الملخص
Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.
الموضوعات
Humans , B7-H1 Antigen/metabolism , Mesenchymal Stem Cells/immunology , T-Lymphocytes/metabolism , Immunomodulationالملخص
Purpose@#Pencil-beam scanning (PBS) is a modern delivery technique used in proton beam therapy (PBT) to reduce normal tissue reactions. No dosimetric correlation between dermatitis and PBS has been reported for breast cancer. The current study aimed to investigate the factors associated with grade 2 or higher dermatitis in patients with breast cancer undergoing PBT using PBS. @*Methods@#The medical data of 42 patients with breast cancer who underwent adjuvant radiotherapy between December 2019 and September 2023 were reviewed. All patients received hypofractionated radiotherapy (HFRT), either 26 Gy (relative biological effectiveness [RBE])/five fractions or 40.05 or 43.5 Gy (RBE)/15 fractions, for the whole breast/chest wall with or without nodal irradiation. The duration of acute radiation dermatitis was defined as within 90 days from the start of radiotherapy. The Kaplan–Meier method and Cox proportional hazards model were used for univariate and multivariate analyses of the actuarial rates of grade 2–3 dermatitis. @*Results@#Twenty-two (52.4%) and 20 (47.6%) patients were diagnosed with grade 1 and 2 dermatitis, respectively. Multivariate analysis revealed a clinical target volume (CTV) ≥ of 320 cc (p = 0.035) and a skin dose of D 10cc ≥ 38.3 Gy (RBE) (p = 0.009) as independent factors of grade 2 dermatitis. The 10-week cumulative grade 2 dermatitis rates were 88.2%, 39.4%, and 8.3% (p < 0.001) for patients with both high, either high, and neither high CTV and D 10cc , respectively. @*Conclusion@#To the best of our knowledge, this is the first study on dosimetric correlations for dermatitis in patients with breast cancer who underwent hypofractionated PBT using PBS. In the era of HFRT, skin dose modulation using PBS may reduce the incidence of dermatitis.
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OBJECTIVE To evaluate the clinical efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery. METHODS Retrieved from PubMed, Embase, the Cochrane Library, CNKI, Wanfang data and VIP, randomized controlled trials (RCTs) and cohort studies about aspirin (trial group) versus other anticoagulants (control group) were collected during the inception and June 1st, 2023. After literature screening, data extraction and quality evaluation, the meta-analysis was conducted by using RevMan 5.4 software. RESULTS A total of 22 studies were included, involving 9 RCTs and 13 cohort studies. RCT results showed that the incidences of deep vein thrombosis (DVT) [RR=1.81, 95%CI(1.36, 2.40), P<0.000 1] and postoperative pulmonary embolism (PE) [RR=1.55, 95%CI(1.01, 2.40), P=0.05] in trial group were significantly higher than control group. There was no statistically significant difference in the incidences of postoperative massive bleeding, postoperative surgical site infection, all-cause death, or any bleeding after surgery between 2 groups. In the cohort study, the incidence of any bleeding in trial group was significantly lower than control group [RR=0.71,95%CI (0.64, 0.79), P<0.000 1], while the differences in other indicators were not statistically significant (P>0.05). The results of subgroup analysis based on different anticoagulants showed that in RCT, the incidences of DVT and PE after surgery in patients using low-molecular-weight heparin (LMWH) were significantly lower than using aspirin (P<0.05); in the cohort study, the incidences of DVT and PE after surgery were significantly lower in patients using direct oral anticoagulants (DOAC) than using aspirin (P<0.05). There was no statistically significant difference in the incidence of major bleeding between patients using aspirin and using DOAC and LWMH (P>0.05) in both RCT and cohort study. CONCLUSIONS Aspirin is equally safe as other anticoagulants for the prevention of thromboembolism after orthopedic surgery, but its efficacy may not be as good as other anticoagulants. After orthopedic surgery, other anticoagulants should be preferred to prevent venous thromboembolism, and aspirin should be carefully considered.
