Application progress of experimental animal model of humanized fecal microbiota transplantation in depression research / 药学学报

The incidence rate of depression is increasing, but its pathological mechanism is still unknown. More evidence shows that the occurrence and development of depression is closely related to the changes of gut microbiome. However, due to the huge differences in bacterial composition among individuals caused by different environmental factors, researchers usually need a large number of samples to get reliable results. Experimental animal models play an important role in the pathogenesis of diseases and the mechanism of drug action because of their highly consistent background, controllable experimental environment, and the characteristics of artificial intervention. Therefore, the selection of appropriate experimental animal models can not only simulate the clinical symptoms of human depression, but also reveal the causal relationship between clinical characteristics and gut microbiome changes. In this review, the development and application of fecal microbiota transplantation technology, the close relationship between flora and depression, the application of humanized fecal microbiota transplantation experimental animal model in the study of depression, as well as the preparation methods and key technologies of humanized fecal microbiota were summarized, which provided a reference for the research on the pathogenesis of depression and the mechanism of antidepressant drugs of humanized fecal microbiota transplantation experimental animal model. This review provides a reference for the reasonable application of this aspect.

Pathogenesis of chronic social defeat stress model induced depressive-like mouse model according to LC-MS/MS-based metabolomics / 中国药理学与毒理学杂志

OBJECTIVE To explore the pathogenesis of depression according to the LC-MS/MS-based metabolo?mics in the mouse model which exhibits social avoidance state induced by the chronic social defeat stress model (CSDS). METHODS Twenty male C57BL/6N mice were randomly divided into control group and model group suffering CSDS, and the ICR retired breeder mice were used to attack the model group for 14 d of chronic social defeated stress. The open field test and source preference test were both used to observe depression-like behavior. Besides, the social inter?action test is used to observe the social interaction state, especially. After the stress, the serum samples of mice were collected, and the changes of endogenous metabolites were analyzed by LC-MS metabolomics technology, and the pathway analysis of the differential metabolites was performed to explore the pathogenesis of the CSDS induced depres?sive-like mouse model. RESULTS After the stress of CSDS was completed, the mice in the model group showed a significant slowdown in body weight growth, a reduction in the source preference rate, and a significant reduction in the total distance and the number of rearing in the open field test. Distinctively, the social interaction rate is remarkably decreasing. There are 24 differential metabolites found in the serum of CSDS model mice. CONCLUSION The mouse who suffered CSDS stress would show depressive-like behavior. Based on the LC-MS/MS metabolomics, 24 differential metabolites were found in the serum of CSDS model mice. The amino acid metabolism might be significant to the patho?genesis of the CSDS induced depressive-like mouse model.

Comparative Study on Content of Medicinal Materials from Three Varieties of Sambucus williamsii / 中国实验方剂学杂志

Objective:To determine the content of active ingredients in root bark,stems,leaves and fruits of three varieties of Sambucus williamsii (Saline-toleratedvariety,Natural Red No. 1 variety,Qingzhou No.15 variety),and identify the chemical patterns of the chemical components. Method:The content of polysaccharides,flavonoids,phenolic acids and triterpene were determined by UV spectrophotometry (UV) colorimetry. The content of anthocyanin was determined by pH differential method. Ursolic acid,oleanolic acid,quercetin,protocatechuic acid,morroniside content were determined by high performance liquid chromatography (HPLC). The root bark,stems,leaves and fruits of three varieties were analyzed by chemical pattern recognition. Result:The quality of different samples was further evaluated by F3 and F6 comprehensive scores in principal component analysis. It was found that the root bark and leaves were higher in the comprehensive ranking,and the results were basically consistent with the quantitative results. The contents of polysaccharide and morroniside in Natural Red No. 1 variety root bark were the highest,which were 161.09 mg·g-1 and 8.33 mg·g-1,respectively. Flavonoids,rutin and quercetin were the highest in the Natural Red No. 1 variety leaf,which were 71.93,4.09 and 3.57 mg·g-1,respectively. Triterpene was the highest in Natural Red No. 1 variety fruit, which was 47.84 mg·g-1. Phenolic acid and anthocyanin were the highest in Saline-tolerated variety fruits,which were 11.25 mg·g-1 and 94.32 mg·g-1,respectively. The Saline-tolerated variety stem had the highest oleanolic acid content, which was 1.41 mg·g-1. Saline-tolerated variety leaf had the highest contents of ursolic acid and gallic acid,which were 2.12 and 0.34 mg·g-1, respectively. The highest content of protocatechuic acid in Qingzhou No. 15 variety root bark, which was 0.12 mg·g-1. Conclusion:The content of Natural Red No. 1 variety is higher than that of the other two varieties,with a good quality.

