Study on the fecal metabolomics of CUMS-susceptible and CUMS-resilient rats / 药学学报

Proton nuclear magnetic resonance (1H NMR) based metabolomics was applied to characterize the fecal metabolic profiles of chronic unpredictable mild stress (CUMS)-depression (CUMS-D) and CUMS-resilience (CUMS-R) rats. The fecal biomarkers and metabolic pathways involved in CUMS-D and CUMS-R were screened and identified, revealing the underlying mechanisms of two different responses of the body to the same stresses. Firstly, the classic depression model, i.e. CUMS, was constructed. According to the fecal metabolomics profiles, the model rats were divided into two groups, i.e. the CUMS-D group and the CUMS-R group. And then, the depression statuses of CUMS-D rats and CUMS-R rats were verified by their sucrose preference rates. Lastly, multivariate data analysis was applied to clarify the fecal biomarkers and corresponding metabolic pathways involving in CUMS-D and CUMS-R. The results show that compared with the control rats, the sucrose preference rates of CUMS-D rats were significantly reduced. By contrast, the sucrose preference rates of CUMS-R rats had no significant difference. At the same time, CUMS-D and CUMS-R showed both unique and shared biomarkers and pathways. Three pathways are significantly related to CUMS-D, including taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and arginine and proline metabolism. Glycerolipid metabolism and tryptophan metabolism are specific pathways related to CUMS-R. This study explores the mechanisms of the emergence of susceptible and resilience of rats under the same stimulus from a metabolomics perspective. The current findings provide not only a new perspective for studying depression, and personalized and precision treatments in clinic, but also the research and development of antidepressants.

Mechanism of Xiaoyao San in treatment of depression,breast hyperplasia,and functional dyspepsia based on network pharmacology / 中国中药杂志

This study aimed to explore the mechanism of Xiaoyao San(XYS) in the treatment of three diseases of liver depression and spleen deficiency, ie, depression, breast hyperplasia, and functional dyspepsia, and to provide a theoretical basis for the interpretation of the scientific connotation of "treating different diseases with the same method" of traditional Chinese medicines. Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to screen the active components of XYS which underwent principal component analysis(PCA) with the available drugs for these three diseases to determine the corresponding biological activities. The targets of XYS on depression, breast hyperplasia, and functional dyspepsia were obtained from GeneCards, TTD, CTD, and DrugBank databases. Cytoscape was used to plot the "individual herbal medicine-active components-potential targets" network. The resulting key targets were subjected to Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis and gene ontology(GO) enrichment analysis. A total of 121 active components of XYS and 38 common targets in the treatment of depression, breast hyperplasia, and functional dyspepsia were collected. The key biological pathways were identified, including advanced glycation and products(AGEs)-receptor for advanced glycation and products(RAGE) signaling pathway in diabetic complications, HIF-1 signaling pathway, and cancer-related pathways. The key targets of XYS in the treatment of depression, breast hyperplasia, and functional dyspepsia included IL6, IL4, and TNF, and the key components were kaempferol, quercetin, aloe-emodin, etc. As revealed by the molecular docking, a strong affinity was observed between the key components and the key targets, which confirmed the results. The therapeutic efficacy of XYS in the treatment of diseases of liver depression and spleen deficiency was presumedly achieved by reducing the inflammatory reactions. The current findings are expected to provide novel research ideas and approaches to classify the scientific connotation of "treating different diseases with the same method" of Chinese medicines, as well as a theoretical basis for understanding the mechanism of XYS and exploring its clinical applications.

