中药配方颗粒的发展现状及国际化对策探讨

近年来,世界各国对天然药物日益重视,而中药配方颗粒既能在中医理论指导下随证加减,又有服用便捷、适宜工业生产等优点,成为推动中药"走出去"的有力助力。通过回顾中药配方颗粒的发展历程、分析相关数据和国内外发展形势,对中药配方颗粒的研究现状、市场情况及国际化发展面临的主要挑战进行探讨,提出利用政府间交往推进中药国际贸易、充分发挥海外资源平台作用、帮助监管部门建立符合中药配方颗粒特点和审批国政策的合理化国际审批方案、争取国际标准主导权的建议,为推动中药配方颗粒产业在世界范围内高质量发展提供参考。     

丹参饮合温胆汤加减对稳定型心绞痛患者心肌缺血的保护机制

目的:观察丹参饮合温胆汤加减治疗痰瘀阻滞型稳定型心绞痛(SAP)的疗效及对心肌缺血的保护机制研究。方法:将132例患者随机按数字表法分为对照组和观察组各66例。除去脱落、失访和剔除病例,两组最后分别完成63例。所有患者进行抗心绞痛药物和控制风险因素药物治疗。对照组口服丹蒌片,5片/次,3次/d;观察组给予丹参饮合温胆汤加减,1剂/d;两组疗程均为治疗3个月。每周进行心绞痛发作情况评分;冠心病心肌缺血情况采用心电图平板运动试验评价,中医症状和生活质量分别进行痰瘀阻滞证、西雅图心绞痛量表(SAQ)评分,血液流变学指标、白细胞介素-6(IL-6),肿瘤坏死因子-α(TNF-α),细胞间黏附分子-1(ICAM-1),胱抑素C(CysC),同型半胱氨酸(Hcy),缺血修饰白蛋白(IMA)和巨噬细胞移动抑制因子(MIF)水平,均治疗前后各评价1次;并进行安全性评价。结果:观察组心绞痛发作次数、持续时间、疼痛程度和硝酸甘油用量评分均低于对照组(P<0.01);观察组Duke评分、总运动时间、出现ST段压低1.0 mm的时间、心绞痛出现时间和代谢当量均多于对照组(P<0.01);观察组SAQ评分高于对照组(P<0.01),痰瘀阻滞证积分低于对照组(P<0.01);观察组心绞痛疗效优于对照组(Z=2.091,P<0.05);观察组ICAM-1,CysC,IL-6,TNF-α水平均低于对照组(P<0.01);观察组全血黏度(低切、高切)、全血还原黏度、血浆黏度、血小板聚集率、纤维蛋白原(FIB)均低于对照组(P<0.01);观察组IMA,Hcy和MIF水平均低于对照组(P<0.01)。没有发现服用丹参饮合温胆汤相关不良反应。结论:在西医常规治疗的基础上,丹参饮合温胆汤加减治疗SAP,可控制心绞痛发作,减轻痰瘀阻滞证症状,提高生活质量,有着较好临床疗效,且安全,并能改善患者血液流变性,抑制炎症反应,减轻管腔狭窄或阻塞,从而改善心肌缺血程度。     

Recognition of moyamoya disease and its hemorrhagic risk using deep learning algorithms:sourced from retrospective studies

