Cognitive impairment （CI） is a clinical syndrome characterized by progressive decline in advanced cognitive functions such as memory， thinking， and judgment. Its etiology and pathogenesis are complex， and there is currently a lack of specific drug interventions. Metformin， as a first-line hypoglycemic drug for type 2 diabetes， not only lowers blood glucose levels but also improves CI. This article reviews and summarizes the pharmacological effects and mechanisms of metformin in improving Alzheimer’s disease， diabetes cognitive impairment， cognitive impairment after chemotherapy， in order to provide novel insights and approaches for the treatment of CI-related diseases. Studies have shown that the mechanism by which MET intervenes in CI mainly includes regulating β-amyloid protein and tau protein metabolism， reducing insulin resistance， inhibiting neuroinflammation， improving synaptic plasticity， improving mitochondrial dysfunction， regulating gut microbiota and lipid metabolism， etc. Future research needs to be conducted through interdisciplinary collaboration， fully integrating multiple omics data， and combining advanced technologies to further reveal their mechanisms of effect.

Objective:To evaluate CT and or MRI imaging in the diagnosis of lateral lymph node metastasis in patients of middle and low rectal cancer.Methods:In this study, 112 lateral lymph nodes were harvested in 79 patients with middle and low rectal cancer. The relationship between the preoperative imaging features of the lateral lymph nodes and the postoperative pathology was evaluated.Result:Thirty-eight cases (48%) were pathologically confirmed to have lateral lymph node metastasis. The diameter of metastasis-positive lateral lymph nodes was significantly larger than that of metastasis-negative lateral lymph nodes ( P<0.01). Multivariate analysis of clinical features and imaging features found that, tumors poorly differentiated, mucinous adenocarcinoma, signet ring cell carcinoma ( P=0.006), and the largest short diameter of the lateral lymph node ≥7 mm ( P=0.024), uneven density or signal ( P=0.022) were independent risk factors for lateral lymph node metastasis. Conclusion:Poor tumor differentiation, lateral lymph node maximum short diameter ≥7 mm, density or signal unevenness are independent risk factors for lateral lymph node metastasis in middle and low rectal carcinoma.

Objective:To investigate the protective effect and mechanism of Acronychia pedunculata water extracts on UV-induced light damage of human keratinocytes.Methods:The experiment was conducted from December 2018 to April 2020 in the Guangxi Medical University Laboratory of Genetics. The photoaged keratinocyte model was used, the cells were co-cultured with different concentrations of Acronychia pedunculata water extracts. The cell proliferation rate was detected by CCK-8 method. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and total antioxidant capacity (T-AOC) of cells were detected by a test kit. The levels of IL-1β, IL-6 and tumor necrosis factor-alpha (TNF-α) were determined by ELISA.Results:The proliferation of HaCaT cells was promoted by 0.5 mg/L-2.0 mg/L of the extracts. Compared with control group, the proliferation rate of HaCaT cells in the experimental group was significantly increased ( P<0.05). Compared with control group, the contents of ROS was decreased ( F=214.67, P<0.05), MDA was decreased ( F=811.88, P<0.05), SOD was increased ( F=28.95, P<0.05), CAT was increased ( F=213.31, P<0.05), GPX was increased ( F=65.10, P<0.05), T-AOC was increased ( F=305.58, P<0.05), IL-1β was decreased ( F=15.46, P<0.05), IL-6 was decreased ( F=59.2, P<0.05), and TNF-α was decreased ( F=33.13, P<0.05). Conclusions:The extracts of 0.5-2.0 mg/L of Acronychia pedunculata have protective effects on the photoaging cell model, which may be related to the increase of SOD, CAT, GPX and other antioxidant enzymes and the level of T-AOC in photoaging HaCaT cells, and the decrease of ROS, MDA content and the expression of inflammatory cytokines.

