Pharmacokinetic of Jiaotai pill in normal and depressed rats / 药学学报

This study was aimed to explore the pharmacokinetics of epiberberine, jatrorrhizine, coptisine, palmatine, berberine of Jiaotai pill in the normal and depressed rats. According to ‘Katz’ method, the model of chronic unpredictable mild stress (CUMS) was established. The extract of Jiaotai pill was orally administered to rats, and the blood samples were collected via the the oculi chorioideae vein according to the time schedule. The concentrations of epiberberine, jatrorrhizine, coptisine, palmatine, berberine in rat plasma were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by DAS1.0 software. Compared with normal rats, the Cmax of palmatine, coptisine, berberine and jatrorrhizine in Jiaotai pill in depressed rats were 1.99, 2.14, 2.3, 1.82 times than the normal group, while the AUC0−t were 1.23, 1.25, 1.29, 1.46 times and the AUC0−∞ were 1.21, 1.25, 1.30, 1.43 times, which were significantly different.

Simultaneous determination of five constituents in Simotang Oral Liquid by HPLC / 中成药

AIM To establish an HPLC method for the simultaneous content determination of five constituents in Simotang Oral Liquid (Aucklandiae Radix,Aurantii Fructus,Arecae Semen,etc.).METHODS The analysis of 50％ methanol extract of this drug was performed on a 35 ℃ thermostatic Agilent Zorbax C18 column (4.6 mm × 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％ formic acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 283 nm.RESULTS Synephrine,norisoboldine,naringin,hesperidin and neohesperidin showed good linear relationships within the ranges of 5.8-185.6 μg/mL (r =0.999 9),0.829-26.52 μg/mL (r =1.000 0),9.775-312.8 μg/mL (r =1.000 0),0.594-19 μg/mL (r =0.999 5) and 5.2-166.4 μg/mL (r =1.000 0),whose average recoveries were 98.93％,98.95％,102.57％,99.67％ and 103.43％ with the RSDs of 1.85％,1.27％,0.52％,0.89％ and 0.43％,respectively.CONCLUSION This simple,accurate and reproducible method can be used for the rapid quality control of Simotang Oral Liquid.

Change of hepatic drug metabolism enzymes in rat depression model with kidney-yang deficiency / 药学学报

This study was designed to explore the impact of depression on kidney-yang deficiency in rats. Rats were repeatedly injected with hydrocortisone for 21 days to establish the depression model with kidneyyang deficiency. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were used as substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1, and CYP2D2 to test the depression impact on drug metabolism. Plasma concentrations of six CYP450 were determined by LC-MS/MS and used as pharmacokinetic parameters. Consequently, metabolism of theophylline, chlorzoxazone and tolbutamide were accelerated significantly in the model relative to the control (P<0.01), but dextromethorphan, omeprazole and midazolam did not exhibit a significant difference. The present study suggests that depression with kidneyyang deficiency had a strong induction of CYP2E1 and moderate induction of CYP1A2, CYP2C6 in the rat model.

[Effects of parecoxib sodium analgesia on serum concentrations of neuron-specific enolase and S-100ß and postoperative cognitive function of elderly patients undergoing acute replacement of femoral head].

