Effects of personalized oral exercises on swallowing function among patients with oral cancer after free flap transplantation: a cluster randomized controlled trial.

Dysphagia is a common complication in patients with oral cancer who have undergone free flap transplantation. The aim of this cluster randomized controlled trial was to evaluate the effect of personalized oral exercises on swallowing function in this group of patients. Eligible patients were randomly assigned to the intervention (n = 34) or control (n = 34) group. Intervention group patients received personalized oral exercises starting on day 6 after surgery. Swallowing function was evaluated on days 6 and 15, and at 1 month postoperative using the Mann Assessment of Swallowing Ability-Oral Cancer tool (MASA-OC). On day 15 and at 1 month after surgery, the total MASA-OC score (P = 0.003, P < 0.001) and the mouth opening (P = 0.001, P < 0.001) and lip seal (both P < 0.001) item scores showed a significantly greater improvement in the intervention group than in the control group. Moreover, the changes in salivation (P < 0.001) and tongue movement (P = 0.025) scores at 1 month after surgery were significantly greater in the intervention group than in the control group. There was no significant difference between the groups in the change in tongue strength scores on day 15 or at 1 month postoperative (P = 0.476, P = 0.223). Personalized oral exercises can improve swallowing function in patients with oral cancer after free flap transplantation.

Curcumin nanoparticles and the therapeutic potential of curcumin for musculoskeletal disorders.

Musculoskeletal disorders (MSD) are a collection of degenerative conditions impacting the body's bones, joints, muscles, tendons, ligaments, and nerves. MSDs affect approximately 1.71 billion individuals worldwide and are a significant cause of disability. Curcumin is a polyphenolic compound with anti-inflammatory, antioxidant, and antitumor properties. In this review, we will discuss the research progress of structural analogs, derivatives, and nanomaterials that can improve the bioavailability of this natural drug. Curcumin may potentially retard the progression of osteoporosis, osteoarthritis, and rheumatoid arthritis. These effects may be related to curcumin's targeting of multiple signalling pathways.

Preoperative oral carbohydrates in elderly patients undergoing free flap surgery for oral cancer: randomized controlled trial.

The aim of this study was to evaluate the safety of carbohydrate intake 2 hours before surgery in elderly patients undergoing free flap surgery for oral cancer. Elderly patients undergoing free flap surgery between September 2019 and January 2021 were randomly divided into control (n = 43) and intervention (n = 43) groups. Control group patients fasted for 6 hours and were forbidden from drinking water for 4 hours before surgery. Intervention group patients fasted for 6 hours and were forbidden from drinking after the oral administration of 5 ml/kg carbohydrate (≤400 ml) 2 hours before surgery. The main outcome measures were aspiration, fasting blood glucose level, insulin concentration, insulin resistance index (fasting at admission, prior to anaesthesia induction, immediately after surgery, and at 6 a.m. on postoperative days 1 and 2), and comfort before and after surgery. No aspiration occurred in any of the patients during anaesthesia. There were significant differences in fasting blood glucose, insulin concentration, and insulin resistance index between the control and intervention groups prior to anaesthesia induction, immediately after surgery, and on day 1 after surgery (P < 0.01). Thirst (P = 0.001) and hunger (P = 0.003) differed significantly between the two groups prior to anaesthesia induction. The intake of oral carbohydrate 2 hours before surgery was both safe and effective for elderly patients with oral cancer undergoing free flap surgery and could relieve the physiological stress response.

Shape-Guided Mixed Metro Map Layout.

Metro or transit maps, are schematic representations of transit networks to facilitate effective route-finding. These maps are often advertised on a web page or pamphlet highlighting routes from source to destination stations. To visually support such route-finding, designers often distort the layout by embedding symbolic shapes (e.g., circular routes) in order to guide readers' attention (e.g., Moscow map and Japan railway map). However, manually producing such maps is labor-intensive and the effect of shapes remains unclear. In this paper, we propose an approach to generalize such mixed metro maps that take user-defined shapes as an input. In this mixed design, lines that are used to approximate the shapes are arranged symbolically, while the remaining lines follow classical layout convention. A three-step algorithm, including (1) detecting and selecting routes for shape approximation, (2) shape and layout deformation, and (3) aligning lines on a grid, is integrated to guarantee good visual quality. Our contribution lies in the definition of the mixed metro map problem and the formulation of design criteria so that the problem can be resolved systematically using the optimization paradigm. Finally, we evaluate the performance of our approach and perform a user study to test if the embedded shapes are recognizable or reduce the map quality.