Research progress in combination applications of antidepressant drugs / 中国中药杂志

Depression is a common affective disorder. The application of antidepressants can significantly alleviate the symptoms of depression, which is the most important way to treat depression in clinical practice. Due to the complex etiology, wide variety, as well as diversity and severity of serious concomitant symptoms, rational addition of other drugs into antidepressants can significantly improve the cure rates of depression, reduce adverse reactions, and improve patient compliances. Therefore, the combined applications of differential drugs have been commonly used in clinic. In this paper, more than 600 literatures about depression from 2010 to 2019 were collected based on the key words of antidepressant, depression, combined medication, synergism and increase efficiency. Based on this, by summarizing and classifying the existing combinations of antidepressant drugs, this paper systematically expounds the current combined applications of antidepressant drugs in three categories, i.e. western medicines combined with western medicines, western medicines combined with traditional Chinese medicines, and traditional Chinese medicines combined with traditional Chinese medicines, in the expectation of providing the direction and basis for the selection of rational combinations of antidepressant drugs in clinic.

Potential quality evaluation approach for the absolute growth years' wild and transplanted Astragali Radix based on anti-heart failure efficacy / 中国天然药物

The quality of Astragali Radix (AR) was closely related to the growth period. However, the current commodity grades of AR were only divided by diameter but not directly related to the growth period, which leads to the contradiction between the grade standard and the quality evaluation index. Therefore, solving this problem will be the key for the quality evaluation of AR. The present study established a potential quality evaluation approach for the absolute growth years' wild Astragali Radix (WAR) and transplanted Astragali Radix (TAR) based on the chemical components and anti-heart failure efficacy through adopting a bare-handed sections approach to rapidly identify the growth years of WAR. In this study, the absolute growth years of WAR were obtained by identifying the growth rings of 1-6 growth years root through the methods. The contents of flavonoids and saponins in 2-6 growth years' WAR were determined by HPLC-UV-ELSD. The contents of 12 chemical components and the anti-fatigue failure effects of WAR (4-year-old) and TAR were compared on rat models of heart failure induced by doxorubicin. Meanwhile, NMR-based untargeted metabolomics studies were performed to investigate the regulative effects of WAR and TAR. The result shows that the numbers of growth rings were consistent with the actual growth periods of AR. The HPLC-UV-ELSD determination indicated that the content of total flavonoids in WAR was significantly higher than that in TAR. Pharmacodynamics analysis revealed that the effects of WAR on cardiac function parameters (EF, FS and LVIDs), contents of serum CK and BNP were superior to those of TAR. 13 metabolites of heart were identified that had a higher rate of change in WAR group than TAR. Overall, a rapid identification method for the growth years of WAR was established, and the fact that WAR were significantly better than TAR in the heart failure rats was first proved in the paper. This study provided a scientific basis for establishing a novel commodity specification and grade of AR for clinical rational drug use.

Effect of electroacupuncture pretreatment on expression of glucose-regulated protein 78 in hippocampus of rats with cerebral ischemia/reperfusion / 中国针灸

<p><b>OBJECTIVE</b>To explore the effects and action mechanism of electroacupuncture (EA) pretreatment on rats with transient cerebral ischemia/reperfusion.</p><p><b>METHODS</b>A total of 144 healthy SD male rats were randomly divided into a sham operation group (group S), an ischemia/reperfusion group (group I/R) and an EA pretreatment group (group EA), 48 rats in each one. The model of cerebral ischemia/reperfusion was established by using 4-vessel occlusion method in the group I/R; after 5 min of cerebral ischemia, the reperfusion was performed. The group EA was treated with EA at "Dazhui" (GV 14) and "Baihui" (GV 20) 5 days before model establishment, 30 min per time, once a day. In group S, bilateral foramen alares were exposed without burning on the vertebral arteries, and bilateral common carotid arteries were unfolded and not occluded. The rats in the group I/R and group EA were sacrificed 6 h, 12 h, 24 h and 48 h after reperfusion and those in the group S were sacrificed at corresponding time to collect hippocampus example. The Western-blot method was used to measure the expression of glucose-regulated protein 78 (GRP 78), and HE staining method was used to count the number of surviving neurons, and TUNEL method was used to measure the number of apoptotic neurons.</p><p><b>RESULTS</b>Compare with the group S, the number of surviving neurons in hippocampus was reduced at each reperfusion time point and the number of apoptotic neurons was increased (all P<0.05) in the group I/R and the group EA; the expression of GRP 78 at each reperfusion time point in group I/R and group EA was increased (P<0.05). Compared with the group I/R, the number of surviving neurons in hippocampus was increased at each reperfusion time point and the number of apoptotic neurons was reduced in the group EA (P<0.05); the expression of GRP 78 at each reperfusion time point was further increased (P<0.05).</p><p><b>CONCLUSION</b>The electroacupuncture pretreatment has obvious cerebral protection on rats with ischemia/reperfusion, which is related with further increasing the expression of GRP 78 in ischemia area, leading to relieved endoplasmic reticulum stress.</p>