OBJECTIVE: To explore the effects of parecoxib sodium analgesia on serum concentrations of neuron-specific enolase (NSE) and S-100ß and postoperative cognitive function of elderly patients undergoing acute replacement of femoral head. METHODS: After the approval of institutional review board and the provision of informed consent, 80 patients over 70 years old, undergoing acute replacement of femoral head under combined spinal and epidural anesthesia and midazolam sedation at Qingdao Municipal Hospital and Qingdao Hiser Medical Center from January 2011 to May 2012, were randomly assigned into control group (group C, n = 40) and parecoxib group (group P, n = 40). In group P, parecoxib sodium 20/40 mg (based on weight 50 kg) was administered via an intravenous injection after admission with 12 hours intervals for six times. In group C, morphine 2/4 mg was given initially. Additional morphine 2 mg was given to maintain the pain visual analog scale (VAS) of 3 points or less in both groups. Primary observation indices: (1) postoperative time and additional amount of morphine; (2) rate of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) at 3 days, 1 week, 3 months and 6 months postoperation (T1-T4); (3) se rum levels of NSE and S-100ß were measured at the timepoints of before analgesia (t0), before anesthesia (t1), end of surgery (t2) and 6 hours, 24 hours, 48 hours postoperation (t3-t5); (4) other serious complications. RESULTS: Compared with group C, the additional amount of morphine, postoperative time, rate of POD and POCD at T1-T4, the level of NSE at t2-t5 and S-100ß at t1-t5 were lower in group P (P < 0.05). No other serious complications were observed. CONCLUSIONS: Parecoxib sodium analgesia reduces the rate of POD and POCD in elderly patients with neuroprotective effects.

[Influence of auricular point sticking on incidence of nausea and vomiting and analgesia effect after gynecological laparoscopy].

OBJECTIVE: To observe the influence of auricular point sticking on incidence of nausea and vomiting and analgesia effect after gynecological laparoscopy, and provide evidence for clinical application of auricular point sticking. METHODS: One hundred and twenty cases of selective gynecological laparoscopy under general anesthesia were randomly divided into an auricular point sticking group and a placebo group, 60 cases in each group. In the auricular point sticking group, the auricular point sticking with vaccaria seeds was applied at Shenmen (TF 4), Wei (CO 4) and Jiaogan (AH 6a) before the operation and 1, 5, 9, 23 h after the operation, which were pressed 5 min each point each time. The two ears were proceeded at the same time. In the placebo group, the same point selection, sticking paste was used as the auricular point sticking group, but no sticking or pressing with vaccaria seeds was adopted. The incidence of nausea and vomiting, the usage rate of tropisetron and morphine within 24 hours of the operation, as well as the score of visual analogue scale (VAS) and other adverse reactions at 2, 6, 10, 24 h after the operation were observed respectively. RESULTS: Compared with the placebo group, the incidence of nausea and vomiting [31.7% (19/60), 16.7% (10/60) vs 58.3% (35/60), 35.0% (21/60)], the usage rate of tropisetron [21.7% (13/60) vs 48.3% (29/60)] and morphine [18.3% (11/60) vs 38.3% (23/60)], the VAS scores at all different time points in the auricular point sticking group were all decreased (all P < 0.05), and no adverse reaction was observed. CONCLUSION: The auricular point sticking could significantly decrease the incidence of nausea and vomiting in patients of gynecological laparoscopy and has positive analgesic effect.

[Effects of transcutaneous electrical stimulation of auricular Shenmen point on postoperative nausea and vomiting and patient-controlled epidural analgesia in cesarean section].

OBJECTIVE: To investigate the effects of transcutaneous electrical stimulation of auricular Shenmen point on postoperative nausea and vomiting and patient-controlled epidural analgesia in cesarean section. METHODS: After IRB approval and informed consent, one hundred and eighty singleton primiparas undergoing elective cesarean section, in Qingdao Municipal Hospital, and Qingdao Hiser Medical Center, from November 2011 to March 2012, were randomly assigned to three groups: transcutaneous electrical stimulation of auricular Shenmen point group (group A, n = 60), transcutaneous electrical stimulation of auricular Eye point group (group B, n = 60) and control group (group C, n = 60). Women of group A received transcutaneous electrical stimulation of auricular Shenmen point (frequency 1.5 HZ) at the time of preoperation, 4, 10 and 22 hours of postoperation for 30 minutes. The strength was controlled by themselves. Women of group B received stimulation of auricular Eye point as group A. Women of group C received pressurization and connected line were the same with group A, but without electrical stimulation. The following indexes was observed: the incidence of postoperative nausea and vomiting (PONV) for 48 hours; the rate of metoclopramide; the visual analogue scale (VAS) score of rest pain, uterine contration pain and dynamic pain at the time of postoperation for 6, 12, 24 and 48 hours (T(1)-T(4)); the total number and effective compressions number of patient-controlled epidural analgesia(PCEA);the dose of analgesia mixture; the anal exhaust time; the volume of postoperative bleeding for 6 hours of postoperation and the other side effects. RESULTS: Compared with group B and group C, the incidence of PONV, the rate of metoclopramide, the VAS score at the time T(1)-T(4), the total number and effective compressions number of PCEA, the ratio of the total number with effective compressions number and the dose of analgesia mixture were decreased in group A (P < 0.05), but no difference compared group B with group C (P > 0.05). The anal exhaust time and the volume of postoperative bleeding for 6 hours of postoperation were no difference in the three groups (P > 0.05). No other side effects were observed. CONCLUSION: Transcutaneous electrical stimulation of auricular Shenmen point can reduce the incidence of PONV and improves analgesia effect of PCEA in postoperation of cesarean section.

