Clinical predictors of prognosis in stroke patients after endovascular therapy.

Endovascular therapy (EVT) is effective in the treatment of large vascular occlusive stroke. However, many factors are associated with the outcomes of acute ischemic stroke (AIS) after EVT. This study aimed to identify the main factors related to the prognosis of AIS patients after EVT. We analyzed the clinical data of AIS patients in the neurology department of our medical center from June 2017 to August 2021 following treatment with EVT. The data included the patients' blood pressure upon admission, blood glucose concentration, National Institutes of Health Stroke Scale (NIHSS) score, 90-day modified Rankin scale (mRs) score follow-up data, and time from LKN to the successful groin puncture (GP). A good outcome was defined as a 90-day mRs score of 0-2, and a poor outcome was defined as a 90-day mRs score of 3-6. A total of 144 patients were included in the study. Admission, smoking, and LKN-to-GP time, NIHSS score of 6-12 was found to be relevant to the prognosis. The results of multivariate analysis showed that prognosis was significantly influenced by baseline NIHSS (odds ratio = 3.02; 95% confidence interval, 2.878-4.252; P = 0.001), LKN-to-GP time (odds ratio = 2.17; 95% confidence interval, 1.341-2.625; P = 0.003), and time stratification (6-12 h) (odds ratio = 4.22; 95% confidence interval, 2.519-5.561; P = 0.001). Our study indicated that smoking, baseline NIHSS score, and LKN-to-GP time were the risk factors for a poor outcome in stroke patients following an EVT. Quitting smoking and shortening LKN time to GP should improve the outcome of AIS after EVT.

Azaphilones from the Fungus Penicillium multicolor LZUC-S2 and Their Antibacterial Activity.

Two new azaphilones, penimultiones A and B, together with seven known analogs were isolated from the culture of Penicillium multicolor LZUC-S2. Their structures were elucidated by detailed spectroscopic data analysis and chemical transformation. Penimultiones A and B belong to a rare class of azaphilones possessing a 1,3-dioxolane moiety. In addition, all compounds were evaluated for their antibacterial activity against five clinically bacterial strains in vitro, and three compounds showed potent antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 12.5 to 50.0 µg/mL.

Two New Eremophilane-Type Sesquiterpenoids from Ligularia sagitta.

Two new eremophilane-type sesquiterpenoids, sagittacins F and G (1 and 2), together with one known isomer of sagittacin F (3) were isolated from the leaves and stems of Ligularia sagitta. Their structures were elucidated by interpretation of spectroscopic data and the absolute configurations of 1 and 3 were determined by X-ray spectroscopy. Compound 1 belongs to a rare class of eremophilane-type sesquiterpenoid featuring an α-oriented hydroxy group at C-1. A nitric oxide (NO) production inhibitory assay was applied to evaluate their anti-inflammatory activities by using LPS-induced RAW 264.7 cells. Compounds 2 and 3 exhibited modest NO production inhibitions with IC50 values of 45.15±2.72 and 49.83±2.34 µM, respectively.

Reversal of Diabesity: Normalization of Insulin Release Curve in Association with Reversal of Non-Alcoholic Fatty Liver Disease.

OBJECTIVE: Type 2 diabetes with obesity is regarded as an incurable, progressive disease with many complications. The hypothesis was tested that glycated haemoglobin (HbA1c) and the insulin release curve can be restored by traceable systematic methods. METHODS: 122 people with diabesity were investigated before and after three and 6 months of traceable systematic management methods. Basal body mass index (BMI), fatty liver, HbA1c, and insulin release curve were measured. RESULTS: After 3 months of traceable systematic management, BMI decreased from 30.76 ± 0.48 to 21.86 ± 0.09 kg/m2 (p < 0.001) and remained stable during the last 3 months (21.82 ± 0.09 kg/m2 at 6 months). Colour Doppler ultrasound showed non-alcoholic fatty liver disease (NAFLD) in all diabesity participants at baseline. At 3 months, only one participant had low-grade fatty liver, and fatty liver was reversed in other participants (p < 0.001). The number and grade of fatty liver at 6 months were the same as at 3 months. Fasting plasma glucose decreased and continued to decrease thereafter (p < 0.001). Two-hour postprandial plasma glucose decreased and continued to decline until 6 months (p < 0.001). HbA1c also decreased and maintained this level at 6 months. At baseline, the peak value of insulin release was 1,141.09 ± 43.02 pmol/L at 2 h after meals, and the early phase of insulin secretion was lost. After 3 months of management, the insulin concentration was 621.62 ± 19.32 pmol/L at 2 h after meals. After 6 months, the value decreased, and the early phase of insulin secretion recovered. CONCLUSIONS: Normalization of the insulin release curve in type 2 diabetes was achieved by traceable systematic methods. This was associated with recovery from NAFLD. Diabesity is reversible by traceable systematic management.

