In silico design of novel proton-pump inhibitors with reduced adverse effects / 医学前沿

The development of new proton-pump inhibitors (PPIs) with less adverse effects by lowering the pKa values of nitrogen atoms in pyrimidine rings has been previously suggested by our group. In this work, we proposed that new PPIs should have the following features: (1) number of ring II = number of ring I + 1; (2) preferably five, six, or seven-membered heteroatomic ring for stability; and (3) 1 < pKa1 < 4. Six molecular scaffolds based on the aforementioned criteria were constructed, and R groups were extracted from compounds in extensive data sources. A virtual molecule dataset was established, and the pKa values of specific atoms on the molecules in the dataset were calculated to select the molecules with required pKa values. Drug-likeness screening was further conducted to obtain the candidates that significantly reduced the adverse effects of long-term PPI use. This study provided insights and tools for designing targeted molecules in silico that are suitable for practical applications.

Review for treatment effect and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis / 中国中药杂志

The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/-catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus and Psoraleae Fructus up-regulated the expression of key proteins and genes of BMP-Smads and Wnt/-catenin signaling pathways to promote bone formation. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix inhibited the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. ②Kidney-tonifying traditional Chinese medicine prevented and treated osteoporosis through a variety of ways: icariin in Epimedii Folium, naringin in Drynariae Rhizoma, osthole in Cnidii Fructus and psoralen in Psoraleae Fructus can regulate BMP-Smads, Wnt/-catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathways to inhibit bone resorption. ③The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.

Clinical effect of single use or combination of dydrogesterone and progestin in treatment of threatened abortion caused by uteal phase defect / 药物评价研究

Objective To explore the clinical effect of single use or combination of dydrogesterone and progestin in treatment of threatened abortion caused by uteal phase defect.Methods Totally 186 patients with threatened abortion caused by uteal phase defect accepted in The First Affiliated Hospital of Henan from April 2015 to April 2016 were selected and randomly divided into groups A,B,and C with 62 cases in each group.Patients in group A were given dydrogesterone,those in group B were given progestin,and those in group C were given dydrogesterone combined with progestin.Then the clinical effect,expression of hormones,treatment outcome,and adverse reaction were observed and compared.Results The total effective rates of groups A and B were 72.58％ and 66.13％,respectively,which were obviously lower than 90.32％ of group C with statistically significance (P ＜0.05).The expression levels of P,E2,and hCG of three groups after treatment were higher than those before,those in group C were the highest among them (P ＜ 0.05).The successful treatment rates of groups A,B,and C were 83.87％,82.26％,and 95.16％,respectively,which had no great difference.Conclusion Combination use of dydrogesterone and progestin has better effective rate in treatment of threatened abortion caused by uteal phase defect compared to single use of these two drugs,which has good safety and worth of clinical application.

Effect of intravenous lornoxicam at different doses on the immune function in patients undergoing total abdominal hysterectomy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of intravenous lornoxicam (LOR) at different doses given preoperatively on the immune function of patients undergoing total abdominal hysterectomy (TAH).</p><p><b>METHODS</b>Forty-five patients undergoing TAH were randomly divided into 3 groups, namely NS group, L8 group and L16 group with intravenous injection of 4 ml saline, 8 mg LOR, and 16 mg LOR before the induction of anesthesia respectively. Venous blood samples were taken before anesthesia (T0), at 30 min during the operation (T1), at the end of the operation (T2), and at 24 h and 48 h after the operation (T3 and T4, respectively) to determine the serum levels of regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), and stromal cell-derived factor 1 alpha (SDF-1alpha) by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The serum RANTES levels in NS group and L8 group at T1-T3 were significantly lower than those at T0 (P<0.05), but the levels in L8 group at each time point were all higher than those in NS group NS (P<0.05). The serum RANTES levels in L16 group L16 only decreased at T1-T2 as compared to those at T0, and were significantly higher than those in NS group and L8 group (P<0.05). The expressions of MCP-1 and SDF-1alpha in the 3 groups all increased at T1 and reached the peak levels after the operation. In L8 group and L16 group, MCP-1 expression at T2-T3 and SDF-1alpha at T1-T2 were both significantly lower than those in NS group (P<0.05). SDF-1alpha expression at T1-T2 was significantly lower in L16 group than in L8 group (P<0.05). The decrements of MCP-1 and SDF-1alpha were more obvious in L16 group than L8 group.</p><p><b>CONCLUSIONS</b>Preoperative intravenous LOR injection may increase serum RANTES level and decrease MCP-1 and SDF-1alpha expressions to effectively relieve the perioperative immune disorders caused by TAH, and the effect is more potent at the dose of 16 mg.</p>

