Network pharmacology analysis of metformin against diabetic retinopathy / 中华实验眼科杂志

Objective:To explore the pharmacological molecular mechanisms of metformin against diabetic retinopathy (DR) based on network pharmacology approach.Methods:After chemical constitution of metformin was acquired from Pubchem database, target genes of metformin were identified by PharmMapper, SwissTargetPrediction and DrugBank database, and the pathological genes were obtained from GeneCards and DisGeNET database.Subsequently, the intersection of metformin targets and pathologic targets of DR were served as therapeutic targets of metformin against DR.The construction of protein-protein interaction (PPI) network was constructed by STRING, gene ontology (GO) and functional pathway were analyzed by Metascape.Results:Overall 31 therapeutic target genes of metformin against DR were obtained.Biological process of the PPI network was mainly enriched in reactive oxygen species metabolic process and nucleotide metabolism; cellular component was mainly enriched in microvillus and adherens junction; molecular function was mainly enriched in cofactor binding and nitric oxide synthase (NOS) activity.Functional pathway was mainly enriched in hemostasis and signaling by vascular endothelial growth factor (VEGF).Conclusions:Metformin prevents the development of DR mainly through affecting cellular tight junctions and reaction to hypoxia, modulating NOS and VEGF signaling pathways.

The clinical characteristics of community-acquired pneumonia patients with aspiration risk factors / 医学研究生学报

Objective　By now, there is no unified definition of aspiration pneumonia. However, patients with community-acquired pneumonia (CAP) often have aspiration risk factors. The aims of our study is to explore the clinical characteristics and outcomes of CAP patients with aspiration risk factors.　Methods　Cases data of all patients hospitalized with CAP in 5 teaching hospitals in Beijing, Shandong Province and Yunnan Province from January 1, 2013 to December 31, 2015 were collected. Data from patients with (AR-CAP) and without (non AR-CAP) aspiration risk factors were compared, including demographic features, clinical and radiologic findings and outcomes. A Cox proportional hazard model was used to determine the impact of aspiration risk factors on the 30-day mortality in CAP patients. Receiver operating characteristic curves (ROCs) was performed to verify the accuracy of CURB-65 score and PSI risk classification as 30-day mortality predictors in AR-CAP patients.　Results　Totally, 3561 CAP cases were entered into the final analysis. AR-CAP cases accounted for 5.1% (180/3561), who showed older age [78.0 yrs (M1,M3: 70.0 yrs, 85.0 yrs) vs 63.0 yrs (M1,M3: 52.0 yrs, 77.0 yrs), P < 0.001), more underlying diseases (91.1% vs 71.3%, P < 0.001), more frequently classified as CURB-65 score ≥ 3 (13.3% vs 1.5%, P < 0.001) and PSI risk classification ≥ Ⅳ (53.7% vs 17.0%，P< 0.001), and higher 30-day mortality (10.0% vs 1.8%, P < 0.001). Adjusted for age, sex, comorbidities and CURB-65/PSI score, aspiration risk factors were associated with increased 30-day mortality of CAP patients (HR 2.844, 95% CI 1.331~6.078, P = 0.007). The area under the ROC curve for predicting 30-day mortality in AR-CAP patients by PSI risk class was 0.716, which was higher than CURB-65 score (AUC=0.518, P = 0.019). The difference was statistically significant.　Conclusion　AR-CAP is a distinctive pneumonia phenotype with unique clinical characteristics, which shows more illness severity and worsen outcomes.

Incidence and risk factors for cardiovascular events in patients hospitalized with community-acquired pneumonia / 中华心血管病杂志

