Morphological and molecular identification of trematode isloates from laying ducks in Nanchang City / 中国血吸虫病防治杂志

Objective To identify the species of trematodes isolated from laying ducks in Nanchang City using morphological and molecular approaches. Methods Trematodes were isolated from the hepatobiliary duct, gallbladder and large intestine of market-sold laying ducks in Nanchang City. Following morphological characterization, total DNA was extracted from all trematode specimens, and internal transcribed spacer region (ITS) and cytochrome C oxidase subunit 1 (Cox1) genes were amplified using PCR assay and sequenced. Sequence alignment was performed using the Blast software, and homology and phylogenetic analyses were done in the trematode isolates based on ITS and Cox1 gene sequences. Results The morphological characteristics of two trematode isolates from the large intestine of laying ducks were similar to those of Echinostoma revolutum and E. miyagawai, and the morphological characteristics of eight trematode samples isolated from the hepatobiliary duct and gallbladder of laying ducks were similar to those of Amphimerus anatis. The ITS and Cox1 gene sequences of the two trematode isolates from the large intestine of laying ducks had 99.3% and 98.9%-99.4% homology with E. miyagawai, and the phylogenetic analysis showed that two trematode isolates had the closest genetic relationship with E. miyagawai based on ITS and Cox1 gene sequences. The ITS gene sequences of eight trematode isolates from the hepatobiliary duct and gallbladder of laying ducks shared 95.1%-95.5% with Opisthorchis sudarikovi and Clonorchis sinensis, while the Cox1 gene sequences of eight trematode isolates from the hepatobiliary duct and gallbladder of laying ducks shared 86.3%-86.4% and 85.5%-85.7% with O. viverrini and O. sudarikovi. ITS gene sequence-based phylogenetic analysis showed that the duck-derived trematode isolates had the closest genetic relationship with C. sinensis, and Cox1 gene sequence-based phylogenetic analysis showed that the duck-derived trematode isolates had the closest genetic relationship with Metorchis orientalis and O. viverrini. Conclusions The trematode isolates from the large intestine of laying ducts in Nanchang City may be E. miyagawai, and the trematode isolates from the hepatobiliary duct and gallbladder may be an unidentified trematode species of the family Opisthorchiidae.

A highly potent and stable pan-coronavirus fusion inhibitor as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases

The development of broad-spectrum antivirals against human coronaviruses (HCoVs) is critical to combat the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, as well as future outbreaks of emerging CoVs. We have previously identified a polyethylene glycol-conjugated (PEGylated) lipopeptide, EK1C4, with potent pan-CoV fusion inhibitory activity. However, PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo. Therefore, we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment (HR2-CF) of HCoV-OC43. Among these lipopeptides, EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike (S) mutants, as well as other HCoVs and some bat SARS-related coronaviruses (SARSr-CoVs) tested. The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes, better metabolic stability in mouse serum, higher thermostability than the PEGylated lipopeptide EK1C4, suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.

The relationship between thrombin activatable fibrinolysis inhibitor and coronary heart disease / 预防医学

Objective@#To analyze the relationship between thrombin activatable fibrinolysis inhibitor ( TAFI ) and coronary heart disease ( CHD ), and to provide evidence for the prevention of CHD. @*Methods@#The patients with CHD in Fushun Central Hospital in Liaoning Province were selected as the case group, the patients without CHD in the same hospital and period were selected as the control group. The demographic information and clinical examination results ( serum TAFI, lipid, glucose, etc. ) were collected to analyze the association between TAFI and CHD by logistic regression models.The multivariate logistic regression analysis was used to explore the relationship between TAFI and CHD.@*Results@#There were 222 cases, including 100 cases of stable angina, 44 cases of unstable angina and 78 cases of acute myocardial infarction, and 222 controls. The median ages of cases and controls were 62 and 57 years old. The results of multivariate logistic regression analysis showed that serum TAFI>22.88 μg/mL ( P75 of controls ) was associated with the risk of CHD ( OR=1.619, 95%CI: 1.011-2.593 ), unstable angina ( OR=2.917, 95%CI: 1.433-5.939 ) and acute myocardial infarction ( OR=2.626, 95%CI: 1.007-6.847 ). @*Conclusion@#The high level of TAFI is related to CHD, unstable angina and acute myocardial infarction.

