辛味中药在治疗消渴证中的应用价值及中药五味理论现代研究的思考

辛味是中药五味学说中的重要性味之一,通常具有“发散”“行气”和“行血”的作用,且辛味中药在传统医学临床应用中占有较大比例。结合中药辛味的功效内涵及传统中医理论对消渴证的认识,阐述辛味中药与消渴证治疗之间的内在联系,总结辛味中药对“消渴三消”的治疗意义与价值。并在此基础上,对中药五味理论的现代研究趋势和发展方向进行思考,为同行研究提供参考。     

Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database

BackgroundConsiderable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization.MethodsThe Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018.ResultsA total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment.ConclusionWe present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.     

An Evidence-Based Review of Total Body Irradiation

The purpose of this literature review is to investigate clinical treatment methods of total body irradiation within the context of a clinical department adopting a paediatric cohort with no existing technique. An extensive review of the literature was conducted using PubMed, Science Direct, Google Scholar, and Clinicians Knowledge Network. Articles were limited to nonhelical tomotherapy, nonparticle therapies, and those using hyperfractionated regimes. Total marrow irradiation was excluded because of national treatment and trial limitations. Of the numerous patient positioning methods present within the literature, the most comfortable and reproducible positioning methods for total body irradiation include both supine and the supine and/or prone combination. These positions increased stability and patient comfort during treatment, while also facilitating computed tomography data acquisition at the simulation stage. Ideally, dose calculations should be performed using a three-dimensional treatment planning system and quality assurance procedures that include in vivo dosimetry measurements. The available literature also suggests inhomogeneity correction factors and intensity modulation are superior to conventional open field techniques and should be implemented within developing protocols. Dynamic machine dose modulation is suggested to reduce department impact, removing the need for tissue compensators and accessory shielding devices, while providing significant improvements to treatment time and dose accuracy. Further long-term survival and intensity modulation studies are warranted, including direct comparisons of both dose modulation and treatment efficiency.     

探究培美曲塞与多西他赛在晚期非小细胞肺癌靶向治疗失败后挽救化疗中的临床疗效

目的 研究培美曲塞与多西他赛在晚期非小细胞肺癌靶向治疗失败后挽救化疗中的应用效果。方法 筛选2018 年1 月～2020 年1 月本院的60 例晚期非小细胞肺癌靶向治疗失败后挽救化疗的患者作为研究对象，依据患者选择的药物种类分为观察组和对照组，每组各30 例，对照组采用多西他赛治疗，观察组予以培美曲塞治疗，对比分析两组的近期治疗效果、生存质量评分和毒副反应发生情况。结果 观察组病症控制率为66.67%，对照组病症控制率为36.67%，观察组病症控制效果更好；观察组生存质量评分为（65.2±3.4）分，对照组生存质量评分为（51.7±4.6）分，两组比较差异有统计学意义（t=12.926，P=0.000）；观察组各项毒副反应发生率均低于对照组，差异有统计学意义（P＜0.05）。结论 在晚期非小细胞肺癌靶向治疗失败后进行挽救化疗中选用培美曲塞有更好的治疗效果，可以较好的进行临床治疗，改善患者的生活质量，且产生的毒副反应较少，在实际临床中的应用价值较高。     

Clinical analysis of peritoneal dialysis in the treatment of rapidly progressive glomerulonephritis