Amyloid β protein suppresses hippocampal theta rhythm and induces behavioral disinhibition and spatial memory deficit in rats / 生理学报

Hippocampal neuronal network oscillation is closely related to the memory, anxiety and behavioral inhibition of mammalian. The cognitive decline and behavioral disinhibition in the patients with Alzheimer's disease (AD) may be relevant to amyloid β protein (Aβ)-induced impairment in hippocampal neuronal cooperative activity. However, it is not well known whether intrahippocampal injection of Aβ could induce behavioral disinhibition and neuronal network disorder, as well as cognition decline in animals. In the present study, we observed the effects of intracerebral injection of Aβ(1-42) on the spatial memory and behavioral inhibition of rats by using Morris water maze and elevated plus-maze tests. Further, we analyzed hippocampal theta rhythm by recording hippocampal local field potential. The results showed that: (1) bilateral hippocampal injection of Aβ(1-42) reduced the anxious behavior of rats, with a significant behavioral disinhibition in the elevated plus-maze test, representing as an increase in the mean entering times and mean residence time in the open arm; (2) Aβ(1-42) injection resulted in a significant impairment of spatial memory in rats, with significantly increased mean escape latencies in hidden platform test; (3) Aβ(1-42) disrupted the induction of theta rhythm induced by tail pinch, with a significant reduction in the peak power, not the peak power frequency of the theta rhythm. These experimental results indicate that intrahippocampal injection of Aβ(1-42) can induce behavioral disinhibition and theta rhythm suppression, as well as spatial memory impairment in rats, which suggests that the cognition deficits and behavior impairments in AD are probably associated with the Aβ-induced disruption of hippocampal theta rhythm and consequent down-regulation of synaptic plasticity.

Gly14-humanin protects against Aβ₃₁₋₃₅-induced impairment of spatial learning and memory in rats / 生理学报

Amyloid β protein (Aβ) is closely involved in the pathogenesis of Alzheimer's disease (AD), and one of the main strategies for AD treatment is antagonizing the neurotoxicity of Aβ or even clearing the Aβ deposited in the brain. The present study was aimed to observe the effects of intrahippocampal injection of Aβ₃₁₋₃₅ on the spatial learning and memory of rats by using Morris water maze technique, and explore the neuroprotective effects and possible mechanism of [Gly14]-humanin (HNG) against Aβ-induced deficits in learning behavior. The results showed that bilateral intrahippocampal injection of 2.0 nmol Aβ₃₁₋₃₅ significantly increased the mean traveled distance of rats in searching for the hidden underwater platform and decreased the distance percentage in the target quadrant in probe test after withdrawal of platform, whereas pretreatment with HNG (0.2 nmol and 2.0 nmol) suppressed Aβ₃₁₋₃₅-induced increase in the traveled distance and decrease in swimming distance percentage. Application of Genistein (40 nmol), a specific tyrosine kinase inhibitor, almost completely blocked the antagonistic effects of HNG against Aβ₃₁₋₃₅. These results indicate that HNG can dose-dependently prevent against Aβ₃₁₋₃₅-induced impairment in spatial learning and memory of rats, and the neuroprotective effects of HNG might involve the activation of endogenous tyrosine kinase pathway, suggesting that up-regulation of the tyrosine kinase signaling by using HNG might be of great significance for the improvement of cognitive function in AD.