Cullin3 aggravates the inflammatory response of periodontal ligament stem cells via regulation of SHH signaling and Nrf2.

It is found that the activation of Sonic Hedgehog (SHH) signaling pathway is related to the degree of inflammation in patients suffering from periodontitis. Cullin3 (CUL3), an important ubiquitin ligase, can control SHH signaling. In this study, we were dedicated to clarify the roles of SHH and CUL3 in P. gingivalis-LPS (Pg-LPS)-treated periodontal ligament stem cells (PDLSCs). In this study, cell viability was detected using cell counting kit-8 (CCK-8). The inflammatory cytokines of PDLSCs were estimated by enzyme-linked immunosorbent assay (ELISA). With the application of western blots, the protein levels of SHH, Gli1 and NF-E2-related factor 2 (Nrf2) were determined. Alkaline phosphatase staining and Alizarin red staining were performed to evaluate the differentiation and mineralization capabilities of PDLSCs. The apoptotic cells were screened using TUNEL staining. The results showed that Pg-LPS inhibited cell viability and triggered inflammation of PDLSCs. Overexpression of CUL3 weakened the differentiation and mineralization capabilities of PDLSCs. Moreover, CUL3 overexpression aggravated inflammation and cell apoptosis induced by Pg-LPS. It is worth noting that although the protein levels of SHH, Gli1 and Nrf2 were elevated in PDLSCs treated with Pg-LPS, overexpression of CUL3 decreased the expressions of Gli1 and Nrf2. Overall, SHH/Gli1 and Nrf2 were involved in the inflammation and cell apoptosis of PDLSCs, which was dominated by CUL3.

High glucose inhibits osteogenic differentiation of bone marrow mesenchymal stem cells via regulating miR-493-5p/ZEB2 signalling.

Diabetic osteoporosis (DOP) is attributed to the aberrant physiological function of bone marrow mesenchymal stem cells (BMSCs) under high glucose (HG) environment. MicroRNAs (miRNAs) are involved in the pathological processes of DOP. We aimed to explore the underlying mechanism of miRNA in DOP. BMSCs were cultured in osteogenic medium with HG to induce osteogenic differentiation, and the interaction between miR-493-5p and ZEB2 was assessed by luciferase assay. Herein, we found miR-493-5p is gradually reduced during osteogenic differentiation in BMSCs. HG treatment inhibits osteogenic differentiation and induces an up-regulation of miR-493-5p leading to reduced level of its downstream target ZEB2. Inhibition of miR-493-5p attenuates HG-induced osteogenic differentiation defects by upregulation of ZEB2. Mechanistically, miR-493-5p/ZEB2 signalling mediates HG-inhibited osteogenic differentiation by inactivation of Wnt/ß-catenin signalling. More importantly, knockdown of miR-493-5p therapeutically alleviated the DOP condition in mice. HG prevents BMSCs osteogenic differentiation via up-regulation of miR-493-5p, which results in reduced level of ZEB2 by directly targeting its 3'-untranslated region of mRNA. Thus, miR-493-5p/ZEB2 is a potential therapeutic target and provides novel strategy for the treatment and management of DOP.

[Study on the mechanism of endothelial progenitor cells in periodontal revascularization during orthodontic tooth movement].

