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.

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.

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.

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.

Conflict of interest and FCTC implementation in China.

OBJECTIVE: To critically review the structure of tobacco control policy making in China, examine conflicts of interest within this structure, and consider how these affected the introduction of on-pack warnings. METHODS: Government policy documents and warning labels were obtained and critically reviewed. RESULTS: Few differences exist between the on-pack warnings formerly used in China and those introduced ostensibly to meet Framework Convention on Tobacco Control (FCTC) obligations. Comparison with tobacco manufactured for export or overseas consumption shows the new Chinese domestic on-pack warnings are demonstrably inferior to those required internationally. The inherent conflict of interest in the Chinese tobacco control agency structure, which must meet commercial and public health objectives, undermined the introduction of new health warnings. CONCLUSIONS: To promote more effective tobacco control policies, the conflict of interest inhibiting the public health function of the State Tobacco Monopoly Administration (STMA) must be removed. Specifically, the public health function must be separated from oversight of commercial production, and packaging must be redesigned with pictorial warnings and messages compliant with Article 11 of the FCTC.

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.

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.

Downregulation of TGF-beta receptor types II and III in oral squamous cell carcinoma and oral carcinoma-associated fibroblasts.

BACKGROUND: The purpose of this study was to assess the expression levels for TßRI, TßRII, and TßRIII in epithelial layers of oral premalignant lesions (oral leukoplakia, OLK) and oral squamous cell carcinoma (OSCC), as well as in oral carcinoma-associated fibroblasts (CAFs), with the final goal of exploring the roles of various types of TßRs in carcinogenesis of oral mucosa. METHODS: Normal oral tissues, OLK, and OSCC were obtained from 138 previously untreated patients. Seven primary human oral CAF lines and six primary normal fibroblast (NF) lines were established successfully via cell culture. The three receptors were detected using immunohistochemical (IHC), quantitative RT-PCR, and Western blot approaches. RESULTS: IHC signals for TßRII and TßRIII in the epithelial layer decreased in tissue samples with increasing disease aggressiveness (P < 0.05); no expression differences were observed for TßRI, in OLK and OSCC (P > 0.05); and TßRII and TßRIII were significantly downregulated in CAFs compared with NFs, at the mRNA and protein levels (P < 0.05). Exogenous expression of TGF-ß1 led to a remarkable decrease in the expression of TßRII and TßRIII in CAFs (P < 0.05). CONCLUSION: This study provides the first evidence that the loss of TßRII and TßRIII expression in oral epithelium and stroma is a common event in OSCC. The restoration of the expression of TßRII and TßRIII in oral cancerous tissues may represent a novel strategy for the treatment of oral carcinoma.

Case report of rapidly progressive proliferative verrucous leukoplakia and a proposal for aetiology in mainland China.

Proliferative verrucous leukoplakia (PVL) is a rare oral leukoplakia and has four features such as chronic proliferation, multiple occurrences, refractoriness to treatment and high rate of malignant transformation. As mentioned above, most PVL cases processed to malignancy over many years, sometimes 20 years. However, this report described a case of rapid progress, which had malignant transformation in a short period. Additionally, the aetiology of PVL was discussed and immunity was proposed as the possible cause.

[Clinicopathologic and immunohistochemical study of 23 cases of mesenchymal chondrosarcoma].

OBJECTIVE: To study the clinicopathologic and immunohistochemical features of mesenchymal chondrosarcoma. METHODS: The clinical and histologic features of 23 cases of mesenchymal chondrosarcoma were analyzed. Immunohistochemical study was also performed in 14 of the cases. RESULTS: The age of patients ranged from 12 to 47 years. Fourteen of them occurred in males. Thirteen cases involved the bony skeleton and 5 cases affected the soft tissue. The patients presented with pain and/or swelling. Histologically, the tumor consisted of a mixture of undifferentiated small round cells and hyaline cartilage. Transition between the two components was demonstrated and growth plate-like cartilage was observed. Immunohistochemical study showed that the small round cells were positive for Sox9 (14/14), CD99 (12/14), vimentin (6/14), CD56 (4/14), CD57 (4/14), neuron-specific enolase (3/14) and desmin(1/14). They were negative for Coll-II, S-100 protein, epithelial membrane antigen, pan-cytokeratin, synaptophysin, chromogranin A, CD34 and c-erbB2. CONCLUSIONS: Mesenchymal chondrosarcoma is a rare malignant tumor. Thorough histologic examination, when coupled with immunohistochemical findings, is helpful in arriving at a correct diagnosis.

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).

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.

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.

Skp2 expression is associated with down-regulation of p27 protein and cell proliferation in salivary adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a malignant salivary gland tumor, which shows frequent recurrence and metastasis, ultimately with a poor outcome. We previously demonstrated that p27 down-regulation is frequently found and is due to an enhancement of its degradation in ACC. In this study, we transfected nondegradable p27 mutant (T187A) and wild-type gene into ACC cell line. Transfection of T187A mutant gene was more effective on inhibition of cell growth of ACC cells, suggesting that aberration of p27 degradation may be present in ACC. As F-box protein S-phase kinase-associated protein 2 (Skp2), which is necessary for ubiquitin-mediated degradation of p27, is involved in p27 down-regulation in various cancers, we examined the Skp2 expression and its association with p27 expression in 50 ACC cases. We found Skp2 expression in 36% of ACC cases and inverse association between the expression of Skp2 and p27. Moreover, Skp2 small interfering ribonucleic acid (siRNA) transfection decreased Skp2 protein and accumulation of p27 protein and inhibited the cell growth of ACC cells in vitro. These findings, overall, suggest that Skp2 may play an important role in ACC development through the down-regulation of p27 and that Skp2 siRNA can be a novel modality of cancer gene therapy for suppression of p27 down-regulation in ACC.

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.

The QSPR (quantitative structure-property relationship) study about the anaerobic biodegradation of chlorophenols.

In this study, based on quantum chemical and physicochemical descriptors, by the use of partial least squares analysis, a good prediction quantitative structure-property relationship for the disappearance rate constant (logK) of chlorophenols (CPs) in the anaerobic culture was obtained. It was found that the resonance energy of the two-center term (J), which described the character of the weakest carbon-chlorine bond, played an important role in the reductive chlorine processes, the greater the sizes of CPs molecules, the higher the logK values. Increasing energy of the lowest unoccupied molecular orbital (E(lumo)) values of the CPs lead to decreasing logK values, and CPs with large absolute hardness values tended to have big logK values.