OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

OBJECTIVE： To analyze the current status and trend of opioids consumption in China， and to provide reference for rational use of opioids. METHODS： Purchasing data on five opioids as fentanyl， morphine， pethidine， oxycodone and hydromorphone， were extracted from the database of the Medicine Economic Information Network from 2014 to 2016. Drug consumption was measured by the daily dose per million population （unit： S-DDD）， and the consumption amount of all opioids and different dosage forms （including oral dosage form， injection and other form） in China and different districts were analyzed and compared. RESULTS： The consumption amount of five opioids increased from 69.62 S-DDD in 2014 to 78.64 S-DDD in 2016. The consumption amount of hydromorphone and oxycodone showed an upward trend， while the consumption amount of morphine was basically unchanged， and the consumption amount of fentanyl and pethidine showed a downward trend. The consumption amount of oral dosage form increased from 39.77 S-DDD in 2014 to 45.61 S-DDD in 2016， the consumption amount of the injection increased from 20.74 S-DDD in 2014 to 24.23 S-DDD in 2016， and the consumption amount of other form decreased from 9.11 S-DDD in 2014 to 8.81 S-DDD in 2016. The consumption amount of oral dosage form was around twice that of injection， with the gap expanding yearly. Regionally， the consumption amount of five opioids in the eastern region was the highest， followed by the western region， and the lowest but the highest growth rate in the central region from 2014 to 2016 （in 2016， consumption amount of eastern， western and central regions were 94.04， 67.90， 63.78 S-DDD， with increase rate of 8.50％， 11.77％， 16.17％， compared with 2014）. Morphine was the most widely used drug in all regions， followed by fentanyl； in the eastern and central regions， the use of oral and injection dosage form increased year by year； in western region， the use of oral dosage forms increased while that of injection decreased year by year. CONCLUSIONS： The opioids consumption in China is increasing overall， with regional differences. Nonetheless， the overall consumption is still low. On the premise of strict supervision， it is necessary to take measures to promote the rational use of opioids in different areas.

Objective To investigate the effect of acupuncture-rehabilitation therapy on the neurological function and the expression of cleaved-caspase-8, cleaved-caspase-3 and cellular inhibitor of apoptosis 1 (cIAP1) in ischemic penumbra of rats with cerebral ischemia. Methods A total of 90 male Sprague-Dawley rats were randomly divided into sham group, model group, acupuncture group, rehabilitation group and acupuncture-rehabilitation group. Each group was divided into three days, seven days and 14 days subgroups (n=6). The cerebral ischemia model was established with the modified Koizumi suture method. The sham group and the model group received no treatment. The acupuncture group received cluster needling of scalp acupuncture, the rehabilitation group received treadmill training, and the acupuncture-rehabilitation group received both acupuncture and treadmill training. Three days, seven days and 14 days after modeling, their neurological function was assessed with modified Neurological Severity Score (mNSS) and Rota-rod test, and the expression of cleaved-caspase-8, cleaved-caspase-3 and cIAP1 protein in cerebral ischemic penumbra were detected with Western blotting. Results Compared with the model group, the mNSS scores decreased, the retention time of Rota-rod test increased, the expression of cleaved-caspase-8, cleaved-caspase-3 protein decreased and the expression of cIAP1 protein increased in each treatment group at each time point (P<0.05). Compared with the other two treatment groups, the mNSS scores further decreased, the retention time further increased, the expression of cleaved-caspase-8, cleaved-caspase-3 protein further decreased, and the expression of cIAP1 protein further increased (P<0.05) seven days and 14 days after modeling in the acupuncture-rehabilitation group.Conclusion Acupuncture-rehabilitation therapy can improve the neurological function in rats with cerebral ischemia, that is better than the simple acupuncture or exercise, which may relate to the inhibition of caspase-8 and caspase-3 protein activation, and promotion of cIAP1 protein expression, to inhibit the apoptotic caspases cascade reaction.