Structural equation modeling analysis of the quality of life′s influencing factors among puerperal women / 中国实用护理杂志

Objective To explore the relationship among social support, postpartum depression and quality of life of puerperal women. Methods A total of 348 puerperal women were investigated with Postnatal Social Support Questionnaire,Edinburgh Postnatal Depression Scale (EPDS) and WHO Quality of Life-BREF (WHOQOL-BREF). Results Pearson correlation analysis showed that there was a significant positive correlation between social support and the quality of life (r=0.483, P < 0.01), and a significant negative correlation to postpartum depression (r=-0.243, P < 0.01),and a significant negative correlation between postpartum depression and quality of life (r=-0.408, P<0.01). Intermediary effect of postpartum depression was tested. Conclusions A good social support system is benefit to improve depression scores for EPDS, and promote the life quality in puerperal women.

Current Trends for ST-segment Elevation Myocardial Infarction during the Past 5 Years in Rural Areas of China's Liaoning Province: A Multicenter Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Since 2010, two versions of National Guidelines aimed at promoting the management of ST-segment elevation myocardial infarction (STEMI) have been formulated by the Chinese Society of Cardiology. However, little is known about the changes in clinical characteristics, management, and in-hospital outcomes in rural areas.</p><p><b>METHODS</b>In the present multicenter, cross-sectional study, participants were enrolled from rural hospitals located in Liaoning province in Northeast China, during two different periods (from June 2009 to June 2010 and from January 2015 to December 2015). Data collection was conducted using a standardized questionnaire. In total, 607 and 637 STEMI patients were recruited in the 2010 and 2015 cohorts, respectively.</p><p><b>RESULTS</b>STEMI patients in rural hospitals were older in the second group (63 years vs. 65 years, P = 0.039). We found increases in the prevalence of hypertension, prior percutaneous coronary intervention (PCI), and prior stroke. Over the past 5 years, the cost during hospitalization almost doubled. The proportion of STEMI patients who underwent emergency reperfusion had significantly increased from 42.34% to 54.47% (P < 0.0001). Concurrently, the proportion of primary PCI increased from 3.62% to 10.52% (P < 0.0001). The past 5 years have also seen marked increases in the use of guideline-recommended drugs and clinical examinations. However, in-hospital mortality and major adverse cardiac events did not significantly change over time (13.01% vs. 10.20%, P = 0.121; 13.34% vs. 13.66%, P = 0.872).</p><p><b>CONCLUSIONS</b>Despite the great progress that has been made in guideline-recommended therapies, in-hospital outcomes among rural STEMI patients have not significantly improved. Therefore, there is still substantial room for improvement in the quality of care.</p>

Establish and use of an epilepsy model in larval zebrafish / 药学学报

Epilepsy is a kind of neurogenic diseases with high prevalence and characterized by seizure, brain paradoxical discharge and convulsion in spontaneous, transient, recurrent and uncontrolled manner. Development of new anti-epilepsy drugs requires a new reliable and high-performance animal models in screening of leading compounds. In this study, an epilepsy model in larval zebrafish was established using pentylenetetrazole (PTZ) compound. The results show that PTZ induced epilepsy-like seizure behavior such as irregular circular swimming, exciting locomotion, high swim velocity and convulsion in zebrafish. Expression patterns of two epilepsy-related gene c-fos and lgi1 were analyzed using RT-PCR and in situ hybridization; c-fos was enhanced and extended and lgi1 expression was reduced in PTZ concentration-dependent in the larval brain. When the model larvae exposed to anticonvulsant valproate (VPA), the epilepsy-like symptom decreased or disappeared, the marker genes c-fos and lgi1, as well as NeuN protein recovered to the normal levels. These responses to PTZ and to antiepileptic drug VPA are consistent with the observations in clinical studies and mouse models. Using this model, we evaluated anti-epilepsy activity of compounds Y53 and BMT, two homolog of berberine. The results show that the model larvae seizure triggered by lighting was partly remedied by Y53; and the larval exciting locomotion under the condition of no stimulation was suppressed by BMT. The findings indicate that the zebrafish larval epilepsy model is able to distinguish compounds with different activities in eleptiform seizure. We conclude that the zebrafish epilepsy model may be as a reliable and useful platform in screening of new anti-epilepsy candidates, which is suitable for basic research in epilepsy pathogenesis.