Antidepressant mechanism of supercritical CO2 extract from Compound Chaigui Precription regulating cAMP signaling pathway / 中草药

Objective: To investigate the antidepressant mechanism of supercritical CO2 extract from Compound Chaigui Precription from the perspective of cAMP signaling pathway. Methods: The rats model were established by chronic unpredictable mild stress (CUMS). The rats were administrated with high, medium and low doses of supercritical CO2 extract from Compound Chaigui Precription and venlafaxine as intervention drugs. The protein expression levels of cAMP, PKA, p-CREB and BDNF in tissues and their corresponding mRNA levels were explored for their antidepressant mechanism. Results: Compared with the blank group, the expression levels of cAMP, PKA, p-CREB and BDNF in the hippocampus of the model group were significantly decreased (P < 0.05, P < 0.01). After the intervention of the Compound Chaigui Precription, compared with the model group, there was a significant difference in the callus of each dose group. At the same time, the mRNA levels of TrkB, PKA, p-CREB and BDNF in the hippocampus of the model group were significantly decreased (P < 0.05, P < 0.01). After the intervention, there was a callback in each dose group compared with the model group, with significant differences. Conclusion: Supercritical CO2 extract from Compound Chaigui Precription can exert antidepressant effect by regulating cAMP-PKA-CREB-BDNF signaling pathway.

Research progress on chemical composition and pharmacological effects of Trichosanthis Fructus and predictive analysis on quality marker / 中草药

Trichosanthis Fructus is a traditional Chinese herbal medicine, which has wide distribution and rich medicine source. With the in-depth study of Trichosanthis Fructus, its effective ingredients and application research has attracted much attention, and has great application prospects. Based on a summary of its chemical composition and main pharmacological effects, according to the definition of quality marker (Q-marker), the quality marker components of Trichosanthis Fructus were predicted from the aspects of the biosynthetic approach and component specificity of chemical components and their correlation with the effectiveness of Chinese medicines and the measurability of components, which provides a scientific basis for quality evaluation of Trichosanthis Fructus.

An exploration into mechanism of leukocyte elevation activity of Lvjiao Buxue granules based on network pharmacology / 药学学报

The mechanism of leukocyte elevation activity of Lvjiao Buxue granules was studied by establishing the active components-targets network and protein interactions network and analyzing the functions and pathways of targets. The main active ingredients of Lvjiao Buxue granules were obtained by TCMSP and literature excavation. Based on the DRAR-CPI, GeneCards and CoolGeN, the active components of Lvjiao Buxue granules were predicted and screened. Cytoscape software was used to construct the drug-active components-target network, and a protein database was constructed by using String database and Cytoscape software. The relation of the main active ingredients and targets were validated by Systems Dock Web Site. The GO and KEGG pathways involved in the targets were analyzed by DAVID databases. Using DisGeNET database to attribute the type of targets. The results showed that 49 active components and 89 targets of Lvjiao Buxue granules were involved. The network results showed that the composition of purine ribonucleosides, the regulation of cell death, especially the biological processes such as neutrophil and oxidative stress were mainly involved in the regulation of metabolic, cancer, tuberculosis, PI3K-Akt signaling and many other pathways to play its elevating leukocytes effect. This study reflects the characteristics of multi-components-multi-targets and multi-pathways of Lvjiao Buxue granules, which laid the foundation for further research into the mechanism of leukocyte elevation activity of Lvjiao Buxue granules.