Objective To observe the effect of acupuncture plus rehabilitation on neurologic deficit and the expression of vascular endothelial growth factor (VEGF) protein in cortex on the infarction side in rats with focal cerebral infarction, and to explore the action mechanism of acupuncture plus rehabilitation in promoting the recovery of impaired function in rats.Method Ninety healthy male Sprague-Dawley (SD) rats were randomized into a model group, an acupuncture group, a rehabilitation group, an acupuncture-rehabilitation group, and a sham operation group, and the five groups were further divided into three subgroups, i.e. 3 d, 7 d, and 14 d subgroups, 6 rats in each subgroup. The modified Zea-Longa method was adopted to prepare the model of middle cerebral artery occlusion (MCAO) on theright side. Rats in the acupuncture group received simulant scalp-points cluster needling; the rehabilitation group was intervened by treadmill exercise; the acupuncture-rehabilitation group was intervened by scalp-points cluster needling plus treadmill exercise; the model group and sham operation group didn't receive any interventions. The modified Neurological Severity Score (mNSS) was adopted to evaluate the rat's neurologic deficit, and Western blotting was used to detect the expression of VEGF protein in cortex on the infarction side.Result Neurologic deficit wasn't found in rats in the sham operation group. After 3-day treatment, the mNSSs in the acupuncture group, rehabilitation group, and acupuncture-rehabilitation group were insignificantly different from the score in the model group (P>0.05), while the differences were statistically significant respectively after 7-day and 14-day treatment (P<0.05). Respectively after 7-day and 14-day treatment, the mNSS of the acupuncture-rehabilitation group was significantly lower than that in the acupuncture group and rehabilitation group (P<0.05); there was no significant difference in comparing the mNSS between the acupuncture group and rehabilitation group (P>0.05). After 3-day treatment, the expression of VEGF protein in each treatment group was insignificantly different from that in the model group (P>0.05), while the expression of VEGF protein in each treatment group was significantly higher than that in the model group respectively after 7-day and 14-day treatment (P<0.05). Respectively after 7-day and 14-day treatment, the expression of VEGF in the acupuncture-rehabilitation group was significantly different from that in the acupuncture group and rehabilitation group (P<0.05); there were no significant differences in comparing the expression of VEGF at each time point between the rehabilitation group and acupuncture group (P>0.05).Conclusion Scalp-points cluster needling and rehabilitation both can improve the neurologic function in rat models of focal cerebral infarction, and enhance the expression of VEGF protein in infarction cortex, and the integration of acupuncture and rehabilitation can achieve a better result; the action mechanism is possibly related to the high expression of VEGF which can better promote the reconstruction and regeneration of the vessels in cerebral infarction area.

Objective To explore the effects of acupuncture-rehabilitation therapy on neurological function recovery and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway activation after permanent focal cerebral ischemia in rats. Methods Ninty male Sprague-Dawley rats were divided into five groups, namely sham group, model group, acupuncture group, rehabilitation group and acupunc-ture-rehabilitation group, and 18 in each group. Each group was further divided into 3 days, 7 days and 14 days subgroups (n=6). Their mid-dle cerebral arteries were occluded except those of sham group. The sham and model groups accepted no treatment, while the acupuncture group accepted cluster needling of scalp acupuncture, rehabilitation group accepted treadmill training, and the acupuncture-rehabilitation group accepted both acupuncture and treadmill training. They were assessed with modified Neurologic Severity Score (mNSS) 3, 7 and 14 days after modeling, while the expression of ERK1/2 and p-ERK1/2 were determined with Western blotting. Results The neurologic severi-ty score reduced in all three treatment groups (P<0.05) compared with that of the model group at every time point, and was the least in the acupuncture-rehabilitation group (P<0.05) 7 and 14 days after modeling among the treatment groups. Meanwhile, the expression of p-ERK1/2 increased in all three treatment groups (P<0.05), and was the most in the acupuncture-rehabilitation group (P<0.05), as well as the rate of (p- ERK1/2)/(ERK1/2) (P<0.05). Conclusion Acupuncture- rehabilitation therapy can promote the neurological function recovery, which may be associated with activation of ERK1/2 signaling pathway.

