Silencing KLF16 inhibits oral squamous cell carcinoma cell proliferation by arresting the cell cycle and inducing apoptosis

Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.     

Diffusion-weighted MRI and PET/CT reproducibility in epithelial ovarian cancers during neoadjuvant chemotherapy

PurposeTo investigate the reproducibility of diffusion-weighted (DW) MRI and ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG)-Positron emission tomography/CT (PET/CT) in monitoring response to neoadjuvant chemotherapy in epithelial ovarian cancer.Materials and methodsTen women (median age, 67 years; range: 41.8–77.3 years) with stage IIIC-IV epithelial ovarian cancers were included in this prospective trial (NCT02792959) between 2014 and 2016. All underwent initial laparoscopic staging, four cycles of carboplatine-paclitaxel-based chemotherapy and interval debulking surgery. PET/CT and DW-MRI were performed at baseline (C0), after one cycle (C1) and before surgery (C4). Two nuclear physicians and two radiologists assessed five anatomic sites for the presence of ≥ 1 lesion. Target lesions in each site were defined and their apparent diffusion coefficient (ADC), maximal standardized uptake value (SUV-max), SUV-mean, SUL-peak, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were monitored (i.e., 10 patients × 5 sites × 3 time-points). Their relative early and late changes were calculated. Intra/inter-observer reproducibilities of qualitative and quantitative analysis were estimated with Kappa and intra-class correlation coefficients (ICCs).ResultsFor both modalities, inter- and intra-observer agreement percentages were excellent for initial staging but declined later for DW-MRI, leading to lower Kappa values for inter- and intra-observer variability (0.949 and 1 at C0, vs. 0.633 and 0.643 at C4, respectively) while Kappa values remained > 0.8 for PET/CT. Inter- and intra-observer ICCs were > 0.75 for SUV-max, SUL-peak, SUV-mean and their change regardless the time-point. ADC showed lower ICCs (range: 0.013–0.811). ANOVA found significant influences of the evaluation time, the measurement used (ADC, SUV-max, SUV-mean, SUV-max, SUL-peak, MTV or TLG) and their interaction on ICC values (P = 0.0023, P< 0.0001 and P =0.0028, respectively).ConclusionWhile both modalities demonstrated high reproducibility at baseline, only SUV-max, SUL-peak, SUV-mean and their changes maintained high reproducibility during chemotherapy.     

Dynamic functional connectivity of the EEG in relation to outcome of postanoxic coma

ObjectiveEarly EEG contains reliable information for outcome prediction of comatose patients after cardiac arrest. We introduce dynamic functional connectivity measures and estimate additional predictive values.MethodsWe performed a prospective multicenter cohort study on continuous EEG for outcome prediction of comatose patients after cardiac arrest. We calculated Link Rates (LR) and Link Durations (LD) in the α, δ, and θ band, based on similarity of instantaneous frequencies in five-minute EEG epochs, hourly, during 3 days after cardiac arrest. We studied associations of LR and LD with good (Cerebral Performance Category (CPC) 1–2) or poor outcome (CPC 3–5) with univariate analyses. With random forest classification, we established EEG-based predictive models. We used receiver operating characteristics to estimate additional values of dynamic connectivity measures for outcome prediction.ResultsOf 683 patients, 369 (54%) had poor outcome. Patients with poor outcome had significantly lower LR and longer LD, with largest differences 12 h after cardiac arrest (LR_θ 1.87 vs. 1.95 Hz and LD_α 91 vs. 82 ms). Adding these measures to a model with classical EEG features increased sensitivity for reliable prediction of poor outcome from 34% to 38% at 12 h after cardiac arrest.ConclusionPoor outcome is associated with lower dynamics of connectivity after cardiac arrest.SignificanceDynamic functional connectivity analysis may improve EEG based outcome prediction.     

Silver Diamine Fluoride: Extending the spectrum of Preventive Dentistry,a literature review

Dental caries continues to be a severe oral health problem despite a decrease in its prevalence over the past few decades. The contemporary philosophy of caries management has shifted from the traditional approach to a newer medical one, that frequently includes utilization of fluoridated and antimicrobial agents. Among these different agents, Silver Diamine Fluoride (SDF)¹ has gained significant recognition. Dr Nishino and Dr Yamaga in Japan, pioneered its application to arrest caries. It is an alkaline, colourless solution composed of diamine-silver and fluoride ions having silver's antibacterial and fluoride's remineralising property. It has been used successfully to arrest and prevent caries in deciduous and permanent teeth, prevent recurrence of secondary caries and treat dentinal hypersensitivity. No adverse systemic effects due to SDF have been noted although black discolouration following its application has raised concerns. When used wisely it is an effective, sustainable and inexpensive option for children with high caries risk, for individuals who cannot endure conventional modalities of restorative treatment and those with special health-care needs. The current review is an insight into the clinical significance and application of SDF based on published literature.     

