Advances in Synthesis and Applications of Single-Atom Catalysts for Metal Oxide-Based Gas Sensors.

As a stable, low-cost, environment-friendly, and gas-sensitive material, semiconductor metal oxides have been widely used for gas sensing. In the past few years, single-atom catalysts (SACs) have gained increasing attention in the field of gas sensing with the advantages of maximized atomic utilization and unique electronic and chemical properties and have successfully been applied to enhance the detection sensitivity and selectivity of metal oxide gas sensors. However, the application of SACs in gas sensors is still in its infancy. Herein, we critically review the recent advances and current status of single-atom catalysts in metal oxide gas sensors, providing some suggestions for the development of this field. The synthesis methods and characterization techniques of SAC-modified metal oxides are summarized. The interactions between SACs and metal oxides are crucial for the stable loading of single-atom catalysts and for improving gas-sensitive performance. Then, the current application progress of various SACs (Au, Pt, Cu, Ni, etc.) in metal oxide gas sensors is introduced. Finally, the challenges and perspectives of SACs in metal oxide gas sensors are presented.

The improvement of postoperative blood pressure and associated factors in patients with hormone-negative adrenal adenoma and hypertension.

OBJECTIVE: To investigate the effect of adrenal surgery on blood pressure (BP) improvements in patients with hormone-negative adrenal adenoma (HNA) concomitant with hypertension and analyze associated prognostic factors. METHODS: We retrospectively reviewed the clinical data of patients with HNA and hypertension and patients with aldosterone-producing adenoma (APA) and hypertension who underwent adrenal surgery at our center between 2019 and 2022. Hypertension outcomes were evaluated in all patients and subjects were divided into three groups according to follow-up BP and the administration of anti-hypertensive agents: a clinical curation group, an improvement group, and a no-improvement group. Logistic regression analysis was performed to predict factors associated with clinical curation in patients with HNA post-surgery. RESULTS: Of the 182 patients with HNA, clinical curation was achieved in 58 patients (31.9%), improvement in 72 (39.5%), and no improvement in 52 (28.6%). The clinical curation, improvement and no improvement rates in patients with APA were 64.8% (n = 118), 15.9% (n = 29), and 19.2% (n = 35). Multivariate logistic regression analysis indicated that a duration of hypertension ≤6 years and a plasma aldosterone level >160 pg/ml were both independent factors for the clinical curation of hypertension in patients with HNA after adrenal surgery. CONCLUSION: Adrenal surgery can cure or improve hypertension in most patients with HNA, especially in a short duration of hypertension and high plasma levels of aldosterone.

Association of obesity and different metabolic status with prognosis in patients with bladder cancer: a retrospective cohort study.

Background and objectives: Patients with bladder cancer (BC) are at high risk for recurrence rates and readmission costs. However, the evidence about obesity and metabolic abnormalities on the BC prognosis was inconsistent. Our primary aim was to determine the impact of obesity and different metabolic status on the readmission risk in patients with BC. Design and methods: We identified 16,649 patients with BC using the 2018 Nationwide Readmissions Database who were hospitalized from January to June 2018 and followed for 180 days. The primary outcome was 180-day readmission. The multivariate Cox regression analysis and ordered logistic regression were performed to analyze data. Results: Obesity and metabolic abnormalities were associated with an increased readmission risk in patients with BC [obesity: adjusted hazard ratio (aHR) = 1.08, 95% confidence interval (CI): 1.01-1.16; hyperglycemia: aHR = 1.11, 95% CI: 1.05-1.17; hypertension: aHR = 1.09, 95% CI: 1.03-1.15]. Compared with non-obese and no metabolic abnormalities, the risk of readmission was significantly increased in patients with metabolic abnormalities, irrespective of obesity (non-obese and metabolic abnormalities: aHR = 1.07, 95% CI: 1.02-1.13; obese and metabolic abnormalities: aHR = 1.20, 95% CI: 1.10-1.31), but not in obese and no metabolic abnormalities. These associations were consistent in patients aged 60 years or older and the surgery group. Moreover, hyperglycemia, hypertension, and a graded increment of metabolic risk were associated with an increased readmission risk. We also found increased length of stay for readmission in patients with obesity and metabolic abnormalities (aOR = 1.17, 95% CI: 1.00-1.36). Conclusion: Obesity with metabolic abnormalities and metabolic abnormalities alone were associated with higher readmission risks in patients with BC. It is suggested that prevention should focus not only on obesity but also on metabolic abnormalities to decrease the risk of readmission.