Objective: To explore the incidence, risk factors of cardiovascular events (CVE) and their impact on 30-day mortality in patients hospitalized with community-acquired pneumonia (CAP). Methods: This is a multicenter, retrospective study. Patients hospitalized with CAP from 5 teaching hospitals in Beijing, Shandong and Yunnan provinces during 1 January 2013 to 31 December 2015 were included and clinical data were retrieved from the Hospital Information System (HIS), and patients were divided into CVE group and non-CVE group. Age, sex, comorbidities, pneumonia severity index(PSI)/CURB-65 score, routine blood test, biochemical examinations, radiological findings on admission and mortality on 30-day after admission were analyzed. The primary endpoint was acute CVE during hospitalization, the secondary endpoint was 30-day death after admission. Multivariate Cox regression analysis was used to explore the risk factors for CVE. Kaplan-Meier survival curve was used to compare the difference on 30-day mortality between CVE patients and non-CVE patients by Log-rank test. Multivariate Cox regression model was used to assess the impact of CVE on the 30-day mortality among CAP patients after adjustment with age, sex, comorbidities, PSI/CURB-65 score. Results: A total of 3 561 CAP patients were included into the final analysis, including 210 (5.9%) patients in CVE group and 3 351 (94.1%) patients in non-CVE group. Compared with patients in non-CVE group, patients in CVE group were older (P<0.001), prevalence of hypertension, coronary heart disease, chronic heart failure, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, aspiration risk and bedrid were significantly higher (all P<0.001); prevalence of CURB-65 score 3-5 and PSI risk class Ⅳ/Ⅴ were also significantly higher (both P<0.001). The proportion of axillary temperature<36 ℃, respiratory rate≥30 beats/minutes, confusion, leukocytes>10×10(9)/L, hemoglobin<100 g/L, platelets>300×10(9)/L, albumin<35 g/L, blood urea nitrogen>7 mmol/L, fasting blood glucose>11 mmol/L, serum C-reaction protein>100 mg/L, serum procalcitonin≥2 μg/L, arterial pH<7.35, arterial PO(2)/FiO(2)≤300 mmHg (1 mmHg=0.133 kPa), and multilobar infiltrates and pleural effusion on chest X-ray or CT scan were significantly higher in CVE group than in non-CVE group(all P<0.05); the 30-day mortality was significantly higher in CVE group than in non-CVE group(P<0.001). The incidence of CVE was significantly higher in patients with cardiovascular and cerebrovascular disease(CVD) than in patients without CVD (13.9%(150/1 079) vs. 2.4%(60/2 482), χ(2)=178.737, P<0.001). Meanwhile, the incidence of CVE increased with PSI in patients with Ⅰ/Ⅱ, Ⅲ and Ⅳ/Ⅴ class, respectively(χ(2)=228.350, P<0.001); and CURB-65 score 0-1, 2 and 3-5, respectively (χ(2)=387.154, P<0.001). Cox regression analysis revealed that age (HR=1.05, 95%CI 1.02-1.09, P=0.002), coronary heart disease (HR=1.88, 95%CI 1.01-3.51, P=0.048), chronic heart failure (HR=4.25, 95%CI 1.89-9.52, P<0.001), PSI risk class (HR=1.66, 95%CI 1.50-2.62, P=0.029) and serum procalcitonin≥ 2 μg/L (HR=3.72, 95%CI 1.60-8.66, P=0.002) were independent risk factors for CVE in CAP patients. Kaplan-Meier curve showed that the survival probability of patients with CVE was significantly lower than patients without CVE (P<0.001). After adjustment for age, sex, comorbidities and PSI/CURB-65 score, Cox regression model showed that CVE was associated with increased 30-day mortality in CAP patients (HR=6.05, 95%CI 3.11-11.76, P<0.001). Conclusions: Although the incidence of CVE is not high in Chinese patients hospitalized with CAP, CVE is common in patients with severe pneumonia and in patients with CVD. Age, cardiovascular disease, PSI risk class and serum procalcitonin are the risk factors for CVE in this patient cohort. CVE is related to increased 30-day mortality in CAP patients.

Regulation of replanted progesterone on stress signal in endoplasmic reticulum stress during menstruation in mice at different periods / 医学研究生学报

Objective　Endoplasmic reticulum stress may be involved in the menstrual process, but the detailed mechanism is unclear. This article is to explore the effect of progesterone replantation at different periods on the endoplasmic reticulum stress-induced autophagy and apoptosis in mice during menstruation.　Methods　Mice were divided into 12h replantation group, 16h replantation group and the withdrawal group according to random number table, with 10 mice in each group. 12h (12h replantation group) and 16h (16h replantation group) after the withdrawal of progesterone, replanted respectively with progesterone tube, and withdrawal group were not replanted. Mice in each group were sacrificed 24h after the withdrawal of progesterone and were collected bilateral uterine horns. The expression and localization of t-PERK, p-PERK, t-eIF2α, p-eIF2α, ATF4, CHOP and Caspase12 mRNA and proteins in mouse endometrial tissues were detected by qPCR, Western blot and immunohistochemistry.　Results　At the mRNA level, the PERK and eIF2α(1.000 ± 0.000) of the 12h replantation group were significantly higher than those of the 16h replantation group (0.450 ± 0.049, 0.330 ± 0.015) and the withdrawal group (0.260 ± 0.233, 0.195 ± 0.014). The difference was statistically significant (P<0.05), and the 16h replantation group was higher than the withdrawal group (P<0.05). At the protein level, p-PERK / t-PERK (0.606 ± 0.051) and p-eIF2α / t-eIF2α (0.795 ± 0.074) in 12h replantation group were significantly higher than those in 16h replantation group (0.367 ± 0.019, 0.503 ± 0.038) and withdrawal group (0.243 ± 0.020, 0.293 ± 0.020). The difference was statistically significant (P<0.05) and the 16h replantation group was significantly higher than the withdrawal group. At the mRNA and protein levels, ATF4 of 12h replantation group were higher than 16h replantation group and the withdrawal group (P <0.05) , and the 16h replantation group was higher than the withdrawal group. The proteins of p-PERK, p-eIF2α and ATF4 are mainly expressed in the cytoplasm of decidual stromal cells which located at the junction of basal layer and decidualized stromal cells. At mRNA and protein levels, the expression levels of CHOP and Caspase12 in 12h replantation group were significantly lower than those in 16h replantation group , were also lower than the withdrawal group, and the 16h replantation group was lower than the withdrawal group (P<0.05). The proteins of CHOP and Caspase12 are mainly localized in cytoplasm of adequately decidualized stromal cells and the glandular epithelium cells.　Conclusion　Replantation of progesterone before the critical period of menstruation (12h) can effectively block the onset of menstruation in mice, which may be achieved by maintaining the expression of PERK/eIF2α/ATF4 signal and blocking the expression of apoptotic signaling pathway members CHOP and Caspase 12 in endometrial stromal cells. And this effect can only be partially achieved by progesterone replantationing after the critical period of menstruation (16h).