Generative models for predicting chemical composition of gallstones.

OBJECTIVE: As we know, gallstones are a gallbladder disease with high incidence around the world. As the population has aged and living habits have changed, the incidence of the disease is increasing year by year. Gallstones are mainly classified into cholesterol, bile pigment and mixed type gallstones based on their chemical composition. Patients with different stone components have different treatment options. Therefore, it is very important to know the chemical type of the stone before treatment. Imaging examination is the main method to identify the components of gallstones in the body. MATERIALS AND METHODS: Deep learning technology has an excellent data mining ability, and thus the combination of deep learning and medical treatment is always a research focus. In this work, we introduce a generative model to learn the features of the training data, to detect the composition of gallstones and to assist medical diagnosis. Furthermore, the theoretical analysis is given in detail. RESULTS: The model could be used to determine the chemical composition of gallstones. CONCLUSIONS: The potential of generative models in predicting the chemical composition of gallstones is shown in this study. In addition, theoretical analysis is also presented.

Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in Beta-lactoglobulin-induced allergic mice model

OBJECTIVES: Β-lactoglobulin (Β-Lg)-sensitized mice model was employed to investigate the correlation between Lactobacillus acidophilus KLDS 1.0738 (Lap KLDS 1.0738) modulating gut microbiota and inducting Toll-like receptors (TLRs) expression. METHODS: The alterations of mice fecal microbiota were analyzed by 16S rRNA gene sequencing. The serum cytokines production and TLR4/NF-κB mRNA expression in the colon tissues were measured by ELISA kit and quantitative RT-PCR, respectively. RESULTS: The results showed that Lap KLDS 1.0738 pretreatment attenuated Β-Lg-induced hypersensitivity, accompanied with a diminished expression of TLR4/NF-κB signaling. Moreover, oral administration of Lap KLDS 1.0738 improved the richness and diversity of fecal microbiota, which was characterized by fewer Proteobacteria phylum and Helicobacteraceae family, and higher Firmicutes phylum and Lachnospiraceae family than allergic group. Notably, TLR4/NF-κB expression was positively correlated with the family of Helicobacteraceae in allergic group, but negatively correlated with the family of Lachnospiraceae, Ruminococcaceae and anti-inflammatory cytokines level. A significant positive correlation was observed between TLR4/NF-κB expression and the production of histamine, total IgE and pro-inflammatory cytokines. CONCLUSIONS: Intake of Lap KLDS 1.0738 can influence the gut bacterial composition, which might result in recognizing TLRs signaling so as to inhibit allergic response

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Correction: Role of integrin-linked kinase in regulating the protein stability of the MUC1-C oncoprotein in pancreatic cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in ß-lactoglobulin-induced allergic mice model.

OBJECTIVES: ß-lactoglobulin (ß-Lg)-sensitized mice model was employed to investigate the correlation between Lactobacillus acidophilus KLDS 1.0738 (Lap KLDS 1.0738) modulating gut microbiota and inducting Toll-like receptors (TLRs) expression. METHODS: The alterations of mice fecal microbiota were analyzed by 16S rRNA gene sequencing. The serum cytokines production and TLR4/NF-κB mRNA expression in the colon tissues were measured by ELISA kit and quantitative RT-PCR, respectively. RESULTS: The results showed that Lap KLDS 1.0738 pretreatment attenuated ß-Lg-induced hypersensitivity, accompanied with a diminished expression of TLR4/NF-κB signaling. Moreover, oral administration of Lap KLDS 1.0738 improved the richness and diversity of fecal microbiota, which was characterized by fewer Proteobacteria phylum and Helicobacteraceae family, and higher Firmicutes phylum and Lachnospiraceae family than allergic group. Notably, TLR4/NF-κB expression was positively correlated with the family of Helicobacteraceae in allergic group, but negatively correlated with the family of Lachnospiraceae, Ruminococcaceae and anti-inflammatory cytokines level. A significant positive correlation was observed between TLR4/NF-κB expression and the production of histamine, total IgE and pro-inflammatory cytokines. CONCLUSIONS: Intake of Lap KLDS 1.0738 can influence the gut bacterial composition, which might result in recognizing TLRs signaling so as to inhibit allergic response.