Expression and roles of poly(ADP-ribose) polymerase-1 and caspase-3 in pancreatic cancer and adjacent tissues / 临床肝胆病杂志

ObjectiveTo investigate the protein expression of poly(ADP-ribose) polymerase-1 (PARP-1) and caspase-3 in pancreatic cancer and adjacent tissues. MethodsA total of 66 cancer tissue samples and 113 samples of adjacent tissues were collected from the patients who underwent surgical treatment with a confirmed diagnosis of pancreatic cancer by postoperative pathological examinations in The First Hospital of Lanzhou University from January 2013 to June 2014, and immunohistochemical examinations were performed to measure the expression of PARP-1 and caspase-3 in these samples. The chi-square test was applied for comparison of categorical data between groups. ResultsOf all the 66 samples of pancreatic cancer, 53 had varying degrees of PARP-1 expression, with a positive rate of 803%; of all the 133 samples of adjacent tissues, 39 had PARP-1 expression, with a positive rate of 34.5%; the expression of PARP-1 in the samples of pancreatic cancer was significantly higher than that in the samples of adjacent tissues (χ2=34.79, P＜0.01). The expression of PARP-1 in moderately and poorly differentiated samples of pancreatic cancer (18/25, 72%; 10/14, 71.4%) was significantly higher than that in highly differentiated samples (3/14, 21.4%) (χ2=10.76, P＜0.01). Of all the 66 samples of pancreatic cancer, 47 had varying degrees of caspase-3 expression, with a positive rate of 71.2%; of all the 133 samples of adjacent tissues, 71 had caspase-3 expression, with a positive rate of 62.8%. The expression of caspase-3 in highly differentiated samples of pancreatic cancer (11/18, 61.1%) was significantly higher than that in moderately and poorly differentiated samples (4/20, 20%; 0/9, 0) (χ2=11.44, P＜001). ConclusionThe expression level of PARP-1 in the samples of pancreatic cancer is significantly higher than that in the samples of adjacent tissues, and the strong positive rate of PARP-1 increases with the decrease in the degree of differentiation; the expression of caspase-3 is similar between pancreatic cancer and adjacent tissues, and the strong positive rate of caspase-3 decreases with the decrease in the degree of differentiation. The expression levels of PARP-1 and caspase-3 may be related to the development and progression of pancreatic cancer.

Diagnostic Value of Soluble Suppression of Tumorigenicity-2 for Heart Failure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Many studies have explored the diagnostic performance of soluble suppression of tumorigenicity-2 (sST2) for heart failure (HF), but the results are inconsistent. Here, we performed a meta-analysis to assess the role of sST2 in the diagnosis of HF.</p><p><b>METHODS</b>We searched PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database from inception to April 2015. Studies that investigated the diagnostic role of sST2 for HF were reviewed. The numbers of true-positive, false-positive, false-negative, and true-negative results were extracted to calculate pooled diagnostic odds ratio (DOR) with 95% confidence interval (CI) and the summary receiver operating characteristic curve and area under the curve (AUC). The Spearman correlation coefficient was used to check the threshold effect. The Cochran Q statistic (P < 0.05) and the inconsistency index (I2 > 50%) were used to assess the nonthreshold effect. Meta-regression was conducted to explore the source of heterogeneity; subgroup analysis showed the results in different subgroups. Finally, the Deeks' test was performed to assess the publication bias.</p><p><b>RESULTS</b>Nine articles including 10 studies were included in the meta-analysis. The pooled sensitivity was 0.84 (95% CI: 0.81-0.86), and pooled specificity was 0.74 (95% CI: 0.72-0.76). The summary DOR was 8.49 (95% CI: 4.54-15.86), and AUC was 0.81 (standard error: 0.03). The Spearman correlation coefficient identified the nonsignificant threshold effect (coefficient = 0.49, P = 0.148), but the nonthreshold effect heterogeneity was significant (Cochran Q = 58.52, P < 0.0001; I2 = 84.6%). Meta-regression found that characteristics of controls might be the suggestive source of nonthreshold effect heterogeneity (P = 0.095). Subgroup analysis found that DOR was 5.65 and 7.86, respectively for the controls of hospital patients and healthy populations. Deeks' test demonstrated that there was no publication bias (P = 0.616).</p><p><b>CONCLUSION</b>The meta-analysis illustrated that sST2 might play a role in diagnosing HF.</p>

