Traditional Chinese medication for oral submucous fibrosis: A systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of various drug therapy methods for treating oral submucous fibrosis (OSF) in terms of increasing mouth opening, reducing VAS score, decreasing lesion area, minimizing side effects, and determining effective proportion. METHOD: A database search was conducted. Only randomized clinical trials were included, and Cochrane checklist was used for assessing the risk of bias. Stata.17 software was employed and effective treatment ranking was used. RESULTS: Thirty-one RCT studies, with a total of 2986 patients, were included in the period of 2010-2022. The combination of oral Chinese herbal medicine formulas (OC) and intralesional Salvia miltiorrhiza (ISM) was found to be the most effective treatment in improving mouth opening. For reducing the burning pain, the combination of intralesional steroids (IS) and oral Salvia miltiorrhiza (OSM) was found to be more effective than the others. In terms of lesion area, IS combined with OC was more effective than the others. IS combined with ISM had the highest effective proportion while having the lowest incidence of side effects which mentioned the incidence of side effects. CONCLUSION: This study indicates that OC and SM can be employed by clinicians for treating OSF effectively.

Study on the expression and function of chordin-like 1 in oral squamous cell carcinoma.

OBJECTIVE: The aim of this study was to investigate the role and related mechanism of chordin-like 1 (CHRDL1) in oral squamous cell carcinoma (OSCC). METHODS: The expressions of CHRDL1 were analyzed in both mRNA and protein levels by bioinformatics analysis, immunohistochemistry, and fluorescence in situ hybridization in OSCC. Survival analysis was used to determine the relationship between CHRDL1 and prognosis. In addition, enrichment analysis was used to suggest signal pathways involved in CHRDL1. Besides, the relationships between CHRDL1 and miRNAs, hypoxia, and immune infiltration were explored. RESULTS: The mRNA level of CHRDL1 in OSCC was significantly lower than that in normal tissues, while the protein level was significantly higher than that in normal tissues. The high mRNA levels of CHRDL1 suggested a poor prognosis in patients with OSCC. The enrichment results showed that CHRDL1 might be involved in the Calcium signaling pathway, dilated cardiomyopathy, and focal adhesion. 7 immune cells were positively correlated with CHRDL1, while Tgd was negatively correlated with CHRDL1. In addition, we also found that hsa-miR-455-3p directly targeted CHRDL1 and reduced the mRNA levels of CHRDL1. CONCLUSION: CHRDL1 plays a vital role in promoting cancer in OSCC and is down-regulated at the mRNA levels by hsa-miR-455-3p.

Overexpression of DEC1 in the epithelium of OSF promotes mesenchymal transition via activating FAK/Akt signal axis.

BACKGROUND: Previous studies on oral submucous fibrosis (OSF) mostly focused on the activation of fibroblasts and collagen metabolism, while little involved in the epithelium. As we have reported the role of differentiated embryo-chondrocyte expressed gene 1 (DEC1) in oral cancer and other precancerous lesions, this research aimed to explore its role in the OSF epithelium. METHODS: Expression of DEC1 and other proteins were investigated in tissue array constructed with 33 OSF and 14 normal oral mucosa (NOM) tissues. Human oral keratinocytes treated with arecoline and/or hypoxia were used to simulate OSF epithelium and detected for morphological and protein alterations. Inhibition of DEC1 was used to explore its mediating role. Finally, animal models of OSF constructed by locally arecoline injecting in buccal mucosa were used to verify our findings. RESULTS: DEC1 overexpression could be detected in the epithelium of OSF compared with that in NOM followed by phosphorylated FAK and Akt, and DEC1 showed a significant positive correlation with them. Cytology experiment revealed that OSF-like treatment could upregulate DEC1 expression followed by phosphorylated FAK, Akt, but inhibit E-cadherin, while knockdown of DEC1 could suppress the effects. In addition, OSF mice revealed higher expression of DEC1 in the epithelium of buccal mucosa, along with synchronized alterations of phosphorylated FAK and Akt. CONCLUSION: In the epithelium of OSF, overexpression of DEC1 induced activation of FAK/Akt signal axis, caused mesenchymal transition in epithelial cells, and may promote malignant transformation of OSF. Targeting DEC1 in OSF could be promising a new target for the diagnosis and treatment of this process.