Objective To observe the clinical characteristics and prognosis of patients with rapidly progressive glomerulonephritis (RPGN) caused by lupus nephritis, antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, or primary glomerulonephritis who were treated with peritoneal dialysis (PD) and then withdrew PD because of renal recovery. Methods Data of the above patients were retrospectively analyzed. The patients were diagnosed as RPGN and received PD therapy in Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University from February 2009 to August 2018. The patients were divided into early withdrawal group (PD time≤183 days, n=24) and late withdrawal group (PD time＞183 day, n=24). The differences of clinical characteristics between the two groups were compared. The cumulative incidence of adverse events in both groups was analyzed using Kaplan-Meier curves. Cox proportional hazards model was used to analyze the risk factors influencing the prognosis of patients. Results Forty-eight RPGN patients were included. The median time of maintaining PD was 178(76, 378) days. Compared with the late withdrawal group, the patients in early withdrawal group had lower levels of urine volume, serum albumin and parathyroid hormone, and lower rates of gross hematuria and hypertension at the beginning of PD, and received higher rates of methylprednisolone impulse, combined immunosuppressive agents, and hemodialysis or continuous renal replacement therapy (all P＜0.05). At the time of PD withdrawal, the levels of serum creatinine, serum calcium, serum albumin and parathyroid hormone in the early withdrawal group were significantly lower than those in the late withdrawal group (all P＜0.05). The Kaplan-Meier curves showed that there was no significant difference in the cumulative survival of patients in both groups (log-rank test χ2=3.485, P=0.062). Cox regression analysis revealed serum creatinine≥209 μmol/L at the time of PD withdrawal was an independent risk factor for poor prognosis (HR=5.253，95%CI 1.757-15.702, P=0.003). Conclusions PD can be used for RPGN patients caused by lupus nephritis, ANCA-associated vasculitis and primary nephritis. Serum creatinine≥209 μmol/L at the time of PD withdrawal is an independent risk factor for poor prognosis.     

PCNA、Survivin蛋白在人绒癌细胞株BeWo合体化过程中表达变化的研究

目的:通过检测人绒癌细胞株Be Wo合体化过程中增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、生存素(Survivin)蛋白表达的变化,探讨滋养细胞合体化后增殖性的变化,为恶性滋养细胞肿瘤,尤其是耐药恶性滋养细胞肿瘤的临床治疗提供新的思路和方法。方法:利用毛喉素(forskolin)诱导Be Wo细胞株融合;应用逆转录聚合酶链反应(RT-PCR)检测促融素(Syncytin)在forskolin作用不同时间的Be Wo细胞株中的表达;应用蛋白质印迹(Western blotting)检测PCNA、Survivin蛋白在forskolin作用不同时间的Be Wo细胞株中的表达;应用噻唑蓝比色分析实验(MTT)法检测forskolin作用不同时间的绒癌细胞株Be Wo的增殖能力。结果:1forskolin作用后的Be Wo细胞株Syncytin基因的表达增强,且随着forskolin作用时间的延长,Syncytin的表达更强,于48 h达到高峰。2forskolin作用后的Be Wo细胞株PCNA、Survivin蛋白的表达降低。3forskolin作用后的Be Wo细胞株的增殖能力下降,且不同作用时间的差异有统计学意义;forskolin作用的时间越长,Be Wo细胞株增殖能力下降越明显。结论:人绒癌细胞株Be Wo合体化后PCNA、Survivin蛋白的表达降低,说明人绒癌细胞株Be Wo合体化后增殖性降低,推测诱导滋养细胞合体化可能对临床治疗恶性滋养细胞肿瘤具有一定作用。     

Deoxynivalenol induces apoptosis in PC12 cells via the mitochondrial pathway

Deoxynivalenol (DON) has broad toxicity in animals and humans. In this study the impact of DON treatment on apoptotic pathways in PC12 cells was determined. The effects of DON were evaluated on (i) typical indicators of apoptosis, including cellular morphology, cell activity, lactate dehydrogenase (LDH) release, and apoptosis ratio in PC12 cells, and on (ii) the expression of key genes and proteins related to apoptosis, including Bcl-2, Bax, Bid, cytochrome C (Cyt C), apoptosis inducing factor (AIF), cleaved-Caspase9, and cleaved-Caspase3. DON treatment inhibited proliferation of PC12 cells, induced significant morphological changes and apoptosis, promoted the release of Cyt C and AIF from the mitochondria, and increased the activities of cleaved-Caspase9 and cleaved-Caspase3. Bcl-2 expression decreased with increasing DON concentrations, in contrast to Bax and Bid, which were increased with increasing DON concentration. These data demonstrate that DON induces apoptosis in PC12 cells through the mitochondrial apoptosis pathway.