基于TCA循环关键酶测定研究督灸治疗早期强直性脊柱炎患者关节活动度的疗效及机制＊

目的 基于TCA循环（三羧酸循环，tricarboxylic acid cycle）关键酶测定研究督灸治疗早期强直性脊柱炎（AS）肾虚督寒证患者关节活动度的疗效及生物学机制。方法 110例早期AS肾虚督寒证患者随机分为观察组和对照组，各55例。对照组口服甲氨蝶呤+洛索洛芬钠，观察组在对照组治疗基础上给予督灸，疗程均为12周。观察治疗前后患者的病情活动指数（bath ankylosing spondylitis disease activity index，BASDAI）、功能指数（bath ankylosing spondylitis fundation index，BASFI）、活动度衡量指数（bath ankylosing measure index activity index，BASMI）、总和指数（bath ankylosing spondylitis patient slobal，BAS-G）、指-地距、枕-墙距、胸廓活动度、Schober试验水平和早期AS肾虚督寒证中医辨证（肾虚督寒证）评分；检测血清炎症因子肿瘤坏死因子-α（TNF-α）、白细胞介素-18（IL-18）、血沉（ESR）和C-反应蛋白（CRP）含量；检测TCA循环关键酶柠檬酸合成酶（citrate synthase，CS）、异柠檬酸脱氢酶（isocitrate dehydrogenase，IDH）及α-酮戊二酸脱氢酶（α-ketoglutarate dehydrogenase，α-KGDHC）的水平；比较治疗12周患者的临床疗效及随访6个月复发率。结果 临床研究过程脱落6例。观察组总有效率96.2%，明显高于观察组的82.4%（P<0.05）；观察组随访6个月复发率5.7%，明显低于对照组的21.6%（P<0.05）。治疗12周后，观察组患者BASDAI、BASFI、BASMI、BAS-G、指-地距、枕-墙距和肾虚督寒证评分较对照组明显下降（P<0.05），胸廓活动度和Schober试验较对照组明显升高（P<0.05）；观察组患者TNF-α、IL-18、ESR、CRP、CS和IDH水平较对照组明显下降（P<0.05），α-KGDHC水平较对照组明显升高（P<0.05）。结论 督灸可以有效改善早期AS肾虚督寒证患者的临床症状，复发率低，值得临床推广应用。     

Post-cardiac arrest intensive care in Sweden: A survey of current clinical practice

Background

European guidelines recommend targeted temperature management (TTM) in post-cardiac arrest care. A large multicentre clinical trial, however, showed no difference in mortality and neurological outcome when comparing hypothermia to normothermia with early treatment of fever. The study results were valid given a strict protocol for the assessment of prognosis using defined neurological examinations. With the current range of recommended TTM temperatures, and applicable neurological examinations, procedures may differ between hospitals and the variation of clinical practice in Sweden is not known.

Aim

The aim of this study was to investigate current practice in post-resuscitation care after cardiac arrest as to temperature targets and assessment of neurological prognosis in Swedish intensive care units (ICUs).

Methods

A structured survey was conducted by telephone or e-mail in all Levels 2 and 3 (= 53) Swedish ICUs during the spring of 2022 with a secondary survey in April 2023.

Results

Five units were not providing post-cardiac arrest care and were excluded. The response rate was 43/48 (90%) of the eligible units. Among the responding ICUs, normothermia (36–37.7°C) was applied in all centres (2023). There was a detailed routine for the assessment of neurological prognosis in 38/43 (88%) ICUs. Neurological assessment was applied 72–96 h after return of spontaneous circulation in 32/38 (84%) units. Electroencephalogram and computed tomography and/or magnetic resonance imaging were the most common technical methods available.

Conclusion

Swedish ICUs use normothermia including early treatment of fever in post-resuscitation care after cardiac arrest and almost all apply a detailed routine for the assessment of neurological prognosis. However, available methods for prognostic evaluation varies between hospitals.