Exploration into mechanism of antidepressant of Bupleuri radix based on network pharmacology / 药学学报

This study was designed to explore the antidepressant mechanism of Bupleuri radix through establishing the active components-targets network and protein interactions network and analyzing the functions and pathways of targets. The main active ingredients of Bupleuri radix were obtained by TCMSP, literature study and the results of our own work. Based on the DRAR-CPI, GeneCards and OMIM were used to predict and screen the active components of Bupleuri radix. The Cytoscape software was used to construct the active components-targets network of Bupleuri radix. The protein interactions network was constructed using the String database and Cytoscape software. The relation of the main active ingredients and targets were validated by Systems Dock Web Site. The GO and KEGG pathways involved in the targets were analyzed by DAVID. Using DisGeNET database to attribute the type of targets. The results showed that 15 active components and 50 targets of Bupleuri radix were involved. The network results showed that the process of metabolism, regulation and response to stress were mainly involved, by adjusting the PI3K-AKT, MAPK, Rap1, Ras, FoxO, neurotrophin and other signaling pathways to play its antidepressant effect. This study reflects the characteristics of multicomponents-multi-targets and multi-pathways of Bupleuri radix, which provides new ideas and clues for further research on the mechanism of anti-depressive effects of Bupleuri radix.

Research advances in psychological suboptimal health / 中国药理学与毒理学杂志

Psychological suboptimal health status is an intermediate state between mental health and mental disease.Without timely intervention,psychological suboptimal health may develop into serious diseases that pose a threat to human physical and mental health,such as depression,anxiety disorders and high blood pressure.This review summarizes the scientific concepts,diagnostic Criteria,intervention and pharmacological research of psychological suboptimal health from the perspective of both modern medicine and traditional Chinese medicine and proposes possible solutions to existing problems in order to contribute to the identification,diagnosis,prevention and treatment of psychological suboptimal health.

Intervention mechanism of psychological sub-health by Baihe Dihuang Tang based on network pharmacology / 药学学报

This study was designed to screen the targets of bioactive ingredients of Baihe Dihuang Tang, and investigate the "multi-components, multi-targets and multi-pathways" intervention mechanism of Baihe Dihuang Tang on psychological sub-health. The ADME/T calculation method was used to screen the active ingredient of Baihe Dihuang Tang, and then using ADME/T calculation method to filtrate the active components of Baihe Dihuang Tang, then Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper database and Medical Subject Headings (MeSH) were combined to forecast and filtrate the targets of the main active ingredients. In addition, the predicted targets were verified by the Surflex-dock in Sybyl. The Cytoscape software was used to construct the Baihe Dihuang Tang ingredients-targets-disease network, while ClueGO software was used to analyze the molecular function and biological process of the targets. There are total 11 active ingredients and 21 targets in Baihe Dihuang Tang. A good interaction between them was supported by the score. The 21 targets were mainly involved in gamma-aminobutyric acid signaling pathway, cAMP metabolic process and monoamine transport relevant biological processes. Thus, Baihe Dihuang Tang may play a role in the intervention of psychological sub-health by regulating the activity of G-protein coupled amine receptor and the expression of monoamine neurotransmitter, which reflects the features of traditional Chinese medicine multi-components, multi-targets and multi-pathways. This research provides evidences on the pharmacological mechanism of Baihe Dihuang Tang effect on psychological sub-health.

Comparative study of the corticosterone and glutamate induced PC12 cells depression model by 1H NMR metabolomics / 药学学报

This study was designed to analyze the change of metabolites in the PC12 cells and its medium induced by corticosterone (CORT) and glutamate (Glu) by proton nuclear magnetic resonance (1H NMR) metabolomics. The multivariate statistical analysis was employed to identify the difference between control groups and induced groups, respectively. In addition, metabolite pathway analysis was performed to explore the characteristic of CORT-induced and or Glu-induced PC12 cells depression model, and to provide the references for the selection of in vitro depression models as well as the further understanding of the mechanism on depressive disorders. We found 36 differential metabolites in CORT-induced PC12 cells and medium and 42 in Glu-induced PC12 cells. Furthermore, correlation analysis results show that serine and 2-oxoisoleucine were associated with most differential metabolites in CORT-induced PC12 cells. Lactate and glutathione were significantly correlated to the vast majority of differential metabolites in Glu-induced PC12 cells. We speculated that CORT-induced PC12 cell models may affect the fatty acid metabolism and cell membrane structure, and Glu-induced PC12 cell models may have a difference in the glycolysis and antioxidants.

