Progress on Prevention and Treatment of Cerebral Small Vascular Disease Using Integrative Medicine / 中国结合医学杂志

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.

The Role of KCNQ1OT1 in Gastric Cancer Based on Bioinformatics Analysis / 中国生物化学与分子生物学报

Long non-coding RNA KCNQ1OT1 is highly expressed in a variety of tumors, but there are few studies in gastric cancer and the results are inconsistent. The relevant research of its specific mechanism in gastric cancer is also scarce. Through the analysis of several TCGA public databases, we found that KCNQ1OT1 was generally highly expressed in gastric cancer, and the prognosis of gastric cancer patients with a high expression of KCNQ1OT1 was poor. The expression of KCNQ1OT1 is closely related to many clinical factors of gastric cancer, especially the mutation of TP53, and its expression is significantly related to immune cell infiltration. KCNQ1OT1 is generally highly expressed in gastric cancer cell lines. Knockdown of KCNQ1OT1 can inhibit the proliferation of gastric cancer cell lines. Co- expression network analysis showed that its expression was closely related to tumor metabolism. Glutaminase 1 (GLS1) is generally highly expressed in gastric cancer, which is closely related to a poor prognosis. There is a significant correlation between the expression of KCNQ1OT1 and GLS1. Knockdown of KCNQ1OT1 can inhibit the expression of GLS1 mRNA, and overexpression of GLS1 can partially rescue the proliferation of gastric cancer cells caused by knockdown of KCNQ1OT1. Therefore, we speculate that KCNQ1OT1 may regulate the growth of gastric cancer cells through GLS1. Our study explored the role of KCNQ1OT1 in gastric cancer through bioinformatics database and experiments, suggesting that KCNQ1OT1 may promote the development of gastric cancer by regulating glutamine metabolism, which provides a new target for the clinical research on targeted treatment in gastric cancer.

Expression of peptide/histidine transporter solute carrier family 15 member 4 in peripheral blood mononuclear cells and its clinical significance in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To investigate the expression and clinical significance of peptide/histidine transporter solute carrier family 15 member 4 (SLC15A4) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE).Methods:Fifty-five patients with SLE were divided into active SLE group and stable SLE group according to SLE disease activity index (SLEDAI) score, and 13 healthy volunteers were used as controls. The expression of SLC15A4 in PBMCs were detected by Western blot method. Moreover, the correlation between the expression of SLC15A4 and clinical and laboratory parameters of SLE patients were analyzed. The expression of SLC15a4 in the three groups was compared based on one-way analysis of variance (ANOVA), and the correlation between SLC15A4 expression level and clinical indicators was analyzed by Pearson correlation.Results:The expression levels of SLC15A4 in active SLE group, stable SLE group and healthy control group were (0.96±0.19), (0.88±0.14), (0.78±0.24), respectively. The expression level of SLC15A4 in SLE with active disease was higher than that in healthy controls ( F=4.47, P=0.015). In addition, the expression of SLC15A4 in PBMCs of SLE patients was positively correlated with the quantity of anti-double stranded DNA (anti-dsDNA) antibody, erythrocyte sedimentation rate (ESR) and systemic lupus erythematosus disease activity index (SLEDAI) ( r=0.29, P=0.031; r=0.36, P=0.007; r=0.32, P=0.017, respectively). However, the expression of SLC15A4 in PBMCs had no significant correlation with 24-h urinary protein ( r=0.45, P=0.127) and C3 ( r=0.20, P=0.133). Conclusion:SLC15A4 is involved in the pathogenesis of SLE and its expression in PBMCs of SLE patients can be used as an index to evaluate disease activity.

Epidemiological investigation of tinnitus in Sichuan and Chongqing / 中华耳鼻咽喉头颈外科杂志