Relationship between PD-1 expression in liver tissues with TCM syndromes and liver pathology in patients with chronic hepatitis B / 国际中医中药杂志

Objective To discuss the relationship between the expression of programmed death-1 (PD-1) in liver with traditional Chinese medicine (TCM) syndromes and pathological diagnosis in chronic hepatitis B.Methods 156 CHB patients treated in our hospital of infectious diseases department were recruited as an observation group. Based on the principle of informed voluntary and approved by the ethics committee, liver biopsy was adopted to make clear liver tissue pathology. According to TCM classification criteria, CHB patients were divided into five groups: a blood stasis group, a damp heat resistance group, a liver and spleen deficiency group, a liver and kidney yin deficiency group, and a spleen and kidney yang deficiency group. In the same period, 12 healthy persons were recruited as a control group. The PD-1 expression was detected with immunohistochemical SP method, and the correlation between expression of PD-1 in liver tissue and TCM syndrome type and liver pathology was analyzed.Results Different degrees of positive cell expression were found in the liver tissue. With the liver inflammation and fibrosis severity, the number of PD-1 positive cells also increased. The PD-1 expression levels varied with mild, moderate, and severe CHB patients (0.24 ± 0.03, 0.36 ± 0.05 vs. 0.43 ± 0.05) , which were statistically significant (P<0.05) . PD-1 expression levels also varied among different TCM type CHB patients, of which, PD-1 expression of blood stasis type was the highest (0.35 ± 0.04), while the liver and spleen deficiency type was the lowest (0.23 ± 0.03).Conclusion The expression levels of PD-1 has a certain correlation with the patients illness, chronic mechanism, and TCM syndromes. CHB patients can be treated by controlling the expression of PD-1.

Effect of beclin1 on vincristine-induced dopaminergic neurons injury in zebrafish / 药学学报

To investigate vincristine-induced dopaminergic neurons toxicity and mechanism, and explore the molecular target to reduce the toxicity, zebrafish was chosen as a model animal, based on RT-PCR, Western blotting, whole mount in situ immunofluorescence and other technical means. The results showed that the transcription levels of tyrosine hydroxylase gene and dopamine transporter protein gene were inhibited. Furthermore, the number of dopaminergic neurons was decreased by vincristine. Autophagy was suppressed and beclin1 gene expression was inhibited in a dose-dependent manner by vincristine in larval zebrafish. Up-regulated beclin1 partly reduced vincristine-induced neurotoxicity, and down-regulated beclin1 increased toxicity. Beclin1 plays an important role in vincristine-induced dopaminergic neurons toxicity.