Current Application Status and Countermeasures of Antibiotics Irrational Use in China / 中国药师

In recent years,antibiotics have been playing more and more important roles in maintaining human health with the increasing variety and quantity.However,under the influence of different reasons caused by subjective or objective factors,antibiotics irrational use has induced bacterial resistance and adverse reactions,which are becoming more and more serious.The paper put forward the countermeasures of antibiotics irrational use and provided reference for rational use of antibiotics based on the present situation analysis in China and foreign experience in order to control the irrational use.

Anti-inflammatory and analgesic effects of Bi-yuan-ling granules / 华中科技大学学报（医学）（英德文版）

Bi-yuan-ling granule (BLG) is a traditional Chinese medicine compound composed mainly of baicalin and chlorogenic acid. It has been demonstrated to be clinically effective for various inflammatory diseases such as acute rhinitis, chronic rhinitis, atrophic rhinitis and allergic rhinitis. However, the underlying mechanisms of BLG against these diseases are not fully understood. This study aimed to explore the anti-inflammatory and analgesic activities of BLG, and examine its protective effects on mouse acute lung injury (ALI). The hot plate test and acetic acid-induced writhing assay in Kunming mice were adopted to evaluate the pain-relieving effects of BLG. The anti-inflammatory activities of BLG were determined by examining the effects of BLG on xylene-caused ear swelling in Kunming mice, the cotton pellet-induced granuloma in rats, carrageenan-induced hind paw edema and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The results showed that BLG at 15.5 mg/g could significantly relieve the pain by 82.5% (P<0.01) at 1 h after thermal stimulation and 91.2% (P<0.01) at 2 h after thermal stimulation. BLG at doses of 7.75 and 15.5 mg/g reduced the writhing count up to 33.3% (P<0.05) and 53.4% (P<0.01), respectively. Additionally, the xylene-induced edema in mice was markedly restrained by BLG at 7.75 mg/g (P<0.05) and 15.5 mg/g (P<0.01). BLG at 5.35 and 10.7 mg/g significantly reduced paw edema by 34.8% (P<0.05) and 37.9% (P<0.05) at 5 h after carrageenan injection. The granulomatous formation of the cotton pellet was profoundly suppressed by BLG at 2.68, 5.35 and 10.7 mg/g by 15.4%, 38.2% (P<0.01) and 58.9% (P<0.001), respectively. BLG also inhibited lung W/D ratio and the release of prostaglandin E2 (PGE2) in ALI mice. In addition, the median lethal dose (LD50), median effective dose (ED50) and half maximal inhibitory concentration (IC50) of BLG were found to be 42.7, 3.2 and 12.33 mg/g, respectively. All the findings suggest that BLG has significantly anti-inflammatory and analgesic effects and it may help reduce the damage of ALI.

1H NMR based metabolomics study of bu-zhong-yi-qi-tang in the spleen-qi deficiency rat model / 药学学报

The present study aimed to investigate the effect and the mechanisms of Bu-zhong-yi-qi-tang (BZYQ) on Spleen-Qi deficiency rat's model using nuclear magnetic resonance (NMR) metabolomics and multivariate statistical analysis methods. The rat Spleen-Qi deficiency model was established as follows: oral administration of Radix Rhei extract, loaded swimming and starvation for 24 h. The body weight and motor behavior of the rats were measured and recorded once a week. BZYQ could significantly improve body weight and behavioral of Spleen-Qi deficiency model rats compared with the model group (P < 0.05, 0.01). After drug administration, the changes in the levels of endogenous metabolites in the spleen including decreasing lactate, taurine and hypoxanthine, increasing glutamate and scyllo-inositol compared with the model group. The metabolomics approach is an effective tool for the investigation of the pharmacologic mechanism of BZYQ and it is helpful to further research.

