ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

Objective To elucidate the molecular mechanism of reserpine-induced depression using network toxicology,molecular docking techniques,behavioral assessments of animal models,and histopathological analyses.Methods Core targets were screened using multi-database network toxicology,followed by the construction of a protein-protein interaction network and validation of core targets through molecular docking.Sprague Dawley rats were divided randomly into control and reserpine(0.5 mg/kg)groups,and administered the corresponding treatments once daily for 4 consecutive days.Behavioral changes were assessed using the forced-swim and open-field tests.Serum neurotransmitters were quantified by enzyme-linked immunosorbent assay and neuropathological damage was observed via tissue staining.Target gene expression regulation was verified by Western blot.Results Network toxicology screening and molecular docking simulation demonstrated that reserpine exhibited significant binding affinity with the dopamine D2 receptor,cyclic-AMP response element binding protein,and serine/threonine-protein kinase 1(AKT1).Animal experiments demonstrated that reserpine-treated rats displayed depression-like behaviors,including motor inhibition(P＜0.01),with decreased serum levels of norepinephrine and 5-hydroxytryptamine(P＜0.01),respectively.Pathological observations revealed microglial proliferation in the cerebral cortex,increased apoptosis,and reduced Nissl bodies in the hippocampal CA1 region.Down-regulation of brain-derived neurotrophic factor(BDNF)in brain tissue and decreased expression of hippocampal AKT1 and phosphorylated AKT1 were also observed.Conclusions Reserpine influences monoamine transmitter metabolism and neuronal structural integrity via the inhibition of BDNF and AKT1 protein expression,resulting in depressive-like behavior and cerebral nerve damage in rats.

Objective To elucidate the molecular mechanism of reserpine-induced depression using network toxicology,molecular docking techniques,behavioral assessments of animal models,and histopathological analyses.Methods Core targets were screened using multi-database network toxicology,followed by the construction of a protein-protein interaction network and validation of core targets through molecular docking.Sprague Dawley rats were divided randomly into control and reserpine(0.5 mg/kg)groups,and administered the corresponding treatments once daily for 4 consecutive days.Behavioral changes were assessed using the forced-swim and open-field tests.Serum neurotransmitters were quantified by enzyme-linked immunosorbent assay and neuropathological damage was observed via tissue staining.Target gene expression regulation was verified by Western blot.Results Network toxicology screening and molecular docking simulation demonstrated that reserpine exhibited significant binding affinity with the dopamine D2 receptor,cyclic-AMP response element binding protein,and serine/threonine-protein kinase 1(AKT1).Animal experiments demonstrated that reserpine-treated rats displayed depression-like behaviors,including motor inhibition(P＜0.01),with decreased serum levels of norepinephrine and 5-hydroxytryptamine(P＜0.01),respectively.Pathological observations revealed microglial proliferation in the cerebral cortex,increased apoptosis,and reduced Nissl bodies in the hippocampal CA1 region.Down-regulation of brain-derived neurotrophic factor(BDNF)in brain tissue and decreased expression of hippocampal AKT1 and phosphorylated AKT1 were also observed.Conclusions Reserpine influences monoamine transmitter metabolism and neuronal structural integrity via the inhibition of BDNF and AKT1 protein expression,resulting in depressive-like behavior and cerebral nerve damage in rats.

With the utilization of more types of radiation with a wider energy range, the application scope of the currently valid operational quantities is limited due to some conceptual defects, so a new group of operational quantities was proposed recently by the International Commission on Radiation Units and Measurements. The unification of protection quantities and operational ones is achieved in conceptual and physical sense. However, to achieve the comprehensive application of these new operational quantities in China, such preliminary work should be done as computational model construction and built-in of a calibration system in monitoring equipment, which depends on the collaborative development of multi-parties.

Operational quantities, which are used to estimate protection quantities in the field of radiation protection, are important in area monitoring. The current operational quantities show certain limitations as the particle types and energy ranges are expanded. The International Commission on Radiation Units and Measurements Report 95 proposed a new system of operational quantities, where the definitions and phantoms of the operational quantities are consistent with the protection quantities, enabling better estimation of the protection quantities over wider ranges of particle types and energies. This paper focuses on the effects of the new recommended operational quantity system in area monitoring from the aspects of phantom application, conversion coefficient updating, and monitor design and calibration.

Objective To investigate the entrance surface dose to the examined patients in radiography using digital and screen-film system in hospitals at different levels in 15 provinces and municipalities in China,in order to provide data for developing diagnostic reference level of radiography suitable for our national physical characteristics.Methods According to the requirements of the Technical Study on Medical Radiation Hazard Assessment and Control,the examined patients aged 20-70 years were selected,with body weight ranging from 55 to 80 kg for male and 50 to 70 kg for female.TLDs were used to measure the entrance surface dose to adult patients in radiography.No less than 10 examined patients were required at each body position,with examined locations including head (PA,LAT),chest (PA,LAT),abdomen (AP),pelvis (AP),lumbar (AP,LAT),and thoracic vertebra (AP,LAT).Results A total of 19 975 individuals undergoing radiography and 1 813 radiographic equipment of different types including screen-film radiography,computed radiography (CR) and digital radiography (DR),were investigated in 342 hospitals in 15 provinces and municipalities throughout the country.For these three types of equipment,the average entrance surface dose to the examined were 1.75,1.9,and 1.15 mGy in head (PA),1.69,1.46and 1.03 mGy in head (LAT),0.75,0.65 and 0.36 mGy in chest (PA),1.81,1.26 and 0.88 mGy in chest (LAT),4.37,3.77 and 2.15 mGy in abdomen (AP),3.73,3.56 and 2.75 mGy in pelvis (AP),5.49,5.84 and 4.17 mGy in lumbar (AP),12.01,9.37 and 6.82 mGy in lumbar (LAT),4.53,3.65 and 2.49 mGy in thoracic vertebra (AP),and 6.91,6.43 and 4.15 Gy in thoracic vertebra (LAT).Conclusions Entrance surface dose caused by radiography examination varies dependent on different exposure locations.Entrance surface doses caused by digital radiography are all lower than by screen-film radiography;those caused by digital radiography are lower than by computed radiography,except for thoracic vertebra (AP).In all examinations,no difference of statistical significance is found between CR and screen-film radiography in entrance surface dose.