Objectives: To investigate the prevalence and associated risk factors of tinnitus in Sichuan and Chongqing. Methods: We designed a tinnitus epidemiological questionnaire. The multi-stage stratified cluster random sampling methods was applied to obtain study subjects in six areas (Nanchong, Jiangjin, Fengdu, Yunyang, Suining and Ya'an), which were selected for epidemiological investigation. Home visit completion of epidemiological questionnaires was conducted. The trained investigators guided the respondents to fill in the tinnitus epidemiological questionnaires, and the epidemiological status of six areas on prevalence and risk factor was investigated. SPSS 22.0 software was used for statistical analysis. Results: Sampling population were 10 289, in which 9 273 were valid questionnaires. There were 4 281 males and 4 992 females, with an average age of 47.3 years, among which 34.83% (3 230/9 273) had tinnitus. 3.99% (370/9 273) were diagnosed with bothersome tinnitus. In a multivariable logistic regression mod, the following factors were associated with onsetting of tinnitus: sleep disorder [Odds Ratio(OR)=3.74] and noise exposure(OR=1.99). The risk of disease was lowest in the age of 30-40 years old, while the risk of disease was higher for people under 30 and over 40. In another multivariable logistic regression mode, the following factors were associated with having bothersome tinnitus: older people were more likely to suffer from tinnitus, sleep disorders (OR=4.68) and noise exposure (OR=1.56). Conclusions: The prevalence of tinnitus in Sichuan and Chongqing is about 34.83%, but most of the tinnitus is short-lived and has low loudness, which will not affect the patients. Only a small number of patients with tinnitus (3.99%) persist and affect their health and need treatment. The occurrence and exacerbation of tinnitus may be related to sleep, age, and noise exposure.

Influencing factors for anxiety and depression in patients with dysphagia after stroke / 预防医学

Objective @#To investigate the influencing factors for depression and anxiety in patients with dysphagia after stroke.@*Methods@# From May 2017 to June 2018,patients with post-stroke dysphagia in the Department of Rehabilitation Medicine of Zhejiang Hospital were recruited to collect their height,weight,education level,serum nutritional indicators and feeding patterns. Self-Rating Anxiety Scale and Self-Rating Depression Scale were employed to assess the incidence of anxiety and depression. Multivariate logistic regression model was used to analyze the influencing factors for depression and anxiety. @*Results @#Among 96 patients enrolled,43 suffered from anxiety and depression,with the incidence of 44.79%. The results of multivariate logistic regression analysis showed that normal albumin（OR=0.208,95%CI：0.054-0.800）was a protective factor for anxiety,while indwelling gastric tube（OR=5.789,95%CI：1.654-20.260）was a risk factor. Normal transferrin（OR=0.189,95%CI：0.042-0.860）was a protective factor for depression,while indwelling gastric tube（OR=13.977,95%CI：1.472-132.667）was a risk factor. @*Conclusion @#Normal albumin and transferrin are the protective factors for anxiety and depression in patients with dysphagia after stroke,and indwelling gastric tube is the risk factor for anxiety or depression.

Meta-analysis of efficacy and safety of Tripterygium Glycosides Tablets combined with desloratadine in treatment of chronic urticarial / 中国中药杂志

To analyze the efficacy and safety of Tripterygium Glycosides Tablets combined with desloratadine as well as desloratadine alone in the treatment of chronic urticaria by Meta-analysis,in order to provide evidence-based reference for clinical treatment.PubMed,CBM,Wan Fang,VIP database and CNKI database were retrieved to collect randomized controlled trials( RCT) about Tripterygium Glycosides Tablets combined with desloratadine( test group) as well as desloratadine alone( control group) in the treatment of chronic urticaria. Meta-analysis was performed by using Rev Man 5. 3 software after data extraction and quality evaluation( a total of 15 RCTs were included,involving 1 411 patients). Meta-analysis showed that the total effective rate( RR = 1. 28,95%CI[1. 22,1. 35],P<0. 000 01) and the quality of life improvement rate( RR = 1. 49,95% CI[1. 33,1. 66],P< 0. 000 01) of the test group were better than those of the control group,and the recurrence rate( RR = 0. 29,95%CI[0. 21,0. 40],P<0. 000 01) was significantly lower than that of the control group,with statistically significant differences; there was no statistically significant difference in the incidence of adverse reactions( RR = 1. 02,95%CI[0. 68,1. 53],P = 0. 92) compared with the control group. Based on the included RCTs,the efficacy of Tripterygium Glycosides Tablets combined with desloratadine in the treatment of chronic urticaria were superior to those of desloratadine alone,with similarity in safety. However,due to the low quality of RCTs and the lack of large-scale multi-center studies,the results shall not be further verified by clinical trials.