Although intracranial hemorrhage in moyamoya disease can occur repeatedly, predicting the disease is difficult. Deep learning algorithms developed in recent years provide a new angle for identifying hidden risk factors, evaluating the weight of different factors, and quantitatively evaluating the risk of intracranial hemorrhage in moyamoya disease. To investigate whether convolutional neural network algorithms can be used to recognize moyamoya disease and predict hemorrhagic episodes, we retrospectively selected 460 adult unilateral hemispheres with moyamoya vasculopathy as positive samples for diagnosis modeling, including 418 hemispheres with moyamoya disease and 42 hemispheres with moyamoya syndromes. Another 500 hemispheres with normal vessel appearance were selected as negative samples. We used deep residual neural network(Res Net-152) algorithms to extract features from raw data obtained from digital subtraction angiography of the internal carotid artery, then trained and validated the model. The accuracy, sensitivity, and specificity of the model in identifying unilateral moyamoya vasculopathy were 97.64 ± 0.87%, 96.55 ± 3.44%, and 98.29 ± 0.98%, respectively. The area under the receiver operating characteristic curve was 0.990. We used a combined multi-view conventional neural network algorithm to integrate age, sex, and hemorrhagic factors with features of the digital subtraction angiography. The accuracy of the model in predicting unilateral hemorrhagic risk was 90.69 ± 1.58% and the sensitivity and specificity were 94.12 ± 2.75% and 89.86 ± 3.64%, respectively. The deep learning algorithms we proposed were valuable and might assist in the automatic diagnosis of moyamoya disease and timely recognition of the risk for re-hemorrhage. This study was approved by the Institutional Review Board of Huashan Hospital, Fudan University, China(approved No. 2014-278) on January 12, 2015.     

Effects of total knee arthroplasty for primary knee osteoarthritis on postural balance: A systematic review

BackgroundKnee osteoarthritis is often related to physical function impairment. Although total knee arthroplasty is considered effective for advanced cases of knee osteoarthritis, its effects on postural balance is a topic of debate.Research questionWhat are the effects of total knee arthroplasty for primary knee osteoarthritis on postural balance compared to preoperative status and/or to healthy controls?.MethodsLongitudinal studies (with more than 1-month follow-up) assessing postural balance measures (either clinical-based such as balance scales or laboratory-based such as postural sway) were considered eligible and selected in a 2-phase process. Six main electronic databases were searched, complemented by 3 grey literature sources. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Tools.ResultsA total of 19 studies were included for qualitative synthesis, of which 14 had low and 5 had a moderate risk of bias. The follow-up period ranged from 1–24 months. Most studies (n = 11) presented comparisons to preoperative status only. From these, 7 studies reported relevant improvements in postural balance, 2 reported partial improvements, and 2 no improvements. The remaining studies (n = 8) presented comparisons to healthy controls and, although improvements following total knee arthroplasty were consistently observed, only one study reported postural balance measures comparable to that of controls.ConclusionsThe majority of studies reported relevant improvements (especially in clinical-based measures) compared to preoperative evaluations, although inconsistencies were found possibly due to variability in studies' populations, assessment tools, and follow-up times. Despite this, persistent deficits in postural balance were commonly observed when compared to healthy controls.SignificanceThis evidence synthesis could better inform clinicians and researchers about the therapeutic effects and limitations of total knee arthroplasty concerning postural balance. Standardization of assessment tools is recommended to strengthen the certainty of cumulative evidence.     

Sleep positions in children with Down syndrome and obstructive sleep apnea

ObjectivesTo assess sleep positions in children with both Down syndrome (DS) and obstructive sleep apnea (OSA) and determine if there is a preferred sleep position by severity of apnea.MethodsA single-center retrospective review of patients with both DS and OSA was performed. Caregivers reported sleep position utilized greater than 50% of observed sleep time. Accuracy of this report was confirmed through review of hypnograms from polysomnography studies.ResultsEighty-two patients met inclusion criteria. Median body mass index (BMI) was 26.6 and 56% of patients had a prior tonsillectomy and/or adenoidectomy. The mean obstructive AHI (OAHI) was 25.33 with 90.4% having severe OSA, 9.6% having moderate OSA, and no patients having mild OSA. Reported sleep positions were skewed towards lateral/decubitus (82.9%) compared to prone (11.0%) and supine (6.1%). This was consistent with hypnogram data where 71% of total sleep time in lateral/decubitus positions compared to prone (13%) and supine (6%). The median changes in sleep position per patient was 5 (IQR: 3–6). Lower BMI (p < 0.001, 95% CI: 0.32–1.13) and tonsillectomy (p < 0.001, 95% CI: 7.7–18.19) were associated with lower OAHI. Sleep position was not associated with age (p = 0.19), sex (p = 0.66), race (p = 0.10), ethnicity (p = 0.68) nor history of tonsillectomy (p = 0.34). Preferred sleep position was not correlated with OAHI (p = 0.78, r = 0.03) or OSA severity (p = 0.72, r = 0.03).ConclusionsThis study highlights the possibility that children with DS may have preferential sleep positions that cater to optimized airflow in the context of OSA although further prospective study is needed.     

