Thiopental sodium attenuates hypoxia/reoxygenation-induced injury in osteoblasts by modulating AKT signaling.

Thiopental sodium (TPTS) is a barbiturate general anesthetic, while its effects on hypoxia/reoxygenation (H/R)-induced injury are still unclear. This study aimed to investigate whether TPTS exerts protective effects against the H/R-induced osteoblast cell injury and explore the underlying mechanisms. Osteoblast cell injury model was induced by the H/R condition, which was treated with or without TPTS. Cell viability and lactate dehydrogenase (LDH) release were determined by the corresponding commercial kits. The levels of oxidative stress were determined in the experimental groups. Cell apoptosis and Caspase-3 activities were determined by propidium iodide staining and substrate-based assay, respectively. Western blotting and qRT-PCR were performed to measure the mRNA and protein levels, respectively. Treatment with TPTS was able to increase cell viability and reduce LDH release in H/R-induced osteoblasts. Additionally, TPTS regulated oxidative stress in H/R-induced osteoblasts by suppressing malondialdehyde (MDA) and reactive oxygen species (ROS) as well as boosting superoxide dismutase (SOD). TPTS was able to suppress cell apoptosis by suppressing Caspase-3 activity and cleavage. TPTS exerted protective effects against cell injury and apoptosis induced by the H/R conditions, which were associated with its regulation of Akt signaling. Moreover, TPTS induced osteoblast differentiation under the H/R condition. In summary, TPTS attenuates H/R-induced injury in osteoblasts by regulating AKT signaling.

A METTL3 Inhibitor Alleviates the Onset of Osteomyelitis in a Mouse Model by Targeting MyD88.

We aimed to study the effects of a methyltransferase 3 (METTL3) inhibitor on osteomyelitis. Bone marrow cells (BMs) and peripheral blood mononuclear cells (PBMCs) were isolated from osteomyelitis patients at our hospital. Primary BM-derived macrophages (BMDMs) were incubated with lipopolysaccharide (LPS), poly(I:C), or PAM3CSK4 after pretreatment with STM2457. S. aureus was injected into the intramedullary canal to construct an osteomyelitis C57BL/6 mice model, which was then treated with STM2457. Body weights, µCT three-dimensional analyses, and bacterial burdens of the mice were obtained. Up-regulated METTL3 expression was found in both BMs and PBMCs of osteomyelitis patients. LPS and PAM3CSK4-induced IL-6 and TNF-α secretion in BMDMs could be inhibited by STM2457 pretreatment, while STM2457 pretreatment did not affect the relative expression of NOS2, IL-6, and TNF-α after incubation with poly(I:C). STM2457 alleviated the symptoms of osteomyelitis in mice with increased body weights, diminished reactive bone formation and cortical bone loss, increased bacterial burdens, and decreased IL-6 and TNF-α secretion. STM2457 pretreatment down-regulated the relative expression of myeloid differentiation factor 88 (MyD88), p-TAK, and p-IKKα/ß in LPS-stimulated BMDMs, while it did not show any effect on poly(I:C)-stimulated BMDMs. STM2457 alleviates the onset of osteomyelitis in mice by down-regulating the relative expression of MyD88 and NF-κB relevant inflammation molecules in macrophages.

Global, regional, and national burden of periodontitis from 1990 to 2019: Results from the Global Burden of Disease study 2019.

BACKGROUND: To evaluate the prevalence and incidence of periodontitis and associated disability-adjusted life years (DALYs) from 1990 to 2019. METHODS: We collected data on periodontitis between 1990 and 2019 from the Global Burden of Disease (GBD) 2019 Study. The global prevalence, incidence, and DALYs attributed to periodontitis were analyzed. The age-standardized rate (ASR) and estimated annual percentage changes (EAPCs) were calculated to quantify the burden of the disease and temporal trends. RESULTS: The ASR of the prevalence, incidence, and DALYs increased worldwide from 1990 to 2019. In 2019, Western Sub-Saharan Africa carried the heaviest burden of periodontitis, whereas the nation with the highest periodontitis burden was Gambia. The burden of periodontitis was negatively associated with the level of socioeconomic development. Although, the majority of periodontitis burden was observed among those aged 55-59 years, the incidence of periodontitis has shown an increasing trend among younger individuals. CONCLUSION: Periodontitis continues to be a global public health problem. Current prevention and control strategies should be enhanced to prevent an increase in periodontitis.