Type 2 diabetes mellitus promotes the proliferation, metastasis, and suppresses the apoptosis in oral squamous cell carcinoma.

BACKGROUND: Our previous study revealed that patients with oral squamous cell carcinoma and concomitant type 2 diabetes mellitus presented a lower 5-year survival rate. Hyperglycemia has been increasingly recognized as a risk factor for more advanced disease and poorer prognosis in patients with oral squamous cell carcinoma. However, its role remains unclear. METHODS: The expressions of BRIP1, Ki67, E-cadherin, and cleaved caspase-3 were detected by immunohistochemistry in oral squamous cell carcinoma tissues with or without type 2 diabetes mellitus. Cell counting kit-8 assay and wound healing assay were used to determine the proliferative and migratory ability of oral squamous cell carcinoma cells cultured with or without high glucose in vitro. Flow cytometry was applied to distinguish the role of high glucose on the cell cycle and apoptosis rates. RESULTS: The expression level of Ki67 was elevated while BRIP1, E-cadherin, and cleaved caspase-3 were downregulated in patients with oral squamous cell carcinoma coexisting with diabetes. The cell proliferation and migration in oral squamous cell carcinoma cell lines were significantly enhanced by high glucose. Flow cytometric analysis suggested that high glucose predisposed cancer cells to stay at S/G2 phase and to exhibit lower apoptosis rates. CONCLUSION: Our results implicated that type 2 diabetes mellitus may play a crucial role in the development and progression of oral squamous cell carcinoma through hyperglycemia, affecting cancer cell proliferation, migration, and apoptosis. This finding might provide a new direction for the prevention and treatment of oral squamous cell carcinoma.

SLC39A5 dysfunction impairs extracellular matrix synthesis in high myopia pathogenesis.

High myopia is one of the leading causes of visual impairment worldwide with high heritability. We have previously identified the genetic contribution of SLC39A5 to nonsyndromic high myopia and demonstrated that disease-related mutations of SLC39A5 dysregulate the TGF-ß pathway. In this study, the mechanisms underlying SLC39A5 involvement in the pathogenesis of high myopia are determined. We observed the morphogenesis and migration abnormalities of the SLC39A5 knockout (KO) human embryonic kidney cells (HEK293) and found a significant injury of ECM constituents. RNA-seq and qRT-PCR revealed the transcription decrease in COL1A1, COL2A1, COL4A1, FN1 and LAMA1 in the KO cells. Further, we demonstrated that TGF-ß signalling, the regulator of ECM, was inhibited in SLC39A5 depletion situation, wherein the activation of receptor Smads (R-Smads) via phosphorylation was greatly blocked. SLC39A5 re-expression reversed the phenotype of TGF-ß signalling and ECM synthesis in the KO cells. The fact that TGF-ß signalling was zinc-regulated and that SLC39A5 was identified as a zinc transporter urged us to check the involvement of intracellular zinc in TGF-ß signalling impairment. Finally, we determined that insufficient zinc chelation destabilized Smad proteins, which naturally inhibited TGF-ß signalling. Overall, the SLC39A5 depletion-induced zinc deficiency destabilized Smad proteins, which inhibited the TGF-ß signalling and downstream ECM synthesis, thus contributing to the pathogenesis of high myopia. This discovery provides a deep insight into myopic development.