miRNA-217 inhibits proliferation of hepatocellular carcinoma cells by regulating KLF5.

OBJECTIVE: The aim of this study was to figure out the effect of microRNA-217 on the proliferation of hepatocellular carcinoma (HCC) cells, and to explore its influence on KLF5 expression and the underlying regulatory mechanisms. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of microRNA-217 in tumor tissues and paracancerous tissues of 60 patients with HCC. Meanwhile, the relationship between microRNA-217 expression and HCC pathological parameters was analyzed. In HCC cell lines, including HepG2 and Bel-7402, negative control group (NC) and microRNA-217 overexpression group were set up, and qRT-PCR was performed to further verify their transfection efficiency. In addition, Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay were performed to analyze the effect of microRNA-217 on the biological function of HCC cells. Finally, the potential mechanism of KLF5, the downstream gene of microRNA-217, was explored using bioinformatics analysis and cell recovery experiments. RESULTS: QRT-PCR results showed that microRNA-217 level in tumor tissues of HCC patients was conspicuously lower than that in adjacent tissues, and the difference was statistically significant. Compared with patients with high expression of microRNA-217, the pathological stage was higher and the overall survival rate was lower in patients with low expression. Compared with the NC group, the cell proliferation ability of the microRNA-217 mimics group was conspicuously decreased. Subsequently, in the HCC cell line and tissue verification, the expression of KLF5 was found remarkably increased, and microRNA-217 exhibited a negative correlation with KLF5 level. In addition, the overexpression of microRNA-217 conspicuously reduced the protein expression of CD31, Ki-67, c-Myc, MMP-2, and MMP-9. In cell recovery experiment, it was found that the overexpression of KLF5 could counteract the effect of microRNA-217 mimics on the cell proliferation of HCC, thereby inhibiting the malignant progression of this disease. CONCLUSIONS: The above studies demonstrated that microRNA-217 was markedly associated with the pathological stage and poor prognosis of HCC, and could inhibit the malignant progression of this disease. In addition, our investigation has showed that microRNA-217 might be capable of inhibiting cell proliferation of HCC via regulating KLF5.

Assessment of mismatch negativity and P300 response in patients with disorders of consciousness.

OBJECTIVE: To evaluate changes in mismatch negativity (MMN) and P300 response in vegetative state (VS) and minimally conscious state (MCS) patients before and after treatment, and their value for prediction of prognosis. PATIENTS AND METHODS: Event-related potentials (ERPs), performed on 11 patients classified as VS (n = 6) or MCS (n = 5), and five healthy participants (i.e., control group). We performed a six months telephone follow-up to monitor changes in consciousness recovery. RESULTS: Comparison of the three groups showed significantly higher MMN latency elicited by salient stimuli and P300 elicited by the subject's own name for the VS group, as well as significant difference in amplitudes of MMN elicited by frequent stimuli and P300 elicited by other first names for this group. The source of MMN and P300 responses was the frontal lobe for the control group, and temporal lobe for the VS and MCS groups. CONCLUSIONS: The sudden increase in MMN amplitude and latency shortening may indicate an improvement in the state of consciousness. Neurophysiological evaluations suggest that patients with vegetative state (VS) and minimally conscious state (MCS) may preserve patterns of higher-order cerebral processing similar to those observed in conscious patients.

Role of integrin-linked kinase in regulating the protein stability of the MUC1-C oncoprotein in pancreatic cancer cells.

