Objective:To investigate the effect and of piperine(PIP)on nerve injury in rats with cerebral infarction.Meth-ods:The rat model of cerebral infarction was prepared by modified thread embolism method.The rats were divided into Sham group,Model group,piperine group(PIP group,20 mg/kg piperine),piperine+PKA inhibitor group(PIP+H-89 group,20 mg/kg PIP+5 mg/kg H-89).The rats were scored for neurological impairment,the volume of cerebral infarction,neuronal damage and neuronal apoptosis were observed,and the levels of cAMP,IL-1β and IL-6 in hippocampus and the protein expressions of GFAP,NSE,AC6,PKA,p-CREB,CREB and BDNF were detected.Results:Compared with Sham group,Model group had large cerebral infarction,cerebral in-farction volume,the neurological deficit score,neuronal apoptosis rate,the levels of IL-6 and IL-1β in hippocampus,and number of GFAP positive cells,the positive expression rates of NSE protein increased,the number of Nissl bodies,and the expressions of cAMP,AC6,PKA,p-CREB and BDNF proteins in hippocampus decreased(P<0.05);compared with Model group,cerebral infarc-tion volume,the neurological deficit score,neuronal apoptosis rate,the levels of IL-6 and IL-1β in hippocampus,and number of GFAP positive cells,the positive expression rates of NSE protein in the PIP group decreased,the number of Nissl bodies,and the ex-pressions of cAMP,AC6,PKA,p-CREB and BDNF proteins in hippocampus increased(P<0.05);the effect of piperine in improving nerve injury in rats with cerebral infarction was able to be reversed by H-89.Conclusion:PIP can inhibit the apoptosis of hippocampal neurons,and improve the neural injury induced by cerebral infarction by activating AC/PKA/CREB signal pathway.

Spermidine, as a natural polyamine with high content in nerve cells, plays roles in regulating synaptic plasticity, promoting autophagy, and alleviating oxidative stress in the nervous system. Spermidine and polyamine metabolism may bring new therapeutic ideas for nervous system injury diseases. This paper reviewed the neuroprotective effects and mechanisms of spermidine in nervous system injury diseases.

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG _FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG _EXP (the mean absolute deviations | Δ G FEP - Δ G EXP |  < 2 kcal/mol) than those ΔG _MM-PBSA or ΔG _MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC₅₀ of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.

Optimization efforts were devoted to discover novel PDE10A inhibitors in order to improve solubility and pharmacokinetics properties for a long-term therapy against pulmonary arterial hypertension (PAH) starting from the previously synthesized inhibitor

Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy . However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors P-gp inhibition. Moreover, Western blot experiments revealed that inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying of multiple mechanisms to reverse MDR in lung cancer.

Objective: To test the reliability and validity of the Chinese version of the Handoff Clinical Examination Exercise (Handoff CEX). Methods: The Chinese version of the Handoff CEX was composed of two parts, one to assess the nurse providing the handoff and another to assess the nurse receiving the handoff. A total of 80 handoffs was evaluated to test the reliability and validity of the Chinese version of the Handoff CEX. Results: A total of 320 evaluations of handoff was obtained. The Cronbach α coefficient was 0.85 for the handoff provider, and that was 0.80 for the handoff recipient. Weighted kappa scores for provider evaluations ranged from 0.31-0.52, and that for recipient evaluations ranged from 0.35-0.55. The correlation coefficients between each factor ranged from 0.23 to 0.62, and that between each factor and the total scale ranged from 0.33 to 0.64 (P<0.05). Experienced nurses (>5 years) received significantly higher mean scores than inexperienced nurses(≤5 years) in all domains except organizational efficiency and professionalism(P<0.05). Conclusion The Chinese version of the Handoff CEX is a reliable and valid tool to assess the nursing handoff, which is useful for educators, supervisors and clinical nurses to provide training, ongoing assessment and feedback to improve the quality of handoff.