PURPOSE: To investigate the mechanism of endothelial progenitor cells(EPCs) bone remodeling during orthodontic tooth movement. METHODS: Experimental tooth movement model was established. EPCs were isolated, cultured, and labeled with 10 µmol/L Brdu and injected into rats through tail vein to observe the distribution in periodontal tissue. VEGF was added to EPCs culture medium, cell proliferation ability was measured by MTT assay, cell adhesion was observed under microscope. Transwell assay was used to observe cell migration ability, and VEGF immunohistochemical staining sections of model rats at different time points were made. The expression of VEGF in periodontal tissues at different time points was defected. All data were imputed into SPSS 20.0 software package for statistical analysis. RESULTS: A rat model of tooth movement was successfully established. EPCs were isolated from cardiac blood. Some spindle-shaped EPCs were observed under microscope and injected into model rats using Brdu-labeled EPCs. With the increase of time, the intensity of fluorescence gradually increased. In the 3d specimen, the fluorescence intensity reached the strongest. The gap between the first and second molars in the experimental group was lower than that in the control group at each time point, with significant difference(P<0.05). The results of VEGF immunohistochemical staining showed that both the tension side and the pressure side of the experimental group were significantly higher than the control group(P<0.05). The expression of VEGF in both osteoblasts and osteoclasts reached a maximum at 14 days. EPCs proliferation and adhesion experiments demonstrated that VEGF promoted proliferation of EPCs and enhanced their adhesion. Transwell experiments showed that VEGF promoted chemotaxis of EPCs.VEGF regulated the biological effects of EPCs. CONCLUSIONS: EPCs can be accumulated in periodontal tissues and participate in periodontal bone remodeling. After EPCs chemotizing to periodontal tissues, they participate in the remodeling of periodontal tissues through mutual regulation of VEGF and other factors, and promote periodontal tissue repair and bone remodeling.

Incidence and Predictors of the In-stent Restenosis after Vertebral Artery Ostium Stenting.

BACKGROUND: The incidence and predictors for in-stent restenosis (ISR) was not fully explored. We aim to investigate the incidence and predictors of ISR after stenting at the origin of vertebral artery. MATERIALS AND METHODS: Two hundred and six patients with 229 stents implantation between July 1, 2005 and July 31, 2015 were included in the study. All patients underwent conventional clinical and angiographic (digital subtraction angiography) follow-up at around 6 months post procedure. ISR was defined as greater than 50% stenosis within or immediately (within 5 mm) adjacent to the stent. Multivariate Cox regression analyses were utilized to investigate the predictors for ISR. RESULTS: The ISR was found in 30 patients (30/206, 14.6%) with 31 lesions (31/229, 13.5%) with the mean follow-up duration of 11.1-month (range: 3 - 92 months). Stent diameter (hazard ratio 0.504, 95% confidence interval 0.294 - 0.864) was an independent predictor for ISR. CONCLUSION: ISR rate after Vertebral artery ostium stent placement is acceptable, which was conversely associated with the stent diameter.

Overexpression of GRIM-19 accelerates radiation-induced osteosarcoma cells apoptosis by p53 stabilization.

AIMS: Osteosarcoma is one of the most aggressive types of primary bone cancer that responds poorly to radiotherapy frequently. The gene associated with retinoid-interferon mortality (GRIM-19) is a tumor suppressor that mediates cell apoptosis in multiple cancer types. However, the role of GRIM-19 in osteosarcoma and the underlying mechanism remain unclear. This study was designed to investigate the role and the underlying mechanism of GRIM-19 in osteosarcoma progression. MATERIALS AND METHODS: Osteosarcoma tissues and cell lines were utilized to analyze the expressions of GRIM-19 in osteosarcoma by qRT-PCR and Western blot. Methods containing flow cytometry, irradiation exposure, cells inoculation, plasmid transfection, and protein immunoprecipitation were used to investigate the underlying mechanisms of GRIM-19 in osteosarcoma progression. KEY FINDINGS: GRIM-19 is downregulated in osteosarcoma tissues and cell lines. Exposure to radiation induces osteosarcoma cell apoptosis by upregulation of p53 both in U2OS (p53-wt) and exogenous p53-introduced MG-63 (p53-null) osteosarcoma cells. Overexpression of GRIM-19 accelerates radiation-induced osteosarcoma cells apoptosis by p53 stabilization ex vivo and in vivo. Mechanistically, forced expression of GRIM-19 diminishes the activity of E3 ubiquitin-protein ligase mouse double minute 2 homolog (MDM2), a specific p53 protease, results in the accumulation of p53 and activation of p53-mediated apoptosis. SIGNIFICANCE: GRIM-19 was proved to modulate radiation-induced osteosarcoma cells apoptosis in a p53 dependent manner by mediating MDM2 activity, which sheds light on the development of GRIM-19-based molecular target therapy on osteosarcoma.