Obesity Metabolic Phenotypes and Unplanned Readmission Risk in Diabetic Kidney Disease: An Observational Study from the Nationwide Readmission Database.

BACKGROUND AND AIM: Obesity is a potentially modifiable factor for reducing readmissions, with heterogeneity that varies according to the metabolic status. Our objective was to examine the independent or mutual relationship between obesity and metabolic abnormalities and diabetic kidney disease (DKD)-related hospitalizations. METHODS: 493,570 subjects with DKD were enrolled in the 2018 Nationwide Readmission Database (NRD, United States). The at-risk population was reclassified into refined obesity subtypes based on the body mass index (BMI) classification of metabolic abnormalities (hypertension and/or dyslipidemia) to investigate the 180 d readmission risk and hospitalization costs related to DKD. RESULTS: The overall readmission rate was 34.1%. Patients with metabolic abnormalities, regardless of obesity, had a significantly higher risk of readmission compared to non-obese counterparts (adjusted HR, 1.11 [95% CI, 1.07-1.14]; 1.12 [95% CI, 1.08-1.15]). Hypertension appeared to be the only metabolic factor associated with readmission among individuals with DKD. Obesity without metabolic abnormalities was independently associated with readmission (adjusted HR,1.08 [1.01,1.14]), especially among males and those >65 years (adjusted HR,1.10 [1.01-1.21]; 1.20 [1.10-1.31]). Women or those ≤65 years with metabolic abnormalities (all p <0.050) had elevated readmission rates, regardless of obesity; however, no such trend was observed in obese subjects without metabolic abnormalities (adjusted HR, 1.06 [0.98,1.16]). Additionally, obesity and metabolic abnormalities were associated with elevated hospitalization costs (all p <0.0001). CONCLUSIONS: Increased BMI and hypertension are positively associated with readmissions and related costs among patients with DKD, which should be considered in future studies.

Association of obesity under different metabolic status with adverse outcomes in patients with chronic myeloid leukemia: A retrospective cohort study.

BACKGROUND: Little is known about the association between abnormal metabolic obesity states and the outcomes of chronic myeloid leukemia (CML), especially in patients with obesity with different metabolic status. Here, we used the Nationwide Readmissions Database to assess the effects of metabolically defined obesity on adverse outcomes of CML. METHODS: Of the 35 460 557 (weighted) patients, we included 7931 adults with discharge diagnoses of CML from January 1, 2018 to June 30, 2018. The study population was observed until December 31, 2018 and divided into four groups based on body mass index and metabolic status. The primary outcome was the adverse outcomes of CML, including nonremission (NR)/relapse and severe mortality risk. Multivariate logistic regression analysis was performed to analyze data. RESULTS: Metabolically unhealthy normal weight and metabolically unhealthy obesity were all risk factors for adverse outcomes of CML compared with metabolically healthy normal weight (all p < 0.01), and a significant difference was not found in the metabolically healthy obese. Female patients with metabolically unhealthy normal weight and metabolically unhealthy obesity had 1.23-fold and 1.40-fold increased NR/relapse risk, while male patients did not have this risk. Moreover, patients with a higher number of metabolic risk factors or with dyslipidemia were at higher risk of adverse outcomes, regardless of obesity status. CONCLUSIONS: Metabolic abnormalities were associated with adverse outcomes in patients with CML, irrespective of obesity status. Future treatment of patients with CML should consider the effects of obesity on their adverse outcomes under different metabolic status, especially in female patients.