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Radiation enteritis (RE) is a common syndrome in the radiotherapy of abdominal and pelvic malignant tumors, heavy influencing living quality, but no specific clinical regimens are available. Long oil (LO) is composed of the fat components from cuttlebone, safflower, walnut oil and rapeseed oil and has been clinically used for wound healing. In this study, oral LO was applied for the prevention and treatment of RE and the mechanisms were explored. Animal experiments were approved by the Ethics Committee of the Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences, and the experiments were conducted in accordance with relevant guidelines and regulations. An RE mouse model was established after single whole abdominal γ-ray radiation of 13 Gy. LO (8 mL·kg-1) was intragastrically administered to the mice 1 h pre-radiation. Compared to the models, the mice of the LO group had more regenerated intestinal crypts and longer villus on day 3.5, and remarkable increase in the abundance of gut microbiota on day 7, especially the amounts of probiotics including Eubacterium and Lactobacillus. Moreover, the mice of the LO group showed longer total movement distance, shorter immobility time, and higher speed than the model mice on day 7. On day 14, the mice of the LO group showed the high descending of proinflammatory factors including tumor necrosis factor-α and interleukin-6, close to the normal levels. Therefore, oral LO can alleviate the inflamed syndromes of RE and improve the repair of damaged intestinal tissues. Moreover, the mice of the LO group had highly low permeability of intestinal mucosa according to the fluorescence labeling experiment, which was close to the normal level. Oral LO can protect intestine mucosa and prevent RE by modification of the intestinal microenvironment, alleviation of the inflammatory response, and promotion of tissue repair.
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The aim of this study was to prepare tandem multimeric proteins of BmSPI38, a silkworm protease inhibitor, with better structural homogeneity, higher activity and stronger antifungal ability by protein engineering. The tandem multimeric proteins of BmSPI38 were prepared by prokaryotic expression technology. The effects of tandem multimerization on the structural homogeneity, inhibitory activity and antifungal ability of BmSPI38 were explored by in-gel activity staining of protease inhibitor, protease inhibition assays and fungal growth inhibition experiments. Activity staining showed that the tandem expression based on the peptide flexible linker greatly improved the structural homogeneity of BmSPI38 protein. Protease inhibition experiments showed that the tandem trimerization and tetramerization based on the linker improved the inhibitory ability of BmSPI38 to microbial proteases. Conidial germination assays showed that His6-SPI38L-tetramer had stronger inhibition on conidial germination of Beauveria bassiana than that of His6-SPI38-monomer. Fungal growth inhibition assay showed that the inhibitory ability of BmSPI38 against Saccharomyces cerevisiae and Candida albicans could be enhanced by tandem multimerization. The present study successfully achieved the heterologous active expression of the silkworm protease inhibitor BmSPI38 in Escherichia coli, and confirmed that the structural homogeneity and antifungal ability of BmSPI38 could be enhanced by tandem multimerization. This study provides important theoretical basis and new strategies for cultivating antifungal transgenic silkworm. Moreover, it may promote the exogenous production of BmSPI38 and its application in the medical field.
الموضوعات
Animals , Antifungal Agents/pharmacology , Escherichia coli/metabolism , Proteins/metabolism , Protease Inhibitors/chemistry , Bombyx/chemistry , Saccharomyces cerevisiae/metabolism , Peptide Hydrolasesالملخص
The purpose of this study was to explore the effect and mechanism of dihydromyricetin (DHM) on Parkinson's disease (PD)-like lesions in type 2 diabetes mellitus (T2DM) rats. The T2DM model was established by feeding Sprague Dawley (SD) rats with high-fat diet and intraperitoneal injection of streptozocin (STZ). The rats were intragastrically administered with DHM (125 or 250 mg/kg per day) for 24 weeks. The motor ability of the rats was measured by balance beam experiment, the changes of dopaminergic (DA) neurons and the expression of autophagy initiation related protein ULK1 in the midbrains of the rats were detected by immunohistochemistry, and the protein expression levels of α-synuclein (α-syn), tyrosine hydroxylase (TH), as well as AMPK activation level, in the midbrains of the rats were detected by Western blot. The results showed that, compared with normal control, the rats with long-term T2DM exhibited motor dysfunction, increased α-syn aggregation, down-regulated TH protein expression, decreased number of DA neurons, declined activation level of AMPK, and significantly down-regulated ULK1 expression in the midbrain. DHM (250 mg/kg per day) treatment for 24 weeks significantly improved the above PD-like lesions, increased AMPK activity, and up-regulated ULK1 protein expression in T2DM rats. These results suggest that DHM may improve PD-like lesions in T2DM rats by activating AMPK/ULK1 pathway.