[Efficacy and safety of patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in cesarean section].

OBJECTIVE: To study the efficacy and safety of patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in cesarean section. METHODS: A randomized controlled clinical trail was conducted on 180 singleton primiparas (SAS > 30) undergoing selective cesarean section. They were randomly assigned to three groups, i. e., the patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) group (Group A, 60 cases), the patient-controlled sedation with transcutaneous electrical stimulation of auricular eye point group (Group B, 60 cases), and the control group (Group C, 60 cases). Patients in Group A received patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in the operating room. The strength was controlled by patients themselves. The stimulation lasted for 30 min before the epidural puncture till ending the surgery. Patients in Group B received stimulation of auricular eye point. Patients in Group C received pressurization with the same connected line as Group A, but without electric stimulation. The following indices were observed: (1) the bispectral index (BIS), heart rate (HR), mean arterial pressure (MAP), Ramsay sedation score when the women entered the operating room (T0), 30 min after stimulation (T1), at the time after removing the fetus (T2), and by the end of surgery (T3); (2) the concentrations of plasma angiotensin II (AngII) and cortisone (Cor) at the aforesaid time points; (3) the use rates of oxytocin, atropine, and ephedrine; the hemorrhage amount, and the neonatal Apgar score. RESULTS: Compared with Group A, the BIS, the plasma concentrations of AngII and Cor increased at T1, T2, and T3 (P < 0.05), and the Ramsay sedation score decreased (P < 0.05). The HR and MAP increased at T1 (P < 0.05) in Group B and Group C. Compared with T0, the BIS, HR, MAP, and Ramsay sedation score, the plasma concentrations of AnglI and Cor were lowered in Group A at T1 (P < 0.05). There was no statistical difference in the use rates of oxytocin, atropine, and ephedrine; the hemorrhage amount, and the neonatal Apgar score (P > 0.05). CONCLUSIONS: Patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in cesarean section had obvious sedative effects. It had no adverse effects on puerperal or neonates.