Preparation and identification of recombinant sarcosine oxidase / 生物医学工程学杂志

An important index determination for clinical diagnosis of renal function is to assay the creatinine concentration in serum. In the analytical process applied with coupled-enzyme, the quality control of sarcosine oxidase (SOX) as a key enzyme is the first problem to be solved. In order to establish an efficient and laboratory-scale production of SOX, the recombinant sarcosine oxidase (r-SOX) gene was a high-level expression in E. coli induced with lactose on a large-scale fermentation in 300 L fermenter. The results suggested that the biomass concentration reached OD600 of 22 and the expression of recombinant sarcosine oxidase in E. coli accounted for about 25% of total soluble protein in culture after fermentation. The cell-free extract obtained from high pressure homogenizer was processed by selective thermal denaturation and then purified with Ni-Sepharose FF chromatography. The sarcosine oxidase with 97% purity, 25 U/mg specific activity and 92.4% activity recovery was obtained. The molecular weight with single peptide chain of 53 kD and 55 kD of recombinant sarcosine oxidase was assessed by SDS-PAGE in presence or absence of 2-mercaptoehanol and Sephacryl S-200 chromatography. This sarcosine oxidase was found to be a conjugated protein, yellow enzyme, which combined with FAD as prosthetic group by covalent linkage. The contaminant of catalase was not detected in the sample pool of this enzyme. In addition, a further test to the thermal stability of sarcosine oxidase was done. According to the above results, the development and utilization of this enzyme has been set up on a reliable foundation.

Clinical research on fire filiform needle combined with mild moxibustion for postherpetic neuralgia / 中国针灸

<p><b>OBJECTIVE</b>To compare efficacy differences between fire filiform needle combined with mild moxibustion and gabapentin combined with sham acupuncture for postherpetic neuralgia (PHN).</p><p><b>METHODS</b>One hundred cases of PHN were randomly divided into a needle group and a medicine group, 50 cases in each one. In the needle group, pricking method of fire filiform needle was given at the Ashi points, and then mild moxibustion was applied for 15 min. In the medicine group, the oral administration of gabapentin capsule and sham acupuncture at non-acupoints in the distal end of lesions were applied. The treatment was required for 21 days in both groups. The visual analogue score (VAS) was recorded before treatment and on the 1st day, 2nd day, 3rd day, 6th day, 9th day and 12th day of treatment. The most severity of pain within last 24 h, preset severity of pain, immediate analgesia effect and starting time of pain relief were observed, also the efficacy was assessed and improvement of symptoms was observed in the follow-up visit.</p><p><b>RESULTS</b>The total effective rate was 94.0% (47/50) in the fire filiform needle group, which was superior to 86.0% (43/50) in the medicine group (P < 0.05). Compared with medicine group, the VAS of the most severity of pain within last 24 h was obviously reduced after the 2nd treatment in the fire filiform needle group while that of present severity of pain was relieved after the 1st treatment (both P < 0.05). The immediate analgesia effect in the fire filiform needle group was obviously superior to that in the medicine group in the first three times of treatment (all P < 0.05). The average time of pain relief was (3.91 +/- 0.82) days in the fire filiform needle group, which was significantly earlier to (6.53 +/- 1.13) days in the medicine group (P < 0.05). 26 cases were cured in the fire filiform needle group in the follow-up visit, which was superior to 2 cases in the medicine group (P < 0.05). The improvement of VAS, pain range and sleep quality in the needle group were also superior to those in the medicine group (all P < 0.05). The direct medical cost in the fire filiform needle group was (232.32 +/- 48.108) yuan, which was significantly lower than (466.00 +/- 41.09) yuan in the medicine group (P < 0.05). There was only one case of adverse effect in the medicine group during the treatment.</p><p><b>CONCLUSION</b>The fire filiform needle combined with mild moxibustion could obviously relieve the pain in PHN patients, which has superior immediate analgesia effect and pain relieving time compared with gabapentin, which also has less adverse effects and cheap cost.</p>