Facilitation of spinal α-motoneuron excitability by histamine and the underlying ionic mechanisms / 生理学报

Spinal α-motoneurons directly innervate skeletal muscles and function as the final common path for movement and behavior. The processes that determine the excitability of motoneurons are critical for the execution of motor behavior. In fact, it has been noted that spinal motoneurons receive various neuromodulatory inputs, especially monoaminergic one. However, the roles of histamine and hypothalamic histaminergic innervation on spinal motoneurons and the underlying ionic mechanisms are still largely unknown. In the present study, by using the method of intracellular recording on rat spinal slices, we found that activation of either H or H receptor potentiated repetitive firing behavior and increased the excitability of spinal α-motoneurons. Both of blockage of K channels and activation of Na-Ca exchangers were involved in the H receptor-mediated excitation on spinal motoneurons, whereas the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels were responsible for the H receptor-mediated excitation. The results suggest that, through switching functional status of ion channels and exchangers coupled to histamine receptors, histamine effectively biases the excitability of the spinal α-motoneurons. In this way, the hypothalamospinal histaminergic innervation may directly modulate final motor outputs and actively regulate spinal motor reflexes and motor execution.

Impact of Prior Use of Inhaled Corticosteroids on the Clinical Outcomes of Obstructive Pulmonary Disease Patients Hospitalised with Community-Acquired Pneumonia / 中山大学学报(医学科学版)

@#【Objective】To evaluate the impact of prior use of inhaled corticosteroids（IC）on the clinical outcomes of chronic obstructive pulmonary disease patients hospitalised with community- acquired pneumonia （COPD- CAP）. 【Methods】This was a multicenter，retrospective study. Data of COPD-CAP patients from five teaching hospitals in Beijing，Shandong and Yunnan Provinces during 1st January 2013 through 31th December 2016 were reviewed. The patients with and without prior use of IC were compared，including demographic characteristics，clinical and radiologic features， and outcomes. A logistic regression model was conducted to explore the impact of prior IC use on the clinical outcomes of COPD-CAP patients. 【Results】Of 725 patients included in the study，13.9%（101/725）were prior IC users. Compared with no-IC users，IC users showed higher frequency of cardiovascular comorbidity（19.8% vs 12.7%）and a CAP history in the last year（20.8% vs 11.2%）；lower occurrence of pleural effusion（13.9% vs 23.7%）；more often classified in Global Initiative for Chronic Obstructive Lung Disease（GOLD）stage 3（35.1% vs 22.9%）and GOLD 4 stage（51.9% vs 21.8%），less often in GOLD 2 stage（10.4% vs 51.0%）. Adjusted by age，gender，underlying diseases，PSI/CURB-65 score and GOLD stage，logistic regression analysis confirmed prior IC use was associated with decreased risk for noninvasive ventilation［OR = 0.220，95% CI（0.052，0.926），P = 0.029］，but not with invasive ventilation［OR = 0.290，95% CI（0.068，1.236），P = 0.094］，needing vasopressor use［OR = 1.261，95% CI（0.456，3.485），P = 0.655］，ICU admission［OR = 1.455，95% CI（0.638，3.320），P = 0.373］and 30-day mortality［OR = 1.650，95% CI（0.575，2.838）， P = 0.352］.【Conclusion】Previous IC use has no major impact on the clinical outcomes of COPD-CAP patients.