Treatment and prognosis of gastrointestinal stromal tumor in small intestine: an analysis of 64 patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate treatment and prognostic factors of gastrointestinal stromal tumor(GIST) in the small intestine.</p><p><b>METHODS</b>The clinicopathological data of 64 patients with GIST in the small intestine admitted to the Tianjin Medical University Affiliated Cancer Hospital between April 2002 and November 2010 were analyzed retrospectively and the prognostic factors were evaluated.</p><p><b>RESULTS</b>No patients in this cohort received chemotherapy or radiation therapy. Fourteen patients underwent post-operative imatinib targeted therapy. The overall 5-year survival rate was 51.2% and the post-operative recurrence rate of 61 cases undergoing R0 resection was 44.3%. Univariate analysis revealed that the complete tumor resection(P=0.001), tumor size(P=0.018), adhesion or invasion to surrounding tissue and organs (P=0.015), concurrent distant metastasis(P=0.000), tumor hemorrhage (P=0.032), Fletcher classification (P=0.027) and symptom(P=0.012) were associated with prognosis. Multivariate analysis demonstrated that adhesion or invasion to surrounding tissue and organs(P=0.026), concurrent distant metastasis(P=0.000) and symptom(P=0.019) were independent prognostic factors for survival.</p><p><b>CONCLUSION</b>The survival evaluation of patients with small intestinal GIST depends on surgery, tumor size, adhesion or invasion to surrounding tissue and organs, concurrent distant metastasis, tumor hemorrhage, symptom, Fletcher classification, and use of targeted therapy.</p>

Oxidative stress and Alzheimer's disease / 生理学报

Alzheimer's disease (AD) has become one of the most important and most interesting focuses in the field of medical and scientific research. Up to now, the pathogenesis of AD has not been completely clarified. However, the high-density of amyloid β-protein (Aβ) in senile plaques of AD brain and the neurotoxicity of Aβ have been indisputable facts. The mechanisms underlying Aβ neurotoxicity are very complicated, involving calcium overload, inflammation, ion channel dysfunction, oxidative stress and so on. Among all of those, the mechanism of oxidative stress in Aβ neurotoxicity and the experimental progress of antioxidants in AD treatment have been widely reported in recent years. This review mainly discussed current research progresses on the oxidative stress of Aβ, so as to provide readers with some clues to the antioxidant therapy of AD.

Significance of preoperative color doppler flow imaging for screening deep vein thrombosis in upper limbs fracture / 中国骨伤

<p><b>OBJECTIVE</b>To explore significance of preoperative color Doppler flow imaging (CDFI) for screening deep vein thrombosis in upper limbs fracture.</p><p><b>METHODS</b>From January 2009 to December 2011, 1200 patients with upper limb fracture caused by trauma were respectively analyzed. There were 833 males and 367 females,ranging from 20 to 78 (mean 41.94 +/- 15.41) years. All patients had swelling and pain in injured limbs when enrolled. CDFI was used to examine upper limbs vein at 3 to 10 d after improvement of swelling, 1 day before reduction. Relationship among occurrence of thrombosis, gender, age and fracture sites were analyzed. Patients with DVT were analyzed with respective study to decide whether combined with diabetes, hypertension and hyperlipidemia.</p><p><b>RESULTS</b>All patients were checked by CDFI,which confirmed 9 cases with DVT. The rate of thrombosis was 0.75%, women than men (P < 0.01). The risk of blood clots occurred over 30 years, and the occurrence of thrombosis in humerus fracture was higher than radius ulnar fracture. One of 9 patients combined with hypertension and hyperlipidemia, 1 case combined with diabetes, and 7 cases with no complication.</p><p><b>CONCLUSION</b>Upper trauma fracture may occur deep vein thrombosis; CDFI should be used to check DVT in qualified hospital,which can maintain medical safety,decrease occurrence of medical disputes, and ganrantee patient's safety.</p>

High Exposure of Chinese Mercury Mine Workers to Elemental Mercury Vapor and Increased Methylmercury Levels in Their Hair