الموضوعات
Rats , Animals , Parkinson Disease , Rats, Sprague-Dawley , AMP-Activated Protein Kinases , Diabetes Mellitus, Type 2 , Autophagy-Related Protein-1 Homologالملخص
OBJECTIVE@#To observe the effect of electroacupuncture (EA) on liver protein kinase B (Akt)/forkhead box transcription factor 1 (FoxO1) signaling pathway in Zucker diabetic fatty (ZDF) rats, and to explore the possible mechanism of EA on improving liver insulin resistance of type 2 diabetes mellitus.@*METHODS@#Twelve male 2-month-old ZDF rats were fed with high-fat diet for 4 weeks to establish diabetes model. After modeling, the rats were randomly divided into a model group and an EA group, with 6 rats in each group. In addition, six male Zucker lean (ZL) rats were used as the blank group. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20). The ipsilateral "Zusanli" (ST 36) and "Weiwanxiashu" (EX-B 3) were connected to EA device, continuous wave, frequency of 15 Hz, 20 min each time, once a day, six times a week, for a total of 4 weeks. The fasting blood glucose (FBG) in each group was compared before modeling, before intervention and after intervention; the serum levels of insulin (INS) and C-peptide were measured by radioimmunoassay method, and the insulin resistance index (HOMA-IR) was calculated; HE staining method was used to observe the liver tissue morphology; Western blot method was used to detect the protein expression of Akt, FoxO1 and phosphoenolpyruvate carboxykinase (PEPCK) in the liver.@*RESULTS@#Before intervention, compared with the blank group, FBG was increased in the model group and the EA group (P<0.01); after intervention, compared with the model group, FBG in the EA group was decreased (P<0.01). Compared with the blank group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were increased (P<0.01), while the protein expression of hepatic Akt was decreased (P<0.01) in the model group. Compared with the model group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were decreased (P<0.01), while the protein expression of hepatic Akt was increased (P<0.01) in the EA group. In the model group, the hepatocytes were structurally disordered and randomly arranged, with a large number of lipid vacuoles in the cytoplasm. In the EA group, the morphology of hepatocytes tended to be normal and lipid vacuoles were decreased.@*CONCLUSION@#EA could reduce FBG and HOMA-IR in ZDF rats, improve liver insulin resistance, which may be related to regulating Akt/FoxO1 signaling pathway.
الموضوعات
Male , Animals , Rats , Rats, Zucker , Proto-Oncogene Proteins c-akt/genetics , Diabetes Mellitus, Type 2/therapy , Insulin Resistance , C-Peptide , Electroacupuncture , Liver , Signal Transduction , Insulin , Lipidsالملخص
【Objective】 To explore the mechanism of macrophage-inducible C-type lectin (Mincle) and microinflammatory state in uremia. 【Methods】 SD rats were randomly divided into uremia group and sham operation group. The morphology and permeability of intestinal tissue, the morphology of intestinal tissue and macrophages were observed by transmission electron microscope, the expression of Mincle was detected in intestinal tissue sections, and the expressions of Toll-like receptor 4 (TLR-4) and NF-kappa B (NF-κB) protein on the surface of macrophages were detected by Western blotting. After the plasma was separated, the levels of endotoxin, C-reactive protein (CRP), interleulin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by Limulus lysate dynamic turbidimetric assay, and enzyme-linked immunosorbent assay (ELISA). The data were analyzed with IBM SPSS19.0 software. 【Results】 The expression of Mincle in the jejunum, ileum, and colon in uremia group was higher than that in sham-operation group (P<0.05). The expressions of TLR4 and NF-κB protein significantly differed in the ileum, jejunum and colon in uremia group (P<0.001). The levels of endotoxin, CRP, IL-6, and TNF-α were significantly increased in uremia group compared with sham-operation group (P<0.05). 【Conclusion】 In uremia, Mincle on the surface of intestinal macrophages increases and further through TLR4/NF-κB pathway mediates the transformation of intestinal macrophages to M1 type, releasing inflammatory products and causing systemic microinflammation.
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Objective:To explore the related risk factors for systemic embolism (SE) in patients aged≥75 years with non-valvular atrial fibrillation (NVAF).Methods:A case-control study. NVAF patients aged≥75 years who were hospitalized at the First Affiliated Hospital of Xinjiang Medical University from October 2018 to October 2020 were divided into no SE ( n=1 127) and SE ( n=433) groups according to the occurrence of SE after NVAF. Multivariate logistic regression was used to analyze SE-related factors in patients with NVAF without anticoagulation treatment. Results:In the multivariate model, the following factors were associated with an increased risk of SE in patients with NVAF: history of AF≥5 years [odds ratio ( OR)=2.75, 95% confidence interval ( CI) 1.98-3.82, P<0.01], lipoprotein(a)>300 g/L ( OR=2.07, 95% CI 1.50-2.84, P<0.01), apolipoprotein (Apo)B>1.2 g/L ( OR=1.91, 95% CI 1.25-2.93, P=0.003), left ventricular ejection fraction (LVEF) of 30%-49% ( OR=2.45, 95% CI 1.63-3.69, P<0.01), left atrial diameter>40 mm ( OR=1.54, 95% CI 1.16-2.07, P=0.003), and CHA 2DS 2-VASc score≥3 ( OR=15.14, 95% CI 2.05-112.13, P=0.01). ApoAI>1.6 g/L was negatively correlated with the occurrence of SE ( OR=0.28, 95% CI 0.15-0.51, P<0.01). Conclusions:History of AF≥5 years, lipoprotein(a)>300 g/L, elevated ApoB, left atrial diameter>40 mm, LVEF of 30%-49%, and CHA 2DS 2-VASC score≥3 are independent risk factors for SE whereas ApoAI>1.6 g/L is a protective factor against SE in patients with NVAF.