Objective: To identify the impeding and promoting factors of role definition in nursing handoff, in order to increase the quality of nursing handoff. Methods: Two nursing managers, 22 head nurses and four nurses were recruited by purpose sampling. Data were collected by using focus group study, and analyzed using content analysis. Results: According to the framework of role transition theory, the factors could be classified as individual factors (37 items, 23.72%), organizational factors (105 items, 67.31%), effectiveness of role definition (11 items, 7.05%), and problems of role definition (3 items, 1.92%). Conclusions Role definition in nursing handoff helping the coming nurse check the performance of the last shift and transfer the nursing responsibility, contributes to the improvement of nursing quality, but there are still many factors affecting the role definition in nursing handoff.

Professor ZHANG Liang-ying in Yunnan University of Traditional Chinese Medicine conducted TCM adjuvant therapy for in vitro fertilization - embryo transfer (IVF-ET) of infertility patients, which has obtained satisfactory results. The use of kidney-based, disease differentiation combined with the treatment, emphasizing preoperative conditioning, psychological adjustment, and appropriate choice, can help improve the IVF-ET pregnancy rate and complications of many problems.

Objective To discuss curative effect of Ganglioside on acute intracerebral hem-orrhage (AICH)and its influence on serum interleukin-1β,IL-6 and IL-8 levels.Methods 76 pa-tients with AICH were divided into observation group and control group by random digital table method with 38 patients in each group.The patients in two groups were given routine medical treatment,such as reducing intracranial pressure and blood pressure,hemostasis,anti-infection, brain cells nutrition and so on.The patients in observation group were additionally given 60 mg Ganglioside by intravenous infusion for once a day,while the patients in control group were addi-tionally given 0.5 g Citicoline Sodium Injection by intravenous infusion,once a day for 10 days. The changes of serum IL-1β,IL-6 and IL-8 levels of patients in two groups before and after medi-cal treatment were observed,and the clinical curative effect and drug adverse reaction (DAR)were compared as well.Results After 10 days′medical treatment,the serum IL-1β,IL-6 and IL-8 lev-els of patients in two groups obviously declined than before (P <0.05 and P <0.01),and the de-clining rate in observation group was much higher than that in control group (P <0.05).The total clinical efficiency of patients in observation group was much higher than that in control group (94.74% vs.78.95%)(χ2=4.15,P <0.05).Adverse effect appeared in 2 and 4 patients in control group and observation group respectively during the medical treatment with light symptom and no serious DAR.After comparing the occurrence rates of adverse effect of patients in two groups,there was no statistical differences (χ2=0.18,P >0.05).Conclusion Ganglioside has favorable curative effect on AICH with high security,whose mechanism of action may inhibit lo-cal inflammatory response to protect the secondary brain injury after intracerebral hemorrhage by reducing the serum serum IL-1β,IL-6 and IL-8 levels.

Objective To discuss curative effect of Ganglioside on acute intracerebral hem-orrhage (AICH)and its influence on serum interleukin-1β,IL-6 and IL-8 levels.Methods 76 pa-tients with AICH were divided into observation group and control group by random digital table method with 38 patients in each group.The patients in two groups were given routine medical treatment,such as reducing intracranial pressure and blood pressure,hemostasis,anti-infection, brain cells nutrition and so on.The patients in observation group were additionally given 60 mg Ganglioside by intravenous infusion for once a day,while the patients in control group were addi-tionally given 0.5 g Citicoline Sodium Injection by intravenous infusion,once a day for 10 days. The changes of serum IL-1β,IL-6 and IL-8 levels of patients in two groups before and after medi-cal treatment were observed,and the clinical curative effect and drug adverse reaction (DAR)were compared as well.Results After 10 days′medical treatment,the serum IL-1β,IL-6 and IL-8 lev-els of patients in two groups obviously declined than before (P <0.05 and P <0.01),and the de-clining rate in observation group was much higher than that in control group (P <0.05).The total clinical efficiency of patients in observation group was much higher than that in control group (94.74% vs.78.95%)(χ2=4.15,P <0.05).Adverse effect appeared in 2 and 4 patients in control group and observation group respectively during the medical treatment with light symptom and no serious DAR.After comparing the occurrence rates of adverse effect of patients in two groups,there was no statistical differences (χ2=0.18,P >0.05).Conclusion Ganglioside has favorable curative effect on AICH with high security,whose mechanism of action may inhibit lo-cal inflammatory response to protect the secondary brain injury after intracerebral hemorrhage by reducing the serum serum IL-1β,IL-6 and IL-8 levels.