Comparative therapeutic efficacy of interferon alfa-2b and combination lopinavir/ritonavir plus interferon alfa-2b against SARS-CoV-2.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) posed an enormous threat to public health. The use of antiviral drugs in patients with this disease have triggered people's attentions. Whether interferon alfa-2b or lopinavir/ritonavir (LPV/r) plus interferon alfa-2b treatment can against SARS-CoV-2 was unknown. The objectives of this study was to evaluate the efficacy and safety of interferon alfa-2b and LPV/r plus interferon alfa-2b for SARS-CoV-2 infection in adult patients hospitalized with COVID-19. METHODS: This is a retrospective cohort study of 123 patients confirmed SARS-CoV-2 infection by PCR on nasopharyngeal swab and symptoms between Jan. 13 and Apr. 23, 2020. All patients received standard supportive care and regular clinical monitoring. Patients were assigned to standard care group (n = 12), interferon alfa-2b group (n = 44), and combination LPV/r plus interferon alfa-2b group (n = 67). The primary endpoints were duration of required oxygen support and virus clearance time. Associations between therapies and these outcomes were assessed by Cox proportional hazards regression. RESULTS: Baseline clinical characteristics were not significantly different among the three groups (P > 0.05). No significant associations were observed between LPV/r/interferon alfa-2b and faster SARS-CoV-2 RNA clearance (HR, 0.85 [95% confidence interval (CI) 0.45-1.61]; P = 0.61 in interferon alfa-2b group vs HR, 0.59 [95% CI 0.32-1.11]; P = 0.10 in LPV/r plus interferon alfa-2b group). Individual therapy groups also showed no significant association with duration of required oxygen support. There were no significant differences among the three groups in the incidence of adverse events (P > 0.05). CONCLUSIONS: In patients with confirmed SARS-CoV-2 infection, no benefit was observed from interferon alfa-2b or LPV/r plus interferon alfa-2b treatment. The findings may provide references for treatment guidelines of patients with SARS-CoV-2 infection.

G3BP1 may serve as a potential biomarker of proliferation, apoptosis, and prognosis in oral squamous cell carcinoma.

BACKGROUND: G3BP1 is a prognostic biomarker for many types of cancers; however, its role in oral squamous cell carcinoma remains unclear. We investigated the role of G3BP1 as a potential biomarker for proliferation, apoptosis, and prognosis in oral squamous cell carcinoma. METHODS: We obtained samples of normal oral mucosa (n = 17), oral squamous cell carcinoma tissues (n = 61), and paired adjacent tissues (n = 47) from Xiangya Hospital for immunohistochemical evaluation to measure the expression of G3BP1, E-cadherin, Ki67, and Cleaved-caspase3. Using data from The Cancer Genome Atlas, we performed bioinformatics analysis to investigate the prognosis, functions, signaling pathways, and immune infiltrate significance related to G3BP1 in oral squamous cell carcinoma. RESULTS: The G3BP1 protein level was significantly upregulated in oral squamous cell carcinoma tissues and was also positively associated with Ki67 and negatively associated with Cleaved-caspase3. Based on information available in online database, the G3BP1 mRNA level was significantly higher in oral squamous cell carcinoma than in normal tissues. High G3BP1 mRNA levels were associated with poor overall survival rates in patients with oral squamous cell carcinoma. Enrichment analysis showed that G3BP1 was involved in the helicase/catalytic/ATPase activity functions and spliceosome/RNA transport/ cell cycle pathways. Furthermore, G3BP1 mRNA levels were positively associated with CD4+ T-cell infiltration. CONCLUSIONS: G3BP1 may serve as a potential biomarker for proliferation, apoptosis, and prognosis of oral squamous cell carcinoma.

Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage.

BACKGROUND: Patients with critical illness due to infection with the 2019 coronavirus disease (COVID-19) show rapid disease progression to acute respiratory failure. The study aimed to screen the most useful predictive factor for critical illness caused by COVID-19. METHODS: The study prospectively involved 61 patients with COVID-19 infection as a derivation cohort, and 54 patients as a validation cohort. The predictive factor for critical illness was selected using LASSO regression analysis. A nomogram based on non-specific laboratory indicators was built to predict the probability of critical illness. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval [CI], 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR < 3.13, and 50% (7/14) patients with age ≥ 50 and NLR ≥ 3.13 were predicted to develop critical illness. Based on the risk stratification of NLR according to age, this study has developed a COVID-19 pneumonia management process. CONCLUSIONS: We found that NLR is a predictive factor for early-stage prediction of patients infected with COVID-19 who are likely to develop critical illness. Patients aged ≥ 50 and having an NLR ≥ 3.13 are predicted to develop critical illness, and they should thus have rapid access to an intensive care unit if necessary.

CD147 promotes proliferation and migration of oral cancer cells by inhibiting junctions between E-cadherin and ß-catenin.