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Purpose: To evaluate changes in the levator palpebrae superioris (LPS) muscle on 3.0 T magnetic resonance imaging (MRI) after triamcinolone acetonide injection for treating upper lid retraction (ULR) with Graves’ ophthalmopathy (GO) and to explore the value of LPS muscle quantitative measurement for clinical treatment. Methods: Patients with GO showing ULR were studied retrospectively and they underwent 3.0 T MRI scans before and after subconjunctival injection o f triamcinolone acetonide. The largest thickness (T) and highest signal intensity (SI) of LPS muscle on the affected eyes were measured in the sequences of coronal T2?weighted, fat?suppressed fast spin echo imaging (T2WI?fs) and T1?weighted, fat?suppressed, contrast?enhanced fast spin echo imaging (T1WI?fs + C), respectively. The SI ratio (SIR) (LPS muscle SI/ ipsilateral temporalis SI) was calculated individually. Depending on the therapeutic effect, patients were divided into effective group and non?effective group. Independent t?test was used to compare SIR and T of LPS muscle in different treatment groups before treatment, and paired sample t?test was used to compare SIR and T of LPS muscle before and after treatment. Then cut?off level for predicting therapeutic effect and the receiver operating characteristic curve (ROC) curve were analyzed. Results: Sixty?two patients (77 eyes) were enrolled. After treatment, the T of LPS muscle showed significant decrease in all sequences in both effective and non?effective treatment groups. However, changes in SIR of LPS muscle in the two groups were different; SIR of LPS muscle on T2WI?fs and T1WI?fs + C decreased after treatment in the effective group (PT2 < 0.001, PT1 + C < 0.001) and SIR of LPS muscle showed no statistically difference in all sequences (all P > 0.05) in the non?effective group. There was a correlation between SIR of LPS muscle before treatment and after treatment with triamcinolone acetonide injection, which was that SIR of LPS muscle in the effective treatment group was lower than that in the non?effective treatment group on T1WI?fs + C (P < 0.001). SIR of LPS muscle on T1WI?fs + C showed 87.5% sensitivity and 66.7% specificity to predict therapeutic effect (area under the ROC curve [AUC] = 0.840). Conclusion: In GO patients with ULR, 3.0 T MRI can be used to evaluate the response of triamcinolone acetonide injection. SIR of LPS may be a predictor of its efficacy
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Objective:To investigate the association between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation, and the independent risk factors affecting left atrial appendage function.Methods:Patients with non-valvular atrial fibrillation, who visited the Atrial Fibrillation Center of the First Affiliated Hospital of Xinjiang Medical University from June 1, 2019 to June 1, 2021, were selected. According to left atrial appendage flow velocity (LAAFV), they were divided into normal left atrial appendage function group (297 patients with LAAFV ≥ 40 cm/s) and abnormal left atrial appendage function group (85 patients with LAAFV<40 cm/s). Baseline data and transesophageal echocardiography images were collected from all the patients. The occurrence of thrombotic events was recorded. Univariate and multivariate unconditional logistic regression analyses were conducted to investigate the correlation between abnormal left atrial appendage function and the occurrence of thrombotic events.Results:There were significant differences in gender, type of atrial fibrillation, CHA 2DS 2-VASc score, anticoagulant therapy, total cholesterol, low-density lipoprotein cholesterol, international normalized ratio (INR), left atrial diameter, proportion of patients with right atrial enlargement, left ventricular ejection fraction, inner diameter, sum of inner diameter, depth, and sum of depth of all angles of the left atrial appendage, and incidence of thrombotic events between the two groups (all P<0.05). After adjusting for confounders, multivariate unconditional logistic regression analyses showed that abnormal left atrial appendage function was closely associated with thrombotic events (β=1.168 P=0.002), and left atrial diameter ( OR=1.084, 95% CI 1.019-1.153, P=0.011) and persistent atrial fibrillation ( OR=2.323, 95% CI 1.226-4.403, P=0.010) were independent risk factors affecting left atrial appendage function. Conclusions:Abnormal left atrial appendage function is closely associated with thrombosis. The left atrial diameter and persistent atrial fibrillation were independent risk factors affecting left atrial appendage function.