Effects of hypoxia and vibration training on bone metabolism and insulin sensitivity in type 2 diabetic osteoporosis rats / 中国组织工程研究

BACKGROUND: Hypoxia program to alleviate type 2 diabetes insulin resistance has been recommended, but this program is still questioned because of the risk of osteoporosis caused by hypoxia in patients with diabetes. OBJECTIVE: To investigate the effect of vibration training on bone mineral density, bone structural mechanics, bone metabolism and insulin sensitivity in type 2 diabetic osteoporosis rats under hypoxia environment. METHODS: Ninety clean Sprague-Dawley rats were randomly divided into two groups, and subjected to high-fat diet (n=60), or normal diet (n=30), for 8 weeks. High-fat rats were given the injection of streptozotocin to establish the rat model of type 2 diabetic osteoporosis. The control rats were subdivided into normoxia control and hypoxia control groups; the model rats were subdivided into hypoxia modeling group, hypoxia modeling vibration group, normoxia modeling group, normoxia modeling vibration group. Hypoxia and vibration program was performed by hypoxia tank and vibration platform (PowerPlate?) for 12 weeks. Glucose metabolism, insulin sensitivity, bone metabolism and bone mineral density and modeling were detected at 4 weeks after modeling and 12 weeks after vibration training. RESULTS AND CONCLUSION: At 12 weeks after intervention, the fast insulin level, fast blood glucose, and homeostasis model assessment of insulin resistance in the hypoxia modeling vibration group were significantly superior to those in the hypoxia modeling, normoxia modeling, and normoxia modeling vibration groups (P < 0.05). The bone mineral density, maximum stress, maximum load, breaking load and elastic modulus in the normoxia modeling vibration and hypoxia modeling vibration groups were significantly lower than those in the normoxia control and hypoxia control groups (P < 0.05). After vibration training, all indexes were significantly increased (P < 0.05). These results suggest that hypoxic environment can promote the insulin sensitivity, improve glucose and lipid metabolism in type 2 diabetic rats, but can lead to a decrease in bone mineral density and increase bone resorption. Vibration training not only can significantly enhance the insulin sensitivity, but also can avoid the decreased bone mineral density, bone metabolism disorder, and biomechanical properties induced by hypoxia.

Role of microRNA-1-mediated AMP-activated protein kinase pathway in cardiac fibroblasts induced by high glucose in rats / 中华危重病急救医学

Objective To investigate the role of microRNA-1 (miR-1) in cardiac fibroblasts induced by high glucose in rats. Methods The primary fibroblasts were cultured from the apical tissue of 1-3 day-old Sprague-Dawley (SD) rats. The cells which were passaged to generation 3 or 4, were randomly divided into normal glucose+lentivector-vehicle group (CON+Lv-Vehicle group), normal glucose+lentivector-miR-1 group (CON+Lv-miR1 group), high glucose+lentivector-vehicle group (HG+Lv-Vehicle group), high glucose+lentivector-miR-1 group (HG+Lv-miR1 group), high glucose+Lv-Vehicle+inhibitor group (HG+Lv-Vehicle+CC group), and high glucose+lentivector-miR-1+inhibitor group (HG+Lv-miR1+CC group). The myocardial fibroblasts were cultured in the concentration of 5.5 mmol/L glucose (normal glucose) or 25.0 mmol/L (high glucose) DMEM medium. Then lentiviral vector containing miR-1 silent sequence or the same volume of lentiviral vector was inoculated into the cells. The AMP activated protein kinase (AMPK) inhibitor Compound C (20 μmol/L) was added to the medium at 12 hours before sampling in inhibitor groups. The expression of phosphorylation of AMPK (p-AMPK), collagenⅠandⅢ, matrix metalloproteinase (MMP-2, MMP-9), and autophagy flux related protein LC3B-Ⅱ and p62/SQSTM1 were measured by Western Blot. Results The purity of rat myocardial fibroblasts in vitro was 97%. Compared with CON+Lv-Vehicle group, there was no significant difference in the expression of p-AMPK in CON+Lv-miR1 group, the expression of p-AMPK in HG+Lv-Vehicle group was significantly decreased (p-AMPK/t-AMPK: 44.72±3.29 vs. 100.00±7.77, 1 < 0.01). The expression of p-AMPK in HG+Lv-miR1 group was higher than that in HG+Lv-Vehicle group (p-AMPK/t-AMPK:60.52±5.16 vs. 44.72±3.29, 1 < 0.05). Compared with HG+Lv-Vehicle group, the expressions of collagen, MMP, LC3B-Ⅱand p62/SQSTM1 in HG+Lv-miR1 group were significantly decreased; after the treatment with AMPK inhibitor, the expressions of collagen, MMP, LC3B-Ⅱ, p62/SQSTM1 were significantly increased (HG+Lv-Vehicle+CC group vs. HG+Lv-Vehicle group: collagen Ⅰ/β-actin: 158.74±13.21 vs. 100.00±7.64, collagenⅢ/β-actin: 177.38± 17.31 vs. 100.00±5.18, MMP-2/β-actin: 130.09±14.31 vs. 100.00±10.47, MMP-9/β-actin: 215.54±20.92 vs. 100.00±11.28, LC3B-Ⅱ/β-actin: 159.34±13.83 vs. 100.00±6.44, p62/SQSTM1/β-actin: 201.01±24.02 vs. 100.00±8.62; HG+Lv-miR1+CC group vs. HG+Lv-miR1 group: collagenⅠ/β-actin: 108.69±9.93 vs. 80.83±7.24, collagenⅢ/β-actin: 127.68±10.46 vs. 81.56±9.97, MMP-2/β-actin: 106.66±10.21 vs. 74.80±7.43, MMP-9/β-actin: 145.65±11.56 vs. 74.63±10.55, LC3B-Ⅱ/β-actin: 150.15±13.28 vs. 22.98±2.87, p62/SQSTM1/β-actin: 130.48±10.74 vs. 49.90±2.27, all 1 < 0.05). Conclusion miR-1 gene silencing inhibits myocardial fibrosis induced by high glucose, its mechanism may be related to the up-regulation of p-AMPK, which can recover autophagy flux.