Prospective multi-center study of female patients with ST-elevation myocardial infarction in Liaoning province, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In cardiology, it is controversial whether gender influences prognosis after acute myocardial infarction (MI). We examined the 30-day and 1-year prognosis for female patients with ST-elevation myocardial infarction (STEMI) in Liaoning province, and we analyzed factors that influenced these outcomes.</p><p><b>METHODS</b>This was a prospective, multicenter, observational study in which patient data were collected by questionnaire at the time of diagnosis and at approximately 30 days and 1 year later by telephone inquiries. Patients were diagnosed with STEMI between June 1, 2009 and June 1, 2010 at any of the 20 hospitals that gave treatment representative of current STEMI treatment in Liaoning Province. Unified follow-up questionnaire was used to visit the STEMI patients.</p><p><b>RESULTS</b>We analyzed data from a total of 1429 consecutive patients with STEMI in Liaoning province. Female patients were older (70.0 vs. 60.3, P < 0.001) and were less likely to receive emergency reperfusion therapy than male ones (39.2% vs. 58.0%, P < 0.001). Female gender was associated with higher unadjusted 30-day mortality rates (HR = 2.118, 95%CI: 1.572 - 2.854, P < 0.001) and higher unadjusted 1-year mortality rates (HR = 2.174, 95%CI: 1.659 - 2.848, P < 0.001). Multivariate Cox regression analysis showed that female gender was not an independent predictor of 30-day mortality rates (HR = 1.273, 95%CI: 0.929 - 1.745, P = 0.133) nor of 1-year mortality rates (HR = 1.112, 95%CI: 0.831 - 1.487, P = 0.475).</p><p><b>CONCLUSIONS</b>Women with STEMI appear to be at increased risk of 30-day and 1-year mortality compared with male STEMI patients, but this difference may be explained by older age and less frequent receipt of reperfusion therapy among the women.</p>

The process of application and implementation on methodologies for comparative effectiveness research / 中华流行病学杂志

Comparative effectiveness research is able to compare the clinical effects of diagnosis and treatment measures effectively,thus providing evidence for making medical decision.In addition that the large-scale clinical randomized controlled trials,cluster randomized trials,quasi-trial,and mathematical models have started to be used in the designing processes of comparative effectiveness research,observational studies on the foundation of electronic medical records have also been paid enough attention.For each research topic,every procedure on the following areas as:generation of a specific piece of evidence,as well as synthesis,communication,translation and application of related data need to have corresponding statistical methods to perform statistical analysis and quality control.

Chemoresistance of CD133+ cancer stem cells in laryngeal carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mounting evidence suggests that tumors are histologically heterogeneous and are maintained by a small population of tumor cells termed cancer stem cells. CD133 has been identified as a candidate marker of cancer stem cells in laryngeal carcinoma. This study aimed to analyze the chemoresistance of CD133(+) cancer stem cells.</p><p><b>METHODS</b>The response of Hep-2 cells to different chemotherapeutic agents was investigated and the expression of CD133 was studied. Fluorescence-activated cell sorting analysis was used to identify CD133, and the CD133(+) subset of cells was separated and analyzed in colony formation assays, cell invasion assays, chemotherapy resistance studies, and analyzed for the expression of the drug resistance gene ABCG2.</p><p><b>RESULTS</b>About 1% - 2% of Hep-2 cells were CD133(+) cells, and the CD133(+) proportion was enriched by chemotherapy. CD133(+) cancer stem cells exhibited higher potential for clonogenicity and invasion, and were more resistant to chemotherapy. This resistance was correlated with higher expression of ABCG2.</p><p><b>CONCLUSIONS</b>This study suggested that CD133(+) cancer stem cells are more resistant to chemotherapy. The expression of ABCG2 could be partially responsible for this. Targeting this small population of CD133(+) cancer stem cells could be a strategy to develop more effective treatments for laryngeal carcinoma.</p>

Zebrafish model for the study on drug ototoxicity of aminoglycoside antibiotics / 药学学报