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Objective:To evaluate the effects and adverse reactions of external skin care products containing oltides and bio-polysaccharides on epidermaligopep barrier function of sensitive skin.Methods:From December 2019 to July 2020, there were 30 sensitive skin volunteers diagnosed and treated in the dermatology clinic of Beijing Tongren Hospital, including 3 males and 27 females, aged 18-57 years, with an average of 34 years, and the course of disease was 1-10 years, with an average of 5.75 years. They were treated once with products containing oligopeptides and biopolysaccharides on the day of enrollment. Before treatment, 1 week and 4 weeks after treatment, we observed and evaluated through VISIA analysis; skin physiological index measurement, subjective and objective improvement assessment, and product safety were evaluated through questionnaire surveys.Results:The VISIA data showed that the red zone was significantly lower than the baseline, and the data at the 4th week and before treatment were significantly improved ( P<0.05). On skin physiology, the test showed that after treatment, the difference between two follow-up visits and the water content before was statistically significant ( P<0.05). TEWL value after 4 weeks of treatment was significantly improved as compared with the baseline ( P<0.05). During the entire study process, no adverse reactions related to the product occurred. Conclusions:This skin care product containing oligopeptides and biopolysaccharides can increase the water content of the sensitive skin, reduce the water loss through the skin, and improve the skin barrier function. Meanwhile, no server adverse reaction is detected through the whole experiment.
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OBJECTIVE To compare the anticoagulant effectiveness and safety of new oral anticoagulants (NOACs)and warfarin after heart valve replacement ,and to provide evidence-based reference for clinical drug use. METHODS Retrieved from PubMed,Cochrane Library ,Embase,Web of Science ,CNKI,Wanfang database and VIP ,clinical studies about the use of NOACs versus warfarin after heart valve replacement were collected during the inception to July 2021. After literature screening and data extrac tion,the quality of included randomized controlled trials (RCTs)were evaluat ed by bias risk assessment tool recommended by Cochrane system evaluator manual 5.2.0. After the quality of the included cohort studies was evaluated by Newcastle-Ottawa scale (NOS),RevMan 5.3 software was used for meta-analysis and sensitivity analysis. RESULTS A E-mail:carolmeng_0813@163.com total of 9 studies involving 4 962 patients were included ,of which 7 were RCTs and 2 were cohort studie s. Results of meta-analysis showed that after biological valve replacement/repair ,the incidence of stroke and systemic embolism (SSE)[OR=0.71,95%CI(0.52,0.97),P=0.03],major bleeding [OR =0.40,95%CI (0.30,0.54),P<0.000 01] and intracranial hemorrhage [OR =0.20,95%CI(0.04,0.95),P=0.04] in trial group were significantly lower than warfarin group ;there was no significant difference in all-cause mortality between 2 groups [OR =1.25,95%CI(0.88, 1.79),P=0.22]. After mechanical valve replacement/repair ,there were no significant difference in the incidence of SSE [OR =1.52, 95%CI(0.04,60.29),P=0.82] or all-cause mortality [OR =0.26,95%CI(0.04,1.84),P=0.18] between 2 groups. The results of subgroup analysis according to the follow-up time showed that after biological valve replacement/repair ,the incidence of SSE in trial group was significantly lower than that in control group when the follow-up time was ≤3 months [OR =0.20,95%CI(0.06, 0.74),P=0.03];but there was no significant difference in the incidence of major bleeding between 2 groups [OR =0.67,95%CI (0.19,2.38),P=0.53];when the follow-up time was longer than 3 months,there was no statistical significance in the incidence of SSE between 2 groups [OR =0.74,95%CI(0.54,1.02),P=0.07],while the incidence of major bleeding in trial group was significantly lower than control group [OR =0.39,95%CI(0.29,0.52),P<0.001]. Subgroup analysis by study type showed that after biological valve replacement/repair ,the incidence of SSE in the RCT in trial group was significantly lower than that in control group [OR =0.51,95%CI(0.29,0.92),P=0.03],but there was no significant difference in the incidence of major bleeding between 2 groups[OR=0.58,95%CI(0.33,1.03),P=0.06]. In cohort study ,there was no significant difference in the incidence of SSE between 2 groups [OR =1.03,95%CI(0.40,2.66),P=0.95],while the incidence of major bleeding in trial group was significantly lower than control group [OR =0.20,95%CI(0.06,0.74),P<0.001]. Sensitivity analysis results showed that the results of the above-mentioned meta-analysis were relatively robust. CONCLUSIONS For the patients underwent biological valve replacement/repair,the effectiveness and safety of NOACs are better than or similar to those of warfarin ;for the patients underwent mechanical valve replacement/repair ,there is no significant difference in the effectiveness and safety between NOACs and warfarin.