Objective To investigate the CT scanning parameters in hospitals at different levels in 15 provinces and cities in China and the doses to patients undergoing CT examination,in order to provide the basis for establishing CT diagnostic reference level suitable for our country.Methods As required in the implementation program for Technical Study on Medical Radiation Hazard Assessment and Control,the information on the patients examined and the CT scanning parameters in clinical practices were investigated.The CT dose index (CTDI100,CTDIW,CTDIVOL) of CT scanner was measured by using the CT ionization chamber.The dose length product (DLP) was calculated on the basis of the scan length of the patients examined.Results A total of 6 524 CT scanning procedures and 483 different types of CT scanning equipment were surveyed in 166 hospitals in 15 provinces in China.For head,chest,abdomen,and lumbar vertebrae,the average weighted CTDIW were 43,15,19 and 25 mGy,respectively,and the third quartile of CTDIw were 50,19,23 and 32 mGy,respectively.The average DLP were 540,397,503 and 376 mGy· cm,respectively.The third quartile of DLP were 659,525,632 and 479 mGy· cm respectively.Conclusions Through this survey,the doses to CT-examined patients in some provinces were basicly ascertained.The third quartile of doses to four body parts of the examined patients are different from the diagnostic reference level given in publications in other countries and regions.It is important to establish the CT diagnostic reference level suitable for our CT-examined patients according to Chinese national physical characteristics and therefor to promote the optimization of medical radiation protection in CT examination.

Objective To evaluate the radiation dose from a dual energy X-ray absorptiometry (DXA) study. Methods A Radcal multifunctional dosimeter (1800 cc ionization chamber, USA) was used, for purpose of comparison, to measure the entrance surface doses (ESD) from Norland XR-800 DXA ( pencil beam scan, 100/46. 8 kVp, 1. 3 mA) and from Hologic Discovery A DXA ( fan beam scan, 140/100 kVp, 5. 0 mA) . Ambient dose equivalent rate at 1 m away from studied phantom center and at 1 m above floor was measured using the US 451P ionizaion chamber survey meter ( Fluke, USA). Results The ESD measured using a Radcal dosimeter for Norland XR-800 DXA was 0. 43 μGy in high speed mode and 0. 73 μGy in standard mode ( AP spine ) , 1. 93 μGy ( hip ) , 0. 40 μGy ( wrist ) and 1. 06 μGy ( mandible) . The ESD measured for Hologic Discovery A DXA was 65. 6 μGy ( AP spine) and 63. 9 μGy ( hip) . The ESD measured for Norland XR-800 at different scan types and scan speeds was <2 μGy while Hologic Discovery A DXA showed a result of <66 μGy ( AP spine and hip scan ) , which were both consistent with the data given in their own respective operational manual. A comparison of DXA scanners with fan beam and pencil beam indicated that ambient equivalent dose rate, measured with 451P survey meter, from fan beam scan was 65 times that from pencil beam scan. Conclusions Compared with other medical X-ray studies, the ESD to the phantom undergoing a DXA study is relatively low. DXA pencil beam scan doses to lumbar spine and hip were about 1/153-1/33 of those from DXA fan beam scan. Pencil beam scan dose to DXA staff was negligible and fan beam scan dose to DXA staff was lower than the personal dose limits of 20 mSv per year.

Objective To fulfill the requirements for uncertainty of the calibration apparatus for dosimeters used in X-ray mammography through setting standard radiation quality at the SSDL and developing calibration procedures.Methods According to IEC 61267-2005 and IAEA TRS No 457 to recommend RQR-M and RQA-M series standard radiation quality,the calibration apparatus was evaluated for long term stability of the radiation field over 8 years from 2006 to 2014,including 10 response quantities,such as field homogeneity,change rate of mean air kerma and scatter radiation contributions and so on.In addition,the reference dose instrument was traced back to the PSDL of PTB in Germany by post during 2008 and 2012.Results The field homogeneity (φ 40 mm) relative error was ± 1.4％.The long term stability of the calibration apparatus was less than ± 2％ (limits of variation).The scatter radiation contributions at their points of test were below 0.12％.The calibration factors traced to PTB were 0.999-1.000.As a result of the calibration apparatus,the expanded uncertainty was ± 3％ (k =2,95％ confidence interval).Conclusions The calibration apparatus may meet the requirements of IEC 61267-2005 and IAEA TRS No 457 and has obtained the license of metrology from national regulatory authority.The laboratory now performs very well to calibrate dosimeters used in X-ray mammography.