Objective: The aim of this study was to determine the level of exposure of mercury (Hg) miners and smelter workers to elemental mercury (Hg0) vapor in China, who work in Hg mines without using protective equipment against Hg0 vapor. In addition, the level of methylmercury (MeHg) intake by the workers was estimated from the MeHg concentration in their hair. Methods: Urinary total mercury (THg) and hair THg and MeHg concentrations were measured in 26 Hg miners and smelter workers (i.e., exposed group), and 48 unexposed people (unexposed group). Results: The exposed group showed high geometric mean THg concentrations in urine (258 ng/ml, 226 μg/g creatinine) and hair (20.0 μg/g). The urinary THg concentration of the smelter workers in particular was extremely high (338 μg/g creatinine in urine). The highest urine THg concentration reached 4577 μg/g creatinine. THg concentrations in urine and hair showed a significant correlation in the exposed group (r=0.62), indicating the adhesion of Hg0 vapor to hair. However, no such significant correlation was found in the unexposed group. Hair MeHg concentration in the exposed group (1.97 μg/g) was about threefold higher than that in the unexposed group (0.60 μg/g). Conclusions: This study shows that smelter workers in a Chinese Hg mine are exposed to extremely high levels of Hg0 vapor, and that Hg miners are exposed to higher levels of MeHg than the unexposed subjects. Further study is needed to determine the cause of the higher hair MeHg concentration in the exposed group.

High exposure of Chinese mercury mine workers to elemental mercury vapor and increased methylmercury levels in their hair

<p><b>OBJECTIVE</b>The aim of this study was to determine the level of exposure of mercury (Hg) miners and smelter workers to elemental mercury (Hg(0)) vapor in China, who work in Hg mines without using protective equipment against Hg(0) vapor. In addition, the level of methylmercury (MeHg) intake by the workers was estimated from the MeHg concentration in their hair.</p><p><b>METHODS</b>Urinary total mercury (THg) and hair THg and MeHg concentrations were measured in 26 Hg miners and smelter workers (i.e., exposed group), and 48 unexposed people (unexposed group).</p><p><b>RESULTS</b>The exposed group showed high geometric mean THg concentrations in urine (258 ng/ml, 226 μg/g creatinine) and hair (20.0 μg/g). The urinary THg concentration of the smelter workers in particular was extremely high (338 μg/g creatinine in urine). The highest urine THg concentration reached 4577 μg/g creatinine. THg concentrations in urine and hair showed a significant correlation in the exposed group (r=0.62), indicating the adhesion of Hg(0) vapor to hair. However, no such significant correlation was found in the unexposed group. Hair MeHg concentration in the exposed group (1.97 μg/g) was about threefold higher than that in the unexposed group (0.60 μg/g).</p><p><b>CONCLUSIONS</b>This study shows that smelter workers in a Chinese Hg mine are exposed to extremely high levels of Hg(0) vapor, and that Hg miners are exposed to higher levels of MeHg than the unexposed subjects. Further study is needed to determine the cause of the higher hair MeHg concentration in the exposed group.</p>