基于一项“多中心、随机对照、双盲”的临床研究探讨影响肾功能进展的因素＊

目的 基于一项前瞻性、多中心、随机、安慰剂对照、双盲的临床试验结果，探索影响肾功能进展的因素。方法 选择343例慢性肾脏病3期的患者，将入组的患者随机分为治疗组和对照组，治疗组给予中药颗粒剂口服，对照组给予安慰剂口服。两组患者均给予基础治疗，疗程24周。评估两组患者肾功能变化情况。治疗结束后，根据患者肾功能情况，以CKD3期为界限，将病情好转者定为A组，该组患者血肌酐下降至CKD2期或CKD1期；病情恶化者为B组，该组患者血肌酐上升至CKD4期或CKD5期；病情稳定者为C组，该组患者血肌酐稳定，仍处于CKD3期，分析各组患者指标的差异。结果 经过24周观察，比较两组患者的血肌酐（Scr）水平，治疗组130.78 ± 32.55 μmol·L^-1，对照组149.12 ± 41.27 μmol·L^-1，两组比较，差异有统计学意义（P < 0.05）。eGFR水平比较，治疗组55.74 ± 50.82 mL/min/1.73 m²，对照组44.46 ± 12.60 mL/min/1.73 m²，差异有统计学意义（P < 0.05）。研究结束后，A组患者血尿酸水平明显低于B组和C组的患者，A组患者血红蛋白水平明显高于B组和C组的患者，A组患者的血磷水平明显低于B组和C组的患者。结论 中药颗粒剂在24周内可以明显改善肾功能，患者的血尿酸水平、血红蛋白及血磷水平对肾功能有一定的影响。     

Cost-effectiveness of maternal immunization against neonatal invasive Group B Streptococcus in the Netherlands

BackgroundNeonatal invasive Group B Streptococcus (GBS) infection causes considerable disease burden in the Netherlands. Intrapartum antibiotic prophylaxis (IAP) prevents early-onset disease (EOD), but has no effect on late-onset disease (LOD). A potential maternal GBS vaccine could prevent both EOD and LOD by conferring immunity in neonates.ObjectiveExplore under which circumstances maternal vaccination against GBS would be cost-effective as an addition to, or replacement for the current risk factor-based IAP prevention strategy in the Netherlands.MethodsWe assessed the maximum cost-effective price per dose of a trivalent (serotypes Ia, Ib, and III) and hexavalent (additional serotypes II, IV, and V) GBS vaccine in addition to, or as a replacement for IAP. To project the prevented costs and disease burden, a decision tree model was developed to reflect neonatal GBS disease and long-term health outcomes among a cohort based on 169,836 live births in the Netherlands in 2017.ResultsUnder base-case conditions, maternal immunization with a trivalent vaccine would gain 186 QALYs and prevent more than €3.1 million in health care costs when implemented in addition to IAP. Immunization implemented as a replacement for IAP would gain 88 QALYs compared to the current prevention strategy, prevent €1.5 million in health care costs, and avoid potentially ~ 30,000 IAP administrations. The base-case results correspond to a maximum price of €58 per dose (vaccine + administration costs; using a threshold of €20,000/QALY). Expanding the serotype coverage to a hexavalent vaccine would only have a limited additional impact on the cost-effectiveness in the Netherlands.ConclusionsA maternal GBS vaccine could be cost-effective when implemented in addition to the current risk factor-based IAP prevention strategy in the Netherlands. Discontinuation of IAP would save costs and prevent antibiotic use, however, is projected to lead to a lower health gain compared to vaccination in addition to IAP.     