MUC1-C overexpression has been associated with the progression of pancreatic tumors by promoting the aggressive and metastatic phenotypes. As MUC1 is a STAT3 target gene, STAT3 plays a major role in regulating MUC1-C expression. In this study, we report an alternative mechanism by which integrin-linked kinase (ILK) post-transcriptionally modulates the expression of MUC1-C by maintaining its protein stability in pancreatic cancer cells. We found that ILK acts in concert with STAT3 to facilitate IL-6-mediated upregulation of MUC1-C; ILK depletion was equally effective as STAT3 depletion in abolishing IL-6-induced MUC1-C overexpression without disturbing the phosphorylation or cellular distribution of STAT3. Conversely, ectopic expression of constitutively active ILK increased MUC1-C expression, though this increase was not noted with kinase-dead ILK. This finding suggests the requirement of the kinase activity of ILK in regulating MUC1-C stability, which was confirmed by using the ILK kinase inhibitor T315. Furthermore, our data suggest the involvement of protein kinase C (PKC)δ in mediating the suppressive effect of ILK inhibition on MUC1-C repression. For example, co-immunoprecipitation analysis indicated that ILK depletion-mediated MUC1-C phosphorylation was accompanied by increased phosphorylation of PKCδ at the activation loop Thr-507 and increased binding of PKCδ to MUC1-C. Conversely, ILK overexpression resulted in decreased PKCδ phosphorylation. From a mechanistic perspective, the present finding, together with our recent report that ILK controls the expression of oncogenic KRAS through a regulatory loop, underscores the pivotal role of ILK in promoting pancreatic cancer progression.

Regulation of miR-92a on vascular endothelial aging via mediating Nrf2-KEAP1-ARE signal pathway.

OBJECTIVE: Various human aging-related diseases start with vascular aging, in which the aging of vascular endothelium is the first step to cause a structural and functional deficit of vascular endothelium, leading to vascular disorders. MicroRNA (miR) participates in various processes of body development and pathological processes via mediating cell proliferation, differentiation, and apoptosis. A previous study showed the correlation between cardiovascular disease and miR-92a, whose role and mechanism in vascular endothelial aging has not been reported. MATERIALS AND METHODS: In vitro, cultured human umbilical vein endothelial cells (HUVECs) were prepared for the vascular endothelial aging model by using 10-6 mM angiotensin II. MiR-92a expression was examined. After transfecting with the miR-92a inhibitor, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was employed to describe cell proliferation, and the Caspase 3 activity assay kit was used to evaluate apoptosis activity. Myeloid peroxidase (MPO) and superoxidase (SOD) activity, plus reactive oxygen species (ROS) content were measured. Nrf2, KEAP1 and ARE mRNA expressions were measured by real-time PCR. Nuclear factor erythroid 2 p45 related factor 2 (Nrf2) protein level, inflammatory factors tumor necrosis factor α (TNF-α) and interleukin-2 (IL-2) were tested by western blot or enzyme-linked immunosorbent assay (ELISA). RESULTS: In model group, miR-92a expression was elevated significantly compared to the control group (p < 0 .05). MiR-92a inhibitor transfection facilitated cell proliferation, decreased Caspase 3 activity, ROS or MPO, expressions of TNF-α, IL-2 and KEAP1, and enhanced SOD level and Nrf2, ARE expressions significantly compared to the model group (p < 0.05). CONCLUSIONS: In aged vascular endothelium, miR-92a was up-regulated. Through inhibiting miR-92a expression and regulating Nrf2-KEAP1-ARE signal pathway, the oxidative stress reaction or inflammation can be suppressed, thus inhibiting endothelial apoptosis and facilitating cell proliferation.

Study on the relationship between the expression of IGF-1 in umbilical cord blood and abnormal glucose metabolism during pregnancy.