Objective To investigate the effect of electroacupuncture or exercise preconditioning on neurological function after focal ce-rebral infarction in rats and the possible mechanism. Methods A total of 24 male Sprague-Dawley rats were randomly divided into model group (n=6), sham group (n=6), exercise preconditioning group (n=6) and electroacupuncture preconditioning group (n=6). The model group and the sham group did not accept any treatment, while the exercise preconditioning group and the electroacupuncture precondition-ing group accepted treadmill training and electroacupuncture for two weeks, respectively. Their middle cerebral arteries were occluded with modified Longa's approach, except the sham group that was ligated the same arteries but did not result in infarction. They were evaluated with Neurologic Severity Scores (NSS) 24 hours after modeling, and the laminin expression in the ischemic area was detected with Western blotting. Results There was no neurological deficit in the sham group. The NSS was lower in both preconditioning groups than in the model group (P<0.05), but was not significant different between preconditioning groups (P>0.05). The expression of laminin was the most in the sham group, and was more in both preconditioning groups than in the model group (P<0.05), but was not significant different between pre-conditioning groups (P>0.05). Conclusion Preconditioning with exercise or electroacupuncture can both reduce the neurological deficits in rats after focal cerebral infarction, which may associate with the protection of laminin from inhibition in early stage.

Objective To explore the effect of acupuncture-rehabilitation therapy on neurological function and expression of Flt-1 and Flk-1, members of vascular endothelial growth factor receptors, after permanent focal cerebral ischemia in rats. Methods Ninety male Sprague-Dawley rats were divided into five groups, namely sham group, model group, acupuncture group, rehabilitation group and acupunc-ture-rehabilitation group, and each group was further divided into 3-day, 7-day and 14-day subgroups, equally. Their middle cerebral arteries were occluded except those of sham group. The sham and model groups accepted no treatment, while the acupuncture group accepted clus-ter needling of scalp acupuncture, the rehabilitation group accepted treadmill training, and the acupuncture-rehabilitation group accepted both acupuncture and treadmill training. They were assessed with modified Neurologic Severity Score (mNSS) 3, 7 and 14 days after model-ing, while the expression of Flt-1 and Flk-1 were determined with Western blotting. Results The mNSS score reduced in all the treatment groups (P<0.05) compared with that of the model group at every time point, and was the least in the acupuncture-rehabilitation group (P<0.05) 7 and 14 days after modeling among the treatment groups. Meanwhile, the expression of Flt-1 and Flk-1 protein increased in all the treatment groups (P<0.05), and was the most in the acupuncture-rehabilitation group (P<0.05). Conclusion Acupuncture-rehabilitation thera-py can promote the neurological function recovery in rat with permanent focal cerebral ischemia, which may be associated with the continu-ous inducement of Flt-1, Flk-1 protein expression in ischemic penumbra cortex.

BACKGROUNDTo evaluate the clinical efficacy and toxicity of GP (gemcitabine+cisplatin) and NP (navelbine+cisplatin) regimens in the treatment of advanced non-small cell lung cancer (NSCLC).

METHODSSeventy-six cases of advanced NSCLC were enrolled. Among them, 36 received GP (gemcitabine 1.0 g/m² D1,8,15+cisplatin 30 mg/m² D1-3), meanwhile 40 were administrated NP regimen (navelbine 30 mg/m² D1,8+cisplatin 30 mg/m² D1-3).

RESULTSThe overall response rates of GP and NP were 52.8% and 47.5% respectively (P > 0.05), and the median survivals were 9.8 and 8.7 months respectively (P > 0.05). The main toxicity was hematological toxicity. The incidences of leukopenia were 58.3% and 92.5% in GP and NP respectively (P < 0.01), and those of grade III-IV leukopenia were 16.7% and 52.5% respectively (P < 0.01 ). There was no significant difference in thrombocytopenia incidence between the two groups, however, GP group had a remarkably higher incidence of grade III-IV thrombocytopenia (33.3%) than NP group ( 10.0% ) (P < 0.05 ).

CONCLUSIONSEfficacy of GP regimen is similar to that of NP and both of them can be well tolerated by patients.