Sclerosing polycystic adenosis of the submandibular gland: Two case reports.

BACKGROUND: Sclerosing polycystic adenosis (SPA) is a rare disease of salivary glands, similar to fibrocystic disease of the breast. It occurs over a wide age range and exhibits a slight female preference. Most SPA cases have occurred in the parotid gland. The exact nature of SPA is unclear, but its tumor nature has recently been proposed. Although SPA has a good prognosis after adequate surgery, atypical lesions might occur, ranging from mild dysplasia to carcinoma in situ in some cases. To the best of our knowledge, only five cases of SPA in the submandibular gland have been reported to date. Here, we present two new cases of SPA involving the submandibular gland. CASE SUMMARY: A 50-year-old woman and a 52-year-old woman were referred to Tongji Hospital in Wuhan, China, with complaints of moderate pain, recurrent swelling, and a mass in the submandibular area. After admission, the two cases of the submandibular mass were examined physically. The boundary of the submandibular tumor was clear, and the range of motion was good. After preoperative examinations, surgery was performed on a selective basis. Postoperative histopathological examination revealed a well-defined mass with acinar structures, ducts, or cystic dilated glands of various sizes scattered in a large number of proliferative sclerosing stroma. There were flat and cuboidal cells, and eosinophils in the duct epithelium. There was also a eosinophilic substance in the lumen of dilated cysts. No atypical epithelial hyperplasia, invasive growth, or carcinoma in situ was found. Based on the above findings, the mass was diagnosed as SPA. Both patients have remained asymptomatic and no recurrence or distant metastasis had occurred by the 7-mo and 5-year follow-up, respectively. CONCLUSION: SPA is a rare disease of the salivary gland. Even though it has a good prognosis after adequate surgery, atypical lesions may occur from mild dysplasia to carcinoma in situ. However, no recurrence, distant metastasis, or mortality has been reported for submandibular gland SPA. Clinicians and pathologists should be familiar with the characteristics of SPA in the submandibular gland to avoid misdiagnosis and overtreatment.

Corrigendum: WGCNA Co-Expression Network Analysis Reveals ILF3-AS1 Functions as a CeRNA to Regulate PTBP1 Expression by Sponging miR-29a in Gastric Cancer.

[This corrects the article DOI: 10.3389/fgene.2020.00039.].

[Advances on selective posterior rhizotomy for lower limb function in patients with cerebral palsy].

Cerebral palsy is a common clinical syndrome of neurological disability in childhood, which seriously affects the quality of life of children and their families, and brings a heavy economic burden to the society. Domestic and foreign scholars had a long history of the application of selective posterior rhizotomy for the treatment of spastic cerebral palsy or mixed cerebral palsy with limb paralysis. It is effective in improving the lower extremity spasm of patients with cerebral palsy, and there are few cases with recurrences. After rehabilitation therapy, the muscle strength of patients with cerebral palsy was significantly improved compared with the previous one. The range of motion was significantly improved after operation, and there is no rebounded in aspect of joint activety in the long-term follow-up. The overall gait of the patient was significant improved. The author thought that selective posterior rhizotomy is effective in improving the motor function of lower limbs in patients with cerebral palsy, and it is worth being spread. However, it has to follow the principle of selecting appropriate cases before surgery, precise operation during operation, and timely and effective rehabilitation treatment after surgery, in order to achieve a better curative effect.

WGCNA Co-Expression Network Analysis Reveals ILF3-AS1 Functions as a CeRNA to Regulate PTBP1 Expression by Sponging miR-29a in Gastric Cancer.

Gastric cancer (GC) is one of the most common types of human cancers worldwide. However, the detail mechanisms underlying GC progression remained to be investigated. The present study identified 2823 differently expressed mRNAs and 441 differently expressed lncRNAs in GC. WGCNA was conducted to identify highly correlated lncRNAs and mRNAs. Bioinformatics analysis observed that these dysregulated lncRNAs were significantly associated with the regulation of angiogenesis, cell division, cell-cell adhesion, blood vessel development, adaptive immune response, gastric acid secretion, immune response. Co-expression analysis identified ILF3-AS1 was a key lncRNA involved in regulating GC progression. Loss of function assays showed that knockdown of ILF3-AS1 significantly suppressed GC cell proliferation and metastasis. Mechanically, the results indicate that ILF3-AS1 could enhance PTBP3 expression as an miR-29a sponge, thereby promoting the proliferation and metastasis of GC cells. Our work suggests that the ILF3-AS1/miR-29a/PTBP3 axis may be a potential target for the clinical diagnosis and treatment of GC.