Objective:To explore the application of digital acoustic analysis in assessing the risk of aspiration among persons with dysphagia using the Praat speech analysis software.Methods:The swallowing of 46 stroke survivors with dysphagia was studied using video fluoroscopy. Each patient was required to pronounce " yi/i/" 3 times before and after taking each mouthful of food, and their voice samples were collected. The subjects were divided into a non-aspiration group of 16 and an aspiration group of 30 based on their penetration-aspiration scale scores. Fundamental frequency, relative average perturbation (RAP), jitter, shimmer, amplitude perturbation quotient and harmonic-to-noise ratio were compared between the two groups before and after taking food.Results:For the non-aspiration group, there was no significant difference in the acoustic data before and after eating. For the aspiration group there were significant differences in fundamental frequency, relative average perturbation and jitter before and after taking food. The average RAP and jitter of the non-aspiration group were significantly better than the aspiration group′s averages before eating. After eating, however, significant differences were observed only in average jitter.Conclusions:Analyzing perturbation and jitter can help to identify persons at risk of aspiration.

Objective:To explore the effect of the pharyngeal pressure feedback training on pharyngeal constriction in persons with swallowing disorders caused by brainstem lesions.Methods:Twenty patients with disordered swallowing caused by a brainstem lesion were randomly divided into a control group and an intervention group, each of 10. Both groups received routine swallowing training including oral sensorimotor training, neuromuscular stimulation and balloon catheter dilation, while the intervention group was additionally provided with two weeks of pharyngeal pressure feedback training. Before and after the treatment, both groups were evaluated in terms of the peak pressure of superior and inferior pharyngeal constriction, endoscopically and also using the functional oral intake scale.Results:There was no significant difference between the two groups in any measure before the intervention. Afterward, both groups had improved significantly by all of the measurements, but the average peak upper pharyngeal pressure, the average intake scale score and the endoscopy results of the intervention group were all significantly better than the control group′s averages.Conclusions:Pharyngeal pressure feedback training can significantly relieve swallowing disorders caused by brainstem lesions.

Objective: To identify the pathophysiological characteristics of cortical stroke survivors′ swallowing. Methods: Sixty cortical stroke survivors with dysphagia and cognitive impairment were enrolled into the observation group, while another 16 with dysphagia but without cognitive impairment formed the unimpaired control group and 16 healthy counterparts were selected for a normal control group. Each subject was recorded videofluoroscopically while swallowing 5ml of a liquid of medium consistency. The occurrence of refusing to eat, mouth opening difficulty, incomplete oral closure, residue in the oral cavity, residue in the pharyngeal cavity, leakage and aspiration were observed. Each subject′s swallowing time and kinematic parameters were analyzed from the fluoroscopic videos. Results: The incidence of refusing to eat (37.5%) and/or incomplete mouth closure (68.75%) were significantly higher in the observation group than in the other two groups. The incidence of difficulty in opening the mouth (37.5%), residue in the oral cavity (81.25%), residue in the pharyngeal cavity (56.25%), leakage (56.25%) and aspiration (50%) of the observation group were significantly higher in the observation group than among the normal controls, but were not significantly different from those incidences among the group without cognitive impairment. The average oral transit time and soft palate elevation time of the observation group were significantly longer than those of the other two groups. The observation group′s average hyoid movement time was significantly longer than that of the normal control group, but not significantly different from that of the group without cognitive impairment. There were no significant differences among the groups in average upper esophageal sphincter opening time, larynx closure time or the kinematic parameters. Conclusions Stroke survivors with dysphagia and cognitive impairment present dysphagia characteristic of oral phase swallowing difficulties.

Objective:To observe the immediate effect of neuromuscular electrical stimulation (NMES) on the initiation of swallowing among stroke survivors with dysphagia.Methods:Forty-two patients with delayed swallowing initiation were asked to eat 3 boluses of a thin liquid before and during NMES stimulation. The process was recorded and analyzed using a digital data acquisition and analysis system, including the initiation of the pharyngeal swallow (IPS), oral transit time (OTT), larynx closure duration (LCD), and pharynx transit time (PTT). They were also evaluated using the Rosenbek penetration-aspiration scale (PAS).Results:During NMES, significant improvement was observed in the average IPS, PAS and OTT results compared to before the intervention. There was, however, no significant difference in the average LCD or PTT. No obvious adverse reactions were observed during the stimulation.Conclusion:NMES has an immediate effect on improving IPS, PAS and OTT, and can be used as a new compensatory early treatment for stroke survivors with dysphagia.

