Research of hospital preparations based on QbD concept: whole process optimization strategy of gynecological antipruritic lotion / 中国中药杂志

The stable quality of hospital preparations is the basis for their clinical efficacy. Gynecological antipruritic prescription is widely used in gynecology clinics of Chinese medicine hospitals. Therefore,in this study,the production process of gynecological antipruritic lotion was optimized based on the concept of quality by design( QbD). The production process of the gynecological antipruritic lotion was developed to ensure its process stability and reliable quality,and enhance its clinical applicability. With total amount of matrine and oxymatrine used as the critical quality attribute( CQA) of the production process,parameter levels were designed based on production practice of hospital preparations,and Plackett-Burman and Box-Behnken experiments were used to optimize the water extraction and alcohol precipitation process of antipruritic lotion based on CQA of intermediates and final product. The soaking time,the first extraction time,and the second extraction time were determined as the critical process parameters( CPPs) of the production process. The optimal preparation process was as follows: water volume of 8 times,soaking for 0. 5 h,extraction for 2 times,the first extraction for 30 min,the second extraction for 56 min,alcohol concentration of 50%,and alcohol precipitation for 3 h. Furthermore,the design space was established based on the binomial regress model between CPPs and CQA,so as to set the optimization target and risk range; and the control space was displayed by overlay plot. The results of three repeated experiments in the control space showed that the relative standard deviation( RSD) of CQA was 4. 70%,and the similarity of chromatogram for gynecological antipruritic lotion was 0. 978,0. 974,and 0. 998,respectively. The above results indicated that the operation in the control space can guarantee the quality and stability of gynecological antipruritic lotion,suitable for practical application.

Design and development of sustained and controlled release preparations in traditional Chinese medicine based on quality by design( QbD) / 中国中药杂志

In this paper,the design and development of sustained and controlled release preparations in traditional Chinese medicine( TCM) based on quality by design( QbD) was put forward,aiming at the current situation that the final product quality is affected by multiple factors during the development of sustained and controlled release preparations in TCM. The important development of sustained and controlled release preparations in western medicine in recent years was summarized. According to the complex process of TCM,the concept of QbD was proposed to design and develop sustained and controlled release preparations in TCM. QbD concept was used to analyze the complex factors affecting sustained and controlled release preparations in TCM,and determine the high risk factors affecting the quality of the final product. The high risk factors were controlled from the process to achieve the goal of quality control.This article could provide research ideas for the sustained and controlled release preparations with complex components in TCM,so as to promote the research and development of sustained and controlled release preparations in TCM.

Toxicity and oxidative damage of different silver nanoparticles to Caenorhabditis elegans / 中国药理学与毒理学杂志

Objective: To investigate the toxic effects of three types of silver nanoparticles (AgNPs): 20 and 50 nm uncoated nanosilver (AgNPs-20 and AgNPs-50) and 20 nm polyvinylpyrrolidone coated nanosilver (AgNPs-PVP-20) to Caenorhabditis elegans (C.elegans). Methods: Wild type C. elegans were exposed to 1% hydroxypropyl methylcellulose (vehicle group) and AgNPs-20, AgNPs-50, AgNPs-PVP-20 (1,10 and 100 mg·L-1) for 48 h, respectively. The survival, head thrash and body bend frequency of the nematodes were recorded. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH) in nematodes were detected by DCFH-DA fluorescence probe, TBA method and colorimetry, respectively. Results: Compared with vehicle group, the survival rate of nematodes was decreased in each dose group of AgNPs-PVP-20,10 and 100 mg·L-1groups of AgNPs-50 and AgNPs-20 (P<0.01). The relative mean lifespan of nematodes in each dose group of AgNPs-PVP-20 was significantly decreased (P<0.01), while that of AgNPs-20, AgNPs-50 (10 and 100 mg·L-1) was decreased (P<0.05). The frequency of head thrashes in 10 and 100 mg·L-1of the three AgNPs groups was decreased (P<0.05), and the frequency of body bends in each dose group of AgNPs-PVP-20 was significantly reduced (P<0.01). The body bends in 100 mg·L-1groups of AgNPs-20 and AgNPs-50 were decreased (P<0.05). The fluorescence intensity of ROS in the three AgNPs groups was significantly higher than that of the control group (P<0.01). Compared with the control group, the content of MDA was increased and the content of GSH decreased (P<0.05) in AgNPs-PVP-20 (10 and 100 mg·L-1) groups. There was no significant difference in MDA or GSH contents between AgNPs-50 and control groups. Conclusion: The relative mean lifespan of nematodes, the head thrash frequency and body bend frequency of nematodes were decreased to different extents with the increasing dose in each of the AgNPs groups, whereas the oxidative stress level of nematodes was increased unexpectedly in all the test samples. The toxic effect of AgNPs-PVP-20 is the strongest, followed by AgNPs-20 and AgNPs-50.