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Aim To investigate the effects of combined administration of loganin and berberine on bone structure and metabolism in diabetic mice and its potential mechanism.Methods The diabetic ICR mouse model was induced by high fat diet(HFD).After 10 weeks of combined intervention, the effects of loganin and berberine on body weight, body fat rate, blood glucose, blood lipid and serum oxidative stress levels were observed.Bone microstructure was scanned by micro-CT.Biomechanical characteristics of bone were measured by three-point bending test, and material properties were detected by fourier transform infrared(FTIR).The pathological changes were observed by HE and TRAP staining.Protein expressions involved in advanced glycation end products(AGEs)and their receptors(RAGE)/nuclear factor-κB(NF-κB)signaling pathway were detected by immunohistochemistry.Results The combined administration of loganin and berberine could significantly inhibit the weight gain, reduce the levels of blood glucose, blood lipid and oxidative stress, as well as improve glucose tolerance.In addition, combined intervention also decreased the expression levels of the proteins involved in AGEs/RAGE/NF-κB signaling pathway, and improved bone microstructure, finally contributing to increasing bone quality in diabetic mice.Conclusions The combination of loganin and berberine could improve bone metabolism in diabetic mice, which may be related to AGEs/RAGE/NF-κB signaling pathway.
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Aim To investigate the effeet of dihydro- myricetin ( DHM ) on cognitive dysfunction in type 2 diabetes mellitus ( T2DM) rats and its mechanism.Methods SD rats were randomly divided into the normal control group ( n = 56) : normal diet and citrate buffer solution (30 mg • kg 1 ) ; T2DM model group (n =60) : high glucose, fat and low dose STZ ( 30 mg • kg 1 ) ( Four unsuccessful rats were eliminated ).Then rats in the above two groups were treated with or without DHM (250 mg • kg 1 • d intragastric).After 12 weeks, eight rats in each group were randomly selected to perform Morris water maze and Y maze test to observe the effect of DHM on cognitive function of rats.The remaining rats in each group were injected ERS antagonist tauroursodeoxycholic acid ( TUDCA ) 10 jxg • d 1 or ERS activator tunicamycin (TUN) 10 jxL, respectively.After the behavioral analysis, the hippocampal tissues of rats were taken out.The expressions of EH stress related proteins GRP78 and P- PERK were detected by Western blot.Results Both DHM and TUDCA could improve cognitive dysfunction in T2DM rats.On the contrary, TIJN reduced the effect of DHM on cognitive dysfunction in T2DM rats.TUDCA decreased the expression of GRP78 and p- PERK proteins in T2DM rats, while TUN increased the expression of GRP78 and p-PERK proteins in T2DM rats treated by DHM.Conclusion DHM improves cognitive dysfunction in T2DM rats, and the mechanism may be related to the inhibition of endoplasmic reticulum stress.
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ObjectiveTo explore the mechanism of Liu Junzitang in preventing and treating muscle atrophy in mice with lung cancer cachexia based on the signal transducer and activator of transcription 3(STAT3)/ubiquitin proteasome pathway in vivo. MethodForty C57BL/6 mice aged six weeks were randomly divided into a blank group, a model group, a Liu Junzitang group, an inhibitor group (stattic group),and a Liu Junzitang + inhibitor group (combination group), with eight mice in each group. The cachectic muscle atrophy model was induced by subcutaneous inoculation of Lewis lung cancer cell line under the right anterior armpit in mice except those in the blank group. On the 8th day after subcutaneous inoculation, the mice in the corresponding groups received Liu Junzitang (9.56 g·kg-1·d-1) by gavage and intraperitoneal injection of stattic [25 mg·kg-1·(2 d)-1]. After three weeks of drug intervention, the body weight and gastrocnemius muscle weight were recorded. Hematoxylin-eosin (HE) staining was used to observe the pathological changes and cross-sectional area of gastrocnemius muscle fibers in mice. Western blot was used to detect the expression of phosphorylated-STAT3 (p-STAT3), STAT3, muscle atrophy F-box (MAFbx), and muscle RING finger protein 1 (MuRF1) in the gastrocnemius muscle. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of STAT3, MAFbx, and MuRF1 in the gastrocnemius muscle. ResultCompared with the blank group, the model group showed lightened body and the gastrocnemius muscle, reduced cross-sectional area of gastrocnemius muscle fibers, and increased protein expression of p-STAT3, STAT3, MAFbx, and MuRF1 and mRNA expression of STAT3, MuRF1, and MAFbx in the gastrocnemius muscle (P<0.05). Compared with the model group, the Liu Junzitang group showed increased body weight, gastrocnemius muscle weight, and cross-sectional area of gastrocnemius muscle fibers (P<0.05), and decreased protein expression of p-STAT3, STAT3, MuRF1, MAFbx, and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle (P<0.05). Compared with the model group, the inhibitor group showed increased body weight and cross-sectional area of gastrocnemius muscle fibers (P<0.05), and reduced protein expression of p-STAT3, STAT3, MuRF1, MAFbx, and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle (P<0.05). Compared with the model group, the combination group showed increased body weight and gastrocnemius muscle weight (P<0.05),and decreased protein expression of p-STAT3, STAT3, MuRF1, and mRNA expression of STAT3 and MAFbx in the gastrocnemius muscle (P<0.05). Compared with the Liu Junzitang group, the stattic group and the combination group showed reduced expression of p-STAT3 protein in the gastrocnemius muscle (P<0.05). ConclusionLiu Junzitang can prevent and treat muscle atrophy in mice with lung cancer cachexia, and its mechanism may be associated with the protein and mRNA expression related to the STAT3-mediated ubiquitin proteasome pathway.