PURPOSE: We investigated the role of tumor-associated macrophages (TAMs) on the epithelial to mesenchymal transition (EMT) of colorectal cancer cells and determined the potential mechanism involved in the metastatic process. MATERIALS AND METHODS: In this study, flow cytometry was used to detect the expression of target proteins. We used transwell assay to evaluate the migration of cancer cells under specific conditions. Using real-time polymerase chain reaction, we examined the expressions of cytokines and EMT-related markers in mRNA level. Animal assay was performed for analysis in vivo and hematoxylin and eosin was used to visualize the effect of TAMs on tumor metastasis. We also used immunohistochemistry and Western blotting to detect the expression of target proteins. RESULTS: Here, we observed enrichment of TAMs in colorectal tumor tissues, resulting in high metastasis in clinical therapy. Moreover, those TAMs could facilitate the EMT progression of colorectal cancer cells, which is induced by the transforming growth factor-β (TGF-β) derived from TAMs, leading to the invasion and migration of cancer cells. CONCLUSION: Our results demonstrated that TAMs contributed the EMT progression through a TGF-β/Smad2,3-4/Snail signaling pathway, and disrupting this pathway with TGF-β receptor inhibitor could suppress metastasis, readjusting our focus to the connection of TAMs and cancer metastasis.
Animals ; Blotting, Western ; Colorectal Neoplasms* ; Cytokines ; Eosine Yellowish-(YS) ; Flow Cytometry ; Hematoxylin ; Immunohistochemistry ; Macrophages* ; Neoplasm Metastasis ; Real-Time Polymerase Chain Reaction ; RNA, Messenger

Objective: To explore the sensitivity and specificity of the Chinese version of the volume and viscosity swallowing test with modified safety and effectiveness indicators (VVST-CV) in assessing deglutition disorders. Methods: The solvent, volume, viscosity, and test index of the volume and viscosity swallowing test were modified before it was used to evaluate 89 patients with swallowing disorders. The positive rates of the safety indexes (coughing, voice changes and blood oxygen saturation decline at least 3%) and the efficiency indexes (poor lip closure, oral residue, pharynx residue and swallowing) were recorded and compared and compared with the positive rates of penetration, aspiration and food residue determined by means of according to the videofluoroscopic swallowing study, then the sensitivity, specificity, positive predictive value and negative predictive value of the modified VVST-CV with regard to the safety and efficiency of swallowing were calculated. Results: The VVST-CV′s sensitivity in detecting dysphagia was 0.97. For impaired safety it was 0.85 and for impaired swallowing efficiency it was 0.95. The sensitivity of the coughing index was 0.65, that of sound change was 0.60 and that of oxygen saturation decrease was 0.42. The positive predictive values for coughing, sound change and oxygen saturation decrease were 0.98, 0.94 and 0.94, respectively. Conclusion The VVST-CV is simple, feasible and sensitive. It can be widely useful in the evaluation of dysphagia in clinical practice.

Objective To study the effects of dichloroacetate (DCA) on cell colony-forming,cell invasion and cell migration of the bladder cancer cells and to study the underlying mechanism.Methods The bldder cancer cells T24 were randomly divided into two groups:the observation group and the control group.Cells in the observation groups were treated with 5 mmol/L,10 mmol/L and 20 mmol/L dichloroacetate,and the control group was treated with the same amount of dimethyl sulfoxide.Colony formation assays were detected with Giemsa staining.Cell wound scratch assay and Transwell assay were applied to evaluate the ability of the T24 cell invasion and migration.Realtime PCR and Western blot were applied to detect the expression of the epithelial-mesenchymal transition (EMT)-related marker,including E-cadherin,N-cadherin,vimentin,Snail and Slug.Results Compared with the control group,the colony formation assays of T24 cells constantly decreased along with the increased doses in the observation group(P ＜ 0.01).The cell wound scratch assay showed that the scratch width of the observation groups were significantly higher along with the increased doses and prolonged time than that in the control group (P ＜ 0.01).The transwell assay showed that the invasion ability of the observation groups were significantly discreased along with the increased doses than that in the the control group (P ＜ 0.01).The expression levels of E-cadherin mRNA and protein in combination the control group were higher than those in the the observation groups (P ＜ 0.05).However,the expression levels of N-cadherin,vimentin,Snail and Slug mRNAs and proteins in combination the control group were lower than those in the the observation groups (P ＜ 0.05).Conclusion Dichloroacetate can inhibit the colony-forming,invasion and migration of bladder cancer T24 cells,and its mechanism may inhibit the expression of epithelial mesenchymal transition in T24 cells by down-regulating the expression of nuclear transcription factor Snail and Slug.