Aminoglycoside antibiotics, due to their strong antibacterial effects and broad antimicrobial spectra, have been very commonly used in clinical practice in the past half century. However, aminoglycoside antibiotics manifest severe ototoxicity and nephrotoxicity, and are one of top factors in hearing loss. In this study, three members of the aminoglycoside antibiotics family, gentamycin, neomycin and streptomycin, were chosen as the representatives to be investigated for their toxicity to the embryonic development and the larva hair cells in zebrafish, and also to their target genes associated with hearing-related genes. The results showed that: (1) the lethal effect of all three drugs demonstrated a significant dependence on concentration, and the severity order of the lethal effect was streptomycin > neomycin > gentamycin; (2) all the three drugs caused the larva trunk bending in resting state at 5 dpf (day past fertilization), probably due to their ototoxicity in the physical imbalance and postural abnormalities; (3) impairment and reducing of the hair cells were observed in all three cases of drug treatment; (4) four genes, eya1, val, otx2 and dlx6a, which play an important role in the development of hearing organs, showed differential and significant decrease of gene expression in a drug concentration-dependent manner. This study for the first time reports the relevance between the expression of hearing genes and the three ototoxic antibiotics and also proved the feasibility of establishing a simple, accurate, intuitive and fast model with zebrafish for the detection of drug ototoxicity.

Meta-analysis on the association between subclinical hypothyroidism and the left ventricular functions under Doppler echocardiography / 中华流行病学杂志

Objective To explore the association between subclinical hypothyroidism and the left ventricular functions under conventional 2D Doppler echocardiography and to provide evidence for the protection of heart function.Methods Literatures regarding the association of subclinical hypothyroidism and the left ventricular functions were retrieved in large databases from home and abroad for the last 12 years.The left ventricular systolic function was assessed by left ventricular ejection fraction and the shortening of left ventricular fraction.The left ventricular diastolic function was assessed by left ventricular early diastolic filling flow velocity,late diastolic filling flow velocity,their ratios(E/A),and the left ventricular isovolumic relaxation time.The relationship between subclinical hypothyroidism and the left ventricular functions were assessed by Meta-analysis with Stata 11 software.The weighted mean difference(WMD)and 95％ confidence interval(CI)were calculated,and the publication bias was assessed by Begg' s test.Results 1 3 eligible papers were included.(1)Statistics on the combined data showed that in the evaluation of left ventricular diastolic function indicators.There were significant differences in left ventricular late diastolic filling flow velocity(WMD=4.51,95％CI:2.41 to 6.61)and E/A(WMD=-0.22,95％CI:-0.30 to-0.13),as well as the left ventricular isovolumic relaxation time(WM D=6.13,95％ CI:2.79 to 9.48)between patients with subclinical hypothyroidism and normal controls but,no significant difference was found in left ventricular early diastolic filling flow velocity.Looking at the left ventricular systolic function indicators.There were no significant differences in the left ventricular ejection fraction and left ventricular fractional shortening between patients with subclinical hypothyroidism and normal controls.(2)Data from the subgroup analysis showed that the differences of left ventricular late diastolic filling flow velocity,E/A and left ventricular isovolumic relaxation time were significantly different between patients with subclinical hypothyroidism and normal controls in the mean heart rate ≥72 bpm group.The difference of left ventricular isovolumic relaxation time was significantly different in the mean heart rate ＜72 bpm group,and the difference of left ventricular late diastolic filling flow velocity was significant in the mean age ＜60-year-old group.Conclusion Subclinical hypothyroidism was associated with the left ventricular diastolic dysfunction,but not associated with the left ventricular systolic dysfunction.The results suggested that subclinical hypothyroidism might change the heart function which could be evaluated by Doppler echocardiography.

Meta analysis on the relationship between subclinical hypothyroidism and the levels of systolic blood pressure / 中华流行病学杂志