BACKGROUND: Although association between oral squamous cell carcinoma (OSCC) with epithelial-mesenchymal transition (EMT) has been demonstrated, we found CD147, one transmembrane protein we previously studied in oral submucous fibrosis, was correlated with E-cadherin, one marker of EMT. Here, we investigated CD147 expression in the different stages of OSCC and assessed its association with epithelial-mesenchymal transition (EMT). MATERIALS AND METHODS: CD147 and E-cadherin expression in tissue microarrays containing 48 OSCC specimens and matched adjacent tissues was analysed using immunohistochemistry. CD147 was overexpressed or knocked down using exogenous cloning vector and RNA interference, respectively, in OSCC cell lines. Cell proliferation and migration were measured using the CCK8 assay and scratch test, respectively. The expression and localization of EMT-associated proteins was analysed by Western blotting and immunofluorescence. RESULTS: CD147 expression in OSCC tissues was significantly higher than that in adjacent tissues and was markedly higher in cancer tissues with metastasis (P < .05). CD147 expression showed significant negative correlation with E-cadherin expression. CD147 overexpression downregulated E-cadherin and inhibited its complex with ß-catenin and then upregulated N-cadherin and vimentin. Additionally, alterations in CD147 protein expression affected proliferation and migration ability in OSCC cells and were related to ß-catenin nuclear translocation. CONCLUSION: CD147 plays an important role in tumorigenesis and metastasis by promoting EMT progression in OSCC. It may be considered as a novel potential diagnostic and therapeutic target for OSCC.

Continuous renal replacement therapy in patients with HIV/AIDS.

BACKGROUND: Acute kidney injury (AKI) is a common complication among human immunodeficiency virus (HIV)-infected patients resulting in increased morbidity and mortality. Continuous renal replacement therapy (CRRT) is a useful method and instrument in critically ill patients with fluid overload and metabolic disarray, especially in those who are unable to tolerate the intermittent hemodialysis. However, the epidemiology, influence factors of CRRT and mortality in patients with HIV/AIDS are still unclear in China. This study aims to study the HIV-infected patients admitted in Intensive Care Unit (ICU) and explore the influence factors correlated with CRRT and their prognosis. METHODS: We performed a retrospective case-control study in the ICU of the Beijing Ditan Hospital Capital Medical University. From June 1, 2005 to May 31, 2017, 225 cases were enrolled in this clinical study. RESULTS: 122 (54.2%) patients were diagnosed with AKI during their stay in ICU, the number and percentage of AKI stage 1, 2 and 3 were 38 (31.1%), 21(17.2%) and 63(51.7%), respectively. 26.2% of AKI patients received CRRT during the stay of ICU. 56.25% CRRT patients died in ICU. The 28-day mortality was 62.5%, and the 90-day mortality was 75%. By univariate logistics analysis, it showed that higher likelihood of diagnosis for respiratory failure (OR = 7.333,95% CI 1.467-36.664, p = 0.015), higher likelihood of diagnosis for septic shock (OR = 1.005,95% CI 1.001-1.01, p = 0.018), and higher likelihood to use vasoactive agents (OR = 10.667,95% CI 1.743-65.271, p = 0.001), longer mechanical ventilation duration (OR = 1.011,95% CI 1.002-1.019, p = 0.011), higher likelihood for diagnosis for PCP (OR = 7.50,95% CI 1.288-43.687, p = 0.025), higher SOFA score at ICU admission (OR = 1.183,95% CI 1.012-1.383, p = 0.035), longer duration of CRRT (OR = 1.014,95% CI 1.001-1.028, p = 0.034) contributed to a higher mortality at ICU. The Cox Analysis for the cumulative survival of AKI 3 patients between the CRRT and non-CRRT groups shows no significant differences (p = 0.595). CONCLUSIONS: There is a high incidence of AKI in HIV-infected patients admitted in our ICU. Patients with severe AKI were more prone to be admitted for CRRT and have a consequent poor prognosis.

High Level of Neutrophil Extracellular Traps Correlates With Poor Prognosis of Severe Influenza A Infection.

