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.

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 evaluate the effect of the rehabilitation software based on information-motivation-behavioral skills(IMB)model on meeting the rehabilitation needs, increasing the continuation of rehabilitation and the rehabilitation compliance, improving the outcome of rehabilitation among elderly patients with fracture. Methods Based on the theory of"information-motivation-behavior"and the unity of human- computer interaction as the design concept, the status quo of rehabilitation training and rehabilitation needs of elderly patients with fracture were reviewed. The rehabilitation training test was applied to 30 patients with fracture in orthopedic department of our hospital. 30 patients in the same period were randomly selected as control group. All patients underwent Self-Rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores before and 1 and 3 months after operation. Differences were tested using Student's t test. Results Developed rehabilitation application software based on information module、motivation module and behavior module. The test group using this software for rehabilitation training was compared with the control group. The results showed that there was no significant difference in preoperative SAS and SDS scores between the two groups (t=-0.648,-0.284, P>0.05). At 1 and 3 months after operation, the SAS scores in the test group were (40.05 ± 6.77), (32.01 ±5.86), which were lower than (45.50 ± 11.32), (39.55 ± 5.67) in the control group (t=-4.14,-4.89, P<0.01). The SDS scores in the test group were (42.30 ± 9.86), (33.23 ± 6.56), which were lower than (46.50 ± 10.32), (38.45 ± 7.80) in the control group (t=-3.52,-3.82, P=0.001). Conclusion Rehabilitation software can influence the rehabilitation behavior of elderly fracture patients from information and motivation factors, provide professional guidance and rehabilitation intervention, and promote the implementation of active rehabilitation.

Objective The aim of this study was to investigate the impact of constructing national key clinical specialty on high quality nursing service.Methods Using the Colaizzi 7-step analysis method to analyze the information,which through using the phenomenology research methods by making interviews with 14 clinicians,nurses and nursing administrators.Results The clinical medical staffs experienced the construction of key clinical specialist,to some extent,that would promote the development of nursing discipline,enhancing the environment and equipment in hospital,having improvement on the ability of nursing service and quality simultaneously,and then the cooperation between medical staffs and patients were more closely,while nurses bearing increased work pressure,with obviously job burnout.Conclusions The national key clinical specialist construction would effectively launching nursing quality care in depth and improving patient satisfaction with medical care,while the working pressure of nurses and the imperfection of post performance management restricted the development of nursing discipline.