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??Objective    To observe the effects of lithium chloride pretreatment on cognitive ability of aged rats after oral and maxillofacial surgery. Methods    A total of 48 aged male SD rats??18 ~ 20 months old??weight 550 ~ 700 g?? were bought from the Experimental Animal Center of China Medical University . These rats were randomly divided into three groups??including the normal control group??group C??n=16????surgery and anesthesia group??group O??n=16????and lithium chloride preconditioning group??group L??n=16??.Rats in each group were randomly divided into two parts??one part was given Morris water maze test three days after the surgery and its characteristics of behavior tested. Another part was decapitated 24 h after the surgery and extracted and the hippocampus brain separated at the same time. Test expression content of IL-1β GSK-3β p-GSK-3β??ser9??in the hippocampus by Elisa and Western blotting detection method respectively. Results    Morris water maze test showed that??the first day after surgery??latencies of group L and O were significantly longer than group C??compared with group C in swimming distance?? latency and swim distances of group L were shorter than group O. With the comparison of multiple analysis of variance??differences were statistically significant??P??0.05??. Groups L and O in the second day were slightly shortened compared to the first day??on the third day after surgery it has also improved over the second day. Space exploration experiments in rats showed that??the dwell time of group C was significantly longer in the platform quadrant and the frequency of crossing the platform also increased compared with groups L and O. In addition??group L and group O were higher in IL-β levels than group C??the difference being statistically significant by analysis of variance??P??0.05????but group L was significantly lower compared with group O??the difference being statistically significant??P??0.05??. The content of GSK-3β of three groups were of no significant difference??P > 0.05????but p-GSK-3β??ser9??content was significantly lower in group L and O than in group C. The content of GSK-3β of group L was higher than in group O??the difference being statistically significant??P??0.05??. Conclusion    Pretreatment with lithium chloride in postoperative aged rats can inhibit the expression of inflammatory cytokines and increase GSK-3β phosphorylation in the hippocampus cells??so p-GSK-3β??ser9??upregulates and inhibites  the apoptosis of brain cells??thereby improved cognitive abilities after the cavity and maxillofacial surgery.     

Endoscopy-Related Bleeding and Thromboembolic Events in Patients on Direct Oral Anticoagulants or Vitamin K Antagonists

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Quality of oral anticoagulation control in Chinese patients with non-valvular atrial fibrillation: a prospective controlled study

Abstract

Objective

The sex, age, medical history, treatment, tobacco use, race risk (SAMe-TT₂R₂) Score; the sex, age, medical history, treatment, tobacco use, genotype combination (SAMe-TT₂G₂) Score; and the so-called modified SAMe-TT₂R₂ scores have been proposed to predict the anticoagulation quality for patients with non-valvular atrial fibrillation (NVAF). The data from a prospective controlled study is used to validate the SAMe-TT₂R₂ and SAMe-TT₂G₂ scores in Chinese NVAF patients treated with warfarin and to evaluate the association of factors with time in therapeutic range (TTR) to predict the quality of oral anticoagulation control.     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

Medical practitioners’ educational competence about oral and oropharyngeal carcinoma: a systematic review and meta-analysis

Medical practitioners’ (MP) role is pivotal in primary prevention, early diagnosis, prompt referral and effective management of oral and oropharyngeal carcinomas (OC/OPC), which raises the importance of their effective OC/OPC education at all levels of medical education. The purpose of this systematic review was to summarise the available scientific evidence about their educational competence in dealing with OC/OPC. We made a systematic search of papers in the English language in MEDLINE, Scopus, Cochrane Library CENTRAL and CINAHL databases from their inception until December 2018. Overall, 23 cross-sectional and three interventional studies have been selected for the systematic review and 18 of these were included in the meta-analyses. Excluding tobacco use (synthesised estimate of 95% of respondents identified tobacco as an OC/OPC risk factor, 95% CI of synthesised estimate 92% to 97%) and alcohol consumption (65%, 95%CI 52% to 77%), less than half of MP (approximately) were knowledgeable about important OC/OPC risk factors including human papilloma virus (42%, 95% CI 30% to 54%), poor diet (34%, 95% CI 17% to 54%), and advancing age (45%, 95% CI 21% to 70%). There was a low to moderate level of awareness among MP regarding common precancerous oral lesions involving leukoplakia (56%, 95% CI 32% to 79%), erythroplakia (30%, 95% CI 8% to 58%), and oral lichen planus (13%, 95% CI 0 to 41%). Moderate knowledge was also recorded about frequent sites of OC development involving the tongue (48%, 95% CI 33% to 64%) and floor of the mouth (37%, 95% CI 19% to 57%). Most MP enquired about tobacco use (86%, 95% CI 74% to 96%), and alcohol consumption (73%, 95% CI 47% to 94%) during history taking, and expressed willingness to be given supplementary OC/OPC education (78%, 95% CI 54% to 96%), as well. With regard to the incidence of intraoral screening, 27% of MP (95% CI 12% to 46%) make an intraoral examination as a routine. Interestingly, studies from each continent yielded significantly different outcomes to some research questions in the review. From the MP’s perspective, clinical time restrictions and deficiencies in organised training were recognised as the main barriers towards their OC/OPC educational competence. The findings of this systematic review indicated the existence of deficiencies in knowledge and misconceptions, neglected preventive responsibilities, and associated barriers towards OC/OPC. A need for improved OC/OPC training at all levels of medical education is required to increase competence worldwide.     

