Objective:To explore the roles and mechanisms of metformin in the improvement of cognitive dysfunction induced by chronic cerebral hypoperfusion in rats.Methods:Total 82 SD male rats (SPF grade) aged 3-4 months were randomly divided into four groups: sham operation control group (Con group, n=15), sham operation with metformin treatment group (Met group, n=20), 2-vessel occlusion group (2VO group, n=22), and 2-vessel occlusion with metformin administration group (2VO+ Met group, n=25). The chronic cerebral hypoperfusion model was established by bilateral common carotid artery ligation, and the carotid arteries of rats in Con group and Met group were only separated without ligation.After 2VO operation, rats in 2VO+ Met group and Met group were given metformin solution in drinking water at a dose of 100 mg/kg per day for 4 weeks.After 4-week continuous intervention with metformin, Morris water maze was performed to test the spatial cognitive function of the rats, in vivo electrophysiological technology was used to detect the long-term potential of the rats, and enzyme-linked immunosorbent assay(ELISA) was used to detect the concentrations of inflammatory factor tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6) in the hippocampus.The density of dendritic spines of hippocampal neurons was observed by Golgi staining, and the synaptic structure of hippocampal neurons, especially the vesicle density, was observed by transmission electron microscopy.SPSS 16.0 software was used for statistical analysis.Repetitive measurement ANOVA was used for the escape latency data of 7 days repeated learning training in water maze.One-way ANOVA was used for the comparison of other data among multiple groups, and Dunnett's t test was used for further pairwise comparison. Results:Morris water maze results showed that during 7 days of learning training, the time and group interaction for escape latency was not significant in the 4 groups of rats ( F=0.93, P>0.05), but the time main effect ( F=25.90, P<0.05) and group main effect ( F=13.20, P<0.05) were significant.Morris water maze test showed that from the 3rd to 7th day, the escape latencies in 2VO group were significantly longer than those in Con group and 2VO+ Met group(all P<0.05). The short-term memory of rats was detected after 1 day of rest.The results showed that the escape latency in 2VO group was significantly longer than that in Con group and 2VO + Met group( P<0.01). The retention time and crossing times in the platform area of 2VO rats were less than those in Con group and 2VO + Met group ( P<0.01). Electrophysiological results showed that the relative field excitatory postsynaptic potential slope of 2VO group (1.29±0.09) was significantly lower than that in Con group (2.07±0.09) and 2VO + Met group (1.69±0.08)( P<0.01). ELISA results showed that TNF-α level in hippocampal tissue of 2VO group was significantly higher than that in Con group and 2VO+ Met group; IL-1β and IL-6 levels in hippocampal tissue of 2VO group were significantly higher than those in Con group and 2VO + Met group.Density of dendritic spines in hippocampal neurons of 2VO group was significantly lower than that in Con group and 2VO+ Met group.The density and proportion of immature dendritic spines in hippocampal neurons of 2VO group were significantly higher than those in Con group and 2VO + Met group.Synaptic vesicle density of neurons in CA1 area of hippocampus in 2VO group ((230.29±19.44) vescicles/μm 2) was significantly lower than that in the Con group ((414.52±13.17) vescicles/μm 2) and 2VO+ Met group ((313.19±12.42) vescicles/μm 2). Conclusion:Metformin can reduce neuroinflammation of hippocampus with chronic cerebral hypoperfusion and improve synaptic plasticity and cognitive dysfunction.It may have potential application value in the treatment of vascular cognitive dysfunction.

