We did not pool the data due to the high heterogeneity (I² = 87%).One study found that the sternocleidomastoid muscle flap may result in little or no difference in other complications including haematoma (RR 2.18, 95% CI 0.09 to 50.16; 36 participants; low-certainty evidence), subjective painful or restricted cervical movement (RR 0.54, 95% CI 0.14 to 2.05; 36 participants; low-certainty evidence) and scar spread in the cervical region (RR 0.71, 95% CI 0.05 to 10.54; 36 participants; low-certainty evidence). Both studies reported the incidence rate of Frey's syndrome assessed by participants, with one reporting no events in either group and the other finding no evidence of a difference (RR 0.63, 95% CI 0.32 to 1.26; 36 participants; low-certainty evidence).Acellular dermal matrix versus no graftOnly one study assessed this comparison. Use of an acellular dermal matrix graft may result in little or no difference to the incidence rate of Frey's syndrome (assessed clinically) in comparison with the no graft group, but the evidence is very uncertain (RR 0.08, 95% CI 0.00 to 1.25; 30 participants; very low-certainty evidence).Acellular dermal matrix may slightly increase the wound infection rate compared with control (RR 17.00, 95% CI 1.02 to 282.67; 64 participants; low-certainty evidence). Acellular dermal matrix may result in little or no difference to the incidence of seromas or sialoceles (RR 2.33, 95% CI 0.66 to 8.23; 64 participants; low-certainty evidence). Acellular dermal matrix may result in little or no difference to the incidence rate of Frey's syndrome (assessed by participants) in comparison with the no graft group (RR 0.33, 95% CI 0.04 to 3.04; 64 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the effectiveness of graft interposition in preventing Frey's syndrome is of low or very low certainty. The use of acellular dermal matrix may be associated with an increase in the wound infection rate, and little or no difference in the incidence of seromas or sialoceles. Further studies are needed to draw reliable conclusions.

Paradoxical roles of TGF-ß signaling in suppressing and promoting squamous cell carcinoma.

Transforming growth factor ß (TGF-ß) signaling either promotes or inhibits tumor formation and/or progression of many cancer types including squamous cell carcinoma (SCC). Canonical TGF-ß signaling is mediated by a number of downstream proteins including Smad family proteins. Alterations in either TGF-ß or Smad signaling can impact cancer. For instance, defects in TGF-ß type I and type II receptors (TGF-ßRI and TGF-ßRII) and in Smad2/3/4 could promote tumor development. Conversely, increased TGF-ß1 and activated TGF-ßRI and Smad3 have all been shown to have tumor-promoting effects in experimental systems of human and mouse SCCs. Among TGF-ß/Smad signaling, only TGF-ßRII or Smad4 deletion in mouse epithelium causes spontaneous SCC in the mouse model, highlighting the critical roles of TGF-ßRII and Smad4 in tumor suppression. Herein, we review the dual roles of the TGF-ß/Smad signaling pathway and related mechanisms in SCC, highlighting the potential benefits and challenges of TGF-ß/Smad-targeted therapies.

Synthesis, characterization, antibacterial activity in dark and in vitro cytocompatibility of Ag-incorporated TiO2 microspheres with high specific surface area.

Postoperative infection associated with medical implants is a devastating complication of orthopedic surgery. Considering the difficulties for the diagnosis and treatment of infection, coating the implant material with antibacterial substances is a promising protocol by which to avoid such an adverse reaction. Nanoparticles (NPs) constructed of anatase microspheres, one form of titanium dioxide (TiO2), with a high specific surface area are fabricated in this study in a facile one-step process using homogeneous precipitation at 90 °C under atmospheric pressure using titanium sulfate (Ti[SO4]2) and urea as the titanium source and precipitant, respectively. The molar ratio of silver (Ag) to TiO2 can be changed by varying the amount of silver nitrate (AgNO3). The high specific surface area of the TiO2 microspheres combined with Ag particles (Ag/TiO2) exhibit excellent antibacterial properties against both Staphylococcus aureus and Escherichia coli. In addition, the Ag/TiO2 material in this work possesses satisfactory biological performance on MC3T3-E1 cells. The high specific surface area of Ag/TiO2 together with good antibacterial properties and cytocompatibility provide promising applications in dentistry, orthopedics, and other fields of medicine that use biomedical devices.

Interventions for the treatment of Frey's syndrome.