Experience of minimally invasive treatment in upper ureteral calculi complicated with urinary tract infection: 40 cases report / 中国医师进修杂志

Objective To summarize the experience of minimally invasive treatment in upper ureteral calculi complicated with urinary tract infection.Methods Retrospectively analyzed the clinical data of 40 cases with upper ureteral calculi complicated with urinary tract infection who were treated from December 2009 to December 2013.Results Twenty-one cases were performed with retrograde catheterization at cystoscopy and 11 cases were performed with percutaneous nephrostomy directed by B-ultrasound in the stage Ⅰ,the infection were controlled after operation 2-6 d.These patients were successfully cured by extracorporeal shock-wave lithotripsy (ESWL),ureterorenoscope lithotripsy (URL) or percutaneous nephrolithotomy (PCNL) in the stage Ⅱ].The remaining 8 cases were successfully cured by URL with antiinfection therapy in the stage Ⅰ.All patients had no ureteral perforation,laceration,urine derived sepsis and severe bleeding complications.All of ureteral calculi were drained after 2-10 weeks.The average hospital stay was 13.4 d.Patients were followed up for 1-12 months after the stone expulsion,the average was 6 months.There was 3 patients who with preoperative renal dysfunction had been improved after URL,and other patients' renal function returned to normal.Conclusions The therapy of retrograde catheterization at cystoscopy and percutaneous nephrostomy directed by B-ultrasound in the stage Ⅰ,combined with ESWL,URL or PCNL in the stage Ⅱ in treating upper ureteral calculi complicated with urinary tract infection have more advantage such as less complication,rapid control of infection and complete removal of stones.It is an ideal method.

1H NMR based metabolomics study of bu-zhong-yi-qi-tang in the spleen-qi deficiency rat model / 药学学报

The present study aimed to investigate the effect and the mechanisms of Bu-zhong-yi-qi-tang (BZYQ) on Spleen-Qi deficiency rat's model using nuclear magnetic resonance (NMR) metabolomics and multivariate statistical analysis methods. The rat Spleen-Qi deficiency model was established as follows: oral administration of Radix Rhei extract, loaded swimming and starvation for 24 h. The body weight and motor behavior of the rats were measured and recorded once a week. BZYQ could significantly improve body weight and behavioral of Spleen-Qi deficiency model rats compared with the model group (P < 0.05, 0.01). After drug administration, the changes in the levels of endogenous metabolites in the spleen including decreasing lactate, taurine and hypoxanthine, increasing glutamate and scyllo-inositol compared with the model group. The metabolomics approach is an effective tool for the investigation of the pharmacologic mechanism of BZYQ and it is helpful to further research.

Chloramphenicol improved expression of recombinant cholera toxin B subunit in Escherichia coli and its adjuvanticity / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cholera toxin B subunit (CTB) was shown to be a potent adjuvant for protein immunogen, especially when inoculated through mucosal route. We aimed to optimize the expression approach for CTB and thereafter to determine the adjuvant effect on DNA vaccine.</p><p><b>METHODS</b>Wild type CTB coding gene was amplified and cloned into prokaryotic expression vector pET-30a, and the recombinant CTB was expressed in the presence of different concentration of chloramphenicol and isopropyl β-D-thiogalactoside. Purified recombinant CTB was mixed with HIV-1 AE2f tat-rev-integrase-vif-nef fusion gene DNA vaccine and female BALB/c mice were vaccinated with a DNA priming-recombinant vaccinia vectored vaccine boosting regimen through intramuscular injection. Interferon γ (IFN-γ) enzyme-linked immunospot (Elispot) assay was used to read out the specific T-cell immunity.</p><p><b>RESULTS</b>Chloramphenicol was essential for the efficient expression of recombinant CTB (rCTB) in pET-30a/BL21 (DE3) system and could be optimized at the concentration of 0.625 µg/ml in the presence of chloramphenicol. The purified rCTB could bind with GM1 efficiently. INF-γ Elispot data showed the T-cell response induced in CTB adjuvanted group ((734 ± 240) spot forming cells/10(6) splenocytes) was higher than that induced by non-adjuvanted ((520 ± 150) spot forming cells/10(6) splenocytes), all responses against different antigens were enhanced in parallel.</p><p><b>CONCLUSION</b>CTB could be efficiently expressed in the presence of chloramphenicol and purified CTB is functional and capable of enhancing the specific T cell responses elicited by DNA vaccine, the mechanism needs to be explored in the future.</p>

