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。     

Positive Cultures Can Be Safely Ignored in Revision Arthroplasty Patients That Do Not Meet the 2018 International Consensus Meeting Criteria

BackgroundDuring aseptic revision total joint arthroplasty (TJA), one or more cultures may occasionally isolate an organism. The hypothesis of this study was that in a portion of patients undergoing revision arthroplasty for aseptic failure, culture may isolate an organism(s) that can be left untreated.MethodsAll patients undergoing revision TJA from 2000 to 2017 at two institutions were retrospectively reviewed. Patients were categorized as aseptic if they were appropriately investigated preoperatively and did not meet the 2018 International Consensus Meeting criteria. In the aseptic revision cohort, patients with a single positive culture or multiple cultures positive for different organisms (“organism-positive”) and patients who had negative intraoperative cultures (“organism-negative”) were compared based on demographics, comorbidities, operative details, subsequent reoperations, and periprosthetic joint infection (PJI).ResultsIn total, 3,234 International Consensus Meeting–negative aseptic revision TJAs were included, of which 215 patients (6.6%) were organism-positive, 196 (91.2%) had a single positive culture, and 19 (8.8%) were positive for 2 or more distinct organisms (ie, polymicrobial). The most prevalent organisms were coagulase-negative Staphylococci (37.5%), Staphylococcus epidermidis (9.6%), and Cutibacterium acnes (8.0%). Demographics and operative details were comparable between the groups. Using multiple regressions there was no association between culture positivity and the rate of reoperation or PJI.ConclusionIsolation of organisms by culture in patients undergoing revision for aseptic failure was not uncommon. As long as these patients were appropriately investigated preoperatively and PJI was excluded, these findings suggest that culture results may be ignored without subjecting patients to additional antimicrobial treatment.     

VAC结合游离植皮治疗儿童大面积皮肤缺损疗效观察及对患儿生活质量的影响

目的:探讨负压创面治疗技术(Vacuum assisted closure,VAC)结合游离植皮治疗儿童大面积皮肤缺损疗效及对患儿生活质量的影响。方法:选取2015年2月-2019年2月笔者医院收治的60例大面积皮肤缺损患儿作为研究对象,按照随机数表法分为干预组和对照组,每组30例。对照组采用游离植皮术治疗,干预组在对照组的基础上结合VAC治疗,以皮片成活时间、皮片成活率、换药次数及住院天数评估疗效,以长海痛尺分级法评估患儿疼痛等级,以抑郁自评量表(Self-rating depression scale,SDS)、焦虑自评量表(Self-rating anxiety scale,SAS)评估患儿心理状态,以术后不良反应发生率评估患儿预后情况,以自制生活质量表评估患儿生活质量水平。结果:干预组患儿皮片成活时间、换药次数与住院天数均小于对照组,差异有统计学意义(P<0.05)。干预组患儿皮片成活率为93.33%高于对照组的76.67%,差异有统计学意义(P<0.05)。干预组治疗后疼痛感、SDS与SAS评分低于治疗前,且低于对照组,差异有统计学意义(P<0.05)。干预组患儿术后不良反应发生率为6.67%显著低于对照组23.33%,差异有统计学意义(P<0.05)。两组治疗前活动能力、心理健康及社交能力均低于治疗后,干预组治疗后活动能力、心理健康及社交能力均高于对照组(P<0.05)。结论:VAC结合游离植皮治疗儿童大面积皮肤缺损疗效显著,能有效降低患儿生理疼痛与心理焦虑,减少伤口感染等不良反应的发生,提高患儿生活质量,具有推广价值。     

肝癌组织LncRNA TINCR表达水平对术后长期生存的影响

目的 探讨肝癌组织中LncRNA TINCR 表达水平对术后长期生存的影响。方法 回顾性分析2013 年4 月～2016 年2 月间在本院接受手术治疗的157 例肝细胞肝癌患者的临床资料。RT-PCR 法检测肝癌标本内LncRNA TINCR 表达水平，采用ROC 曲线和Kaplan-Meier 法分析LncRNA TINCR 表达水平对肝癌术后长期生存的影响。结果 肝癌组织LncRNA TINCR 表达水平对术后长期生存预测的曲线下面积（AUC）为0.812，特异度为73.77%，灵敏度为79.17%，最佳判读值为1.89（P＜0.0001）。根据ROC 曲线分析结果，将肝癌组织LncRNA TINCR 相对表达水平大于1.89 的93 例（59.24%）患者纳入高表达组，而肝癌组织LncRNA TINCR 相对表达水平小于或等于1.89的64 例（40.76%）患者纳入低表达组。Kaplan－Meier 法生存分析发现高表达组术后3 年内有76 例患者死亡，3 年总生存率为18.28%（17/93）；低表达组术后3 年内有20 例患者死亡，3 年总生存率为68.75%（44/64），低表达组3 年总生存率明显优于高表达组（P＜0.0001，两组间死亡风险比为3.7534，95%可信区间为2.5158～5.6000）。结论 肝癌组织LncRNA TINCR 表达水平与肝癌术后长期生存显著相关，LncRNA TINCR 表达水平升高则预示着预后不佳。     

