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.

Manganese suppresses the development of oral leukoplakia by activating the immune response.

OBJECTIVE: Manganese ion (Mn2+ ) is reported to promote the antitumor immune response by activating the cGAS-STING pathway, but it is unknown whether Mn2+ can prevent the malignant transformation of precancerous lesions. The effects of Mn2+ in treating oral leukoplakia (OLK) were explored in this work. METHODS: Peripheral blood Mn analysis of the patients was performed using inductively coupled plasma atomic emission spectroscopy (ICP-AES). A coculture model of dendritic cells (DCs)/macrophages, CD8+ T cells, and dysplastic oral keratinocytes (DOKs) was employed to analyze the role and mechanism of Mn2+ in a simulated OLK immune microenvironment. Western blot, RT-PCR, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and lactate dehydrogenase (LDH) assays were adopted to detect the mechanism of Mn2+ in this model. 4-nitroquinoline oxide (4NQO)-induced OLK mice were used to assess the role of Mn2+ in suppressing OLK progression, and a novel Mn2+ -loaded guanosine-tannic acid hydrogel (G-TA@Mn2+ hydrogel) was fabricated and evaluated for its advantages in OLK therapy. RESULTS: The content of Mn in patients' peripheral blood was negatively related to the progression of OLK. Mn2+ promoted the maturation and antigen presentation of DCs and macrophages and enhanced the activation of CD8+ T cells in the coculture model, resulting in effective killing of DOKs. Mechanistic analysis found that Mn2+ enhanced the anti-OLK immune response by activating the cGAS-STING pathway. Moreover, Mn2+ suppressed the development of 4NQO-induced carcinogenesis in the mouse model. In addition, the G-TA@Mn2+ hydrogel had better anti-OLK effects. CONCLUSIONS: Mn2+ enhanced the anti-OLK immune response by activating the cGAS-STING pathway, and the G-TA@Mn2+ hydrogel is a potential novel therapeutic approach for OLK treatment.

The role of doped-Mn on enhancing arsenic removal by MgAl-LDHs.

To meet the challenges posed by global arsenic water contamination, the MgAlMn-LDHs with extraordinary efficiency of arsenate removal was developed. In order to clarify the enhancement effect of the doped-Mn on the arsenate removal performance of the LDHs, the cluster models of the MgAlMn-LDHs and MgAl-LDHs were established and calculated by using density functional theory (DFT). The results shown that the doped-Mn can significantly change the electronic structure of the LDHs and improve its chemical activity. Compared with the MgAl-LDHs that without the doped-Mn, the HOMO-LUMO gap was smaller after doping. In addition, the -OH and Al on the laminates were also activated to improve the adsorption property of the LDHs. Besides, the doped-Mn existed as a novel active site. On the other hand, the MgAlMn-LDHs with the doped-Mn, the increased of the binding energy, as well as the decreased of the ion exchange energy of interlayer Cl-, making the ability to arsenate removal had been considerably elevated than the MgAl-LDHs. Furthermore, there is an obvious coordination covalent bond between arsenate and the laminates of the MgAlMn-LDHs that with the doped-Mn.

TGF-ßRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation.

Cancer-associated fibroblasts (CAFs) are highly heterogeneous and differentiated stromal cells that promote tumor progression via remodeling of extracellular matrix, maintenance of stemness, angiogenesis, and modulation of tumor metabolism. Aerobic glycolysis is characterized by an increased uptake of glucose for conversion into lactate under sufficient oxygen conditions, and this metabolic process occurs at the site of energy exchange between CAFs and cancer cells. As a hallmark of cancer, metabolic reprogramming of CAFs is defined as reverse Warburg effect (RWE), characterized by increased lactate, glutamine, and pyruvate, etc. derived from aerobic glycolysis. Given that the TGF-ß signal cascade plays a critical role in RWE mainly through metabolic reprogramming related proteins including pyruvate kinase muscle isozyme 2 (PKM2), however, the role of nuclear PKM2 in modifying glycolysis remains largely unknown. In this study, using a series of in vitro and in vivo experiments, we provide evidence that TGF-ßRII overexpression suppresses glucose metabolism in CAFs by attenuating PKM2 nuclear translocation, thereby inhibiting oral cancer tumor growth. This study highlights a novel pathway that explains the role of TGF-ßRII in CAFs glucose metabolism and suggests that targeting TGF-ßRII in CAFs might represent a therapeutic approach for oral cancer.

Primordial odontogenic tumour: a case report.

Odontogenic primary tumor is a rare benign odontogenic tumor in the maxillofacial area. A case of odontogenic primary basal tumor is reported. The clinicopathological features and treatment principles are discussed in the literature.

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.