[Effects of different puncture levels in bilateral percutaneous vertebroplasty on distribution of bone cement and effectiveness of osteoporotic thoracolumbar compression fractures].

Objective: To investigate the effects of different puncture levels on bone cement distribution and effectiveness in bilateral percutaneous vertebroplasty for osteoporotic thoracolumbar compression fractures. Methods: A clinical data of 274 patients with osteoporotic thoracolumbar compression fractures who met the selection criteria between December 2017 and December 2020 was retrospectively analyzed. All patients underwent bilateral percutaneous vertebroplasty. During operation, the final position of the puncture needle tip reached was observed by C-arm X-ray machine. And 118 cases of bilateral puncture needle tips were at the same level (group A); 156 cases of bilateral puncture needle tips were at different levels (group B), of which 87 cases were at the upper 1/3 layer and the lower 1/3 layer respectively (group B1), and 69 cases were at the adjacent levels (group B2). There was no significant difference in gender, age, fracture segment, degree of osteoporosis, disease duration, and preoperative visual analogue scale (VAS) score, and Oswestry disability index (ODI) between groups A and B and among groups A, B1, and B2 ( P>0.05). The operation time, bone cement injection volume, postoperative VAS score, ODI, and bone cement distribution were compared among the groups. Results: All operations were successfully completed without pulmonary embolism, needle tract infection, or nerve compression caused by bone cement leakage. There was no significant difference in operation time and bone cement injection volume between groups A and B or among groups A, B1, and B2 ( P>0.05). All patients were followed up 3-32 months, with an average of 7.8 months. There was no significant difference in follow-up time between groups A and B and among groups A, B1, and B2 ( P>0.05). At 3 days after operation and last follow-up, VAS score and ODI were significantly lower in group B than in group A ( P<0.05), in groups B1 and B2 than in group A ( P<0.05), and in group B1 than in group B2 ( P<0.05). Imaging review showed that the distribution of bone cement in the coronal midline of injured vertebrae was significantly better in group B than in group A ( P<0.05), in groups B1 and B2 than in group A ( P<0.05), and in group B1 than in group B2 ( P<0.05). In group A, 7 cases had postoperative vertebral collapse and 8 cases had other vertebral fractures. In group B, only 1 case had postoperative vertebral collapse during follow-up. Conclusion: Bilateral percutaneous vertebroplasty in the treatment of osteoporotic thoracolumbar compression fractures can obtain good bone cement distribution and effectiveness when the puncture needle tips locate at different levels during operation. When the puncture needle tips locate at the upper 1/3 layer and the lower 1/3 layer of the vertebral body, respectively, the puncture sites are closer to the upper and lower endplates, and the injected bone cement is easier to connect with the upper and lower endplates.

Changes in Clinical Manifestations Due to AFLD Retyping Based on the New MAFLD Criteria: An Observational Study Based on the National Inpatient Sample Database.

(1) Background: As the introduction of "positive" diagnostic criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) does not exclude alcohol consumption, some patients originally diagnosed with alcoholic fatty liver disease (AFLD) may be diagnosed with dual- etiology fatty liver disease (AFLD&MAFLD), which requires us to urgently explore the impact of the changes in this classification of AFLD on clinical manifestations. (2) Methods: Utilizing data from the Nationwide Inpatient Sample database 2016-2018, a total of 9269 participants with AFLD were selected. With the definition of MAFLD, these patients were further categorized into two groups: single AFLD and AFLD&MAFLD. The primary outcome was the risk of comorbidities and organ failures. The secondary outcomes were the length of stay, total charges, and in-hospital all-cause mortality. (3) Results: The patients with AFLD&MAFLD were older, were predominantly male, and had more comorbidities and organ failures compared to the patients with AFLD. These comorbidities included coronary atherosclerosis, myocardial infarction, cerebrovascular disease, arrhythmia, asthma, chronic obstructive pulmonary disease, and chronic kidney disease (all p values < 0.05). The patients with AFLD&MAFLD were more likely to develop acute and chronic heart and/or kidney failures than those with single AFLD (all p < 0.05). The length of stay and total charges of the patients in the AFLD&MAFLD group were greater than the single AFLD group (p = 0.029 and p < 0.001, respectively). No significant difference in all-cause mortality was observed. (4) Conclusions: The patients with AFLD&MAFLD have more comorbidities and organ failures, longer hospital stays, and higher hospitalization costs than the patients with single AFLD. Hence, patients with dual-etiology fatty liver disease deserve more attention from clinical staff during treatment.