Objective:To explore the protective effects and mechanisms of L-carnitine (LCAR) on cognitive dysfunction in chronic cerebral hypoperfusion rats.Methods:Totally 90 SD male rats (SPF class) aged 3-4 months were divided into four groups according to random number talbe: sham operated control group (SHAM group, n=15), sham operated with L-carnitine treatment group (LCAR group, n=25), 2-vessel occlusion group (2VO group, n=25), and 2-vessel occlusion with L-carnitine treatment group (2VO+ LCAR group, n=25). The chronic cerebral hypoperfusion model was established by bilateral common carotid artery ligation, and the carotid arteries from SHAM group and LCAR group were only separated without ligation.L-carnitine was administered intraperitoneally (300 mg·kg -1·d -1) for 30 days after surgery in the LCAR and 2VO+ LCAR groups.After 30 days of L-carnitine intervention, Morris water maze was performed to test the spatial cognitive function of the rats, the ATP level of hippocampal tissue was detected by chemiluminescence, the mitochondrial structure and synaptic structure of hippocampal neurons were observed by transmission electron microscopy, the degree of mitochondrial damage was scored, the vesicle density was counted and measured, the level of N-methyl-D-aspartate receptor subunit 2A or 2B(NR2A/B) and postsynaptic density 95(PSD95) in hippocampal tissue were detected by Western blot.The expression and distribution levels of transcription factor cAMP response element-binding protein(CREB) in brain tissues were observed by immunofluorescence.SPSS 16.0 software was used for statistical analysis.The escape latency data of repeated learning training in Morris water maze was conducted by repetitive measurement ANOVA, while other data were adopted by one-way ANOVA, and Dunnett's t test was used for further pairwise comparison. Results:(1)Morris water maze results showed that the time and group interaction of escape latency was not significant among the 4 groups of rats ( F=1.4, P>0.05), but the time main effect and group main effect were significant( F=21.6, 15.2, both P<0.05). Morris water maze results showed that platform position learning from 3rd to 7th day, the escape latencies in 2VO group were longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). The results of short-term memory showed that the escape latency in 2VO group was longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). Meanwhile, the retention time and crossing times in the platform area of 2VO group were less than those in SHAM group and 2VO+ LCAR group (all P<0.05). (2) The absolute and relative levels of ATP in hippocampus showed that the difference among the 4 groups were statistically significant ( F=14.6, 13.2, both P<0.05). ATP level of hippocampus in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.05). Electron microscopic observation of mitochondrial morphology showed that the Flameng score of mitochondrial damage in the hippocampus of rats in 2VO group (2.82±0.17) was higher than those in SHAM group (0.25±0.07) and 2VO+ LCAR group (1.76±0.09) (both P<0.05). (3) The density of synaptic vesicles in the hippocampus of rats in 2VO group ((289.09±22.41)/μm 2)was lower than those in SHAM group ((497.49±28.89)/μm 2)and 2VO+ LCAR group ((401.23±45.09)/μm 2) (both P<0.01). Western blot results showed that the relative levels of synaptic proteins NR2A/B, PSD95 and CREB in 2VO group were lower than those in SHAM group and 2VO+ LCAR group (all P<0.05). Immunofluorescence results showed that the relative level of CREB expression in hippocampal subregions and cortex in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.01). Conclusion:L-carnitine can improve spatial learning and memory dysfunction in rats with chronic cerebral hypoperfusion, which are related with promoting ATP production and protecting mitochondrial morphology, and promoting synaptic vesicle synthesis and synaptic protein expression.

ObjectiveTo observe the effect of aqueous extract of Sophorae Tonkinensis Radix et Rhizoma （STRR） on rheumatoid arthritis （RA） and to explore the anti-bone destruction mechanism based on phosphatidylinositol 3-kinase （PI3K）/serine/threonine-protein kinase （Akt） pathway. MethodHigh-performance liquid chromatography （HPLC） was used to determine the content of main active components in aqueous extract of STRR， and type Ⅱ collagen to induce RA （CIA） in mice. The blank group， model group， methotrexate （MTX） group （0.5 mg·kg^-1）， and low-dose （100 mg·kg^-1） and high-dose （200 mg·kg^-1） STRR aqueous extract groups were designed. Joint swelling was observed and clinical scores of CIA mice were calculated. Pathological changes of mouse joints were observed based on hematoxylin and eosin （HE） staining， and Micro-CT was performed to monitor joint destruction. TRAP staining was used to observe osteoclast formation in mouse joint， and Western blot to detect the expression of key proteins in PI3K/Akt signaling pathway in mouse joint tissue. ResultThe model group demonstrated higher degree of joint swelling， clinical scores of CIA， and degrees of synovial hyperplasia， inflammatory cell infiltration （P<0.01）， and joint destruction， more osteoclasts， and higher levels of matrix metallopeptidase-9 （MMP-9）， cathepsin K （CTSK）， nuclear factor of activated T-cells cytoplasmic 1 （NFATc1）， PI3K， and phosphorylated-Akt （p-Akt） proteins than the blank group （P<0.01）. Compared with the model group， the low-dose and high-dose aqueous extract of STRR alleviated joint swelling， reduced the clinical scores of CIA mice （P<0.05， P<0.01）， relieved the pathological changes of joint tissue （P<0.01） and joint destruction， decreased osteoclasts （P<0.05， P<0.01）， and lowered the levels of PI3K/Akt signaling pathway-related proteins in joint tissue of mice （P<0.01）. ConclusionThe aqueous extract of STRR can significantly delay the inflammatory response of RA and especially inhibit bone destruction by down-regulating the PI3K/Akt signaling pathway.