A preliminary study on traditional Chinese medicine syndrome rating scale for acute gastrointestinal injury in sepsis / 中国中西医结合急救杂志

Objective To develop a traditional Chinese medicine (TCM) syndrome score scale for acute gastrointestinal injury (AGI) in sepsis, and to carry out its reliability and validity analyses and its clinical preliminary application. Methods ① According to the characteristics of intensive care unit (ICU) patients, combined with the understanding of etiology, pathogenesis and physical signs of TCM and literature search, a preliminary framework of scoring system for TCM syndromes of AGI in sepsis was constructed to carry out the scoring by this scale. ② After the scale and data were obtained, the analyses of split-half reliability (indicated by Guttman's split-half reliability of the a and b groups), test-retest reliability and the internal consistency reliability (expressed by the Cronbach's coefficient α) were carried out, and the structural validity and criterion validity were also analyzed. ③ The AGI patients were divided into two groups according to the 28-day survival and death conditions, and the AGI TCM syndrome score, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, and multiple organ dysfunction syndrome (MODS) score were compared between the two groups to determine the best cut-off point for survival analysis. Results ① The first draft of the septic AGI TCM syndrome rating scale was prepared, The TCM syndrome indicators include: abdominal distension, constipation/diarrhea, diet situation, vomiting/stomach retention, tongue proper, tongue coating, pulse manifestation, belching, body temperature, and accompanied syndrome, there were 6 points for scoring, 0 - 6 points, and they were divided into normal (0 points), mild (2 points), moderate (4 points), and severe (6 points) in severity. ② Eighty-eight patients with septic AGI were included in the final statistics. The retest of correlation coefficient of this scale was R = 0.974 (> 0.85), Guttman's split-half reliability was 0.793 (> 0.7) and the Cronbach's coefficient α was > 0.7. This scale was suitable for factor analysis. After rotation, 3 factors were determined, which were named as TCM syndrome differentiation, related physical signs, and gastrointestinal tolerance. After modeling, the confirmatory factor analysis showed that the model approximate error root mean square (RMSEA) was 0.07 (< 0.08), and the goodness of fit index (CFI) = 0.90; the Pearson correlation analyses between the criteria validity of APACHE Ⅱ, SOFA, MODS scores and TCM 1 score and TCM 2 score of this scale showed that the r values were 0.802 and 0.752, 0.524 and 0.519, 0.619 and 0.590, respectively, all P < 0.01. ③ Compared with the survival group, TCM score (33.73±5.95 vs. 37.28±5.26, t = 2.945, P = 0.004), the APACHE Ⅱ score (19.90±4.47 vs. 22.28±5.79, t = 2.069, P = 0.043), SOFA score (8.73±1.11 vs. 9.64±1.38, t = 3.329, P = 0.020) in the death group were significantly decreased; MODS score in the death group showed a decreasing trend (6.65±1.22 vs. 7.28±1.60, t = 2.078, P = 0.050). Cox regression analysis showed that when the survival analysis was performed with a cut-off point of 35, the 28-day survival rate of patients with TCM syndrome score ≥ 35 was significantly lower than that of patients with < 35 score, χ2= 6.362, P = 0.012. Conclusions The TCM syndrome rating scale for AGI in sepsis was successfully prepared. The statistical reliability and validity of this scale are good. Preliminary clinical application shows that this scale can predict the prognosis and severity of patients with septic AGI. Trial registration China Clinical Trial Registry Center, ChiCTR-IOR-15007625.

Correlation of corneal basal nerve changes with type 2 diabetic renal microangiopathy based on confocal laser microscopy / 眼科新进展

Objective To investigate the relationship between corneal basal nerve change and type 2 diabetic retinopathy based on confocal laser microscopy.Methods Together 118 patients with type 2 diabetes (T2D) were collected in our hospital from February 2016 to February 2017,including 57 patients with diabetic retinopathy (DR group) and 61 patients without DR (NDR group).For comparison,60 healthy volunteers were selected as the control group.And all the subjects were examined by corneal confocal laser microscopy to analyze the relationship between the morphological parameters of the corneal nerve and clinical variables.Results Corneal nerve fiber density,corneal nerve branch density and corneal nerve branch length in DR group were (20.03 ±4.22) · mm-2,(22.01 ± 7.05) · mm-2 and (9.50 ± 1.76) mm ·mm-2,significantly less than those of the control group and NDR group (all P ＜ 0.05);and corneal nerve fiber curvature was (0.30 ± 0.03),significantly higher than that of the control group and NDR group (all P ＜ 0.05);In DR patients,phase Ⅲ patients had smaller the corneal nerve fiber density,corneal nerve branch density and corneal nerve branch length,but the larger corneal nerve fiber curvature than the phase Ⅰ and Ⅱ patients (all P ＜ 0.05);course of disease of DR group was (12.04 ± 2.48) years,which was significantly higher than that of NDR group (P ＜ 0.05),while fasting C peptide and fasting insulin were (1.41 ± 0.58) μg · L-1 and (20.05 ± 7.91) mU · L-1,respectively,significantly lower than those of NDR group (all P ＜ 0.05);The duration of T2D was negatively correlated with the corneal nerve branch density and corneal nerve branch length (r =-0.322,-0.317,all P ＜0.05);Fasting C peptide was positively correlated with the corneal nerve branch density (r =0.298,P ＜ 0.05),and negatively correlated with the corneal nerve curvature (r =-0.311,P ＜ 0.05).Conclusion Patients with T2D retinopathy have abnormal morphology of corneal nerve.And confocal laser scanning microscopy is conducive to the early detection of microvascular disease in T2D patients with a longer course of disease or a low level of fasting C peptide.