Expression of AQP2, AQP4 and AQP 8 in mouse intestine induced by unprocessed and processed Euphorbia lathyris

The present research was designed to study expression of AQP2, AQP4 and AQP8 in mouse intestines induced by unprocessed and processed Euphorbia lathyris. KM mice were given by different dose lavage of unprocessed and processed Euphorbia lathyris, Euphorbia factor L1, Euphorbia factor L2, Euphorbia factor L3. Samples of mouse intestine were collected for protein levels of AQP2, AQP 4 and AQP 8 which were assessed by immunohistochemical staining and mRNA expression of AQP2, AQP 4 and AQP 8 which were quantified by Real Time-PCR. Comparing to the normal control group, the protein levels of AQP2, AQP 4 and AQP 8 were significantly decreased [P<0.05]by Semen Euphorbiae group and Semen Euphorbiae Pulveratum group [unprocessed and processed Euphorbia lathyris] induced. Protein expression of AQP2, AQP 4 and AQP 8 in the Euphorbia factor L1, Euphorbia factor L2 and Euphorbia factor L3 group were not significantly lower than normal control group. There had no differences on the levels of AQP2 and AQP 8 mRNA expressions between the high-dose group of semen Euphorbiae group, semen Euphorbiae Pulveratum group and positive control group, while significantly lower than normal control group [P<0.05]. Expression of AQP4 mRNA in the Semen Euphorbiae group and Semen Euphorbiae Pulveratum group has not significantly decreased. But levels of AQP2, AQP 4 and AQP 8 mRNA in the Euphorbia factor L1 group had no significant differences in normal control group and positive control group. These findings suggest that semen Euphorbiae could regulate expression of AQP2, AQP 4 and AQP 8 protein and mRNA, which may be the possible one reason of semen Euphorbiae induces diarrhea. The semen Euphorbiae group has more significant effects on the levels of AQP2, AQP 4 and AQP 8 protein and mRNA than semen Euphorbiae Pulveratum group, which may be one of the mechanisms of processing attenuation

Chromatographic fingerprint analysis of Toosendan Fructus by HPLC-CAD coupled with chemometrics methods / 药学学报

A new method was developed for the chromatographic fingerprint analysis of Toosendan Fructus by HPLC coupled with the charged aerosol detector (CAD) in the present study. Samples were well separated on an Agilent ZOBAX SB C18 column (4.6 mm×250 mm, 5 μm) by gradient elution using acetonitrile and water containing 0.1% formic acid (v/v) at the flow rate of 1.0 mL·min-1. The column temperature was 30℃ and the injection volume was 5 μL. The nitrogen inlet pressure of the charged aerosol detector (CAD) was 35 psi, and the nebulizer chamber temperature was 35℃. In addition, the method of the chromatographic fingerprints combined with multivariate statistical analysis was effective and reasonable lead to an accurate classification of 20 batches of samples from different locations. The results showed that 28 common peaks were observed in the fingerprint and the samples were classified into three clusters. The established method was well validated, and showed high precision, good repeatability, and satisfactory stability. It may serve in the quality control and evaluation of Toosendan Fructus.

