中药生产过程质量控制关键技术研究进展

中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。     

超脉冲CO2点阵激光联合PRP治疗面部痤疮凹陷性瘢痕疗效分析

目的:探究超脉冲CO2点阵激光联合富血小板血浆(PRP)治疗面部痤疮凹陷性瘢痕的疗效。方法:72例面部痤疮凹陷性瘢痕患者,随机分为观察组(36例)和对照组(36例)。对照组采用超脉冲CO2点阵激光治疗,观察组采用超脉冲CO2点阵激光联合PRP治疗。比较两组患者的灰度差异、时间指标、瘢痕程度、疼痛、不良反应及视觉评估。结果:观察组的并发症发生率为11.11%,低于对照组的36.11%,差异具有统计学意义(P<0.05)。治疗后,两组患者的灰度差异率均减小,且观察组患者的灰度差异率显著低于对照组,差异具有统计学意义(P<0.05)。治疗后,观察组的炎性渗出时间、红肿时间、愈合时间、停工时间及瘢痕程度评分均低于对照组,差异均具有统计学意义(P<0.05);但疼痛度评分组间比较,差异无统计学意义(P>0.05)。结论:超脉冲CO2点阵激光联合PRP治疗面部痤疮凹陷性瘢痕效果较好,可有效降低瘢痕程度,减少治疗时间及并发症的发生,帮助患者迅速回归正常工作与生活,值得临床推广使用。     

Long-term vardenafil therapy improves hemodynamics in patients with pulmonary hypertension.

The phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, has been reported to produce sustained pulmonary vasodilatation in patients with pulmonary hypertension (PH). Recently, vardenafil, a more potent and selective PDE-5 inhibitor than sildenafil, has been approved for the treatment of erectile dysfunction. However, the long-term effects of oral vardenafil in patients with PH are unknown. We studied five consecutive patients with PH; one with primary pulmonary hypertension, two with chronic pulmonary thromboembolism, one with Eisenmenger syndrome (ventricular septal defect) and one with secondary pulmonary hypertension after a ventricular septal defect closure operation. In an acute hemodynamic trial, vardenafil (5 mg) significantly decreased both the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) with an increase in cardiac output. In a chronic hemodynamic trial, the maintenance dose of vardenafil (10 to 15 mg) for 3 months significantly decreased the PVR, but not the SVR, with a 20.7% reduction of the PVR/ SVR ratio. Plasma brain natriuretic peptide (BNP) levels were also significantly decreased after 3 months. This pilot study demonstrates that long-term oral vardenafil therapy may be a safe and effective treatment for patients with PH.     

Risk factors and ankle brachial indexes in cerebral infarction combined with peripheral arterial disease

BACKGROUND: Ankle brachial index(ABI)is widely involved in researches and clinical application of peripheral vascular injury of patients with diabetes (DM);however ,the application in cerebral infarction(CI)is rare.OBJECTIVE: To investigate the possible risk factor of cerebral infarction plus peripheral arterial disease(PAD),compare metabolic characteristics of patients who having CI plus PAD or only having CI,and understand the significance of ABI on screening and diagnosing CI plus PAD of lower limb.DESIGN: Contrast observation based on CI patients.SETTING: Deparment of Neurology,Nanxishan Hospital of Guangxi Zhang Autonomous Region.PARTICIPANTS:A total of 124 CI patients were selected from Department of Neurology.Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2005 to April 2006,including 72 males and 52 females aged from 45 to 88 years.All patients met the diagnostic criteria of cerebrovascular disease established by National Academic Conference of Cerebrovascular Diseases in 1995 and determined as cerebral infarction with MRI or CT examination.All patients provided informed consent.There were 46 cases(37.2%)with CI plus PAD and 78 cases(62.8%)only with CI.METHODS: Blood pressure of bilateral ankles and upper extremities was measured at plain clinostatism with DINAMAP blood pressure monitor(GE Company).The ratio between average systolic pressure of lateral ankle and average systolic pressure of both upper extremities was regarded as ABI.The normal ABI was equal to or more than 0.9.If ABI＜0.9 occurred at one side,patients were diagnosed as PAD.On the second morning after hospitalization,blood was collected to measure fasting blood glucose(FBG),2-hour postprandial blood glucose(PBG2h),glycosylated hemoglobin(HbAlc),triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).Among them,blood glucose.lipid and other biochemical markers were measured with enzyme chemistry assay and HbA1c was measured with HbA1c meter based on high liquid phase.Measurement data and enumeration data were compared with t test and Chi-square test.and multiple factors were deat with Logistic regression analysis and multivariate linear regression analysis.MAIN OUTCOME MEASURES: Results of correlation between ABI and metabolic markers with multivariate linear regression analysis;risk factors of CI plus PAD with Logistic regression analysis;comparisons of metabolic markers between PAD and non-PAD patients.RESULTS:All 124 patients with acute CI were involved in the final analysis.①Comparisons of metabolic markers:Levels of serum LDL-C and uric acid(UA)were higher of PAD patients than those of non-PAD patients(t=2.051 9,3.339 1,P＜0.05);however,there were no significant differences among other metabolic markers(P＞0.05).②Results of multivariate linear regression analysis:PBG2h,LDL.C and UA were obvious correlation with ABI of posterior tibial artery of lower limb and dorsal pedis artery rpartial regression coefficient:-0.231 to-1.010,P＜0.05).③Risk factors of CI plus PAD with Logistic regression analysis:Age.Smoking history,sum of CI focus(≥3)and LDL-C were independent risk factor of CI plus PAD(OR=1.524-5.422,P＜0.05-0.01 ).CONCLUSION:①Levels of serum LDL-C and UA of patients with CI plus PAD are high.②ABI of lower limbs is correlation with PBG2h,LDL-C and UA.In addition,measuring ABI is beneficial for early diagnosing PAD of lower limbs of patients who have poorly controlled blood glucose,abnormal lipid and poor renal function.③Age,LDL-C and sum of CI focus(≥3)are independent risk factors of CI plus PAD.It is of significance for screening non-PAD patients to evaluate risk degrees and prognosis and select therapeutic methods based on ABI measurement.     

Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme.

Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2.     

膀胱移行细胞癌P16、P15、P14基因5＇CpG岛甲基化检测

目的 探讨P16、P15、P14基因5＇CpG岛在膀胱移行细胞癌中甲基化状态及其临床意义。方法 应用甲基化特异性PCR（methylation—specific PCR，MSP）方法检测40例膀胱移行细胞癌P16、P15、P14基因甲基化程度，χ^2检验分析其甲基化程度与膀胱癌病理分级分期间关系。结果 膀胱移行细胞癌P16、P15、P14 5＇CpG岛甲基化扩增阳性化率分别为27．5％、17．5％、35％，而正常膀胱组织中均未检测到三种基因5＇CpG岛甲基化。P16、P14基因甲基化与膀胱癌病理分级分期有显著性差异（P〈0．05），P15基因则没有显著性差异（P〉0．05）。结论 P16、P15、P14基因在膀胱癌组织中的甲基化率较高，三种抑癌基因5＇CpG岛异常高甲基化，在膀胱癌的发生、发展中具有重要作用。     

神经外科重症监护病房常见病原菌的分布与耐药性研究

目的调查珠江医院神经外科重症监护病房(ICU)病原菌的分布与耐药情况,分析ICU院内感染的发生原因,探讨防治对策。方法应用法国VITEKⅡ全自动细菌鉴定仪鉴定病原菌,用纸片扩散法检测药敏结果。结果神经外科ICU菌群主要以革兰阴性杆菌(71.6%)为主,鲍曼不动杆菌占16.7%,大肠埃希菌占15.7%,铜绿假单胞菌占13.7%,肺炎克雷伯菌占13.7%等。但葡萄球菌、粪肠球菌等阳性球菌(28.4%)也有增加的趋势。亚胺培南和头孢哌酮/舒巴坦仍保持最高抗菌活性,细菌的耐药率分别为15.3%和30.6%。结论我院神经外科ICU感染主要病原菌是革兰阴性杆菌,对常用抗菌药物耐药性较高,但革兰阳性球菌所占比例呈增高趋势。控制第二、三代头孢菌素以及制酸剂(质子泵抑制剂)的预防性用药,减少耐药菌株的产生,有针对性地使用抗生素是控制危重病人感染的有效措施。     

Correction of frequency and phase variations induced by eddy currents in localized spectroscopy with multiple echo times.

As a consequence of the time-varying magnetic field induced by eddy currents, frequency drifting occurs when the sampling window of localized spectroscopy continuously shifts. The frequency drifting and the concomitant phase variations can severely affect spectroscopy results when data are acquired with multiple echo times (TEs), such as in the measurement of glutamate (Glu) concentration using the TE-averaged method. Specifically, the averaged spectra are further broadened and distorted in the presence of residual eddy currents, and editing of the coupled spins of Glu C4 protons is affected, resulting in errors in the measured relative intensity ratio. Postacquisition correction using unsuppressed water as reference can effectively minimize this detrimental effect, as manifested by the significantly enhanced signal intensity. Also, it is demonstrated that the methyl signals of creatine (Cr) at 3.0 ppm and choline (Cho) at 3.2 ppm can be used as internal references in finding frequency and phase disparities between different TEs.