Subthalamic nucleus: from circuits, functions to a deep brain stimulation target for the treatment of Parkinson's disease / 生理学报

The subthalamic nucleus (STN) is the only excitatory glutamatergic nucleus in the basal ganglia circuitry. It not only is a key node in the classical indirect pathway, but also forms the "hyperdirect" pathway directly connecting the cortex, and even is implicated as a pacemaker for activity of whole basal ganglia. Due to the key position of STN in the basal ganglia circuitry, the STN is an optimal target for deep brain stimulation (DBS) in the neurosurgical treatment of Parkinson's disease (PD). However, the therapeutic mechanisms underlying the amelioration of parkinsonian motor dysfunctions induced by DBS on STN remain enigmatic. This paper reviews recent progresses in the studies on the input-output configurations and functions of STN in the basal ganglia circuitry, and summarizes the hypotheses for mechanisms of DBS for the treatment of motor dysfunctions in PD. Studying on the DBS mechanisms will not only help to develop strategies for treatment of PD, but also contribute to the understanding of functions of the basal ganglia circuitry.

IVS8+1 DelG, a Novel Splice Site Mutation Causing DFNA5 Deafness in a Chinese Family / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Nonsyndromic hearing loss (NSHL) is highly heterogeneous, in which more than 90 causative genes have currently been identified. DFNA5 is one of the deafness genes that known to cause autosomal dominant NSHL. Until date, only five DFNA5 mutations have been described in eight families worldwide. In this study, we reported the identification of a novel pathogenic mutation causing DFNA5 deafness in a five-generation Chinese family.</p><p><b>METHODS</b>After detailed clinical evaluations of this family, the genomic DNA of three affected individuals was selected for targeted exome sequencing of 101 known deafness genes, as well as mitochondrial DNA and microRNA regions. Co-segregation analysis between the hearing loss and the candidate variant was confirmed in available family members by direct polymerase chain reaction (PCR)-Sanger sequencing. Real-time PCR (RT-PCR) was performed to investigate the potential effect of the pathogenic mutation on messenger RNA splicing.</p><p><b>RESULTS</b>Clinical evaluations revealed a similar deafness phenotype in this family to that of previously reported DFNA5 families with autosomal dominant, late-onset hearing loss. Molecular analysis identified a novel splice site mutation in DFNA5 intron 8 (IVS8+1 delG). The mutation segregated with the hearing loss of the family and was absent in 120 unrelated control DNA samples of Chinese origin. RT-PCR showed skipping of exon 8 in the mutant transcript.</p><p><b>CONCLUSIONS</b>We identified a novel DFNA5 mutation IVS8+1 delG in a Chinese family which led to skipping of exon 8. This is the sixth DFNA5 mutation relates to hearing loss and the second one in DFNA5 intron 8. Our findings provide further support to the hypothesis that the DFNA5-associated hearing loss represents a mechanism of gain-of-function.</p>

Study on effect of total flavanones of Sedum sarmentosum on apoptosis of hepatic stellate cells and its mechanism / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of total flavanones of Sedum sarmentosum (SSTF) on the apoptosis of rat hepatic stellate cells (HSC-T6) and its mechanism.</p><p><b>METHOD</b>Different concentrations of SSTF and HSC-T6 cells were co-cultured for different period of time. The MTT assay was used to detect the inhibitory effect of SSTF on the proliferation of HSC-T6 cells. The flow cytometry Annexin-V/PI double staining method was adopted to detect SSTF's effect on HSC-T6 cell apoptosis. Western blotting and Real-time PCR methods were applied to observe the effect on the protein and mRNA expressions of apoptosis-related cytokines Bcl-2, Bax and Caspase-3.</p><p><b>RESULT</b>SSTF significantly inhibited HSC-T6 cell proliferation and induced cell apoptosis in a dose and time dependent manner. According to Western blotting result, SSTF promoted apoptosis by inhibiting Bcl-2, Bax and promoting the protein expression of Caspase-3; according to a further Real-time PCR study, Bcl-2 mRNA levels can inhibit Bcl-2 and promote Bax and Caspase-3 expressions.</p><p><b>CONCLUSION</b>SSTF has the effect of promoting the apoptosis of HSC-T6 mainly by inhibiting Bcl-2 and promoting protein and mRNA expressions of Bax and caspase-3.</p>