Study on transdermal mechanism of Sophora flavescens alkaloids nanoemulsions and nanoemulsion-based gels / 中草药

Objective: To prepare nanoemulsions (NE) and nanoemulsion-based gels (NBGs) with Sophora flavescens alkaloids (SFA) as model drug to illuminate its mechanism of transdermal delivery basically. Methods: Using scanning electron microscopy (SEM) method, HE staining method, and confocal laser scanning microscope (CLSM) method to investigate the effect of SFA-NEs and SFA-NBGs on stratum corneum (SC) and ultrastructure. Results: The results of SEM showed that the SC of normal mouse was smooth and finishing. And slightly crimp the saline group after 6 h of treatment appeared, while it was damaged in varying degrees hurt after 2 h and 6 h of action by SFA-NEs and SFA-NBGs, respectively. HE staining results indicated that the skin structure of saline group was basically intact. But the hierarchy structure of SFA-NBGs group was not obvious, basal layer arranged unclearly and SC loosed apparently, as well as that the hierarchy structure of SFA-NEs group disordered, the gap increased, SC loosed and thinned. The result of confocal laser scanning microscope indicated that fluorescence in surface was stronger while weaker in depth among control group, SFA-NEs group, and SFA-NBGs group, and fluorescence in hair follicles and around its appendages was also stronger. Conclusion: SFA-NEs and SFA-NBGs could permeate skin mainly through breaking SC and ultrastructure so as to perform therapeutic action. At the same time, hair follicles and its appendages play a role on drug transdermal course.

Stiletto needle and needle-knife for influence of gravity index in treating knee osteoarthritis / 中国骨伤

<p><b>OBJECTIVE</b>To explore stiletto needle and needle-knife for influence of double sufficient weight in treating knee osteoarthritis patients.</p><p><b>METHODS</b>One hundred and thirteen early and medium term knee osteoarthritis patients were randomly divided into three groups, including stiletto needle group(38 cases), needle-knife group (38 cases) and voltaren group (37 cases). In stiletto needle group, there were 13 males and 25 females with an average of(55.87±7.72) years old, treated by stiletto needle once a week, and 2 weeks were a course; there were 11 males and 27 females in needle-knife group with an average of(57.11±7.07) years old, treated by acupotome once a week, and 2 weeks were a course; there were 12 males and 25 females in voltaren group with an average age of(57.62±8.08) years old, treated by votalin emulsion smearing 3 to 5 cm on painful area of knee joint, three times a day for 2 weeks; 36 patients in normal group, including 11 males and 25 females with a mean age of (55.28±7.55) years old, treated with nothing. Gravitational four lattice used to measure bipedal back and forth load before and after treatment in further observe weight-bearing situation among three groups, d value, which was the distance from center of gravity to original point, was measured as a obvervational index, JOA score was used to evaluate clinical effect.</p><p><b>RESULTS</b>Five patients were fall out, including 2 patients in stiletto needle group, 2 patients in needle-knife group and 1 patient in voltaren group. Other 108 patients were followed-up from 28 to 35 d with an average of 30 d, and without untoward effect. There was significant difference in d value between treatment group and control group at 1 month after treatment(<0.05); there was significant difference in d value among treatment group at 1 month after treatment(>0.05), and d value was decreased before treatment than that of after treatment. There was no significant difference in JOA score among treatment group after treatment at 1 month(<0.05); while had significant difference between groups(>0.05) after treatment at 1 month.</p><p><b>CONCLUSIONS</b>Stiletto needle, needle-knife and voltaren for the treatment of knee osteoarthritis at early and middle stage, center of gravity is closer to original point, and weight-bearing is improved. It is a easy method of four lattice to measure change of weight-bearing in KOA patients after treatment.</p>

Ultrasound assessment of left ventricular segmental myocardial transmural displacement characteristics in patients with hypertrophic cardiomyopathy / 中华医学超声杂志（电子版）