Global and regional burdens of oral cancer from 1990 to 2017: Results from the global burden of disease study.

BACKGROUND: Data on the incidence, mortality, and other burden of oral cancer as well as their secular trends are necessary to provide policy-makers with the information needed to allocate resources appropriately. The purpose of this study was to use the Global Burden of Disease (GBD) 2017 results to estimate the incidence, mortality, and disability-adjusted life years (DALYs) for oral cancer from 1990 to 2017. METHODS: We collected detailed data on oral cancer from 1990 to 2017 from the GBD 2017. The global incidence, mortality, and DALYs attributable to oral cancer as well as the corresponding age-standardized rates (ASRs) were calculated. The estimated annual percentage changes in the ASRs of incidence (ASRI) and mortality (ASRM) and age-standardized DALYs of oral cancer were also calculated according to regions and countries to quantify the secular trends in these rates. RESULTS: We tracked the incidence, mortality, and DALYs of oral cancer in 195 countries/territories over 28 years. Globally, the incidence, mortality, and DALYs of oral cancer increased by about 1.0-fold from 1990 to 2017. The ASRI of oral cancer showed a similar trend, increasing from 4.41 to 4.84 per 100,000 person-years during the study period. The ASRM remained approximately stable at about 2.4 per 100,000 from 1990 to 2017, as did the age-standardized DALYs, at about 64.0 per 100,000 person-years. ASRI was highest in Pakistan (27.03/100,000, 95% CI = 22.13-32.75/100,000), followed by Taiwan China, and lowest in Iraq (0.96/100,000, 95% CI = 0.86-1.06/100,000). ASRM was highest in Pakistan (16.85/100,000, 95% CI = 13.92-20.17/100,000) and lowest in Kuwait (0.51/100,000, 95% CI = 0.45-0.58/100,000). CONCLUSIONS: The ASRI of oral cancer has increased slightly worldwide, while the ASRM and age-standardized DALY have remained stable. However, these characteristics vary between countries, suggesting that current prevention strategies should be reoriented, and much more targeted and specific strategies should be established in some countries to forestall the increase in oral cancer.

Global, regional, and national burden of nasopharyngeal carcinoma from 1990 to 2017-Results from the Global Burden of Disease Study 2017.

BACKGROUND: The aim of this study is to estimate the incidence, mortality, and disability-adjusted life years (DALYs) of nasopharyngeal carcinoma from 1990 to 2017. METHODS: We collected detailed information on nasopharyngeal carcinoma from 1990 to 2017 based on data from Global Burden of Disease (GBD) study 2017. The global incidence, mortality, and DALYs attributable to nasopharyngeal carcinoma was reported, as well as the age-standardized rates (ASRs). RESULTS: The ASR of nasopharyngeal carcinoma incidence decreased from 1.88 (95% UI: 1.76-2.00) in 1990 to 1.35 (95% UI: 1.28-1.42) in 2017. The ASR of mortality decreased from 1.19 (95% UI: 1.13-1.25) in 1990 to 0.86 (95% UI: 0.82-0.89) in 2017, while ASR-DALYs decreased from 38.2 (95% UI: 35.9-40.2) in 1990 to 25.4 (95% UI: 24.4-26.5) in 2017. CONCLUSIONS: The ASR of incidence, mortality, and DALYs of nasopharyngeal carcinoma have decreased slightly worldwide. East Asia carried the heaviest burden of nasopharyngeal carcinoma. The majority of nasopharyngeal carcinoma burden was observed in men, especially among male aged 55 to 69 years.

Lactate Promotes Cancer Stem-like Property of Oral Sequamous Cell Carcinoma.

Accumulation of lactate in tumor has been linked to poor prognosis of oral squamous cell carcinoma (OSCC), but the underlying mechanism remained largely uncertain. Previous studies have suggested that presence of cancer stem cells (CSCs) closely correlated with cellular malignancy of OSCC. Here, using 3D organoid culture model, we investigated whether lactate promoted CSCs phenotype in primary OSCC cells. We generated organoids using fresh OSCC specimens and verified that organoids recapitulated histopathology and cellular heterogeneity of parental tumor. Organoids were then transfected with a Wnt reporter to visualize Wnt activity. The sphere forming assay demonstrated that high Wnt activity functionally designated CSCs population in OSCC cells. Further investigations indicated that lactate treatment promoted Wnt activity and increased the expression of CSCs (i.e. CD133+ cells) in organoids. Moreover, silencing monocarboxylate transporter 1 (MCT1), the prominent path for lactate uptake in human tumor with siRNA significantly impaired organoid forming capacity of OSCC cells. Together, our study demonstrated that lactate can promote CSCs phenotype of OSCC, and MCT1 may be a therapeutic target against OSCC growth.