As(III) removal from wastewater and direct stabilization by in-situ formation of Zn-Fe layered double hydroxides.

In order to remove and stabilize As(III) simultaneously from wastewater, a novel and effective method based on the in-situ formation of As(III)-containing Zn-Fe layered double hydroxides (ZnFe-As-LDHs) was developed. The influence of pH, Zn/Fe, Fe/As and adding rate on the formation of ZnFe-As-LDHs were investigated. Under the optimal conditions, the concentration of As(III) decreased from 100 to 0.13 mg/L and As leaching concentration of the ultimate sludge was 1.87 mg/L, which could meet the arsenic leaching criteria (5 mg/L) regulated by US EPA. Compared with the "ex-situ" sludge obtained by As(III) adsorbed on the pre-formed ZnFe-LDHs, the As(III) removal efficiency increased by 21.6 % and the stability of the sludge increased by 94.2 % on the in-situ formation of LDHs, which mainly attributed to 55.06 % oxidation of As(III) and co-precipitation of As with Zn and Fe. Additionally, a possible in-situ formation pathway for ZnFe-As-LDHs was illustrated. At the beginning of the process, non-crystalline ferric arsenate formed and then transformed to amorphous ferrihydrite as precursors, followed by the formation of LDHs. This work demonstrated that co-precipitating As with Zn and Fe in the wastewater to in-situ form LDHs exhibited excellent potential for removal and direct stabilization of As(III).

Persistent effects of adverse childhood experiences on the course of pubertal development / 中国学校卫生

Objective@#To explore the influence of adverse childhood experiences (ACEs) on pubertal development of boys and girls and to provide a reference for the development of intervention measures.@*Methods@#A stratified cluster sampling method was used to select a total of 1 156 students in grades three and four in the boarding school system and public primary schools in Huangshan City and surrounding towns in September 2018, using the Childhood Trauma Questionnaire (CTQ) and the Pubertal Development Scale (PDS). For the baseline self-assessment survey, according to different dimensions, abuse children score no exposure groups. Children were divided into an exposure group and a high exposure level group, according to their childhood experiences. PDS self-report questionnaire was administered two years later, and an analysis of ACE type and severity of the continuous impact of youth development was conducted.@*Results@#In the baseline survey, there were 53 girls (11.32%) and 51 boys (7.41%) who developed earlier. The rate of early development in girls was higher than that of boys, and the difference was statistically significant(χ 2=5.21, P<0.05). Univariate analysis showed gender differences in the effects of type and severity of ACEs and abuse on adolescent development at both baseline and follow-up. There were gender differences in the rate of early development between boys and girls at baseline and at follow-up between the exposure groups. Regression analysis showed that the higher the degree of emotional abuse, emotional neglect, and sexual abuse in girls, the higher the PDS score(B=0.22, 0.15, 0.08, P<0.05). In boys, the more severe the emotional abuse experienced, the higher the PDS score, and the more severe the physical abuse experienced, the lower the PDS score(B=0.20, 0.04, P<0.05).@*Conclusion@#Attention should be paid to the influence of ACEs and gender differences during youth development among male and female students, and more longterm studies should also be carried out.

Short Bowel Syndrome in an Extremely Low Birth Weight Premature Infant with Wernicke Encephalopathy: A Case Report.

BACKGROUND Short bowel syndrome in infants is relatively rare. It consists of malabsorption caused by a congenital short bowel or extensive resection of a large part of the small intestine. The postoperative mortality rate is high and surviving patients develop many complications. Wernicke encephalopathy is caused by vitamin B1 (thiamin) deficiency. Delayed treatment may lead to irreversible neuron necrosis, gliosis, severe amnesia, Korsakoff psychosis, or even death. CASE REPORT We report the case of a premature infant with extremely low birth weight and short bowel syndrome. He was treated with early enteral nutrition combined with succus entericus reinfusion with no complications. Four months after discharge, he was diagnosed with Wernicke encephalopathy. He was treated with intravenous vitamin B1 (100 mg IV/d) and was administered oral vitamin B1 (20 mg 3 times daily) by his wet nurse. Vitamin B1 levels returned to normal after 4 days (69.8 nmol/L). Physical development was normal at the follow-up at a corrected age of 2 years. CONCLUSIONS Preventive measures for Wernicke encephalopathy should be implemented in patients with long-term malnutrition or absorption disorders. The risk of vitamin B1 deficiency increases in patients receiving parenteral nutrition and medical staff should be aware of the importance of the vitamin B1 status.

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.

Formation of high crystalline LDH sludge for removing Cu and Zn from wastewater by controlled double-jet precipitation.