Objective To evaluate the segmental myocardium of left ventricular wall in patients with myocardial hypertrophic cardiomyopathy (HCM) by TDI-Q, explore whether the segmental myocardium contractile function is changed or not and determine the myocardial mechanics parameters variation. Methods Thirty-two healthy volunteers and twenty-one patients with hypertrophic cardiomyopathy were included and the standard dynamic two-dimensional tissue Doppler imaging (TDI) of mitral, papillary muscle and apical short axis view were collected in three consecutive cardiac cycles. The mechanical parameters variation and characteristics of systolic radial peak displacement (RD) and time to peak in left ventricle subendocardial, mid-myocardium and epicardial myocardium at different level and segment were analyzed.Results In healthy control group, at left ventricular basal, apical and papillary muscle level, there was no significant difference for time to peak and systolic radial peak displacement (F=0.74, 1.28 and 1.79, all P>0.05). In patients with HCM, time to peak of systolic RD at left ventricular different level was asynchronous. Time to peak of RD in septum at papillary muscle levels and apical lateral wall were longer than those of other segments. In healthy control group, except for apical inferior and lateral wall, RD of subendocardial myocardium was significantly greater than that of epicardial myocardium at different segments (t=-1.903, 4.574,-3.552,-2.614,-1.728,-1.790,-1.836,-2.794 and 2.733, all P<0.05 ). In patients with HCM, RD of subendocardial myocardium was significantly greater than that of epicardial myocardium in posterior wall, septum at basal level and in inferior wall, posterior wall and lateral wall at papillary muscle level (t=-2.305,-2.148, 3.550,-1.182 and-3.602, all P < 0.05). At the same segment, transmural RD of subendocardial and subepicardial myocardium in healthy subjects were greater than that in patients with HCM. In inferior wall, posterior wall, lateral wall and septum at basal level, in inferior wall, posterior wall and septum at papillary muscle level, and in lateral wall and septum at apical level, differences of transmural RD were statistically significant (t=-3.787,-2.983,-4.325,-6.972,-2.352, 2.823,-3.274,-1.338 and-2.857, all P<0.05). Conclusions In patients with HCM, synchrony of left ventricular motion at different level was abnormal and transmural RD of endocardial and epicardial myocardium was decreased, which suggested regional systolic dysfunction. Ultrasound assessment of left ventricular segmental transmural mechanics can further reveal left ventricular mechanical characteristics in patients with hypertrophic cardiomyopathy.

Assessment of segmental left ventricular systolic function with real-time 3-dimensional echocardiography in patients with hypertensive hypertrophic cardiomyopathy / 中华医学超声杂志（电子版）

Objective To evaluate left ventricular function in patients with hypertensive hypertrophic cardiomyopathy(HHC)using real-time 3-dimensional echocardiography(RT-3DE).Methods Thirty patients with HHC and 32 control subjects were studied.Full-volume RT-3DE data from apical window were acquired,and regional volumetric time curves of 17 segments were obtained by fast 3-dimensional border detection software.Several left ventricular function parameters were calculated semiautomatically,including global left ventricular end-diastolic volume(EDV),end-systolic volume(ESV),left ventricular ejection fraction(LVEF),the ratio of ESV/EDV of 17 segments,the standard deviation(SD)and difference(Dif)(adjusted by the R-R interval) of time to minimum systolic volume(Tmsv)in 16 segments(Tmsv16-SD and Tmsv16-Dif).Results EDV and ESV were significantly larger in patients with HHC than that in control subjects[(88±29)ml vs (72±15) ml,t=-2.680,P=0.008;(28±10)ml vs (22±6 )ml,t=-2.613,P=0.01].HHC had a higher ratio of ESV/EDV at interventricular septum(IVS)compared with control group[mid-segments of anterior IVS:(40.51±20.28)% vs (26.43±10.10)%,t=-3.378,P=0.002;mid-segments of posterior IVS:(41.44±23.55)% vs (24.46±8.12)%,t=-3.688,P=0.001;apical segments of IVS:(30.96±21.31)% vs (19.53±7.33)%,t=-2.745,P=0.01].In patients with HHC,Tmsv16-SD and Tmsv16-Dif were significantly longer[(2.48±1.38)% vs (1.16±0.26)%,t=-5.117,P＜0.001;(7.67±5.07)% vs (3.95±1.48)%,t=-3.865,P＜0.001].And the prevalence of left ventricular dyssynchrony was higher than that in control subjects(43% vs 3%).Conclusions HHC patients may have regional left ventricular systolic dysfunction before global changes,and have a higher prevalence of left ventricular dyssynchrony.RT-3DE is a useful imaging modality for assessing left ventricular systolic function.