Role of PFKFB3 and CD163 in Oral Squamous Cell Carcinoma Angiogenesis.

6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), an enzyme producing fructose 2, 6-bisphosphate (F-2, 6-BP), serves as a switch to activate phosphofructokinase-1, and is a critical enzyme for endothelial glycolysis, mediating circadian control of carcinogenesis. Also, tumor-associated macrophages (TAMs) play an important role in the progression and prognosis of numerous cancers. However, the role and clinical significance of PFKFB3 and TAMs in oral squamous cell carcinoma (OSCC) have not been elucidated. The present study was designed to investigate the correlation between PFKFB3 expression, CD163+ TAMs infiltration and tumor angiogenesis in OSCC by tissue microarray. Tissue microarrays containing 117 OSCC specimens and 56 matched paracarcinoma tissues were studied by immunohistochemistry. The expression levels of PFKFB3, CD163 and CD31 were significantly increased in OSCC specimens as compared with normal oral mucosa (P<0.05), and PFKFB was signifcantly correlated with tumor differentiation and tumor size (P<0.05), and CD163 was significantly correlated with areca nut chewing habit among OSCC tissues (P<0.05). Furthermore, Pearson's correlation analysis revealed that PFKFB3 was signifcantly correlated with both CD163 and CD31 (P<0.05), meanwhile CD163 was signifcantly correlated with CD31 (P<0.001), suggesting PFKFB3 may promote angiogenesis in tumor progression and metastases by regulating CD163+ TAMs infiltration in OSCC.

Nomograms for predicting long-term overall survival and cancer-specific survival in lip squamous cell carcinoma: A population-based study.

BACKGROUND: The goal of this study was to establish and validate two nomograms for predicting the long-term overall survival (OS) and cancer-specific survival (CSS) in lip squamous cell carcinoma (LSCC). METHODS: This study selected 4175 patients who were diagnosed with LSCC between 2004 and 2015 in the SEER (Surveillance, Epidemiology, and End Results) database. The patients were allocated randomly to a training cohort and validation cohort. Variables were selected using a backward stepwise method in a Cox regression model. Based on the predictive model with the identified prognostic factors, nomograms were established to predict the 3-, 5-, and 8-year survival OS and CSS rates of LSCC patients. The accuracy of the nomograms was evaluated based on the consistency index (C-index), while their prediction accuracy was evaluated using calibration plots. Decision curve analyses (DCAs) were used to evaluate the performance of our survival model. RESULTS: The multivariate analyses demonstrated that age at diagnosis, marital status, sex, race, American Joint Committee on Cancer stage, surgery status, and radiotherapy status were risk factors for both OS and CSS. The C-index, area under the time-dependent receiver operating characteristic curve, and calibration plots demonstrated the good performance of the nomograms. DCAs of both nomograms further showed that they exhibited good 3-, 5-, and 8-year net benefits. CONCLUSIONS: We have developed and validated LSCC prognosis nomograms for OS and CSS for the first time. These nomograms can be valuable tools for clinical practice when clinicians are helping patients to understand their survival risk for the next 3, 5, and 8 years.

Application of Delayed Surgical Managements in Patients with Stensen's Duct Injury.

The study aimed to retrospectively evaluate surgical treatment outcomes after delayed parotid gland and duct injuries. Nine patients subjected to parotid gland and duct injuries with 1- to 3-month treatment delay were retrospectively evaluated with special reference of etiology, past medical history, and injury location. Conservative treatment, microsurgical anastomosis, and diversion of salivary flow or ligation were chosen for delayed parotid gland and duct injuries concerning to their site of injury, time of repair and procedures. Assistant treatment as pressure dressing was adopted thereafter. All patients experienced an uneventful recovery at the time of finalizing the study. Two patients received Stensen's duct ligation, 5 received microsurgical anastomosis and 2 accepted salivary flow diversion for 5 patients with sialoceles and 4 patients with fistulas, and no re-occurrence was found. Facial paralysis occurred after surgery in 4 patients, and 3 of them recovered after the nerve nutrition treatment. Our study suggested that appropriate surgical treatment is efficient for the re-establishment of the tissue function and facial aesthetic for delayed injury of the parotid and its duct.