Background: Most patients with severe infection with influenza A virus (IAV) progress to acute respiratory distress syndrome and even multiple organ dysfunction syndrome (MODS). Neutrophil extracellular traps (NETs) can be induced by pathogens and are responsible for immune tissue damage. We conducted a prospective study on the production and effects of NETs in H7N9 and H1N1 patients. Methods: We investigated NET production in plasma and supernatant of cultured neutrophils by measuring cell-free deoxyribonucleic acid (DNA) and myeloperoxidase (MPO)-DNA complexes with PicoGreen dye and enzyme-linked immunosorbent assay methods, respectively. We also observed NET structure by immunofluorescence staining. Results: We found that patients with severe influenza showed elevated plasma NET level on the day of admission. Neutrophils from these patients showed higher capacity to release MPO-DNA complex in response to interleukin-8 or lipopolysaccharide stimulation. We also found that NETs from H7N9 and H1N1 patients increased the permeability of alveolar epithelial cells, and, consequently, NET production was positively correlated with acute physiology and chronic health evaluation (APACHE) II score and MODS. Conclusions: These data indicate that high level of NETs contributes to lung injury and is correlated with severity of disease. Thus, NETs might be a key factor to predict the poor prognosis in IAV patients.

Evaluation of the criteria of hepatorenal syndrome type of acute kidney injury in patients with cirrhosis admitted to ICU.

INTRODUCTION: Acute kidney injury (AKI) is a common and devastating complication in patients with cirrhosis. In 2015, the International Club of Ascites (ICA) proposed the definition of hepatorenal syndrome (HRS) type of AKI (HRS-AKI) in patients with cirrhosis. This study aims to evaluate the criteria of HRS-AKI in patients with cirrhosis admitted to ICU with regard to the prognosis. METHODS: A total of 349 cirrhotic patients consecutively admitted to intensive care unit (ICU) from 2010 to 2017 were retrospectively analyzed. Demographic parameters and clinical variables were collected with case report forms. The occurrence of AKI was determined according to ICA-AKI criteria. The phenotypes of AKI comprised pre-renal azotemia (PRA), acute tubular necrosis (ATN) and HRS. In our study, patients with PRA or ATN were classified to the non-HRS-AKI group. RESULTS: The incidence of AKI was 73.0%, comprising PRA (18.6%), ATN (16.3%) and HRS (38.1%). The overall hospital mortality was 64.5%. Patients with AKI had a significantly higher in-hospital (76.1%) and 180-d (86.7%) mortality. AKI type was an independent risk factor for in-hospital mortality by a multivariate logistic regression. The in-hospital and 180-d mortality rates were of no significant difference among patients with HRS-AKI stages 1-3. CONCLUSIONS: AKI is common in patients with cirrhosis admitted to ICU, associated with significant in-hospital mortality. HRS-AKI was the most common and severe type of AKI in patients with cirrhosis admitted to ICU. The current staging system may not be applicable for HRS-AKI in patients with cirrhosis admitted to ICU.

The prognostic value of T Lymphoma Invasion and Metastasis 1 (TIAM1) expression in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm with high rate of lymph node metastasis and recurrence. The aim of this study is to evaluate the expression profile of T Lymphoma Invasion and Metastasis 1 (TIAM1) in OSCC and its correlation with clinical outcomes including lymph node metastasis and recurrence. Detection of TIAM1 expression in tumor samples from 56 OSCC patients and oral mucosa samples from 20 healthy people was performed by immunohistochemistry. Then immunostaining score of each patient was calculated. The results revealed that TIAM1 was aberrantly expressed in the OSCC group compared with the normal group. Furthermore, high expression of TIAM1 was significantly correlated with lymph node metastasis and the timing of recurrence. Assessment of TIAM1 expression might represent a valid tool in clinical practice for prediction of metastasis, recurrence, and prognosis of OSCC.

Change and pathological significance of glycogen content in oral squamous cell carcinoma and oral submucous fibrosis.