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ObjectiveTo explore the mechanism of Cordyceps in treating bronchial asthma and chronic renal failure with the concept of "same treatment for different diseases" in traditional Chinese medicine (TCM) by network pharmacology and molecular docking technology. MethodThe active components and potential targets of Cordyceps were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction. The disease targets were obtained from Therapeutic Target Database (TTD), DrugBank, GeneCards and other databases. The common targets were obtained from the intersection of potential targets and disease targets. The protein-protein interaction (PPI) network was constructed by STRING11.5, and the ''component-target-diseas'' network of Cordyceps was established by Cytoscape 3.9.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out by Metascape, and molecular docking was performed by Autodock 4.2. ResultSixty common targets of disease and drug were screened out. The core targets mainly involved protein kinase B1 (Akt1), non-receptor tyrosine kinase, sarcoma virus protein (SRC), TP53, matrix metalloproteinase-9 (MMP-9), and prostaglandin endoperoxide synthase 2 (PTGS2). The potential targets were mainly enriched in the signaling pathways of renin-angiotensin system (RAS), RAP1, phosphoinositide 3 kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), etc. ConclusionThe active components of Cordyceps inhibited inflammatory response and reduced fibrosis and cell apoptosis in a multi-target and multi-pathway manner. The findings of this study preliminarily revealed the potential targets and modern biological mechanism of Cordyceps in treating bronchial asthma and chronic renal failure with the concept of ''same treatment for different diseases'', and provided references for in-depth experimental verification and clinical application.
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Objective:To explore the effect of hospital-community-family trinity linkage home visiting on quality of life of convalescent patients with traumatic brain injury.Methods:A total of 100 convalescence patients with traumatic brain injury admitted to Shanghai Yangzhi Rehabilitation Hospital from January 2019 to January 2020 were selected as the research objects, and randomly divided into the intervention group ( n=51) and the control group ( n=49) by random number table method. The control group received routine rehabilitation nursing guidance. Patients in the intervention group were treated with hospital-community-family triple linkage family visit for nursing intervention for 10 months. The Medical Outcomes Study 36-Item Short-Form (SF-36), General Self-Efficacy Scale (GSES) and Exercise of Self Care Agency Scale (ESCA) were used to compare the quality of life of 2 groups before intervention, 1, 4, 6, 8 and 10 months after intervention. Results:After 6 months of the intervention, eight dimensions of SF-36 such as physiological function, role-physical, body pain, general health, vitality, social function, role-emotional, and mental health scored 29.61 ± 9.21, 38.73 ± 14.42, 41.96 ± 8.25, 38.63 ± 8.43, 50.10 ± 8.03, 42.40 ± 18.28, 43.14 ± 15.34, 38.31 ± 8.88 in the intervention group, and 35.92 ± 8.02, 52.04 ± 14.29, 50.00 ± 11.90, 47.76 ± 9.08, 56.12 ± 7.66, 56.99 ± 19.40, 55.10 ± 16.03, 44.96 ± 7.73 in the control group. The difference between two groups showed significant difference ( t values were -5.21--3.81, all P<0.05). The GSES scores and ESCA scores after 1,4,6,8,10 months of the intervention showed an distinct advantage in the intervention group than the control group ( t values were -20.99-11.55, all P<0.05). Conclusions:The hospital-community-family trinity linkage home visiting could improve the quality of life, self-efficacy, and self-care ability of patients with traumatic brain injury, and promote their rehabilitation effect when they returned to family and society.
