[In vivo comparison of estradiol metabolism in liver microsomes of human, Beagle dog and rat].

The inter-species differences of estradiol metabolism were investigated in human, Beagle dog and rat liver microsomes by comparing enzyme kinetics of parent drug and the formation of its major metabolites. The incubation systems of estradiol with liver microsomes of the three species were optimized in terms of estradiol concentration, microsomal protein content and incubation time. The concentrations of estradiol and its metabolites were measured by LC-MS/MS method. The t1/2, CLint, CLh, Km and Vmax of estradiol incubated with male human liver microsomes were 40.02 +/- 8.32 min, 41.39 +/- 6.57 mL x min(-1) x kg(-1), 13.81 +/- 12.36 mL x min(-1) x kg(-1), 26.8 +/- 6.99 micromol x L(-1) and 0.75 +/- 0.92 micromol x L(-1) x min(-1), respectively. The corresponding parameters of female human were 44.71 +/- 10.21 min, 29.85 +/- 8.97 mL x min(-1) x kg(-1), 0.01 +/- 0.68 mL x min(-1) x kg(-1), 44.2 +/- 7.73 micromol x L(-1) and 1.27 +/- 4.41 micromol x L(-1) x min(-1), that of male dog were 21 +/- 7.33 min, 165.53 +/- 29.33 mL x min(-1) xkg(-1), 26.01 +/- 8.39 mL x min(-1) x kg(-1), 19.5 +/- 7.34 micromol x L(-1) and 1.6 +/- 0.65 micromol x L(-1) x min(-1), that of female dog were 25.5 +/- 5.32 min, 135.11 +/- 42.34 mL x min(-1) x kg(-1), 0.24 +/- 3.18 mL x min(-1) x kg(-1), 8.33 +/- 6.32 micromol x L(-1) and 0.51 +/- 2.15 micromol x L(-1) x min(-1), that of male rat were 5.11 +/- 3.84 min, 485.63 +/- 36.52 mL x min(-1) x kg(-1), 49.57 +/- 15.29 mL x min(-1) x kg(-1), 62 +/- 13.74 micromol x L(-1) and 19.16 +/- 9.67 micromol x L(-1) x min(-1), and that of female rat were 7.0 +/- 3.69 min, 354.82 +/- 33.33 mL x min(-1) x kg(-1), 8.04 +/- 3.23 mL x min(-1) x kg(-1), 35.38 +/- 7.65 micromol x L(-1) and 8.39 +/- 4.91 micromol x L(-1) min(-1), respectively. There were nine metabolites detected from all the three species, but the relative amounts of the metabolites generated were different in three species. The results indicted that the major phase I metabolic pathway of estradiol was similar in the liver microsomes from all the three species. However, the inter-species differences were found in the view of relative amounts of the metabolites as well as the metabolic characteristics of estradiol in liver microsomal incubation.

Efficacy of Yangyin Yiqi Huoxue Granule () in Treatment of Ischemic Stroke Patients with Qi-Yin Deficiency and Blood Stasis Syndrome: A Randomized, Double-Blind, Multicenter, Phase-2 Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of Yangyin Yiqi Huoxue Granule (, YYHG) in the treatment of ischemic stroke (IS) patients with qi-yin deficiency and blood stasis syndrome (QYDBSS), and to explore its effective dosage. METHODS: The total of 288 patients were randomly assigned to the YYHG high-dose, YYHG low-dose, positive control (administered Xiaoshuantong Granule, XSTG, ), or placebo control (administered inert granule) groups (72 cases per group) by software-drived competitive block randomization. The trial was conducted for a 28-day period, with a 180-day follow-up period. The primary outcome was the comprehensive curative evaluation, and secondary outcomes were the National Institute of Health Stroke Scale (NIHSS) score, Barthel activities of daily living (ADL) index score, the quality of life index (QLI) score, and the Chinese medicine syndrome (CMS) score. All analyses were done on an intention-to-treat basis. The clinical safety was also assessed. RESULTS: The total of 288 participants were recruited between June 1, 2008 and September 30, 2009, and 287 patients received intervention; the treatment groups were well balanced at baseline. The comprehensive cure rates of YYHG high-dose, low-dose, positive and placebo control groups were 63.38%, 31.94%, 36.11% and 6.14%, respectively; there was a statistical difference between the two groups (P<0.01), while the high-dose YYHG treatment group was significantly higher than the other 3 groups (P<0.01). The improvement of NIHSS, ADL, QLI and CMS scores of the YYHG high-dose and low-dose groups was significantly better than that of the positive control group and the placebo control group (P<0.05). In terms of improving the classification of the NIHSS scale and the assessment of the ADL scale, the YYHG high-dose group was significantly better than the other three groups (P<0.05), and the YYHG low-dose group was better than the placebo control group (P<0.01). At the same time, except for the QLI score, the high-dose group was better than the low-dose group (P<0.05). In terms of safety, adverse reactions after YYHG treatment were generally mild (3.78%), and no serious adverse reactions have been reported. CONCLUSION: YYHG is safe and effective in the treatment of IS patients with QYDBSS.