OBJECTIVE: To explore the relationship between the expression of insulin-like growth factor-1 (IGF-1) in neonatal umbilical cord blood and abnormal glucose metabolism during pregnancy. PATIENTS AND METHODS: We have selected 63 cases of delivery randomly, term birth and maternal from January 2015 to January 2016 in our hospital, gestational diabetes mellitus for Group A, abnormal gestational glucose tolerance for Group B and normal for Group C with 21 cases in each group. The venous blood samples were collected from all the pregnant females 2 weeks before delivery, and the levels of HbA1c in serum were detected by Elisa method. During the delivery, the umbilical cord blood was collected and the levels of IGF-1 were measured by double site immune enzyme analysis. The neonatal weight was recorded and the correlation analysis was made in respect of the measurement results. RESULTS: The level of HbA1c in Group A was significantly higher than that in Group C (p < 0.05); IGF-1 level and neonatal weight of Group B were significantly higher than that of Group C (p < 0.05), IGF-1 has a significant correlation with neonatal weight in Group C, and HbA1c and IGF-1 were positively correlated (p < 0.05); IGF-1 was positively correlated with neonatal weight in Group A and Group B (p < 0.05). There was a significant positive correlation between the IGF-1 level of neonatal umbilical cord blood and the neonatal weight (p < 0.05). Also, the level of HbA1c was positively correlated with the level of IGF-1 in neonatal umbilical cord blood at the end of pregnancy (p < 0.05). CONCLUSIONS: The expression level of IGF-1 in the final stage of pregnant females can be detected to predict the expression level of IGF-1 in newborn infants and then the growth status of the fetus can be obtained.

Reactivation of Tert in the medial prefrontal cortex and hippocampus rescues aggression and depression of Tert(-/-) mice.

The role of telomerase reverse transcriptase (TERT) has been extensively investigated in the contexts of aging and cancer. Interestingly, Tert(-/-) mice exhibit additional but unexpected aggressive and depressive behaviors, implying the potential involvement of TERT function in mood control. Our conditional rescue experiments revealed that the depressive and aggressive behaviors of Tert(-/-) mice originate from Tert deficiency in two distinct brain structures. Reactivation of Tert in the hippocampus was sufficient to normalize the depressive but not the aggressive behaviors of Tert(-/-) mice. Conversely, re-expression of Tert in the medial prefrontal cortex (mPFC) reversed the aggressive but not the depressive behavior of Tert(-/-) mice. Mechanistically, decreased serotonergic signaling and increased nitric oxide (NO) transmission in the hippocampus transduced Tert deficiency into depression as evidenced by our observation that the infusion of a pharmacological agonist for serotonin receptor 1a (5-HTR1A) and a selective antagonist for neuronal NO synthase into the hippocampus successfully normalized the depressive behavior of Tert(-/-) mice. In addition, increased serotonergic transmission by the 5-HTR1A agonist in the mPFC was sufficient to rescue the aggressive behavior of Tert(-/-) mice. Thus, our studies revealed a novel function of TERT in the pathology of depression and aggression in a brain structure-specific manner, providing direct evidence for the contribution of TERT to emotional control.

Effect of exercise on the auditory discrimination task in perimenopausal women: a preliminary study.

Background The climacteric phase of menopausal transition (perimenopause) is marked by reproductive hormone fluctuations and reduced cognitive capacity. Exercise enhances neurocognitive performance. However, auditory perceptual sensitivity has not been examined. Purpose This study aimed to determine the effect of aerobic exercise on the response speed (reaction time) and error rate during auditory processing among perimenopausal women. Methods Three pitches (500, 1000, and 2000 Hz) were used during a simple auditory discrimination task, which was performed before and after exercise. We included 14 perimenopausal women and 17 right-handed young women (aged 46-54 years and 18-22 years, respectively). To achieve similar exercise intensity in both groups, we proposed two types of physical activities for each group. Mixed models statistics were used to analyze the reaction time and error rate before and after training in the two groups. Results Perimenopausal women exhibited a significantly longer reaction time than young women during the baseline auditory discrimination task (p < 0.05) but not during the second test. The error rate decreased significantly after exercise among perimenopausal women (p < 0.05) but not among young women. Thus, exercise had a stronger beneficial influence on auditory plasticity or sensitivity for perimenopausal women than for young women. Conclusion The ability of aerobic exercise to modulate auditory neurocognitive performance differs between the two groups. Aerobic exercise improves auditory discrimination performance specifically for perimenopausal women. These results provide preliminary evidence concerning the acoustic features of middle-aged women, underscoring the importance of exercise for preventing decline in auditory cognitive function in perimenopausal women.