Association between Metabolic Obesity Phenotypes and the Burden of Hospitalized Postmenopausal Patients Concomitant with Osteoporosis: A Retrospective Cohort Study Based on the National Readmission Database.

BACKGROUND: The present definition of obesity based on body mass index (BMI) is not accurate and effective enough to identify hospitalized patients with a heavier burden, especially for postmenopausal hospitalized patients concomitant with osteoporosis. The link between common concomitant disorders of major chronic diseases such as osteoporosis, obesity, and metabolic syndrome (MS) remains unclear. Here, we aim to evaluate the impact of different metabolic obesity phenotypes on the burden of postmenopausal hospitalized patients concomitant with osteoporosis in view of unplanned readmissions. METHODS: Data was acquired from the National Readmission Database 2018. The study population was classified into metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) patients. We estimated the associations between metabolic obesity phenotypes and 30- and 90-day unplanned readmissions. A multivariate Cox Proportional Hazards (PH) model was used to assess the effect of factors on endpoints, with results expressed as HR and 95% CI. RESULTS: The 30-day and 90-day readmission rates for the MUNO and MUO phenotypes were higher than that of the MHNO group (all p < 0.05), whereas no significant difference was found between the MHNO and MHO groups. For 30-day readmissions, MUNO raised the risk mildly (hazard ratio [HR] = 1.110, p < 0.001), MHO had a higher risk (HR = 1.145, p = 0.002), and MUO further elevated this risk (HR = 1.238, p < 0.001). As for 90-day readmissions, both MUNO and MHO raised the risk slightly (HR = 1.134, p < 0.001; HR = 1.093, p = 0.014, respectively), and MUO had the highest risk (HR = 1.263, p < 0.001). CONCLUSIONS: Metabolic abnormalities were associated with elevated rates and risks of 30- or 90-day readmission among postmenopausal hospitalized women complicated with osteoporosis, whereas obesity did not seem to be innocent, and the combination of these factors led to an additional burden on healthcare systems and individuals. These findings indicate that clinicians and researchers should focus not only on weight management but also metabolism intervention among patients with postmenopausal osteoporosis.

Macrophages contribute to periodontal wound healing mainly in the tissue proliferation stage.

OBJECTIVE: The aim of this study was to determine the preliminary role of macrophages in different stages of periodontal healing. BACKGROUND: Macrophages are promising target cells for periodontal regeneration. However, the stage at which they play a more important role during periodontal repair has not been elucidated till date. METHODS: First, the dynamic changes in M1 and M2 macrophages were analyzed in a rat periodontal-defect model at Days 1, 3, 5, 7, 14, 21, and 28 post-surgery. Macrophages were then depleted after 1, 6, and 14 days of surgery, and the healing results were evaluated via micro-computed tomography and histopathological detection. Finally, the effects of M1 and M2 macrophages on the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) were verified in vitro. RESULTS: During natural periodontal healing, the number of M1 macrophages increased the most during the early stage of healing (3 days post-operation), and subsequently, it decreased rapidly. The number of M2 macrophages was at its peak during the middle and late stages of tissue healing (5-21 days post-surgery). Interestingly, the highest number of M2 macrophages was observed at 5-14 days post-operation in the alveolar bone, while it was observed at 21 days post-operation in the cementum area. On the first and 14th day post-operation, the clearance of macrophages had no significant effect on tissue healing; however, on the sixth day post-operation, macrophage depletion significantly inhibited tissue regeneration (p < .05). In vitro studies showed that M2 macrophages, rather than M1 macrophages, could significantly promote the proliferation of MSCs (p < .01). CONCLUSION: It is better to intervene in tissue proliferation phase when a M2 macrophage regulation-based periodontal regenerative therapy is planned in the future.