Patient-controlled subcutaneous analgesia using sufentainil or morphine in home care treatment in patients with stage III-IV cancer: A multi-center randomized controlled clinical trial.

PURPOSE: Patient-controlled subcutaneous analgesia (PCSA) with sufentanil is an alternative analgesia strategy in patients with stage III-IV cancer; however, its efficacy and safety have not been fully investigated. METHODS: From May 10, 2017 to November 10, 2017, 120 patients with stage III-IV cancer suffering from moderate to severe pain were prospectively enrolled from six hospitals and randomized to receive PCSA with morphine (control group) or sufentanil (intervention group). Before the PCSA and on days 1, 3, 7, 14, 28, and 56 after treatment, the numeric rating scale (NRS) and 36-item Short Form health survey (SF-36) were completed for each patient and the side effects were also recorded. RESULTS: No significant differences (P > .05) were observed in the preoperative NRS score and the SF-36 parameters between the two groups. Patients in the intervention group achieved better pain relief, as indicated by lower NRS scores at days 14 (P = .040), 28 (P < .001), and 56 (P < .001) after PCSA device implantation (vs control group). Furthermore, the patients in the intervention group also achieved a better life quality, as indicated by the physical role, general health, social function body pain, and mental health scores. Finally, the patients receiving sufentanil showed lower levels of nausea and somnolence than those in the control group. CONCLUSION: PCSA with sufentanil achieves better pain control and life quality as well as fewer adverse reactions in stage III-IV cancer patients with pain and may be a promising pain management in these patients. TRIAL REGISTRATION: This study was registered at chictr.org.cn with the trial number: ChiCTR-IPR-17011280.

[Responses of photosynthetic characteristics in leaves of Physocarpus amurensis and P opulifolius to drought stress]. / ä¹¡åœŸé£Žç®±æžœå’Œç´«å¶é£Žç®±æžœå¶ç‰‡å ‰åˆç‰¹æ€§å¯¹åœŸå£¤å¹²æ—±çš„å“åº”.

This experiment was conducted to study the responses of photosynthetic gas exchange parameters and the chlorophyll fluorescence parameters in leaves to soil drought. Furthermore, the drought resistance abilities of the endangered native Physocarpus amurensis and the introduced P. opulifolius as well as their differences were studied. The results showed that the leaves of P. opulifolius wilted significantly, while the leaf water content and water use efficiency of the native P. amurensis were higher on the 7th day after soil drought. Soil drought reduced the net photosynthetic rate, stomatal conductance, and transpiration rate in the leaves of the two Physocarpus species, while the observed decrease of P. opulifolius was significantly higher than that of P. amurensis. On the 7th day after soil drought, the intercellular CO2 concentration (Ci) of P. opulifolius was higher than that without drought treatment, while the Ci of P. amurensis was lower than that without drought treatment. The electron transfer rate (ETR) and photochemical quenching coefficient (qP) in leaves of P. amurensis were clearly decreased, while differences of the light energy capture efficiency (Fv'/Fm') in the PS2 reaction center were non-significant. However, Fv'/Fm', ETR, and qP in the lea-ves of P. opulifolius were all significantly decreased to greater extents compared to those in P. amurensis. On the 7th day after soil drought, a non-significant change was observed on the relative variable fluorescence (VJ) at site J of the OJIP curve of P. amurensis leaves, while VJ in leaves of P. opuli-folius was increased. The carbon assimilation ability of P. opulifolius leaves and the sensibility of PS2 function to soil drought were significantly higher than those of P. amurensis. The reduction in the photosynthetic capacity induced by soil drought was mainly due to the limitation of the stomatal factors for P. amurensis, but mainly due to the limitation of the non-stomatal factors for P. opulifolius.

[Changes of Ag-NORs of T lymphocytes and hemorheological indexes in old patients with blood stasis syndrome].