Role of autophagosomes clearance in delayed cardioprotection in rats with ischemia-reperfusion injury by sevoflurane preconditioning in vivo / 中华急诊医学杂志

Objective To evaluate role of autophagosomes clearance in delayed cardioprotection by sevoflurane preconditioning in rats with ischemia-reperfusion injury in vivo.Methods Forty-five adult male Sprague-Dawley rats,weighing 270-350 g,were randomly (random number) divided into 3 groups:sham operation group (sham group),ischemia-reperfusion group (CON group),sevoflurane preconditioning group (SWOP group).Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch (LAD) of coronary artery followed by reperfusion for 2 h,and myocardial infarct size was stained by triphenyltetrazolium chloride.Cardiomyocyte apoptosis was evaluated by terminal deoxyribonucleotidyl transferase-mediated biotin-16dUTP nick-end labeling.Autophagosomes were detected under transmission electron microscope.Expression of LC3-Ⅱ,cathepsin B,p62 and cleaved caspase-3 were assessed by western blotting.Statistical analysis were performed using one or two way analysis of variance (SPSS 15.0,Chicago,USA) test followed by Dunnet-t or LSD-t test.Results Sevoflurane preconditioning reduced myocardial infarct size and the number of autophagosomes (P =0.027),attenuated cardiomyocyte apoptosis (P =0.042).Sevoflurane preconditioning decreased the level of LC3-Ⅱ (P =0.033),p62 (P =0.041)and cleaved caspase-3 (P =0.037),but increased the level of cathepsin B (P =0.046).Conclusions Delayed cardioprotection by sevoflurane preconditioning increased myocardial clearance of autophagosomes against the delayed ischemia reperfusion injury.

Role of microRNA-1 on fibrosis induced by high glucose cultured cardiac fibroblasts / 中华危重病急救医学