Objective To investigate the association between subclinical hypothyroidism and levels of systolic blood pressure (SBP), so as to provide evidence for the development of prevention strategy and understanding the etiology of hypertension. Methods The articles on the association of subclinical hypothyroidism and systolic blood pressure levels were retrieved by searching international and national databases from 1999 to 2010. The relationship between subclinical hypothyroidism and systolic blood pressure levels was assessed by meta analysis with Stata 11software. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated,and the publication bias was assessed by Begg's test and Egger's test. Results (1) There was significant difference in SBP levels between patients with subclinical hypothyroidism and normal subjects (WMD= 2.04 mm Hg, 95% CI: 0.64 to 3.45, P＜ 0.05 ). (2) Subgroup analysis indicated that there was significant difference seen in thyroid stimulating hormone (TSH) mean difference values ＜7 mU/L group(WMD=2.33 mm Hg,95%CI:0.60 to 4.06,P＜0.05) but not in the group that TSH mean difference values were ＞7 mU/L. There was significant difference seen in the Asian group (WMD=2.62 mm Hg, 95%CI: 1.69 to 3.55,P＜0.05) in the community group(WMD=2.77mm Hg, 95%CI: 1.61 to 3.93, P＜0.05) but not in the European group and or in the hospital group.There was significant difference in the cross-sectional group (WMD=2.77 mm Hg, 95%CI: 1.61 to 3.93, P＜0.05), but not in the case-control group. (3) Results from both Begg' s test and Egger's test did not show significant difference, indicating that there was no publication bias existed.Conclusion Subclinical hypothyroidism was associated with the elevated systolic blood pressure. In terms of the role of subclinical hypothyroidism that might serve as one of the potential risk factor for the elevated systolic blood pressure. Well designed and large sample-sized prospective studies were necessary to confirm the association between subclinical hypothyroidism and systolic blood pressure.Random controlled trials were also needed to study whether the treatment could lower the risk. Active treatment for subclinical hypothyroidism might be useful for prevention and treatment of hypertension.

Interactomic study on interaction between lipid droplets and mitochondria

An increasing body of evidence shows that the lipid droplet, a neutral lipid storage organelle, plays a role in lipid metabolism and energy homeostasis through its interaction with mitochondria. However, the cellular functions and molecular mechanisms of the interaction remain ambiguous. Here we present data from transmission electron microscopy, fluorescence imaging, and reconstitution assays, demonstrating that lipid droplets physically contact mitochondria in vivo and in vitro. Using a bimolecular fluorescence complementation assay in Saccharomyces cerevisiae, we generated an interactomic map of protein-protein contacts of lipid droplets with mitochondria and peroxisomes. The lipid droplet proteins Erg6 and Pet10 were found to be involved in 75% of the interactions detected. Interestingly, interactions between 3 pairs of lipid metabolic enzymes were detected. Collectively, these data demonstrate that lipid droplets make physical contacts with mitochondria and peroxisomes, and reveal specific molecular interactions that suggest active participation of lipid droplets in lipid metabolism in yeast.

Teratogenesis and gene targets of 17alpha-ethynylestradiol on embryonic development in zebrafish / 药学学报

The pharmaceutical ethynylestradiol (EE) is a potent endocrine modulator. Application enlargement of ethynylestradiol in clinics and abuse in livestock farming and fishing make it important to explore ethynylestradiol toxicological action on vertebrate embryonic development and to establish an in vivo method for EE toxicity detection efficiently and conveniently. In the present study, using a model animal zebrafish and 17alpha-ethynylestradiol as a representative compound, we have investigated EE2 teratogenicity, target tissues and target genes on zebrafish embryo. The results show that median teratogenesis concentration (TC50) of EE2 is 0.8 microg x mL(-1), and median lethal dose (LD50) is 3.3 microg x mL(-1). Targets of EE2 action were implicated in brain, eyes, heart, muscle, skeleton, pigment and viscera. Embryonic cardiac arrhythmia caused by EE2 is probably resulted from heart abnormal structure. The embryonic stage sensitive to EE2 mainly started at cleavage and last up to the organogenesis with time-accumulating effect. RT-PCR results indicate that EE2 treatment disturbed gene expression pattern at the early period of zebrafish embryonic development by suppressing transcription of gene boz that promotes brain development, upregulating genes for trunk and tail, such as ntl, spt, shh, and perturbing Nodal signal expression of TGFbeta superfamily, for example, cyc, sqt and oep. Using zebrafish, an efficient in vivo method for quick evaluation of EE toxicity on embryonic development has been developed.