OBJECTIVE: To observe the changes of Ag-NORs of T lymphocytes and hemorheological indexes in old patients with blood stasis (BS) syndrome. METHODS: Ag-NORs of T lymphocytes and hemorheological indexes in 54 old patients with blood stasis syndrome in the BS group were determined and compared with those in the control group consisted of 36 healthy persons. RESULTS: Contents of Ag-NORs of T lymphocytes in the BS group and the control group were 5.857 +/- 0.396 and 6.111 +/- 0.541, respectively, showing significant difference (P < 0.05). Some abnormal hemorheological indexes were seen in the BS group, which were significant different to those in the control group (P < 0.05 ). Correlation analysis showed that RVP, ESR, K1 and K2 were negatively correlated with Ag-NORs of T lymphocytes (r = -0.273, -0.335, -0.301, -0.276 respectively; P < 0.01 or P < 0.05), while aggregation index was positively correlated with Ag-NORs of T lymphocytes (r = 0.389, P < 0.05). CONCLUSION: The lowered Ag-NORs of T lymphocytes and abnormal hemorrheological changes might be one of the important reasons for the lowered immunity of aged patients with BS syndrome.

[On the history of the evolution of Evidence-based medicine and its revelation].

The notions of Evidence-based medicine developed through two phases, which successively looked into the doctor-patient relationship and decision-making background. One of the new trends in evidence-based medicine deals with how to make theory into practice. Applying the practical model from post-SSK to interpret how the notions of evidence-based medicine changed, it is found that evidence-based medicine is an indivisible practical network integrating many natural and social factors as well as material and cultural factors which interconnect through "translation". Therefore, the involvement of various factors such as natural matter, social relations, regional factors, resources of traditional culture and scientific instruments leads up to the ultimate theory becoming the result of multiple factors in a continuous process of seeking the best way in scientific practice. In this motile process, the borderline between nature and society, material and human, natural science and social science vanishes and a new stage called humanistic medicine appears.

[Analysis on the background of arising of Evidence-based medicine].

Science is coming from the background of social culture. Evidence-based medicine (EBM) was generated at the early 90's of 20th Century, and there were some landmark things before its appearance. The background of EBM included: (1) risk control of medical techniques at the 70s of 20th Century; (2) ethical ideas of Protestant, including secularism, rationalism and utilitarianism; (3) British positivism and its tradition.

[The basic concept of patient safety and its evolution].

Patient safety has become a hot topic and a big challenge for healthcare services globally during the past ten years. Patient safety is not a new concept but has its explicit cultural root. There were some related elaborations early in the collected works of Hippocrates. Reviewing the origin and developmental process of the concept of patient safety can benefit acquiring a deeper recognition of the basic concept of patient safety. "Medical risk is everywhere" has become the consensus of healthcare professions globally. Patient safety is a perpetual task of the medical area as well as the most basic starting point and final destination in healthcare service.

[Effect and safety of the therapies for acute myocardial infarction patients with failed thrombolytic therapy: a systematic review].

OBJECTIVE: To assess the effect and safety of therapies in common use for acute myocardial infarction (AMI) patients with failed thrombolytic therapy. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2006), MEDLINE (1966 to July 2006), EMBASE (1984 to July 2006), China National Knowledge Infrastructure (CNKI, 1994 to July 2006), China Biomedicine Database disc (CBMdisc, 1980 to July 2006). We also searched several key Chinese journals in the field of cardiovascular diseases. The language was limited to Chinese and English. We included all the randomized controlled trials (RCTs) for acute myocardial infarction patients with failed thrombolytic therapy. Two authors independently assessed the methodological quality of the included studies, the data were analyzed by RevMan 4.2.8 from the Cochrane Collaboration. RESULTS: Nine RCTs met the inclusion criteria. A significant difference was found between the rescue percutaneous coronary intervention (PCI) group and conventional treatment group in the mortality rate at the end of the follow-up [RR=0.64, 95%CI (0.41, 0.98)]. Thromboembolic stroke and bleeding in rescue PCI group were significantly higher than that in conventional treatment group [RR=4.39, 95%CI (1.14, 16.87), and RR=2.79, 95%CI (1.55, 5.02), respectively]. Compared with conventional therapy, rescue thrombolytic treatment was associated with a significantly higher reperfusion rate [RR=2.92, 95%CI (1.75, 4.85)]. Comparison between rescue PCI with rescue thrombolytic treatment revealed that the revascularization rate in rescue PCI group was significantly lower than that in rescue thrombolytic group [RR=0.57, 95%CI (0.34, 0.95)], and the incidence of bleeding was significantly higher in rescue PCI group [RR=2.15, 95%CI (1.27, 3.63)]. Comparison of glycoprotein (GP)IIb/IIIa receptor antagonists with standard treatment showed no significant difference between them in the mortality rate and bleeding rate at the end of the follow-up. CONCLUSION: Current evidence does not confirm the effect or safety of the therapies for AMI patients with failed thrombolytic therapy, nor support the routine use of these therapies in clinical practice except for rescue PCI that reduces mortality compared with traditional treatment. Further high-quality randomized controlled trials are needed to provide reliable evidence for the treatments of AMI patients with failed thrombolytic therapy.