Objective To explore the influence of family-integrated transition care on the daily living ability of discharged patients with stroke.Methods Seventy-eight patients with stroke who were admitted to Renmin Hospital of Wuhan University from May 2016 to October 2017 were selected by convenience sampling and were divided into a control group and a family-integrated transition care group (hereinafter referred to as transition care group).The patients in the control group received routine neurological health education,while those in the transition care group received a family-integrated transition care intervention in addition to routine neurological health education.The family-integrated transition care included team building,skills training for family members,family-integrated guidance for discharged patients,and regular visits.The scores of the modified Barthel index were compared between the two groups of patients at discharge,three months after intervention,and six months after intervention.Results Among the 71 patients that were finally included,35 cases were included in the control group,of which 17 cases were men (49％),18 cases were women (51％),and their mean age was (70.1±3.7) years;the transition care group comprised 36 cases,of which 18 cases were men (50％),18 cases were women (50％),and their mean age was (69.8±4.5) years.The baseline scores of the control group and transition care group on the day of discharge were (49.1 ± 7.5) and (49.7 ± 7.9),respectively,with no significant difference (P＞0.05).In terms of time effects,the scores of the patients in the two groups had statistically significantly improved at six months after discharge (P＜0.05).In the group comparison,the scores of the patients in the transition care group after the intervention were significantly higher compared to the scores of those in the control group (P＜0.05).In terms of time and inter-group effects,there was an interaction (P＜0.05),and therefore,the influence of time effects was excluded and the same timepoint was compared between the two groups.The scores at three months (63.9±8.8) and six months (76.9± 10.1) in the transition care group were higher than those in the control group (58.1 ±8.1 and 66.0 ±9.3,respectively).The difference was statistically significant (P ＜ 0.05).Conclusion Family-integrated transition care can effectively improve daily living ability and isworthy of promoting.

Objective To explore patients' experience in the orthodontic orthognathic combined treatment outpatient service.Methods Purposive sampling method was used to select 6 patients who were admitted to the orthodontic orthognathic combine treatment outpatient service in Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine in February 2017. Research data were collected in the form of face-to-face and semi-structured in-depth interview, and analyzed by Colaizzi content analysis.Results In the research, 3 topics were extracted: patients experience, communication experience, and waiting experience.Conclusions The orthodontic orthognathic combined outpatient service provides convenience for patients and plays an significant role in the diagnosis and treatment of disease. However, there is still room for improvement in the service of combination outpaitent.

Objective To evaluate the therapeutic efficacy and adverse reactions of raltitrexed plus oxaliplatin (RALOX project) and S1 in patients with advanced primary liver cancer.Methods Seventy-one patients with advanced primary liver cancer admitted to 6 cancer centers from July 2013 to July 2015 were divided into 2 groups according to the wishes of the patients and their families:RALOX group (34 patients) and S1 group (37 patients).The therapeutic efficacy such as objective remission rate (ORR),disease control rate (DCR),median overall survival (mOS),median progression free survival (mPFS),one year survival rate (SR),and adverse reactions in these patients were evaluated.Results Thirty-one patients could be evaluated in RALOX group,and 6 patients obtained partial response (PR),10 stable disease (SD) and 15 progressive disease (PD).Thirty-three patients could be evaluated in S1 group,and 3 patients obtained PR,8 patients SD and 22 PD.The ORR,DCR,and one year SR were 19.4％ vs.9.1％,51.6％ vs.33.3％,and 22.6％ vs.12.1％ respectively,and there were no statistically significant differences in the two groups (x2 =1.393,P =0.238;x2 =2.190,P =0.139;x2 =1.229,P =0.268).The mOS and mPFS were 7.2 months vs.6.1 months and 3.4 months vs.2.8 months,and there were statistically significant differences in the two groups (x2 =6.433,P =0.011;x2 =4.078,P =0.043).There was more serious peripheral nerve toxicity (29.0％ vs.3.0％,x2 =6.344,P =0.012) and lighter hand-foot syndrome (9.7％ vs.30.3％,x2 =4.201,P =0.040) in RALOX group than S1 group.But the incidences of other adverse effects were similar in the two groups.Condnsion RALOX project is safe and effective to the patients with advanced primary liver cancer.Compare with S1 project,RALOX project has better curative effects and the majority of adverse reactions are tolerable.The patients have good condition control and survival benefit.