Application of magnetic resonance imaging in diagnosis and treatment of pelvic neoplasms / 上海第二医科大学学报

Objective To study the value of magnetic resonance imaging(MRI) in the diagnosis and treatment of pelvic neoplasms. Methods The patients who were suspected of malignant pelvic neoplasms were performed MRI.The surgical approach was determined according to the MRI results.The MRI results were compared with operation findings and pathological reports. Results The MRI results were consistent with operation findings and pathological reports in 22 cases highly suspected of pelvic neoplasms and 15 cases with abnormal endometrial echo.Therapeutic regimen was designed for 5 cases with uterine cervix cancer according to MRI stages,and favourable surgical curative effects were obtained. Conclusion MRI provides a reliable guideline for surgical approach and may improve the outcomes.

Surveillance of pathogens from patients with hospital infection in intensive care unit / 上海第二医科大学学报

Objective To analyze the distribution and antimicrobial resistance of pathogens from patients with hospital infection in intensive care unit(ICU),and to discuss the corresponding strategy of prevention and treatment. Methods Clinical data of 891 patients hospitalized in the ICU of our hospital between Jan 2002 and Dec 2005 were collected.All the specimens were analyzed for pathogen distribution and resistance to antibiotics. Results Of all the isolated 1 155 strains,Gram-negative(G-)bacteria were the most popular pathogen(57.84%),whereas Gram-positive(G+) bacteria and fungi accounted for 21.39% and 20.78%,respectively.Most G-bacteria were less sensitive to imipenem(0-10.16%),and Pseudomonas aeruginosa was least sesitive to amikacin(6.89%) and cefoperazone-sulbactam(33.97%).G+ bacteria were most sensitive to vancomycin.Most fungus were Candida albicans(42.92%) and yeast species(22.90%). Conclusion Epidemiological investigation of pathogens in ICU is of great importance to the rational use of anti-biotics and may help to reduce the emergence of resistant strains.

Multicentral randomized controlled study on effects of acupuncture at Zusanli (ST 36) and Xuanzhong (GB 39) on cerebrovascular function in the patient of ischemic stroke / 中国针灸

<p><b>OBJECTIVE</b>To explore effect of acupuncture at Zusanli (ST 36) and Xuanzhong (GB 39) on cerebrovascular function in the patient of ischemic stroke.</p><p><b>METHODS</b>Three central, single blind, randomized controlled trial method was adopted, and 160 cases were randomly divided into an acupuncture group and a control group, 80 cases in each group. The two groups were treated by routine treatment for ischemic stroke with acupuncture at Zusanli (ST 36) and Xuanzhong (GB 39) added in the acupuncture group. Changes of TCD cerebrovascular blood flow indexes before and after treatment were evaluated.</p><p><b>RESULTS</b>After treatment, TCD indexes significantly improved in the acupuncture group (P < 0.05, P < 0.01) with a significant difference as compared with that in the control group (P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture at Zusanli (ST 36) and Xuanzhong (GB 39) can significantly improve cerebral vasomotoricity, cerebral blood flow auto-regulative function, cerebral hemisphere collateral circulation comprehental function in the patient of ischemic stroke.</p>

Analysis of coronary arteriographic and fluorescence fundus angiographic characteristics in type 2 diabetic patients with coronary heart disease / 中华内分泌代谢杂志

Objective To study the relationship between coronary arteriographic and fluorescence fundus angiographic characteristics in type 2 diabetic patients with coronary heart disease.Methods The study was carried out by the analysis of the data from coronary arteriography and fluorescence fundus angiography in 203 type 2 diabetic patients with coronary heart disease in different groups divided according to age or total cholesterol level. Logisitic regression analysis was applied to explore various risk factors to angiographic characteristics.Results With advancing age,there were more involvement of 3 coronary vessels or the left main branch along with stageⅢretinopathy,but less single vessel diseases in the coronary arteries and less stageⅠretinopathy.The difference in coronary angiographic and fluorescence fundus angiographic characteristics between groups with different total cholesterol levels was not significant.Logistic regression analysis suggested that coronary artery diaease was related to age,sex and blood glucose and triglyceride levels while diabetic retinopathy was related to blood glucose level and age.Conclusion There is great difference in coronary arteriography and fluorescence fundus angiography among different age groups.Aging may aggravate the lesions both in the coronary arteries and fundal vessels in type 2 diabetic patients with coronary heart diseease.