Changes of regulatory T cells and FoxP3 gene expression in the aging process and its relationship with lung tumors in humans and mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Immunosuppressive regulatory T cells (Tregs) participate in tumor immune evasion and the number and suppressive function of Tregs change with the aging process, but it is not clear whether such change leads to a higher incidence of tumors in the elderly. To this end, we designed experiments to explore the changes of Tregs and the functional gene Forkhead box P3 (FoxP3) in the aging process and its relationship with lung tumors in humans and mice.</p><p><b>METHODS</b>The percentage of CD4(+)CD25(+)CD127(low) Tregs and expression of FoxP3 mRNA were analyzed using flow cytometry (FCM) and real-time fluorescence-based quantitative polymerase chain reaction (FQ-PCR). Markers were analyzed in the peripheral blood (PB) of 65 elderly patients (age ≥ 65 years) with primary non-small cell lung cancer (NSCLC), 20 younger patients (aged < 55 years) with NSCLC, 30 elderly healthy individuals and 30 young healthy individuals. Furthermore, we set up the Lewis lung cancer model with C57BL/6 female mice. Thirty-six mice were divided into a young healthy group, a middle-aged healthy group, an elderly healthy group, a young tumor group, a middle-aged tumor group, and an elderly tumor group. The percentage of CD4(+)CD25(+)FoxP3(+) Tregs and the expression level of FoxP3 mRNA in splenocytes were determined in the six groups.</p><p><b>RESULTS</b>The percentage of peripheral CD4(+)CD25(+)CD127(low) Tregs and the expression of FoxP3 mRNA were significantly increased in elderly patients with NSCLC comparing with the other groups and in elderly healthy individuals compared with young healthy individuals. Further analysis showed that the percentage of CD4(+)CD25(+)CD127(low) Tregs and the expression of FoxP3 mRNA were closely associated with tumor node metastasis (TNM) staging in elderly patients with NSCLC. In the mouse model, the percentage of CD4(+)CD25(+)FoxP3(+) Tregs and the expression of FoxP3 mRNA in splenocytes of the tumor groups were significantly higher than in the healthy groups, with the highest expression in the elderly tumor group. In the healthy groups, the elderly healthy mice had the highest percentage of Tregs and expression of FoxP3 mRNA. The elderly mice had larger and heavier tumors than did the young and middle aged mice.</p><p><b>CONCLUSIONS</b>The up-regulation of Tregs and the FoxP3 gene with aging may play an essential role in oncogenesis and development of lung tumors in an elderly population.</p>

[Efficacy and delivery outcomes of women underwent double-catheter epidural block during labor].

OBJECTIVE: To investigate the efficacy and pregnancy outcomes of women receiving double-catheter epidural block in labor analgesia, and compare the results with single-catheter epidural block. METHODS: A double-blind clinical trial was conducted on 206 full-term singleton primiparas, aged 25 - 35 and at the 37 - 42 weeks of gestation who delivered at the Department of Obstetrics, Qingdao Municipal Hospital from August 2006 to December 2008, which were randomly divided into two groups: double-catheter epidural block (group D, n = 103) and single-catheter epidural-block (group S, n = 103). Women in group D were given mixture of 0.1% repivacaine hydrochloride and 0.5 mg/L sufentinil 4 - 6 ml as initial dose. Patient control epidural analgesia pump (PCEA) was connected with the upper catheter after 45 minutes. A bolus dose of 4 - 6 ml analgesia mixture was infused according to the condition through the lower catheter. Women in group S received analgesia mixture 10 - 15 ml as initial dose and PCEA pump was connected after 45 minutes. Oxytocin was infused in both groups according to uterine contraction after 30 minutes. The following indexes was observed: (1) visual analogue scales (VAS); (2)modified Bromage Scores; (3) the total dose of analgesia mixture, the percentage of oxytocin infusion, duration of labor and duration of the second stage of labor; (4) fetal birth weight and Apgar scores (1, 5 minutes); (5) mode of delivery; (6) the concentration of plasma cortisol and angiotension II at the beginning of regular uterine contraction and at the time when cervical dilated to 4 cm and 10 cm and fetal disengagement; (7) anesthesia-related complications. RESULTS: (1) The neonatal birth weight and Apgar scores (1, 5 minutes) of group D were (3456 ± 468) g, 9.8 ± 0.6 and 9.9 ± 0.7, respectively, while (3399 ± 569) g, 9.8 ± 0.5 and 9.9 ± 0.7 in group S (P > 0.05). No motor function block was reported in any group and the modified Bromage score was zero. (2) The total dose of analgesia mixture in group D was similar to that in group S [(57 ± 9) ml vs. (58 ± 11) ml, P > 0.05]. However, the percentage of women received oxytocin in group D was smaller [59.2% (61/103) vs. 81.6% (84/103), P < 0.01], and the total time of labor and the duration of second stage of labor in group D were shorter [(532 ± 140) minutes vs. (608 ± 150) minutes; (46 ± 31) minutes vs. (60 ± 34) minutes, P < 0.05]. (3) There were no significant differences in VAS at 30 minutes after initial dose and in the first stage of labor between group D and S (1.2 ± 1.1 vs 1.2 ± 1.1, 1.1 ± 1.1 vs. 1.2 ± 1.0, P > 0.05). VAS at the second stage of labor stage was lower in group D than in group S (1.2 ± 1.1 vs. 4.5 ± 2.2, P < 0.01). (4) The rate of cesarean section, instrumental delivery and episiotomy in group D were lower than in group S (7.8% vs. 17.5%, 7.8% vs. 15.5%, 10.7% vs. 18.4%, P < 0.05). The incidence of fetal distress and meconium-stained amniotic fluid as the indication of cesarean section were similar between the two groups (P > 0.05). Lower incidence of fetal malpresentation and arrested second stage of labor were shown in group D than in group S (2.9% vs. 9.7%, 1.0% vs. 5.8%, P < 0.05). (5) The concentration of plasma cortisol and angiotension II were lower in group D than in group S [(86 ± 25) ng/L vs. (100 ± 20) ng/L, (278 ± 53) nmol/L vs. (311 ± 53) nmol/L, P < 0.05] only at the end of second stage of labor, but not at any other times (P > 0.05). (6) No serious anesthesia-related complications were reported in any groups. Some light backache around the puncture point were complained by 29.1% (30/103) of the women in group D and 31.1% (32/103) in group S (P > 0.05). CONCLUSION: Double-catheter epidural block can provide better analgesia effect during labor than single-catheter epidural block, without any adverse influence on delivery outcomes.

