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。     

In Vivo Kinematics of Functional Ankle Instability Patients and Lateral Ankle Sprain Copers During Stair Descent

Patients with mechanic ankle instability experience increased tibiotalar and subtalar joint laxity. However, in vivo joint kinematics in functional ankle instability (FAI) patients and lateral ankle sprain (LAS) copers, especially during dynamic activities, are poorly understood. Ten FAI patients, 10 LAS copers, and 10 healthy controls were included in this study. A dual fluoroscopic imaging system was used to analyze the tibiotalar and subtalar joint kinematics during stair descent. Five key poses of stair descent were analyzed. Kinematic data from six degrees of freedom were calculated utilizing a solid modeling software. The range of motion and joint positions in each degree of freedom were compared among the three groups. The tibiotalar joints of FAI patients and LAS copers were significantly more inverted than those of healthy controls during the foot strike (p = 0.016, = 0.264). The subtalar joints of FAI patients were significantly more anteriorly translated (pose 2, p = 0.003, = 0.352; pose 3, p < 0.001, = 0.454; pose 4, p = 0.004, = 0.334), inverted (pose 4, p = 0.027, = 0.234; pose 5,p = 0.034, = 0.221), and externally rotated (pose 4, p = 0.037, = 0.217; pose 5; p = 0.004, = 0.331) than those of healthy controls during the mid‐stance and the heel off. The FAI patients showed excessive tibiotalar inversion and subtalar joint hypermobility during stair descent. Meanwhile, the LAS copers maintained subtalar joint stability, and only showed excessive tibiotalar inversion in foot strike. These data provide insight into the mechanisms behind the development of FAI after initial LAS. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1860–1867, 2019     

还原型谷胱甘肽联合甘草酸二铵对腹部开放伤后海水浸泡犬肝功能损伤的治疗作用

Objective To investigate effect of reduced glutathione and diammonium glycyrrhizinate on the treatment of hepatic damage in experimental dogs following open abdominal injuries coupled with seawater immersion. Methods Twenty-four dogs with open abdominal injuries were randomly divided into 3 groups: the control group (given with simple observation after 1.5 h seawater immersion); the routine treatment group (given routine care and fluid transfusion after 1.5 h seawater immersion) ; the hepatic treatment group (given routine are, fluid transfusion and hepatic treatment as well, after 1.5 h seawater immersion). Each group consisted of 8 dogs. Blood samples were taken at different time points to measure total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), prothromin time (PT), endotoxin, tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and pathological examination was also made at the same time. Results For the control group, contents of TB, ALT, AST and LDH increased significantly and survival time was less than 24 hours. Contents of TB, ALT, AST and LDH of the routine treatment group also increased significantly, but survival time of all the experimental animals was mere than 24 hours. Reduced glutathione and diammonium glycyrrhizinate could reduce the extent of lesion quite significantly 12～24 hours following open abdominal injuries. Conclusions Reduced glutathione and diammonium glycyrrhizinate seemed to have good effects on the treatment and prevention against hepatic damage induced by trauma coupled with seawater immersion. It could be used as a primary means for the treatment of such kind of hepatic damage.     

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK(-/-) mice.

Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK(-/-)) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK(-/-) mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK(+/+)) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK(-/-) mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1beta, TNFalpha, and RANKL. However, the UHMWPE-induced inflammation in RANK(-/-) mice was not associated with the osteoclastic bone resorption observed in RANK(+/+) mice. In RANK(+/+) mice subjected to UHMWPE stimulation, a large number of TRAP(+) cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP(+) cells were found in UHMWPE-containing pouch tissues of RANK(-/-) mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK(-/-) mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (microCT)] of implanted bone was observed in RANK(-/-) mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK(-/-) mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response.     

门诊输液室流水式操作模式探讨

目的提高门诊输液室的工作效率,减少差错失误的发生,同时提高患者满意度.方法将30个工作日输液的前50例次患者(共1 500例次)按单、双日分为常规组和观察组.常规组由3名护士独自完成从接输液单到输注操作的全过程;观察组则按流水操作模式,1名负责接输液单、贴瓶签、摆药、皮试(舍看结果)、巡视、接瓶、拔针及处理输液故障等,1名负责核对药物及配药,另1名负责输注.比较两组每天连续完成50例次输液所用时间、差错失误率及患者满意度.结果观察组完成50例次输液所用时间及差错失误率显著低于常规组(P＜0.05,P＜0.01),患者满意度显著高于常规组(P＜0.01).结论门诊输液室采用流水式操作模式有利于提高工作效率,减少差错失误率,同时提高患者的满意度.     

采用泌尿道前列腺切除器经肛门内镜切除直肠肿瘤：131例患者应用的经验

目的：直肠腺瘤和其他疑似为良性的病变应用经肛门内镜切除术并未普及。该项研究旨在评估经肛门内镜切除术的效能和安全性。方法：回顾性研究分析在1993-2004年之间3所斯德哥尔摩医院中经肛门内镜切除术的患，内容包括患自身及病变特性、并发症、随访时间和复发率。结果：180例中共131例行经肛门内镜切除术。160例经组织学诊断为腺瘤，12例为癌瘤，其余8例分别为增生、纤维化或正常黏膜。直肠腺瘤患中，77例仅行单次经肛门内镜切除术，16例因巨大腺瘤而多次行该手术，27例因复发而需另行经肛门内镜切除术或其他手术。中位复发时间为7个月，但未出现直肠癌。16例手术患出现并发症。2例患必须行Hartman手术，1例因肠穿孔，另1例因出血。手术期间无死亡。未复发的中位随访期为32个月（极差0—67）。[编按]     

创伤性膈疝21例临床分析

我院自１９８９年３月至１９９５年１０月手术治疗２１例创伤性膈疝，２１例疝愈。 发病机理与胸腹腔压力差、腹腔脏器冲击膈肌及胸腔负压有关。同时简要介绍了创伤性膈疝的诊断和治疗。     

The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

地塞米松促胎儿肺成熟的三种用药方式对母体糖代谢的影响

【目的】探讨地塞米松的用药方式对孕妇糖代谢的影响。【方法】对 1999年 9月至 2 0 0 1年 1月在本院住院的15 0名不同用药方式使用地塞米松促胎儿肺成熟的孕妇进行研究 ,在用药前及用药后 18～ 2 4h抽取肘前静脉血查空腹血糖、血浆C肽 ,糖负荷后 2h血糖、血浆C肽。【结果】使用地塞米松后 ,空腹血糖值、糖负荷后 2h血糖值、空腹C肽及糖负荷后 2hC肽值较用药前高 ;用药方式对母体空腹血糖值和空腹C肽值的影响差异无统计学意义 (P >0 0 5 ) ,对母体糖负荷后 2h血糖值和糖负荷后 2hC肽值的影响差异有统计学意义 (P <0 0 5 ) ;不同糖代谢状态的受试者使用地塞米松后 ,空腹C肽值、糖负荷后 2hC肽值的改变差异有统计学意义 (P <0 0 5 )。【结论】孕妇使用地塞米松促胎儿肺成熟对母体的糖代谢均有一定程度的影响 ,用药过程中和用药后需严密监测母体血糖和胎儿宫内状况