OBJECTIVE: This study aimed to investigate the change and pathological significance of glycogen content in oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). METHODS AND MATERIALS: 13 normal oral mucosa (NOM), 12 OSF mucosa, and 35 pairs of OSCC tissues and their corresponding adjacent mucosa tissues (AT) were collected from Xiangya Hospital for PAS staining to detect glycogen. Transcriptome sequencing data from OSCC were used to compare glycogen metabolism gene expression differences. Kaplan-Meier method was conducted to estimate Recurrence-free survival (RFS). RESULTS: Glycogen levels were lower in OSF than in NOM and lower in OSCC than in AT. Transcriptome sequencing data analysis showed the expression of most glycogenolysis genes was increased and the expression of glycogen synthesis genes including PPP1R3C and GBE1 was decreased in OSCC tissues. High glycogen level was correlated with poor prognosis in OSCC patients under the background of OSF. CONCLUSION: Glycogen may be used as a potential diagnostic biomolecule for OSF and OSCC, as well as a potential prognostic factor for OSCC in the context of OSF.

Near-infrared-II Ag2S quantum dot probes targeting podoplanin enhance immunotherapy in oral squamous cell carcinoma.

Partial epithelial-mesenchymal transition (pEMT) plays a vital role in oral squamous cell carcinoma (OSCC) cervical lymph node metastasis and tumor immune escape as an immune barrier. However, targeted interventions for pEMT have yet to be established. In this study, we generated an αPDPN-Ag2S probe by modifying a Podoplanin(PDPN) monoclonal antibody on the surface of near infrared (NIR)-II Ag2S quantum dots (QDs) with carboxyl groups through an amide reaction. Then, we evaluated its in vivo targeting ability, therapeutic efficacy of eliminating pEMT using αPDPN-Ag2S-mediated NIR-II photoimmunotherapy (PIT) and biological safety. Here, we found that pEMT is related to CD8 + T-cell infiltration in our human OSCC tissue microarray. Compared with PdpnWT SCC7, the slower growth rate of subcutaneous graft tumors implanted with PdpnKD SCC7 was associated with a change in the tumor immune microenvironment (TIM) in an immunocompetent C3H/HeJ mouse model. In vitro, αPDPN-Ag2S plus NIR 808 nm laser irradiation induced SCC7 cell death. In vivo, NIR-II imaging results show that the αPDPN-Ag2S probe has a good active-targeting ability in a 4-nitroquinoline 1-oxide (4NQO)-induced C57 mouse OSCC model and C3H/HeJ SCC7 subcutaneous graft tumor model. Elimination of pEMT cells by NIR-II αPDPN-Ag2S probe-mediated PIT significantly reversed the local immunosuppressive tumor microenvironment and enhanced PD-1 immunotherapy efficacy. The safety profiles of αPDPN-Ag2S in BALB/c mice were also acceptable. Thus, αPDPN-Ag2S has important clinical translational value in predicting the risk of cervical lymph node metastasis. Importantly, our study proposed a new way to improve the efficacy of tumor immunotherapy.

Favorable Outcomes of Liver Transplantation for Hepatopulmonary Syndrome.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of chronic liver disease, which develops insidiously as a result of chronic liver disease. The prognosis for untreated patients with HPS is extremely poor, and liver transplantation (LT) serves as the only effective means for treating this condition. Here, we performed a retrospective analysis to evaluate the efficacy of LT on the survival and long-term prognosis of patients with HPS. METHODS: Clinical data, including survival and postoperative efficacy, from patients with HPS from records as obtained over the period from January 1 to December 31, 2022. All records were from a waiting list for LT at the Beijing Friendship Hospital Affiliated with Capital Medical University. RESULTS: Among the 274 patients on the LT waiting list, 37 were diagnosed with HPS (13.50%) and were enrolled. Survival rates of patients with HPS receiving an LT were greater, whereas a statistically significant difference was obtained between patients with LT vs non-LT with moderate to severe HPS (P = .003). The overall time until death without LT was 4-72 days after their initial HPS diagnosis. Patients with HPS receiving an LT showed a significant improvement in the state of oxygenation after surgery (P = .001). CONCLUSION: Comprehensive preoperative screening of patients on the waiting list for LT is critical to identify those patients with HPS who would maximally benefit from LT. Survival rates of patients with moderate to severe HPS are significantly increased after LT, a procedure that should be performed as soon as possible in these patients with HPS.

A prognostic model for oral squamous cell carcinoma patients with type 2 diabetes mellitus.