Relationship between corrected spatial memory in diabetic rats and protein kinase Cγ, caveolin-1 in the hippocampus and neuroprotective effect of catalpol / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The mechanisms underlying diabetic encephalopathy are largely unknown, and no effective treatments are available. Catalpol has received much attention due to its numerous biological effects, especially in neuroprotective studies. The aim of this study was to investigate the effects of catalpol on cognitive functions in diabetic rats and the underlying mechanisms.</p><p><b>METHODS</b>A rat model of diabetes was established by streptozotocin injection, followed by intraperitoneal infusion of catalpol after 10 weeks. Two weeks later, the Morris water maze was used to test the spatial learning performance. Nissl staining was performed to evaluate the morphological changes in the hippocampus. Expression of protein kinase Cγ (PKCγ) and caveolin-1 (Cav-1) in the hippocampus were assessed by reverse transcription PCR and Western blotting. Activities of anti-oxidative enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) and levels of malonaldehyde (MDA) were measured using commercial kits.</p><p><b>RESULTS</b>Significant hippocampal neuronal injury was observed in rats with streptozotocin-induced diabetes. Moreover, cognitive dysfunction was associated with markedly increased oxidative stress in the brain. Catalpol treatment significantly attenuated cognitive deficits, neuronal damage, and oxidative stress in the brain of diabetic rats. Biochemical analyses showed that catalpol reversed the down-regulation of PKCγ and Cav-1 expression in the diabetic rats.</p><p><b>CONCLUSIONS</b>Spatial memory in diabetic rats is associated with the expression of PKCγ and Cav-1. Catalpol treatment markedly attenuated oxidative stress, reversed the alteration of PKCγ, Cav-1 and spatial memory deficits.</p>

The effect of maternal hypothyroidism on microRNA expression profiles in the brain of rat offsprings / 中华内分泌代谢杂志

Objective To analyse the differential expression of miRNAs in the brain of offsprings of hypothyroid and normal rats,and to explore the molecular mechanism underlying the effect of hypothyroidism on brain development in the offspring.Methods Forty-eight female Wistar rats were assigned to (1) control group (n =24),and (2) hypothyroid group after complete thyroidectomy (n =24).Serum TSH and Total thyroxine (T4) were measured one month after the surgery.Brain samples of fetal or postnatal rats were obtained during four different developmental stages:embryonic days (E) 13,E17,postnatal days (P) 0 and P7.The hippocampus and cortex were separated on P7.MiRNAs were isolated from tissues and two samples were used at each time point studied to reduce the influence of individual differences.The brain samples were detected by Gene Chip miRNA arrays (Affymetrix).Results In the brain tissues of fetal or neonatal rats of maternal hypothyroid rats,two miRNAs (mir-206,-324-5p) on E13,three miRNAs (mir-34c,-204,-194) in cortex on P7,and five miRNAs (mir-146b,-532-5p,-384-5p,-215,-212) in hippocampus on P7 were up-regulated by over 2 folds.Five miRNAs (mir-200b,-200c,-217,-672,-139-5p) on E17,one miRNA (mir-376-3p) on P0,and four miRNA (mir-672,-204,-335,-376-3p) in hippocampus on P7 were decreased by 50％ or more.Conclusion The miRNA expression profiles in the rat brain of offspring with maternal hypothyroidism are characterized by miRNA arrays.The identification of a subset of brain expressed miRNAs in the brain may explain the brain development abnormalities resulting from maternal hypothyroidism.

Angelica sinensis polysaccharides delay aging of hematopoietic stem cells through inhibitting oxidative damge / 中国中药杂志