Clinical research of heart rate turbulence on predictive value in patients with acute myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess the predictive value of heart rate turbulence (HRT) in patients with acute myocardial infarction.</p><p><b>METHODS</b>One hundred and twenty-five patients with acute myocardial infarction were enrolled in this study. During the period from 6 to 21 days after onset of acute myocardial infarction, they were undergone 24-hour Holter recordings to collect the mean RR interval and heart rate variability (HRV) SDNN. The Holter files were processed with software of "HRT! View V0.60-1" to obtain the value of Turbulence Onset (TO) and Turbulence Slope (TS) and the value of "heart rate variability (HRV) SDNN". LVEF and EDD were measured by Ultrasonic Cardiography. Endpoint of follow-up was cardiac death. According to the results, patients were divided into two groups (the "survivors" and the "nonsurvivors"). The predictive value for high-risk patients with acute myocardial infarction was assessed by variables between the two groups.</p><p><b>RESULTS</b>In the period of follow-up (mean 225.4 +/- 99.8 days), 14 patients died and 111 patients survived. In the univariate Cox regression analysis, "TS" was a strong univariate predictor of mortality (hazard ratio 11.46, P < 0.01); "TO" was a relatively weak predictor and the hazard ratio was 2.76 (P > 0.05). Combination of abnormal TO and abnormal TS was the strongest mortality predictor (hazard ratio 26.70, P < 0.01); in the multivariate Cox regression analysis, TS < or = 2.5 ms/RR and EDD > or = 5.6 cm were the independent predictors of mortality with hazard ratios 9.49 (P < 0.01) and 3.64 (P < 0.05), respectively.</p><p><b>CONCLUSIONS</b>The absence of the heart rate turbulence after ventricular premature beats is a very potent post-infarction risk predictor which is independent of and stronger than other known risk predictors.</p>

Effects of hair treatment on hair mercury-The best biomarker of methylmercury exposure?

<p><b>OBJECTIVES</b>Exposure misclassification is a major obstacle to obtain accurate dose-response relationships. In order to solve this problem, the impact of hair treatment on total mercury in hair was assessed in Japanese women.</p><p><b>METHODS</b>A cross-sectional study was carried out among 327 women at age 24-49 years to determine hair mercury levels and estimate daily mercury intakes from seafood by using a food frequency questionnaire.</p><p><b>RESULTS</b>Hair mercury levels in the women and daily mercury intake ranged from 0.11 to 6.86 (median 1.63) μg/g and from 0.77 to 144.9 (median 15.0) μg/day, respectively. The hair mercury was positively correlated with the daily mercury intake (p<0.001). When the women were divided into two subgroups based on artificial hair-waving, hair coloring/dyeing, residence (non-fishing and fishing areas), and working status, a significant difference in the hair mercury level was observed between the women with and without artificial hair-waving only (p<0.001). The multiple regression analysis showed that the log-transformed hair mercury level was significantly related to the log-transformed daily mercury intake (standardized regression coefficient βs=0.307) and artificial hair-waving (βs=-0.276); but not to hair coloring/dyeing, residence, working status or age. Permanent hair treatment was estimated to reduce total mercury in hair by approximately 30%, after adjusting for daily mercury intake and other possible factors.</p><p><b>CONCLUSIONS</b>These findings suggest that hair mercury is not the best biomarker of methylmercury exposure when a study population includes women with artificial hair-waving.</p>

Effects of Hair Treatment on Hair Mercury---The Best Biomarker of Methylmercury Exposure?

Objectives: Exposure misclassification is a major obstacle to obtain accurate dose-response relationships. In order to solve this problem, the impact of hair treatment on total mercury in hair was assessed in Japanese women. Methods: A cross-sectional study was carried out among 327 women at age 24-49 years to determine hair mercury levels and estimate daily mercury intakes from seafood by using a food frequency questionnaire. Results: Hair mercury levels in the women and daily mercury intake ranged from 0.11 to 6.86 (median 1.63) μg/g and from 0.77 to 144.9 (median 15.0) μg/day, respectively. The hair mercury was positively correlated with the daily mercury intake (p<0.001). When the women were divided into two subgroups based on artificial hair-waving, hair coloring/dyeing, residence (non-fishing and fishing areas), and working status, a significant difference in the hair mercury level was observed between the women with and without artificial hair-waving only (p<0.001). The multiple regression analysis showed that the log-transformed hair mercury level was significantly related to the log-transformed daily mercury intake (standardized regression coefficient βs=0.307) and artificial hair-waving (βs=−0.276); but not to hair coloring/dyeing, residence, working status or age. Permanent hair treatment was estimated to reduce total mercury in hair by approximately 30%, after adjusting for daily mercury intake and other possible factors. Conclusions: These findings suggest that hair mercury is not the best biomarker of methylmercury exposure when a study population includes women with artificial hair-waving.