[Use of visual analogue scale and pain-related factors to evaluate the impact of different orthodontic forces on human dental pulp in patients who underwent fixed dental treatment].

PURPOSE: To investigate the role of visual analogue scale (VAS) and pain-related factors, like tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL- 8), interleukin-6 (IL-6) and interleukin-1 beta (IL-1ß) in evaluation of the impact of different orthodontic forces on human dental pulp in patients who underwent fixed dental treatment. METHODS: From January 2014 to April 2015, 156 patients with maxillary bilateral premolar treated with tooth fixed were randomly divided into 4 groups, 42 patients in control group, 40 patients in 100 g-force group, 40 patients in 150 g-force group, and 39 in 200 g-force group. VAS was used to evaluate before and after removed. TNF-α, IL-8, IL-6 and IL-1ß in pulp tissues were measured by ELISA and pathological changes of pulp were observed on HE staining sections. The data were analyzed with SPSS 13.0 software package. RESULTS: Except for the control group, all patients in other groups had pain after 1-7 days, and the pain peaked at 3~5 days. The pain reaction disappeared on 10th day, and VAS increased in a force dependent manner (P<0.05). TNF-α, IL-8, IL-6 and IL-1ß were higher in different force groups than in control group after 1~2 weeks of treatment, and in a force dependent manner (P<0.05). After 3~4 weeks, the expression of IL-8, IL-6 and IL-1ß returned to normal (P>0.05). Except for the control group, blood vessels on the pulp tissue increased and thickened at 1 week after application of force. Occasionally, odontoblast nucleus was enlarged and the nuclear chromatin and cytoplasmic basophilic staining were enhanced, some odontoblasts displayed vacuolar degeneration, connective tissue in the central pulp presented edema; with the increase of applied force, the changes above mentioned became more obvious, in a force dependent way. CONCLUSIONS: The larger the sustained force, the pain, pain-related factors and pathological changes became more obvious, but restored to normal within 3 weeks.

WITHDRAWN: SIRT6 protects against lipopolysaccharide (LPS)-induced apoptosis in human dental pulp cells by deacetylation of Ku70.

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Pain-Induced Pulsograph Changes in Patients with Primary Dysmenorrhea: A Pilot Study.

Objectives. To investigate changes in pulsograph caused by pain in primary dysmenorrhea (PD) patients. Methods. Pulsograph and pain level of PD patients were detected using electropulsograph and Visual-Analogue Scale (VAS), respectively, at four time points, 7-10 days before menstruation (T0), maximal pain during menstruation (T1), immediately after acupuncture analgesia (T2), and 30 mins after acupuncture analgesia (T3). Parameters (t, h, w) and normalized time parameters (t') of pulsograph were analyzed. Results. VAS pain scores decreased from 6.40 ± 1.13 at T1 to 0.70 ± 0.75 at T2 to 0.11 ± 0.32 at T3 (P < 0.001 and 0.001). At T1, compared with those at T0, w1, h3, and h4 significantly increased (P < 0.01), and t2, t2', t3', and h(d) significantly decreased (P < 0.01, 0.001, 0.05, and 0.001). At T2, compared with those at T1, t1, w1, w2, h2, h3, t1', and t4' significantly decreased (P < 0.05, 0.01, 0.01, 0.001, 0.01, 0.001, and 0.05), and h(d) significantly increased (P < 0.001). There was no difference between T2 and T3. Conclusions. There are almost opposite changing trends in pulsographic parameters when pain occurs and when it is relieved in PD patients.