Objective To investigate the effect of microRNA-1 (miR-1) on the fibrosis of cardiac fibroblasts induced by high glucose. Methods The primary cultured fibroblasts from 1-3 days old Sprague-Dawley (SD) rats, were randomly divided into 4 groups (n = 3): normal glucose + lentivector-vehicle (CON+Lv-Vehicle group), normal glucose + lentivector-miR-1 (CON+Lv-miR1 group), high glucose + lentivector-vehicle (HG+Lv-Vehicle group), high glucose + lentivector-miR-1 (HG+Lv-miR1 group). Fibroblasts were cultured in glucose concentration 5.5 mmol/L and 25 mmol/L DMEM culture, and were injected lentiviral vector carrying miR-1 silencer sequence or the same volume of lentiviral vector. After 12 hours, the medium was replaced with fresh complete medium. After 3 days when transfection efficiency was up to 90%, the cellular miR-1 content was detected by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The secretion of collagen Ⅰ and Ⅲ were measured by enzyme linked immunosorbent assay (ELISA). Expression of collagen Ⅰ and Ⅲ, matrix metalloproteinase 2 and 9 (MMP-2, MMP-9), autophagy related protein LC3B-Ⅱ, P62/SQSTM1 and Cathepsin D were assessed by Western Blot. Results Compared with the CON+Lv-Vehicle group, the content of miRNA in the CON+Lv-miR1 group had no statistical significance. Compared with the CON+Lv-Vehicle group, high glucose increased the amount of miR-1 (2-ΔΔCt: 1.82±0.17 vs. 1.00±0.04), collagen Ⅰ and Ⅲ secretion (mg/L: 14.55±0.33 vs. 7.28±0.22, 157.50±13.22 vs. 61.25±8.54) and expression (gray value: 432.35±56.00 vs. 100.00±15.00, 320.35±47.00 vs. 100.00±15.00), the level of MMP-2, MMP-9 and the expression of autophagy related protein LC3B-Ⅱ and P62/SQSTM1 (gray value: 249.0±21.0 vs. 100.0±15.0, 142.3±20.0 vs. 100.0±16.0, 178±19 vs. 100±14, 378.3±20.0 vs. 100.0±15.0), decreased the expression of lysosomal associated protein Cathepsin D (gray value: 60±14 vs. 100±10), and the differences were statistically significant (all P < 0.01). Compared with the HG+Lv-Vehicle group, the amount of miR-1 in the HG+Lv-miR1 group was significantly decreased (2-ΔΔCt: 1.21±0.10 vs. 1.82±0.17), collagen Ⅰ and Ⅲ secretion (mg/L: 10.68±0.54 vs. 14.55±0.33, 87.25±13.55 vs. 157.50±13.22) and expression (gray value: 179.41±45.00 vs. 432.35±56.00, 173.41±50.00 vs. 320.35±47.00), the level of MMP-2, MMP-9 and the expression of autophagy related protein LC3B-Ⅱ and P62/SQSTM1 (gray value: 172.0±23.0 vs. 249.0±21.0, 90.0±17.0 vs. 142.3±20.0, 138±15 vs. 178±19, 265.0±17.0 vs. 378.3±20.0) in the HG+Lv-miR1 group were decreased and the expression of lysosomal associated protein Cathepsin D was higher (gray value: 110±17 vs. 60±14), and the differences were statistically significant (all P < 0.05). Conclusions The expression of miRNA-1 was up-regulated in cardiac fibroblasts cultured in high glucose, and miRNA-1 silencing inhibited cardiac fibroblast induced fibrosis in high glucose. The mechanism may be related to the recovery of autophagy flux, up-regulation of Cathepsin D expression and inhibition of collagen production.

CT perfusion study of acute local cerebral infarction in rhesus monkeys / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the value of CT perfusion in early diagnosis and management of superacute local cerebral infarction in rhesus monkeys.</p><p><b>METHOD</b>Acute local cerebral infarction was induced in the rhesus monkeys during digital subtraction angiography (DSA) by introduction of pale thrombus prepared from autologous blood into the M1 branch of the middle cerebral artery (MCA). Plain CT scan and CT perfusion scanning were performed at different time points before and after DSA operation, and the results were analyzed in conjunction with the pathologic changes.</p><p><b>RESULTS</b>Ischemic lesions were displayed on CT perfusion images, which showed local hypoperfusion, reduced cerebral blood flow and volume, and mean transit time delay in the compromised area. Local hypointense infarct area was identified in plain CT scan 24 h after the DSA operation, and the results were in good agreement with pathological examination during autopsy.</p><p><b>CONCLUSION</b>CT perfusion imaging of the brain can accurately capture the cerebral perfusion deficits in acute ischemic stroke before morphologic changes take place, and therefore provides good means for thrombolytic treatment evaluation of stroke.</p>