In order to improve the heavy metal wastewater treatment by avoiding formation of amorphous sludge phase, we develop a faster formation of high crystalline layered double hydroxide (LDH) sludge to remove Cu and Zn from wastewater by controlled double-jet precipitation (CDJP) without hydrothermal or heat aging post-treatment. A series of experimental procedures are conducted to determine the optimal parameters. Results show that the optimal adding rate, pH value, and stirring rate is 0.5 mL min-1, 9.0, and 500 rpm, respectively. The CuZnAl-LDH phase sludge is formed in a well-crystallized hexagonal platelet, which assembled into a flower-like architecture. Comparative studies show that the formation of amorphous LDH sludge in conventional precipitation (CP) could be divided roughly into two stages-from the mixed copper hydroxide, zinc hydroxide, and scarbroite to the mixed low crystallinity CuAl-LDH and ZnAl-LDH. However, in CDJP method, the high crystalline LDH sludge evolved from a new four-step evolution process that is the formation of an amorphous (quasi-)multinary metastable ternary CuZnAl-LDH phase, followed by the indiffusion of cations and substitution of anions to fabricate crystalline LDH, the integrated LDH hexagonal platelets assembled into a flower-like architecture by the screw dislocation growth mechanism, the coarsening growth of each ternary LDH platelet, respectively. Thereinto, the formation of (quasi-)multinary metastable LDH phase instead of metal hydroxide in initial stage would be an obvious advantage of the CDJP method compared to CP method due to the former skipping the sequential precipitation.

Extramammary Paget's disease of the oral mucosa and perioral skin.

Extramammary Paget's disease (EMPD) is an unusual intraepidermal adenocarcinoma. Only 2 cases of EMPD in the oral mucosa have been reported previously. Here, we present the first report of a rare case of Paget's disease of the oral mucosa and perioral skin with extensive contiguous erythematous and erosive manifestations. Ultimately, the patient was treated with oral thalidomide for 8 weeks. We noticed an improvement with resolution of symptoms. A 3-year follow-up showed no relapse. Thus, this case may provide new insights to clinicians about treatment of EMPD. More importantly, we advise that dentists be vigilant about the possibility of some clinically significant conditions in patients with extensive nonspecific clinical lesions mimicking inflammatory or infectious diseases in the oral and maxillofacial regions, especially lesions that are refractory to long-term treatment. Requesting consultations with relevant clinical departments promptly and obtaining histopathologic confirmation at an early stage are crucial for early therapy and a better prognosis.

Persistent and refractory thrush with unknown cause.

Oral thrush is considered as the opportunistic infection, which is caused by fungus Candida albicans. Various kinds of immunodeficiency diseases, such as HIV infection, immunosuppressive therapy, use of broad-spectrum antibiotics, and invasive surgical procedures such as solid organ or bone marrow transplantation, lead to increased susceptibility to fungal infections, but persistent and refractory thrush, with typical clinical signs of oral fungal infection and without any other sign of immunodeficiencies, has not been reported so far. We describe a case of persistent and refractory thrush with Klinefelter syndrome (47, XXY) as the unusual cause.

A systems biology approach identifies effective tumor-stroma common targets for oral squamous cell carcinoma.

The complex interactions between cancer cells and their surrounding stromal microenvironment play important roles in tumor initiation and progression and represent viable targets for therapeutic intervention. Here, we propose a concept of common target perturbation (CTP). CTP acts simultaneously on the same target in both the tumor and its stroma that generates a bilateral disruption for potentially improved cancer therapy. To employ this concept, we designed a systems biology strategy by combining experiment and computation to identify potential common target. Through progressive cycles of identification, TGF-ß receptor III (TßRIII) is found as an epithelial-mesenchymal common target in oral squamous cell carcinoma. Simultaneous perturbation of TßRIII in the oral cancerous epithelial cells and their adjacent carcinoma-associated fibroblasts effectively inhibits tumor growth in vivo, and shows superiority to the unilateral perturbation of TßRIII in either cell type alone. This study indicates the strong potential to identify therapeutic targets by considering cancer cells and their adjacent stroma simultaneously. The CTP concept combined with our common target discovery strategy provides a framework for future targeted cancer combinatorial therapies.

[Siblings present different clinical manifestations in white sponge nevus].

White sponge nevus (WSN) is a rare, autosomal-dominant hereditary disease. This article reported two siblings affected by white sponge nevus. Because of smoking or not, they presented different clinical manifestations.

[Mucinous adenocarcinoma of salivary gland: a case report].

Mucinous adenocarcinoma is a rare epithelial malignant tumor which usually arises in appendix, pancreas, breast and other sites, rarely occurs in salivary gland. In this article, a mucinous adenocarcinoma of salivary gland was reported and relevant literatures were reviewed.