Direct oral anticoagulants (DOACs) and neck of femur fractures: Standardising the perioperative management and time to surgery

Demographic projections for hip fragility fractures indicate a rising annual incidence by virtue of a multimorbid, ageing population with more noncommunicable diseases (NCDs). NCDs are characterised by slow progression and long duration ranging from ischaemic cardiovascular disease, cerebrovascular disease, diabetes, chronic obstructive pulmonary disease to various cancers. Management of this disease burden often involves commencing patients on oral anticoagulants to reduce the risk of thromboembolic events. The use of direct oral anticoagulants (DOACs) in clinical practice has increased due to their rapid onset of action, short half-life and predictable anticoagulant effects, without the need for routine monitoring. Safe and timely surgical intervention relies on reversal of anticoagulants. However, the lack of specific evidence-based guidelines for the perioperative management of patients on DOACs with hip fractures has proved challenging; in particular, the accessibility of DOAC-specific assays, justification of the cost-benefit ratio of targeted reversal agents and indications for neuraxial anaesthesia. This has led to potentially avoidable delays in surgical intervention. Following a literature review of the pharmacokinetic and pharmacodynamics of commonly used DOACs in our region including the role of surrogate markers, we propose a systematic, evidence-based guideline to the perioperative management of hip fractures DOACs. We believe this standardised protocol can be easily replicated between hospitals. We recommend that if patients are deemed suitable for a general anaesthesia, with satisfactory renal function, optimal surgical time should be 24 h following the last ingested dose of DOAC.     

Preoperative intra-arterial chemotherapy with docetaxel,cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil for oral squamous cell carcinoma

The objectives of this study were to evaluate survival in 141 patients with stage II–IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.     

Helicobacter pylori and gastric hyperacidity,and their association with recurrent aphthous stomatitis

Helicobacter pylori is an established cause of gastric ulcers. Its role in causing recurrent aphthous stomatitis (RAS) remains controversial. Fifty-two RAS patients and 52 sex-matched controls were recruited in this case–control study. All subjects were screened for hematinic deficiencies and H. pylori. The latter was assessed quantitatively using the ¹⁴C-urea breath test. The χ² test and Wilcoxon signed ranks test were used to compare H. pylori and hematinic indices between cases and controls, while conditional logistic regression was used to assess the associations between the occurrence of RAS and independent factors. H. pylori was positive in 56.7% of the overall sample, with no difference between RAS patients (50.8%) and controls (49.2%) (P = 0.843). The median H. pylori and haematological indices values did not show any association with ulcer diameter, number, or frequency. Interestingly, gastric hyperacidity was significantly associated with RAS, and this association was independent from tobacco smoking, alcohol drinking, and H. pylori (odds ratio 14.99, 95% confidence interval 2.47–90.95; P = 0.003). This study found no association between H. pylori and RAS. The association between RAS and gastric hyperacidity suggests that gastric refluxate, not H. pylori, has an effect on the oral mucosa that favours an ulcerative change.     

Clinicopathologic factors associated with malignant transformation of oral leukoplakias: a retrospective cohort study

It is clinically challenging to identify oral leukoplakias that have a high risk of undergoing malignant transformation. The aim of this retrospective study was to elucidate the associations between malignant transformation of oral leukoplakias and various clinicopathologic factors. Patients with a diagnosis of clinical oral leukoplakia, verified through histopathologic examination and with access to digital images of the lesion, were retrospectively included for the period 2003–2013. Using the clinical images, all lesions were re-evaluated regarding diagnosis and clinical subtype. Of the 234 included patients, with a median follow-up of 9 years, 27 (11.5%) developed oral squamous cell carcinoma. Among the clinicopathologic factors investigated, non-homogeneous oral leukoplakia (OL), OL with dysplasia, and OL localized to the tongue showed statistically significant increased rates of malignant transformation in the multivariate Cox regression analysis. Non-homogeneous OL showed a 15.2-times higher transformation rate than homogenous OL (P < 0.001). Dysplastic leukoplakias developed into carcinomas 2.4-times more often than did non-dysplastic leukoplakias (P = 0.048). OL located on the tongue showed a 2.8-times higher malignant transformation rate than OLs at other oral locations (P = 0.018), when other locations were combined into one group. Non-homogeneous OL, OL with dysplasia, and OL localized to the tongue have higher transformation rates.