Effects of etomidate infusion on serum cortisol in patients undergoing radical resection of lung cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of etodimate infusion on serum cortisol in patients undergoing radical resection of lung cancer operations during the perioperative period.</p><p><b>METHODS</b>Forty ASA I-II patients undergoing radical resection of lung cancer were randomly divided into etomidate group (Group E) and propofol group (Group P) (n=20). The serum cortisol was measured at 8:00 am (T(0)) before anesthesia, 4:00 pm (T(1)) on the day of operation and 24 h after the operation (T(2)) by radioimmunoassay.</p><p><b>RESULTS</b>Compared with that at T0, the serum level of cortisol significantly increased at 24 h after the operation in both groups (P<0.01); serum cortisol decreased lightly at T1, which was not statistically significant (P>0.05), and remained higher than the normal level. At each of the time points, serum cortisol levels were comparable between the two groups (P>0.05).</p><p><b>CONCLUSION</b>Etomidate infusion can not inhibit the synthesis of cortisol in patients undergoing radical resection of lung cancer.</p>

Effect of controlled hypotension with different drugs combined with acute hypervolemic hemodilution on bleeding volume and gastrointestinal perfusion in nasal endoscopic surgery / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of controlled hypotension using different drugs on gastrointestinal perfusion and bleeding volume in nasal endoscopic surgery.</p><p><b>METHODS</b>Thirty ASA class I or II patients scheduled for nasal endoscopic surgery were randomized into three groups, including a routine general anesthesia group (group A) and two controlled hypotension groups (groups B and C). After anesthesia induction, anesthesia was maintained with 1%-2% isoflurane and vecuronium. ECG, mean arterial blood pressure (MAP), heart rate (HR), SpO(2) and PETCO(2) were continuously monitored. TRIP tonometry catheter 14 F was inserted into the stomach and connected to Tonocap (Datex-Ohmeda, Finland ). In groups B and C, hypotension was induced with isoflurane (1%-2%) and sodium nitroprusside (0.3-3 microg.kg(-1).min(-1)), and with isoflurane (1%-2%) and glonoine (0.5-5 microg.kg(-1).min(-1)), respectively, and the MAP was reduced to 50-55 mmHg in 10-15 min. In groups B and C, blood samples were taken for blood gas analysis after anesthesia (T(0)), after acute hypervolemic hemodilution (T(1)), at 30 and 60 min after controlled hypotension (T(2) and T(3)), and 30 min after recovery from hypotension (T(4)). In group A, blood samples were taken at different time points in the perioperative period.</p><p><b>RESULTS</b>The patients in groups B and C had smaller bleeding volume than those in group A. HR was decreased after moderate acute hypervolemic hemodilution, and increased after controlled hypotension (T(2) and T(3)) in comparison with that at T(1) to a level similar to that at T(0). No significant changes were found in pHi at T(2) and T(3) in comparison with that at T(1) in the three groups.</p><p><b>CONCLUSION</b>When appropriate measures are taken, induced hypotension at 50-55 mmHg does not necessarily produce disturbance in gastrointestinal perfusion. Induced hypotension with glonoin can decrease the bleeding volume better than sodium nitroprusside in nasal endoscopic surgery.</p>

Effect of mechanical ventilation with different tidal volumes on the respiratory function during general anesthesia / 中南大学学报(医学版)

OBJECTIVE@#To determine the effect of mechanical ventilation with different tidal volumes on the respiratory function during general anesthesia and to seek optimum way and parameters of mechanical ventilation during general anesthesia.@*METHODS@#Forty ASA I-II patients scheduled for elective craniotomies in the supine position were included in this study. According to latin square design, the patients were randomly divided into 4 groups. Every group has its own tidal volume sequence. Each patient used 4 tidal volumes in turn. Every tidal volume maintained 30 minutes. The rate of mechanical ventilation was 15. But ECG, blood pressure, heart rate, SPO2, ETCO2, airway pressure, lung compliance, and blood gas analysis were continuously monitored.@*RESULTS@#A-aDO2, P(a-ET)CO2, P(PEAK), P(MEAN), P(PLAT), C(DYN), and C(STAT) significantly increased as the tidal volume increased (P0.05).@*CONCLUSION@#The optimum tidal volume of mechanical ventilation is not 4 mL/kg at the rate of 15 respiratory rate during general anesthesia in the supine position because of a high arterial carbon dioxide tension. Yet 6-8 mL/kg is better for neurosurgical anesthesia. Increasing the tidal volume alone may not improve the respiratory function impairment during general anesthesia.