الملخص
Objective:To investigate the effect of hospital-community-family transitional rehabilitation care model on patients with brain trauma and explore an economic, effective, all-sided rehabilitation approach.Methods:A total of 82 in-patients with brain trauma were recruited from January 2018 to June 2019 in Shanghai Yang Zhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center). The participants were allocated into 2 groups based on randomized digital tables. Forty patients in the observation group received the hospital-community-family transitional rehabilitation care, and forty-two patients in the control group received routine rehabilitation care. All the participants completed assessments with the Fugl-Meyer Assessment Scale (FMA), the Barthel Index for the Activities of Daily Living (BI) and the Hamilton Anxiety Scale (HAMA) before the intervention, at discharge, 1 month, 4 months, 6 months and 10 months after discharge, respectively.Results:Before the intervention, no statistical significance was identified in the total scores of FMA, BI and HAMA between the two groups ( P>0.05). Compared to the control group, the total scores of FMA, BI and HAMA in the observation group were significantly improved at the discharge, 1 month, 4 months, 6 months and 10 months after discharge, respectively ( t values were -13.82 - 10.28, all P<0.05). Significant differences were observed in the level of FMA, BI and HAMA between the two groups across 6 time points ( Ftime×group=20.34, 18.34, 19.55, Ftime=183.24, 184.30, 179.09, Fgroup=28.86, 32.19, 26.63, all P<0.05). Conclusions:The hospital-community-family transitional rehabilitation care model which is based on medical consortium effectively improved traumatic brain-injured patients′motor function, the level of activities of daily living, and patients′anxiety. In addition, the model also improved the quality of medical services.
الملخص
Objective:To explore the clinicopathological characteristics and prognosis of pancreatic gastrointestinal interstitial tumors(pGISTs).Methods:Three cases of pGISTs diagnosed in the Affiliated Tumor Hospital of Guangxi Medical University from August 2015 to October 2019 were analyzed retrospectively. Relevant literatures at home and abroad were searched and reviewed through PubMed, China knowledge Network, Wanfang and VIP databases. The sex, age, tumor size, tumor location, cystic or solid tumor, mode of treatment, mitosis, gene mutation, survival status and survival time were recorded, and the correlation between tumor cystic-solid characteristics and clinicopathological parameters was analyzed. Kaplan-Meier′s method was used to calculate the overall survival (OS) rate and disease-free survival (DFS) rate. Univariate and multivariate Cox regression models were used to analyze the independent risk factors affecting the prognosis of pGISTs.Results:In this group, 3 cases were combined with 71 cases reported in the literature, and a total of 74 cases of pGISTs were included. Among them, 36 cases were male and 38 were female, the age of onset was 55(19-84) years, and the diameter of the tumor was 8 cm(2-35 cm). The tumor location of 71 patients was recorded by literature; 30 cases (42.3%) were located in the head of the pancreas. The solid-cystic characteristics of tumor in 63 patients were recorded by literature, and 33 cases (52.4%) were solid. The mode of treatment of 74 patients was recorded, and 60 cases (81.1%) underwent radical resection. The mitosis figures of 59 patients were recorded, and 33 cases (55.9%) were <5/50 high power field of vision (HPF). The gene mutation of 14 patients was recorded, and 11 cases (78.6%) were c-kit exon gene mutation. Correlation analysis showed that the cystic-solid characteristics of the tumor were significantly correlated with tumor location, tumor diameter and mitosis figures, but not with age, sex, histological type, Ki-67 index and modification National Institutes of Health(mNIH) classification. The 5-year OS rate of 51 patients after radical resection was 88.8%, and the 5-year DFS rate was 60.3%. The 1-year OS rate of patients receiving palliative treatment was 51.9%, and the 1-year fatality rate was 33.3%. Univariate Cox regression analysis showed that male ( P=0.083), mitosis figures >5/50 HPF ( P=0.008)and CD 34 negative ( P=0.055)were risk factors for postoperative recurrence of pGISTs, while multivariate Cox regression analysis showed that mitosis figures >5/50 HPF ( P=0.023)was an independent risk factor for the prognosis of pGISTs. Kaplan-Meier survival analysis showed that patients with mitosis figures ≤5/50 HPF had a higher survival rate ( P=0.0003), but there was no significant difference on prognosis between patients with 10/50 HPF and >10/50 HPF( P=0.3075). Conclusions:pGISTs usually occured in the head of pancreas, and the tumor volume was usually found to be large. The main treatment was radical operation, and the main mutation type was exon mutation of c-kit gene. Nuclear fission image figures >5/50HPF was an independent risk factor for postoperative recurrence.