Clinical application of indocyanine green fluorescence navigation technology to determine the safe margin of advanced oral squamous cell carcinoma.

Background: Advanced oral squamous cell carcinoma (OSCC) has large lesions and deep infiltration, and the control of safe surgical margins was difficult. If residual tumor remains after incomplete tumor resection, it can lead to local tumor recurrence or even distant metastasis. This study sought to investigate the clinical application of indocyanine green (ICG)-based near-infrared fluorescence (NIF) molecular imaging in the intraoperative detection of surgical margins of advanced OSCC. Methods: Twenty-nine patients with advanced OSCC treated at the First Ward of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital were divided into the ICG group and non-ICG group. In the ICG group, the tumors were removed with the assistance of ICG fluorescence navigation technology. In the non-ICG group, the tumors were removed with conventional methods, and the cutting-edge tissues of the two groups underwent frozen biopsies. The margin abnormality rates were calculated and compared. Results: Under the excitation of NIF in the ICG group, tumor fluorescence development was observable in all lesions, and the tumor boundary was clear. The abnormal rates of the incisional margin in the ICG group and non-ICG group were 0.78% and 6.25%, respectively (P<0.05). Conclusions: ICG-mediated NIF imaging technology provides a new method for observing and completely resecting tumors under direct vision during operation, and finding residual tumors at the cutting edge in time. These results will inform the treatment of advanced OSCC.

Comparison of velopharyngeal morphology of two palatoplasty techniques in patients with hard and soft cleft palate.

Purpose: The study aims to compare the velopharyngeal morphology of hard and soft cleft palate (HSCP) patients after Furlow and Sommerlad palatoplasty. Patients and methods: A total of 51 patients (20 cases in Furlow palatoplasty group, 16 cases in Sommerlad palatoplasty group and 15 normal children in the control group) were included in our study. Velopharyngeal function and speech outcomes of patients with HSCP who had either Furlow palatoplasty or Sommerlad palatoplasty for cleft palate repair were evaluated by perceptual speech assessment (PSA), lateral cephalometric radiographs and nasopharyngoscopy. To assess velopharyngeal morphology of patients treated with two techqiques, we analyzed measurements such as velar length, pharyngeal depth, and the Adequate ratio (the ratio of velar length to pharyngeal depth). Furthermore, skeletal landmarks including cranial base, cervical vertebrae, posterior nasal spine which were defined as the pharyngeal triangle were measured. Finally, the position of the point U relative to the pharyngeal triangle were compared. Results: Velopharyngeal closure (VPC) rate in Furlow palatoplasty group accounted for 90%, while that in Sommerlad palatoplasty group was 81.3%. PSA of the former group was significantly better than that of the latter group (P < 0.05). Velar length, pharyngeal depth and the Adequate ratio (1.37 ± 0.14 vs. 1.41 ± 0.15) were comparable between the Furlow group and control group (P > 0.05), while Sommerlad group had a shorter velar length, deeper pharyngeal depth and a smaller Adequate ratio (1.20 ± 0.18) compared to the above two groups (P < 0.05). Furhermore, the point U of Sommerlad group in the pharyngeal triangle was higher than that of the other two groups. Conclusions: In the treatment modality of patients with HSCP, both Furlow palatoplasty and Sommerlad palatoplasty seem to be effective. Furlow palatoplasty appears to have velopharyngeal morphology similar to normal control group., while Sommerlad group shows a shorter velar length, deeper pharyngeal depth and a smaller Adequate ratio.