Suture Technique to Prevent Air Leakage during Negative-Pressure Wound Therapy in Fournier Gangrene.

BACKGROUND: The use of negative-pressure wound therapy (NPWT) for Fournier gangrene management is well documented; however, it is difficult to fixate GranuFoam dressings and maintain an airtight seal over the perineum area. We developed a simple method to facilitate GranuFoam fixation and improve airtight sealing. METHODS: The Fournier's gangrene severity index (FGSI) score less than 9 was collected in from January 2015 to October 2016. All 13 patients underwent fasciotomy, and NPWT was applied directly on fasciotomy wounds after the debridement of infected tissue. Partial wound closure was performed, and a portion of GranuFoam was inserted to facilitate fixation. The seal check was converted to a 0-10 scale score that was recorded every 4 hours during NPWT. Patient profiles including medical history, FGSI, method of wound closure, and length of stay were collected in this study. RESULTS: The median age of the patients was 62 (38-76) years. The mean FGSI score was 4.3 ± 3.1. The average duration of NPWT was 17.5 ± 11.5 days, and the average seal check score was 0.8 ± 0.5. No seal check alarms were noted during the study. Successful wound closure was achieved in all patients without using additional reconstruction methods such as skin grafting or muscle flap coverage. CONCLUSIONS: The present results suggest that partial wound-edge closure and in situ GranuFoam fixation improve the NPWT leaks in Fournier gangrene wounds. Furthermore, this method is simple to learn and can be useful in applying NPWT to anatomically difficult areas.

Source composition and seasonal variation of particulate trace element fluxes in Prydz Bay, East Antarctica.

Particulate fluxes of trace elements (Al, Fe, Mn, Cu, Pb, Zn, Cd and Co) in the polynya area of Prydz Bay were measured using time series sediment trap lasting from December 16th 2010 to December 16th 2011. The comparison of annual fluxes from different regions, the seasonality and sources of trace element, and their association with organic matters were investigated. The fluxes of Cu, Zn and Cd in the polynya area of Prydz Bay are dominated by marine biogenic sources. Their similar seasonality with the export of biological materials (biogenic silica, organic carbon, and calcite carbonate) is strongly related to the ice coverage and biological production. Mineral debris derived from Antarctic continent is suggested to account for the particulate fluxes of Al, Fe, Mn, Pb and Co in the polynya. Their seasonal variations are most likely controlled by ice melting and freezing process. Furthermore, their fluxes are also influenced by scavenging onto biogenic material for Pb and uptake by phytoplankton for Co. The excess fluxes of Cu, Zn and Cd have good relationship with organic carbon export. The coupling patterns are mainly regulated by source composition of trace elements and non-lithogenic input from atmospheric deposition or upwelling, and partly influenced by biological uptake process.

The impact of different nursing skill mix models on patient outcomes in a respiratory care center.

BACKGROUND: Many hospitals have reformed hospital policies and changed nursing models to cope with shortages in nursing staff and control medical costs. However, the nursing skill mix model that most successfully achieves both cost effectiveness and quality care has yet to be determined. AIM: The aim of this study was to explore the impact of different nurse staffing models on patient outcomes in a respiratory care center (RCC). METHODS: Retrospective data from 2006 to 2008 were obtained from records monitoring nursing care quality, as well as patient records and nursing personnel costs in an RCC as a medical center, in southern Taiwan. A total of 487 patients were categorized into two groups according to the RCC's mix of nursing staff. The "RN/Aide" group comprised 247 patients who received RN and aide care, with a 0.7-0.8 proportion of RNs, from July 2006 to June 2007. The other 240 patients ("All-RN") received 100% RN care from January 2008 to December 2008. RESULTS: The results of this study indicated no significant differences in occurrence of pressure ulcer or respiratory tract infections, days of hospitalization, mortality, or nursing costs. However, significant differences were observed in ventilator weaning and occurrence of urinary tract and bloodstream infections. CONCLUSIONS: A higher proportion of RNs was associated not only with a lower rate of urinary tract infection but also with more patients being weaned successfully from ventilators. The findings of this study have implications for how managers and administrators manage nurse staffing in respiratory care.