BACKGROUND: Frey's syndrome is a rare disorder, the symptoms of which include sweating, flushing and warming over the preauricular and temporal areas following a gustatory stimulus. It often occurs in patients who have undergone parotidectomy, submandibular gland surgery, radical neck dissection, infection and traumatic injury in the parotid region, and is caused by the aberrant regrowth of facial autonomic nerve fibres. Currently there are several options used to treat patients with Frey's syndrome; for example, the topical application of anticholinergics and antiperspirants, and the intradermal injection of botulinum toxin. It is uncertain which treatment is most effective and safe. OBJECTIVES: To assess the efficacy and safety of different interventions for the treatment of Frey's syndrome. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; ICTRP and additional sources for published and unpublished trials. The date of the search was 28 April 2014. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials (RCTs) in participants diagnosed with Frey's syndrome using a clinical standard such as Minor's starch-iodine test. We planned to include trials in which participants received any intervention versus no treatment (observation) or an alternative intervention, with or without a second active treatment. Our primary outcome measures were success rate (as assessed clinically by Minor's starch-iodine test, the iodine-sublimated paper histogram method, blotting paper technique or another method) and adverse events. Our secondary outcome measure was success rate as assessed by patients (disappearance or improvement of symptoms). DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We identified no RCTs or quasi-RCTs that fulfilled the inclusion criteria. Our searches retrieved eight potentially relevant studies, but after assessment of the full-text reports we excluded all of them due to the absence of randomisation or because the patients did not have Frey's syndrome. We excluded one randomised controlled trial that compared two different doses of botulinum toxin in patients with Frey's syndrome because the comparator was not an alternative treatment. AUTHORS' CONCLUSIONS: We are unable to establish the efficacy and safety of the different methods used for the treatment of Frey's syndrome.RCTs are urgently needed to assess the effectiveness of interventions for the treatment of Frey's syndrome. Future RCTs should include patients with Frey's syndrome of different ranges of severity and report these patients separately. Studies should investigate all possibly effective treatments (such as anticholinergics, antiperspirants and botulinum toxin) compared to control groups using different treatments or placebo. Subjective assessment of Frey's syndrome should be considered as one of the outcome measures.

Submandibular gland transfer for the prevention of postradiation xerostomia in patients with head and neck cancer: a systematic review and meta-analysis.

BACKGROUND: Submandibular gland transfer has been widely used to prevent postradiation xerostomia in head-and-neck cancers. However, there are still some controversies. METHODS: Six databases were searched, data extraction was performed and the risk of bias was assessed by 2 reviewers independently. The meta-analysis was performed using Review Manager, version 5.2. RESULTS: A total of 7 trials (12 articles) and 369 participants were included. CONCLUSIONS: The present clinical evidence suggests that submandibular gland transfer might be highly effective to prevent postradiation xerostomia in head-and-neck cancers without serious adverse events. However, more randomized controlled trials are still needed to confirm this conclusion.

Functional Property and Regulatory Mechanism of Macrophages in Complementary and Alternative Medicine: From Bench to Clinic.

Complementary and alternative medicine (CAM) includes a wide range of treatments that are gaining acceptance among the public. It is increasingly being recognized as a viable option for treating various diseases with minimal side effects. Common avenues of this therapy include herbal medicine, acupuncture, physical exercise, aromatherapy, dietary therapy, and homeopathy etc. Macrophages are highly heterogeneous cells that play multiple regulatory roles. Practices such as herbal medicine, acupuncture, physical exercise, aromatherapy and dietary therapy exert curative effects by modulating the polarization status and the secretory phenotype of macrophages directly. Furthermore, herbal medicine, acupuncture, and physical exercise influence the crosstalk between macrophages and other types of cells, including cancer cells and T cells. Mechanistically, herbal medicine and acupuncture produce curative effects in diverse diseases, including inflammatory diseases and tumors, mainly by influencing the phosphorylation of signaling proteins in macrophages. Therefore, targeting macrophages offers theoretical support for advancing the scientific understanding of this therapy and aids in identifying potential therapeutic options. Hence, in this review, we systematically summarize the different regulations of macrophages in herbal medicine, acupuncture, physical exercise, aromatherapy, dietary therapy and homeopathy, and further highlight the therapeutic potential of targeting macrophages in complementary and alternative medicine.

[Study on the influence of light intensity on near-infrared diffuse reflectance spectra of pear soluble solids content].

The objective of the present research was to study the influence of four kinds of light intensity of near-infrared diffuse reflectance spectra on the determination of pear soluble solids content. Qualitative analysis of the four spectra showed that the differences between them were too slight to find. After further analysis by principal component regression (PCR), stepwise multiple linear regression (SMLR) and partial least squares regression (PLSR) as well as comparisons among them, the results of PCR model and SMLR models which had low correlation coefficients (r) were worse than those of PLSR model. The model based on PLSR was further optimized by the second order derivative pretreatments of the spectra, and its correlation coefficients ranged from 0.947 to 0.970. The relative coefficients in PLSR model based on spectra from four sets were 0.958. The results indicate that light intensity has little influence on the determination of pear soluble solids content based on near-infrared diffuse reflection spectra.