For nasotracheal intubation, which nostril results in less epistaxis: right or left?: A systematic review and meta-analysis.

BACKGROUND: Nasotracheal intubation is usually required in patients undergoing oromaxillofacial, otolaryngological or plastic surgery to prevent the airway encroaching into the operating field. Epistaxis is the most common complication, but which nostril is associated with a lower incidence and severity of epistaxis is still unclear. OBJECTIVE: When both nostrils are patent, to determine the preferred nostril for nasotracheal intubation under general anaesthesia. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). The primary outcome was the incidence of epistaxis and the secondary outcomes included the incidence of severe epistaxis, the time required to pass the tube through the nasal passage and total intubation time. DATA SOURCES: PubMed, Embase and the Cochrane Register of Controlled Trials were searched from database inception to 1 March 2020. ELIGIBILITY CRITERIA: The only studies included were RCTs comparing epistaxis related to nasotracheal intubation via right or left nostril, in adult surgery patients undergoing general anaesthesia. RESULTS: Ten RCTs with 1658 patients were included. Compared with the left nostril, intubation via the right nostril was associated with a significantly lower incidence of epistaxis: risk ratio (RR) and 95% confidence intervals (CI) were 0.78 (0.62 to 0.99), P = 0.04: a lower incidence of severe epistaxis (five studies, n=923), RR 0.40 (0.22 to 0.75), P = 0.004: and a shorter intubation time (three studies, n=345), mean difference -7.28 (-14.40 to -0.16) seconds, P = 0.05. In two studies (n=310), no significant difference between the right and left nostril was observed in the time to pass the tube through the nasal passages, mean difference -0.59 (-1.95 to 0.77) s, P = 0.40. CONCLUSION: On the basis of the current available evidence, when both nostrils are patent, the right nostril is more appropriate for nasotracheal intubation, with a lower incidence and severity of epistaxis and faster intubation time. TRIAL REGISTRATION: The study protocol has been registered in PROSPERO (CRD42020169949).

ITGB2-mediated metabolic switch in CAFs promotes OSCC proliferation by oxidation of NADH in mitochondrial oxidative phosphorylation system.

Objectives: Integrins, the coordinator of extracellular and intracellular signaling, are often found to be aberrant in tumors and can reshape the tumor microenvironment. Although previous studies showed that integrin beta 2 (ITGB2) is important for host defense, its expression profile and role in tumors, especially in cancer associated fibroblasts (CAFs) are still unknown. Methods: Immunofluorescence stain and fluorescence activated cell sorting were used to analyze the ITGB2 expression profile in oral squamous cell carcinoma (OSCC). RT-PCR and western blot were used to compare ITGB2 expression in normal fibroblasts (NFs) and cancer associated fibroblasts (CAFs). Clinical data and function-based experiments were used to investigate the promoting tumor growth ability of ITGB2 expressing CAFs. Enhanced glycolysis activity was identified by using bioinformatics analyses and GC/MS assays. MCT1 knockdown OSCC cell lines were constructed to explore the pro-proliferative mechanisms of ITGB2 expressing CAFs in multiple in vitro and in vivo assays. Results: We found that CAFs exhibited significantly higher ITGB2 expression than the matched NFs. In addition, higher ITGB2 expression in CAFs was correlated with higher TNM stages and more Ki67+ tumor cells, indicating its ability to promote OSCC proliferation. Further, co-culture assay demonstrated that ITGB2-mediated lactate release in CAFs promoted OSCC cell proliferation. Mechanically, ITGB2 regulated PI3K/AKT/mTOR pathways to enhance glycolysis activity in CAFs. Accordingly, lactate derived from ITGB2-expressing CAFs was absorbed and metabolized in OSCC to generate NADH, which was then oxidized in the mitochondrial oxidative phosphorylation system (OXPHOS) to produce ATP. Notably, inhibiting the OXPHOS system with metformin delayed the proliferative capacity of OSCC cells cultured in the ITGB2-expressing CAFs medium. Conclusions: Our study uncovered the ITGB2high pro-tumoral CAFs that activated the PI3K/AKT/mTOR axis to promote tumor proliferation in OSCC by NADH oxidation in the mitochondrial oxidative phosphorylation system.