<p><b>OBJECTIVE</b>The effect of angelica sinensis polysaccharides (ASP) on the production of reactive oxygen specie (ROS), the capability of total anti-oxidant (T-AOC), and the expression of p16 in mRNA level in mice hematopoietic stem cells (HSCs) were observed to explore the underlying mechanism that ASP delay aging of HSCs in vivo.</p><p><b>METHOD</b>C57BL/6J mice were randomly divided into normal group, aging group, and the above groups treated with ASP. Mice were uniformly explored in X-ray (3.0 Gy/8 F) to erect model of aging. Normal and aging ASP intervention groups mice were treated with ASP by intragastric administration, while normal and aging groups were treated with equal-volume NS during X-ray irradiation. Mice HSCs were isolated by magnetic cell sorting and cultured in vitro. Senescence-associated beta-galactosidase (SA-beta-Gal) staining was used to detect aging HSCs. Cell cycles analysis and CFU-Mix cultivation were used to evaluate the capability of self-renewing and colony forming in HSCs. The production of ROS in HSCs was evaluated by flow cytometry analysis and immunofluorescence assess, respectively. T-AOC was detected by chemical colorimetric method. The expression of p16 was determined by real-time quantitative PCR (qRT-PCR).</p><p><b>RESULT</b>Exogenous X-ray irradiation induced HSCs aging was compared with normal group without irradiation. Biological feature of HSCs in aging group with X-ray irradiation as follows: The percentage of SA-beta-Gal positive cells, the ratio of G1 stages and the production of ROS were significantly increased , the expression of p16 in mRNA level was also upregulated. The capacility of colony forming and T-AOC in HSCs were decreased. ASP could significantly decrease the percentage of SA-beta-Gal positive cells, the ratio of G1 stages and the production of ROS in HSCs, and downregulate the expression of p16 in mRNA level in HSCs contrast to aging group without ASP treatment. In addition, ASP could remarkably increase T-AOC and the capacility of colony forming in HSCs compared with aging group without ASP treatment.</p><p><b>CONCLUSION</b>X-ray (3.0 Gy/8 F) could induce mice HSCs aging. ASP could delay senescence HSCs aging which maybe partly ascribed to the inhibition of oxidative damage and the downregulation of p16 mRNA expression.</p>

The protective effects of catalpol on kidney of diabetic rats / 中华内分泌代谢杂志

This study was designed to explone whether catalpol exerts a protective effects on kidney of diabetic rats and its possible mechanism.Insulin-like growth factor- I ( IGF- I ) and protein kinase B (PKB/Akt)mRNA and protein expression in kidney of diabetic rats were up-regulated as results of assessments by RT-PCR,immunohistochemistry and Western blot.Catalpol could partially reduce IGF- Ⅰ and Akt expressions in kidney of diabetic rats,and thus alleviate the damage of kidney.

Association of β-amyloid peptide 40/42 with type 2 diabetes mellitus and atherosclerosis / 中华内分泌代谢杂志

Serum p-amyloid peptide(Aβ)40 and Ap42 levels in patients with type 2 diabetes mellitus (T2DM)and atherosclerosis(AS)were detected by ELISA.The results showed that serum Ap40 level in T2DM group was significantly higher than that in the control group[(274.70±159.51 vs 162.63±87.58)pg/ml,P<0.05],especially in the diabetic patients accompanied with AS[(616.95±195.13)pg/m],P<0.01].Serum Ap40 level in simple AS group was also higher than that in control group[(318.52± 188.65)pg/ml,P<0.05].These results suggest that Ap40 is a risk factor of T2DM complicated with AS.However,there was no difference in serum Ap42 levels among various groups.

Association between myocardial connexin 40 and 45 expression and myocardial fibrosis in the rapid atrial pacing canine model / 中华心血管病杂志

<p><b>OBJECTIVE</b>Electrical and structural remodeling are of importance for the occurrence and maintenance of atrial fibrillation. We observed association between atrial connexin protein expression and fibrosis in a canine model of prolonged rapid atrial pacing.</p><p><b>METHODS</b>"J"-type electrodes were placed in the right atrial appendage under the guidance of X-ray in 16 dogs, Animals in model group (n = 8) received fast pacing (400 beats/min) for 10 weeks while animals in control group (n = 8) maintained at sinus rhythm. Limb-lead ECGs were recorded at 2, 4, 6, 8 weeks respectively. Burst stimulation was applied to induce atrial fibrillation in all animals after 10 weeks, animals were sacrificed thereafter and the left atrial tissues were taken for myocardial collagen measurement (Masson staining) and myocardial ultrastructure examination and detection of protein expression of connexin (Cx) 40 and 45 (immune staining). Procollagen type III N-terminal peptide and type IV collagen in serum were also detected by radioimmunoassay.</p><p><b>RESULTS</b>Two dogs died in model group due to atrial rupture induced cardiac tamponade or lung emboli. Spontaneously atrial fibrillation was not observed in all animals, but two dogs developed atrial flutter and atrial premature beats. Atrial fibrillation was induced by burst stimulation in 4 out of 6 dogs in model group and in none of the dogs in control group. Atrial myocardial collagen volume fraction was significantly increased in model group compared with the control group (P < 0.05). Ultrastructure examination in atrial tissue evidenced disorder, fracture, collagen fiber proliferation, mitochondrial swelling, blurred cristae, and intercalated disc distortion, expansion, part of gap junction disappears in model group. The serum levels of procollagen type III N-terminal peptide and type IV collagen in model group were significantly higher than in the control group (P < 0.05). The protein expression of Cx 40 in atrial myocardium in model group was significantly higher than in control group (P < 0.05), while Cx 45 protein expression was similar between two groups (P > 0.05). The left atrial CVF was positively correlated with Cx 40 (r = 0.671, P < 0.01).</p><p><b>CONCLUSION</b>Increased myocardial fibrosis is positively correlated with upregulation of myocardial Cx 40 protein expression in left atrium in rapid atrial paced canine.</p>