Objective To explore the clinical efficacy and drug-toxic reactions of raltitrexed combined with oxaliplatin (RALOX protocol) and 5-fluorouracil + calciumfolinate + oxaliplatin (FOLFOX 4 protocol) in the treatment of patients with middle and advanced primary liver cancer (PLC).Methods A total of 72 patients with PLC were selected and randomly divided into RALOX group (n =34) and FOLFOX 4 group (n =38).The objective response rate (RR) was evaluated every 6 weeks after chemotherapy,while objective remission rate (OR),disease-control rate (DCR),median survival rate (mOS),median progression-free survival (mPFS),1-year survival rate (SR) as well as toxic and adverse reactions were observed.Results In RALOX group,31 patients were evaluable,with OR,DCR,mOS,mPFS,and 1-year SR being 19.4％,51.6％,7.2 months,3.4 months,and 22.6％,respectively.In FOLFOX 4 group,29 patients were evaluable,with OR,DCR,mOS,mPFS,and 1-year SR being 13.8％,48.3％,6.9 months,3.3 months and 20.7％,respectively.RALOX group was significantly lower than FOLFOX 4 group in the incidence rates of gastrointestinal reactions,liver toxicity,cardiac toxicity,peripheral nervous toxicity and hand-foot syndrome,but there were no significant differences in the incidence rates of renal toxicity and myelosuppression between two groups.Conclusion RALOX is safe and effective in the treatment of patients with middle and advanced PLC,and is superior to FOLFOX 4 protocol in clinical efficacy with mild adverse reactions.

Objective To explore the clinical efficacy and drug-toxic reactions of raltitrexed combined with oxaliplatin (RALOX protocol) and 5-fluorouracil + calciumfolinate + oxaliplatin (FOLFOX 4 protocol) in the treatment of patients with middle and advanced primary liver cancer (PLC).Methods A total of 72 patients with PLC were selected and randomly divided into RALOX group (n =34) and FOLFOX 4 group (n =38).The objective response rate (RR) was evaluated every 6 weeks after chemotherapy,while objective remission rate (OR),disease-control rate (DCR),median survival rate (mOS),median progression-free survival (mPFS),1-year survival rate (SR) as well as toxic and adverse reactions were observed.Results In RALOX group,31 patients were evaluable,with OR,DCR,mOS,mPFS,and 1-year SR being 19.4％,51.6％,7.2 months,3.4 months,and 22.6％,respectively.In FOLFOX 4 group,29 patients were evaluable,with OR,DCR,mOS,mPFS,and 1-year SR being 13.8％,48.3％,6.9 months,3.3 months and 20.7％,respectively.RALOX group was significantly lower than FOLFOX 4 group in the incidence rates of gastrointestinal reactions,liver toxicity,cardiac toxicity,peripheral nervous toxicity and hand-foot syndrome,but there were no significant differences in the incidence rates of renal toxicity and myelosuppression between two groups.Conclusion RALOX is safe and effective in the treatment of patients with middle and advanced PLC,and is superior to FOLFOX 4 protocol in clinical efficacy with mild adverse reactions.

Cerebral stroke has a high incidence, mortality and disability rate, which lead to many se-quelae especially hemiplegia. Patients who got hemiplegia always had limb dysfunction and cannot live on their own, so the burden of taking care of patients are on the shoulder of caregivers. This paper reviewed the needs of caregivers from the following four parts: the classification of caregivers' needs, the influencing factors of the de-mand, the evaluation methods of the demand and the interventions that the caregivers need. From this article we know the needs of caregivers would change with the change of the state of patients, but their needs generally in-clude the disease knowledge, exercise guidance, emotion management, and community resource utilization, etc.

Objective To detect the physical and psychological function of traditional Chinese emotional nursing versus normal nursing on coronary heart disease patients. Methods Searching the major clinical databases of Cochrane library, PubMed, China National Knowledge Infrastructure, Wanfang database and VIP database to collect the relevant randomized controlled trial (RCT) about routine nursing combined with traditional Chinese medicine emotion care on coronary heart disease. After study selection, assessment and data extraction for RCT according to the inclusion and exclusion criteria, Meta-analysis were performed by using the RevMan5.2 software. Results Fourteen relevant studies as much as 1 164 patients were included in the study. Compared with the normal therapy, the figures support that the Chinese medicine emotional care group had a better curative effect (Z=6.74, P<0.01, OR=0.21, 95%CI:0.15-0.26), and the score of Hamilton Depression Scale (Z=8.84, P<0.01, MD=6.64, 95%CI:5.11-8.18), Self-Rating Depression Scale (Z=4.79, P<0.01, MD=8.21, 95%CI:4.89-11.66), and Self-Rating Anxiety Scale (Z=11.15, P < 0.01, MD=8.23, 95%CI:6.79-9.68) were all significantly decreased. Conclusions Compared to the conventional nursing combined with traditional Chinese emotional nursing and coronary heart diseaseroutine nursing care, the degree of depression and anxiety in patients is decreased significantly, and the total clinical efficacy is dramatically increased. However, the original study of quality constraints, muchmore high-quality, large sample of RCT is needed for further demonstration.