Levels of TNF-α, IL-6 and IL-10 in bronchoalveolar lavage fluid in children with Mycoplasma pneumoniae pneumonia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the levels and roles of cytokines TNF-α, IL-6 and IL-10 in bronchoalveolar lavage fluid (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP).</p><p><b>METHODS</b>The levels of TNF-α, IL-6 and IL-10 in BALF were measured using ELISA in children with MPP at acute stage (n=45) and at remission stage (n=30). Twenty children without lung lesions severed as the control group.</p><p><b>RESULTS</b>The TNF-α, IL-6 and IL-10 levels in BALF were higher in children with MPP at acute stage than those in the control group (P<0.05). The levels of TNF-α and IL-6 in BALF at remission stage were reduced to the levels similar to the control group and were significantly lower than those at the acute stage in children with MPP. However, the levels of IL-10 in BALF remained at higher levels at remission stage in children with MPP.</p><p><b>CONCLUSIONS</b>The levels of TNF-α, IL-6 and IL-10 in BALF increase in children with MPP at acute stage, suggesting that the cytokines may be involved in the pathogenesis of MPP.</p>

Primary diffuse large B-cell lymphoma of testis: a clinicopathologic study of 14 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunohistochemical findings and prognosis of primary diffuse large B-cell lymphoma (DLBCL) of testis.</p><p><b>METHODS</b>Fourteen cases of primary DLBCL of testis, diagnosed according to the 2001 World Health Organization staging standards for hematopoietic and lymphoid tumors, were retrospectively studied. Immunohistochemical study was performed and follow-up information analyzed.</p><p><b>RESULTS</b>The median age of the patients was 62 years. There were 10 patients in stage I, 3 in stage II and 1 in stage IV. Follow-up information was available in 11 patients (78.6%). Three of which were still alive and eight died (with duration of survival ranging from 5 to 19 months). The patients usually presented with unilateral painless enlargement of testis. Histologically, the lymphoma cells of all cases showed a centroblastic appearance. One case belonged to the germinal center B cell-like subtype on immunohistochemical study, while the remaining 13 cases were classified as non-germinal center B cell-like subtype. Ten of the 14 cases (71.4%) showed overexpression of p53 protein. Most cases demonstrated high proliferation index. Six of the 14 cases (42.9%) were positive for bcl-2 protein. The overall 1-year, 2-year and 5-year survival rates were 45.5%, 17.0% and 17.0%, respectively.</p><p><b>CONCLUSIONS</b>Most cases with primary DLBCL of testis were of peripheral activated B-cell origin. The prognosis is usually not favorable, with propensity of local relapse and systemic dissemination. Accurate pathologic diagnosis relies on detailed histologic examination and immunohistochemical study.</p>

Differentiation of Mouse Embryonic Stem Cells into Neural Cells on Silk Fibroin Scaffolds / 中国生物工程杂志

Induced the mouse embryonic stem(ES)cells into neural cells on silk fibroin via the improved 4-/4+ RA method to explore the effect of the silk fibroin to the ES-derived neurons' growth,adherence and differentiation.Suspended the ES cells into EBs and then transferred them to three different substrates-coated 35 mm dishes including gelatin,Bombyx mori silk fibroin(SF) and Tussah silk fibroin(TSF) to identify the adherence and proportion of ES cells-derived neurons under these three substrates.The results showed that the EBs adhered to the gelatin and TSF are faster than to the SF.The average adhesive rate on gelatin and TSF are 90.3% and 84.4% respectively,and only 38.5% on SF,all the proportion of ?-Ⅲ-Tubulin positive cells is approximately 40%.It may provide important experimental information for tissue engineering,in which ES cells-derived neuron cells and silk fibroin materials are scaffolds,and also offer a source for cell therapy research of neurodegenerative disease.