The Correlation between Thyrotropin and Dyslipidemia in a Population-based Study

This study investigated the relationship between serum thyrotrophin levels and dyslipidemia in subclinical hypothyroid and euthyroid subjects. A total of 110 subjects with subclinical hypothyroidism and 1,240 euthyroid subjects enrolled in this study. Patients with subclinical hypothyroidism had significantly lower high density lipoprotein cholesterol (HDL-C) levels than those who were euthyroid. The lipid profiles were each categorized and mean thyrotrophin levels were higher in subjects in the dyslipidemia subclasses than subjects in the normal subclasses. Thyrotrophin was positively associated with serum triglyceride and negatively associated with serum HDL-C in women. Thyrotrophin was also positively associated with total cholesterol (TC) in the overweight population along with TC and LDL-C in overweight women. In the euthyroid population, thyrotrophin was positively associated with TC in the overweight population. In conclusion, serum thyrotrophin was correlated with dyslipidemia in subclinical hypothyroid and euthyroid subjects; the correlation was independent of insulin sensitivity.

Effects of losartan and simvastatin on collagen content, myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overload rat hearts / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of simvastatin(Sim) and losartan(Los) on cardiac fibrosis and myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overloaded rat hearts.</p><p><b>METHODS</b>The pressure overload model was induced by descending aortic constriction (DAC) in rats. SD rats were randomized into 6 groups (n = 20 each): normol control group, control sham group, DAC group, Los group (DAC + Los, 5 mg/kg), Sim group (DAC + Sim, 2 mg/kg), Los + Sim group (DAC + Los + Sim, Los 5 mg/kg, Sim 2 mg/kg). Water, Los or Sim drug was administrated by gavage daily beginning from day 5 after operation for 30 days. Collagen was measured on Masson stained myocardial sections, and the level of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in left ventricle were detected by RT-PCR.</p><p><b>RESULTS</b>Collagen volume fraction (CVF) in DAC group was significantly higher than the normal control and sham groups (P < 0.01) which could be significantly reduced by Los and Sim (P < 0.05), especially in DAC + Los + Sim group (P < 0.01). The levels of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA were also significantly higher in DAC group than in normal control and sham groups (P < 0.01). Treatment Sim and Los alone and especially in combination significantly decreased the TIMP-1 mRNA, TIMP-2 mRNA expressions (P < 0.01) while MMP-2 mRNA, MMP-9 mRNA levels remained unchanged (P > 0.05).</p><p><b>CONCLUSION</b>Upregulation of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA expressions might contribute to myocardial fibrosis in this model, Sim and Los significantly inhibited myocardial fibrosis possibly by downregulating myocardial TIMP-1 mRNA, TIMP-2 mRNA expressions in this model.</p>

Effects of five-year intensive multifactorial intervention on the serum amyloid A and macroangiopathy in patients with short-duration type 2 diabetes mellitus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A five-year follow-up study of intensive multifactorial intervention was undertaken to assess the changes of circulating serum amyloid A (SAA) levels and the incidence of atherosclerosis (AS) in patients with short-duration type 2 diabetes mellitus (T2DM) without macroangiopathy, and whether intensive multifactorial intervention could prevent or at least postpone the occurrence of macroangiopathy.</p><p><b>METHODS</b>Among 150 patients with short-duration T2DM, 75 were assigned to receive conventional outpatient treatment (conventional group) and the others underwent intensive multifactorial integrated therapy targeting hyperglycemia, hypertension, dyslipidemia and received aspirin simultaneously (intensive group).</p><p><b>RESULTS</b>Plasma SAA levels were higher in diabetic patients than those in healthy control subjects, and decreased obviously after intensive multifactorial intervention. The levels of SAA were positively correlated with body mass index (BMI), waist hip ratio (WHR), triglyceride (TG), high sensitive C-reactive protein (hs-CRP) and common carotid intima-media thickness (CC-IMT). The standard-reaching rates of glycemia, blood pressure and lipidemia were significantly higher in intensive group than those of conventional group. The incidence of macroangiopathy decreased by 58.96% in intensive group compared with conventional group.</p><p><b>CONCLUSIONS</b>Intensive multifactorial intervention may significantly reduce the SAA levels and prevent the occurrence of AS in short-duration patients with T2DM. SAA might be one of the risk factors of T2DM combined with AS.</p>