Early life Adversity,functional connectivity and cognitive performance in Schizophrenia: The mediating role of IL-6

ObjectiveExposure to childhood trauma (CT) is associated with cognitive impairment in schizophrenia, and deficits in social cognition in particular. Here, we sought to test whether IL-6 mediated the association between CT and social cognition both directly, and sequentially via altered default mode network (DMN) connectivity.MethodsThree-hundred-and-eleven participants (104 patients and 207 healthy participants) were included, with MRI data acquired in a subset of n = 147. CT was measured using the childhood trauma questionnaire (CTQ). IL-6 was measured in both plasma and in toll like receptor (TLR) stimulated whole blood. The CANTAB emotion recognition task (ERT) was administered to assess social cognition, and cortical connectivity was assessed based on resting DMN connectivity.ResultsHigher IL-6 levels, measured both in plasma and in toll-like receptor (TLR-2) stimulated blood, were significantly correlated with higher CTQ scores and lower cognitive and social cognitive function. Plasma IL-6 was further observed to partly mediate the association between higher CT scores and lower emotion recognition performance (CTQ total: β_indirect −0.0234, 95% CI: −0.0573 to −0.0074; CTQ physical neglect: β_indirect = −0.0316, 95% CI: −0.0741 to −0.0049). Finally, sequential mediation was observed between plasma IL-6 levels and DMN connectivity in mediating the effects of higher CTQ on lower social cognitive function (β_indirect = −0.0618, 95% CI: −0.1523 to −0.285).ConclusionThis work suggests that previous associations between CT and social cognition may be partly mediated via an increased inflammatory response. IL-6′s association with changes in DMN activity further suggest at least one cortical network via which CT related effects on cognition may be transmitted.     

基于方剂构成信息的知识发现和关联网络构建挖掘海洋中药海马历代用药经验＊

目的 通过对含海马方剂构成信息进行数据挖掘和知识发现，构建关联网络，分析海马的历代应用情况，挖掘海马用药配伍经验，发现海马潜在功效和主治病症，为海马的临床应用和开发提供依据。方法 以《中医方剂大辞典》《中国药典》《中华医典》等多部著作为方源，收集含有海马的相关方剂，并进行频数分析、关联规则挖掘和关联网络的构建。结果 共筛选有文献记载的含海马方剂154首。从剂型看，大多为散剂，从方剂分布年代来看，海马的应用虽然有很长历史，但是古代应用并不广泛，现代应用较多。通过对配伍药物进行分析发现，与海马配伍频率较高的是“鹿茸”、“熟地黄”、“肉苁蓉”等补益药物。从功效主治方面看，大多数方剂具有“补肾”、“温阳”、“益精”等传统功效外，还具有健脑等功效；主治病症中，除“阳痿”、“癥瘕”、“疔疮”等《中国药典》所记载的疾病之外，还可治疗“虚劳”、“健忘”、“瘿病”、“不寐”、“痹证”、“小便淋沥或不通”等。对其进行关联关系分析发现，海马配伍补肾温阳的效果较为明显，多用于治疗阳痿，且腰痛、虚劳、遗精、健忘、不育等疾病的治疗与补肾关系密切；在治疗癥瘕时，多与醋、樗鸡、干漆、硇砂、斑蝥、水蛭、没药、当归配伍。结论 该研究不仅发现了含海马方剂的常用剂型、分布年代和药物配伍规律，发现了历代医家应用海马的临床经验，还探索了海马的潜在应用价值。海马作为一味海洋中药，具有温、补、托、消等特性，除常用于治疗阳痿外，还可用于治疗腰痛、健忘、瘿病、不寐、痹证等病症，这些研究结果可为拓展海马的临床应用提供理论基础及依据。