[Effect of scaling and root planing on serum C-reactive protein levels in patients with moderate to severe chronic periodontitis: a systematic review and Meta-analysis].

OBJECTIVE: To evaluate the effect of scaling and root planing (SRP) on serum C-reactive protein (CRP) levels in patients with moderate to severe chronic periodontitis. METHODS: We searched the PubMed, Web of Science, EMBASE, Cochrane, CNKI, Wanfang, and VIP databases from the inception to July 8th, 2019. Two reviewers independently screened literature, extracted data, and evaluated the bias risk of included studies. Then, a meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 13 randomized controlled clinical trials and 12 prospective clinical trials were included. Meta-analysis showed that serum CRP levels decreased at 2 and 3 months after SRP (P<0.05), and no significant difference in serum CRP levels was found at 6 months (P=0.49). CONCLUSIONS: SRP can reduce serum CRP levels in systematically healthy patients with moderate to severe chronic periodontitis at 2 and 3 months after SRP.

Tumor-Infiltrating CD1a+ DCs and CD8+/FoxP3+ Ratios Served as Predictors for Clinical Outcomes in Tongue Squamous Cell Carcinoma Patients.

Tumor-infiltrating immune cells engage in an extensive crosstalk with tumors and act as two-edged swords by inhibiting or promoting cancer growth. Therefore, identifying the density and prognostic values of tumor-infiltrating immune cells will provide valuable tips for cancer treatments. In this study, we identified the density of tumor inflammatory infiltrates and the number of tumor-infiltrating immune cells, including CD3+, CD4+, CD8+, FoxP3+ T cells and CD1a+ dendritic cells (DCs) in 153 tongue squamous cell carcinomas (TSCC). High inflammatory cell infiltration was associated with better overall survival (OS) and disease free survival (DFS). Moreover, the number of CD3+, CD4+, FoxP3+ and CD1a+ cells were associated with tumor differentiation (P<0.001) and the number of FoxP3+, CD1a+ cells and CD8+/FoxP3+ ratios were also associated with tumor stage (P<0.01, P<0.01, P<0.05). In addition, patients with higher CD1a+ DCs had better OS and increased CD8+/FoxP3+ ratios were associated with improved OS and DFS (P = 0.037; P = 0.047; P = 0.033). In conclusion, our results indicated that tumor-infiltrating CD1a+ DCs and CD8+/FoxP3+ ratios were associated with favorable clinical outcomes but not independent prognostic factors for TSCC patients.

Increased LGALS3BP promotes proliferation and migration of oral squamous cell carcinoma via PI3K/AKT pathway.

Previous studies showed that lectin galactoside-binding soluble 3 binding protein (LGALS3BP) is an important participant in tumor progression. However, its prognostic value and functional mechanism in oral squamous cell carcinoma (OSCC) are still unclear. In this study, we analyzed LGALS3BP expression in OSCC tissues via Oncomine databases and immunohistochemical staining. LGALS3BP was significantly up-regulated in OSCC tumor tissues. IHC analysis showed that LGALS3BP was predominantly expressed in tumor cells and correlated with poor clinical characteristics. In addition, high LGALS3BP expression predicted poor clinical outcomes and multivariate analysis revealed that LGALS3BP expression was as an independent prognostic factor for OS, DFS and RFS (p < .0001, p = .002, p = .002). Mechanically, LGALS3BP regulated OSCC proliferation and migration via PI3K/AKT pathways, which was abrogated by PI3K inhibitor LY294002 in a dose-dependent manner. Our results suggested that LGALS3BP could be served as a novel independent prognostic factor as well as a potential therapeutic target for OSCC treatment.