The application of poly (glycerol-sebacate) as biodegradable drug carrier.

Poly (glycerol-sebacate) (PGS) is an elastomeric biodegradable polymer which possesses the ideal properties of drug carriers. In the present study, we prepared a series of PGS implants (5-FU-PGSs) loaded with different weight percent of 5-fluorouracil (2, 5, 7.5 and 10%). We studied the infrared spectrum properties, in vitro degradation and drug release, in vivo degradation and tissue biocompatibility of 5-FU-PGSs, in order to provide detailed information for the application of PGS as biodegradable drug carrier in cancer therapy. Macroscopically, all 5-FU-PGS wafers in phosphate buffer solution (PBS) kept their geometries during the degradation period of 30 days. The in vitro degradation rates of 5-FU-PGSs were accelerated when higher concentration of 5-FU was doped. Scanning electron microscopy observation showed that the surfaces of 5-FU-PGSs with higher concentration of 5-FU had irregular pits. The cumulative drug release profiles of 5-FU-PGSs exhibited a biphasic release with an initial burst release in the first day. After 7 days, almost 100% cumulative release of 5-FU was found for all 5-FU-PGSs.The degradation rate of 5-FU-PGSs in vivo was much quicker than that in vitro. Hematoxylin and eosin staining showed that no remarkable inflammations were observed in the tissue surrounding 5-FU-PGS implants, suggesting 5-FU-PGSs had good biocompatibility and no tissue toxicity. In vitro anti-tumor activity assay suggested that 5-FU-PGSs exhibited anti-tumor activity through sustained-release drug mode. These results demonstrate that PGS is a candidate of biodegradable drug carriers.

[Efficacy of continuous propofol infusion via the common carotid artery for general anesthesia].

OBJECTIVE: To investigate the efficacy of continuous propofol infusion via the common carotid artery for general anesthesia. METHODS: Forty adult patients scheduled for abdominal surgery were randomly assigned into 2 groups to receive propopol via the common carotid artery (IC group, n=20) or via the median cubital vein (IV group, n=20). Anesthesia was induced with intravenous administration of drugs and maintained with continuous propofol infusion via the common carotid artery or the median cubital vein, with the CSI stabilized at 40-/+5 till the end of the operation. During the anesthesia, intravenous injection of fentanyl (3 microg.kg(-1).h(-1)) and vecuronium (50 microg.kg(-1).h(-1)) were given intermittently to maintain the analgesia and muscular relaxation. The dose of propofol used, hemodynamics and recovery of the patients were observed. RESULTS: The dose of propofol used during the surgery to maintain a CSI of 40-/+5 was significantly lower in group IC and than in group IV (2.57-/+0.67 vs 5.72-/+1.37 mg.kg(-1).h(-1), P<0.01). In group IC, the blood pressure was elevated in more than half of the patients and in some cases, the elevation exceeded one third of baseline value and needed intervention with hypotensive drugs. In the IV group, the patients' blood pressure remained stable and varied within the amplitude of 15% of the baseline level. Recovery of spontaneous breathing and consciousness was more quickly in group IC than in group IV (P<0.05). CONCLUSION: Loss of consciousness and nervous reflex can be achieved with propofol infusion via the common carotid artery, which reduces propofol dose by about 50% in comparison with intravenous infusion and allows more rapid recovery of spontaneous breath and consciousness.

[Effects of carotid arterial and intravenous propofol administration for electrocerebral silence on circulation and respiration in dogs].

OBJECTIVE: To compare the effects of common carotid artery and femoral vein administration of propofol for electrocerebral silence (ES) on circulatory and respiratory function and the dosage of propofol required during ES in dogs. METHODS: Eight dogs were anesthetized by common carotid arterial and femoral vein administration of propofol for ES for 1 h. The time of consciousness loss and recovery, dose of propofol during ES, mean arterial pressure, heart rate, respiration rate, end-tidal carbon dioxide, SpO2, cerebral state index (CSI) and anal temperature were continuously monitored. Changes in the outcome variables were analyzed at 7 time points, namely the baseline, upon loss of consciousness, at 10 s, 30 min and 1 h of CSI=0, and recovery of CSI and consciousness. RESULTS: Carotid artery propofol administration produced ES with only half of the dose for intravenous administration. Compared with the baseline values, the mean artery pressure and respiration rate remained unchanged or decreased transiently during ES with carotid artery propofol administration. In contrast, intravenous propofol administration resulted in systemic hypotension and severe respiratory depression. CONCLUSION: Carotid artery propofol administration produces ES with a much smaller dose than intravenous propofol administration without causing systemic hypotension or respiratory depression.