Etiology of renal artery stenosis in 2047 patients: a single-center retrospective analysis during a 15-year period in China.

Systematic investigation with large sample size of the distribution of etiologies of renal artery stenosis (RAS) is scant in both Western countries and China. We retrospectively analyzed the etiology of RAS in 2047 consecutive inpatients diagnosed with RAS for hypertension at Fuwai Hospital between 1999 and 2014. The number of patients with atherosclerosis was 1668 (81.5%), 259 (12.7%) with Takayasu's arteritis (TA), 86 (4.2%) with fibromuscular dysplasia (FMD), 34 (1.6%) with other causes. There was an obvious increase with age in the proportion of atherosclerotic RAS (P<0.001). In patients aged ⩽40 years (n=319) the predominant etiology of RAS was TA (60.5%), followed by FMD (24.8%). In patients aged >40 years (n=1728) the major cause of RAS was atherosclerosis (94.7%), followed by TA (3.8%).The proportion of TA and FMD in female patients was significantly higher than that in male patients (P<0.001). In female patients aged ⩽40 years (n=215), the top three etiologies of RAS were TA (68.4%), FMD (27.9%) and atherosclerosis (1.4%). The present analysis showed that atherosclerosis, TA and FMD were sequentially the top three causes of RAS in the National Center of China. Age and gender had a significant effect on the distribution of etiologies of RAS.

A Mixture Dose-Response Model for Identifying High-Dimensional Drug Interaction Effects on Myopathy Using Electronic Medical Record Databases.

Interactions between multiple drugs may yield excessive risk of adverse effects. This increased risk is not uniform for all combinations, although some combinations may have constant adverse effect risks. We developed a statistical model using medical record data to identify drug combinations that induce myopathy risk. Such combinations are revealed using a novel mixture model, comprised of a constant risk model and a dose-response risk model. The dose represents the number of drug combinations. Using an empirical Bayes estimation method, we successfully identified high-dimensional (two to six) drug combinations that are associated with excessive myopathy risk at significantly low local false-discovery rates. From the curve of a dose-response model and high-dimensional drug interaction data, we observed that myopathy risk increases as the drug interaction dimension increases. This is the first time that such a dose-response relationship for high-dimensional drug interactions was observed and extracted from the medical record database.

Inappropriate prescribing of intravenous fluid in adult inpatients-a literature review of current practice and research.

WHAT IS KNOWN AND OBJECTIVE: It is known that mismanagement of intravenous (IV) fluid therapy may cause serious complications. The 2013 NICE guideline on intravenous fluid therapy in hospitalized adults also emphasizes the importance of appropriate prescribing of IV fluid. So far, no systematic review of the incidence and types of inappropriate prescribing of IV fluid has been conducted. Therefore, this study was undertaken to review the research literature on inappropriate prescribing of IV fluid in adult patients and develop corresponding strategies for improving practice. METHODS: A comprehensive literature search was performed. Critical appraisals were conducted on the articles drawn from the search, and an analysis was performed on the results. RESULTS AND DISCUSSION: Incorrect volumes and types of IV fluids prescribed, classified as misprescribing, was the most common type of inappropriate prescribing. Commonly, patients on IV fluid therapy were prescribed a greater volume of fluid and amount of sodium in excess of normal requirements. Doctors did not always check the body weight, serum electrolyte level and serum creatinine before prescribing IV fluid for patients. The other common type of inappropriate prescribing was incomplete/incorrect prescription writing. These common inappropriate prescribing of IV fluid could be caused by insufficient knowledge and training of the prescribers. In addition, the ignorance of the importance of IV fluid prescribing also contributed to this behaviour. WHAT IS NEW AND CONCLUSION: There is an urgent need to make doctors aware of these problems and enhance appropriate training on IV fluid prescribing, especially on the appropriate volume and amount of electrolytes. Pharmacists could exert a role in reviewing the fluid prescription chart for improving clinical practice.