OBJECTIVE: To build a prognostic model for oral squamous cell carcinoma patients with type 2 diabetes mellitus. DESIGN: Oral squamous cell carcinoma patients with type 2 diabetes mellitus in Xiangya Hospital were studied. Patients during January 2011 to January 2015 were included in training set (n = 146), and those during January 2017 to December 2020 were included in test set (n = 81). Univariate and multivariate Cox regressions were used to screen independent prognostic variables. Nomogram was used to show the model. C-index, internal bootstrap resampling and external validation were used to evaluate the model. RESULTS: Six independent prognostic factors (T stage, N stage, pathological grade, metformin use, sulfonylureas use, and fasting blood glucose) were screened from training set. Based on the six variables, nomogram was constructed to predict the prognosis of oral squamous cell carcinoma patients with type 2 diabetes mellitus. C-index value was 0.728, and result of internal bootstrap resampling showed better prediction efficiency for one-year survival. All patients were divided into two groups according to total points calculated based on the model. Group with low total points experienced better survival than that with high total points both in training set and test set. CONCLUSIONS: The model provides a relatively accurate method to predict the prognosis of oral squamous cell carcinoma patients with type 2 diabetes mellitus.

A2b and A3 adenosine receptors may act as promotive and prognostic factors in oral squamous cell carcinoma.

This study aimed to examine the expression and potential effects of adenosine receptors in oral squamous cell carcinoma (OSCC). Data on mRNA expression of adenosine receptors in OSCC samples were collected from The Cancer Genome Atlas database. Adenosine-regulated signaling pathways and biological processes were investigated via immune cell infiltration analysis, bioinformatics analysis, and immunohistochemistry. Overexpression of A2bR and A3R was significantly correlated with the prognosis of OSCC (P < 0.05). A3R expression in OSCC patients was significantly and positively correlated with the infiltration of six types of immune cells: B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and myeloid dendritic cells. A2bR expression weakly and negatively correlated with B-cell infiltration only. The expression of A2bR in OSCC was positively correlated with E-cadherin and PCNA, while the expression of A3R was positively correlated with that of cleaved caspase-3. Within the limitations of the study it seems that the overexpression of A2bR and A3R results in the poor prognosis of OSCC, suggesting that A2bR promotes cell proliferation in OSCC, while A3R may be involved in OSCC progression by regulating tumor cell apoptosis and immune microenvironment.

Unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Although overall losses of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been previously observed, a genome-wide, single-base-resolution, and simultaneous mapping of 5mC and 5hmC in OSCC is still unaccomplished. Similarly, the mechanism of how 5mC and 5hmC collectively lead to abnormal gene expression in OSCC is largely unexplored. Using parallel whole-genome bisulfite sequencing (WGBS) and whole-genome oxidative bisulfite sequencing (oxWGBS), we characterized 5mC- and 5hmC-profiles at single-nucleotide resolution in paired primary OSCC samples and their normal adjacent tissues (NATs). We also analyzed the effect of 5mC- and 5hmC-modifications on differential gene expression in OSCC using multi-omics analysis. Results: An overall reduction of both 5mC and 5hmC in various genomic regions have been observed in OSCC samples. At promoter regions, a total of 6,921 differentially methylated regions and 1,024 differentially hydroxymethylated regions were identified in OSCC. Interestingly, compared to bidirectional modification with 5mC and 5hmC, unidirectional modification with 5mC and 5hmC at the promoters is associated with bigger change in the gene expression. Additionally, genes bearing unidirectional modification with 5mC and 5hmC at the promoters are enriched in signaling pathways like cell proliferation, cell differentiation, and receptor tyrosine kinase pathway that are essential for the tumorigenesis. Finally, the grouped expression signature of top 20 genes bearing promoter-unidirectional-modification with 5mC and 5hmC tends to correlate with the clinical outcome of certain subtypes of head and neck squamous cell carcinoma. Conclusion: Using parallel WGBS and oxWGBS analyses, we observed an overall reduction of 5mC- and 5hmC-modifications at various genomic regions in OSCC. Unidirectional modification with 5mC and 5hmC at the promoters is associated with enhanced changes in gene expression in OSCC tissues. Furthermore, such differentially expressed genes bearing unidirectional modifications with 5mC and 5hmC at the promoters might have clinical relevance to the outcome of OSCC.