Mitogen-activated protein kinase signaling mediates opioid-induced presynaptic NMDA receptor activation and analgesic tolerance.

Opioid-induced hyperalgesia and analgesic tolerance can lead to dose escalation and inadequate pain treatment with µ-opioid receptor agonists. Opioids cause tonic activation of glutamate NMDA receptors (NMDARs) at primary afferent terminals, increasing nociceptive input. However, the signaling mechanisms responsible for opioid-induced activation of pre-synaptic NMDARs in the spinal dorsal horn remain unclear. In this study, we determined the role of MAPK signaling in opioid-induced pre-synaptic NMDAR activation caused by chronic morphine administration. Whole-cell recordings of excitatory post-synaptic currents (EPSCs) were performed on dorsal horn neurons in rat spinal cord slices. Chronic morphine administration markedly increased the frequency of miniature EPSCs, increased the amplitude of monosynaptic EPSCs evoked from the dorsal root, and reduced the paired-pulse ratio of evoked EPSCs. These changes were fully reversed by an NMDAR antagonist and normalized by inhibiting extracellular signal-regulated kinase 1/2 (ERK1/2), p38, or c-Jun N-terminal kinase (JNK). Furthermore, intrathecal injection of a selective ERK1/2, p38, or JNK inhibitor blocked pain hypersensitivity induced by chronic morphine treatment. These inhibitors also similarly attenuated a reduction in morphine's analgesic effect in rats. In addition, co-immunoprecipitation assays revealed that NMDARs formed a protein complex with ERK1/2, p38, and JNK in the spinal cord and that chronic morphine treatment increased physical interactions of NMDARs with these three MAPKs. Our findings suggest that opioid-induced hyperalgesia and analgesic tolerance are mediated by tonic activation of pre-synaptic NMDARs via three functionally interrelated MAPKs at the spinal cord level. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

PTK7 is a molecular marker for metastasis, TNM stage, and prognosis in oral tongue squamous cell carcinoma.

The prognosis of oral tongue squamous cell carcinoma (OTSCC) is poor, and it would be beneficial to identify prognostic markers for optimization of treatment. Protein tyrosine kinase 7 (PTK7) is a receptor tyrosine kinase that is aberrantly expressed in human cancers. No exploration of the role of PTK7 in OTSCC has been reported. We detected expression of PTK7 protein in a set of tissue samples of OTSCC. The relationship between PTK7 expression and clinicopathologic parameters and overall survival of patients was analyzed. The expression level of PTK7 protein in OTSCC was increased relative to that in normal squamous cells. High expression of PTK7 was positively associated with TNM stage (p = 0.024), tumor differentiation (p = 0.019), and lymph node metastasis (p = 0.077). Patients with high expression of PTK7 had poor overall survival (p = 0.058). Our data indicate that PTK7 protein expression is associated with the prognosis of OTSCC and may serve as a therapeutic target.

Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-κB/HIF-1α signal axis.

Resistance towards chemotherapy is a common complication in treatment of oral cancers, which leads to treatment failure and poor outcome. In recent years, a growing body of evidence has shown that tumour hypoxia significantly contributes to chemoresistance. Metformin, a widely used oral hypoglycaemic drug, can reportedly potentiate the efficacy of chemotherapeutic drugs in various cancers; however, the underlying mechanisms are intricate and have not been fully understood. In this study, we explored the role of metformin in chemosensitivity of oral squamous cell carcinoma cells (OSCC) to cisplatin both in vitro and in vivo, and attempted to elucidate its possible underlying mechanisms. Encouragingly, we found that metformin synergistically enhanced cisplatin cytotoxicity and reversed the chemoresistance to certain extent. This mechanism could likely be related with inhibition of the NF-κB/HIF-1α signal axis and lead to the downregulation of hypoxia-regulated genes products. Therefore, metformin could serve as a chemosensitiser for cisplatin-based regimens for OSCC, thereby providing a theoretical basis for future use in the treatment of oral cancers.