Papillary thyroid carcinoma with a high tumor mutation burden has a poor prognosis

BackgroundTumor mutation burden (TMB) as a prognostic marker for immunotherapy has shown prognostic value in many cancers. However, there is no systematic investigation on TMB in papillary thyroid carcinoma (PTC).MethodsBased on the somatic mutation data of 487 PTC patients from The Cancer Genome Atlas (TCGA), TMB was calculated, and we classified the samples into high-TMB (H-TMB) and low-TMB (L-TMB) groups. Bioinformatics methods were used to explore the characteristics and potential mechanism of TMB in PTC.ResultsHigh TMB predicts shorter progression-free survival (PFS) (P < 0.001). TMB was positively correlated with age, stage, tumor size, metastasis, the male sex and tall cell PTC. Compared to the L-TMB group, the H-TMB group presented with lower immune cell infiltration, a higher proportion of tumor-promoting immune cells (M0 macrophages, activated dendritic cells and monocytes) and a lower proportion of antitumor immune cells (M1 macrophages, CD8⁺ T cells and B cells). Additionally, the characteristics displayed by different TMB groups were not driven by critical driver mutations such as BRAF and RAS.ConclusionsPTC patients with high TMB have a worse prognosis. By stratifying PTC patients according to their TMB, advanced PTC patients who are candidates for immunotherapy could be selected.     

Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.

Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.

Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.     

The Outcome of Cemented Acetabular Components in Total Hip Arthroplasty for Osteoarthritis Defines a Proficiency Threshold: Results of 22,956 Cases From the Australian Orthopaedic Association National Joint Replacement Registry

BackgroundThe declining popularity of cemented acetabular components is incongruous, given the published results of prostheses implanted using contemporary techniques. The outcome of arthroplasty has previously been demonstrated to correlate with surgeon experience and volume of practice. We aim to explore if surgeon volume alters outcomes of cemented acetabular components based on survivorship data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR).MethodsAn observational study was undertaken using a cohort of 22,956 patients with a primary diagnosis of osteoarthritis in the period 2003-2016 in whom cemented acetabular components were implanted. The cohort was stratified by age (greater than or less than 65 years) and annualized surgical volume of ≤10, >10-≤25, and >25 cases.ResultsStratified by age and volume, there was a protective benefit against revision conveyed at volume thresholds of 10 cases per annum and 25 cases per annum for patients ≥65 years of age and <65 years of age, respectively.ConclusionCemented total hip arthroplasty has excellent survivorship out to 15 years based on AOANJRR data. This survivorship is further improved if surgeons perform a higher volume of cases, with >25 cases conferring the greatest benefit. The AOANJRR data set is used to define best practice; surgeons who choose to utilize cemented acetabular fixation should be encouraged to perform this technique in adequate volumes to minimize revision risk and ensure the preservation of this important surgical skill set.     

Surgical Helmets Used During Total Joint Arthroplasty Harbor Common Pathogens: A Cautionary Note

BackgroundThe use of personal-protection surgical helmet/hood systems is now a part of the standard surgical attire during arthroplasty in North America. There are no protocols for the disinfection of these helmets.MethodsThis is a prospective, single-center, observational study. Helmets worn by 44 members of the surgical team and foreheads of 44 corresponding surgical personnel were swabbed at three distinct time points. In addition, 16 helmets were treated with hypochlorite spray to determine if pathogens could be eliminated. Swabs obtained were processed for culture and next-generation sequencing (NGS).ResultsOf the 132 helmet samples, 97 (73%) yielded bacteria on culture and 94 (71%) had evidence of bacterial–deoxyribonucleic acid (DNA) on NGS. Of the swabs sent for bacterial identification at the three time points, at least one from each helmet was positive for a pathogen(s). Of the 132 forehead samples, 124 (93%) yielded bacteria on culture and 103 (78%) had evidence of bacterial-DNA on NGS. The most commonly identified organism from helmets was Cutibacterium acnes (86/132) on NGS and Staphylococcus epidermidis (47/132) on culture. The most commonly identified organism from the foreheads of surgical personnel was Cutibacterium acnes (100/132) on NGS and Staphylococcus epidermidis (70/132) on culture. Sanitization of helmets was totally effective; no swabs taken the following morning for culture and NGS identified any bacteria.ConclusionThis study demonstrates that surgical helmets worn during orthopedic procedures are contaminated with common pathogens that can potentially cause surgical site infections. The findings of this study should at the minimum compel us to develop protocols for the disinfection of these helmets.