An association between immunosenescence and CD4(+)CD25(+) regulatory T cells: a systematic review / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Age-related increment of the prevalence of CD4(+)CD25(+) regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence.</p><p><b>METHODS</b>Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells.</p><p><b>RESULTS</b>It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8(+) T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4(+)CD25(+) T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease (AD) and Parkinson disease (PD). The impaired condition of CD4(+) T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years.</p><p><b>CONCLUSIONS</b>Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.</p>

Anti-angiogenic effect of vinorelbine in combination with cetuximab in vitro and in vivo / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This experiment aims to study the anti-angiogenic ability of vinorelbine combined with cetuximab in vitro and in vivo.</p><p><b>METHODS</b>Human lung adenocarcinoma A549 cells were used as control group. Proliferation of human umbilical vein endothelial cells (HUVEC) was assessed by MTT assay. Furthermore, we used Transwell chambers, capillary tube formation and flow cytometry to observe the effects of vinorelbine combined with cetuximab on HUVEC migration, tube formation and cell apoptosis, respectively. In addition, the anti-angiogenic ability of the drugs was checked using chicken chorioallantoic membrane (CAM) model.</p><p><b>RESULTS</b>The inhibitory rate of HUVEC growth was 25.8%, 39.2%, 54.0% for vinorelbine at the concentration of 0.1 ng/ml, 0.4 ng/ml, and 0.8 ng/ml, respectively; that of 0.25 microg/ml cetuximab was 19.7%, and that of 0.1 ng/ml vinorelbine + 0.25 microg/ml cetuximab, 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab and 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 29.5%, 46.4%, 64.6%, respectively. The inhibitory rates of the drugs at the above mentioned combinations of migration and tube formation of HUVEC were 51.9%, 68.2%, 95.0%, respectively. The inhibitory rate of 0.1 ng/ml + 0.25 microg/ml cetuximab and 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab on tube formation of HUVEC was 38.8% and 57.7%, respectively, showing a sub-additive effect, and that of combination of 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 78.9%, showing a synergistic effect. In addition, the apoptotic rate of HUVEC induced by 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 59.9%, showing a synergistic effect. The in vivo experiment also showed that the combination of the two drugs had a synergistic anti-angiogenic effect.</p><p><b>CONCLUSION</b>Both low dose vinorelbine and cetuximab have an anti-angiogenic effect in vitro and in vivo, and the combination of the two drugs has sub-additive or synergistic inhibitory effect on angiogenesis.</p>