[Application progress on taste evaluation methods for oral preparations].

Taste is an important factor affecting the medicinal properties of oral preparations and patient compliance with medication, and also an important evaluation index for oral preparation design and clinical application. How to characterize the taste objectively, accurately, simply, and efficiently is a bottleneck problem that restricts the taste design, development, and utilization of oral preparations. At present, the commonly used taste assessment methods for oral preparations are traditional human taste panel, electronic tongue, animal preference test, in vitro release study, and electrophysiological test. The traditional human taste panel is the first choice for taste evaluation, but it is limited by poor subjectivity and reproducibility. Therefore, despite some limitations, the other four taste assessment methods have been applied in the pharmaceutical industry as auxiliary methods. This study reviewed the detection principles, applicability, advantages, and disadvantages of the above methods to provide references for the taste correction research and taste assessment of oral preparations, improve patient compliance and the competitiveness of oral preparation products in the industry, and promote the development of oral preparation technologies.

[Quality standard and quality value transfer of reference samples of classical prescription Huagan Decoction].

The detection method of characteristic spectrum for reference samples was established by preparing 15 batches of the reference samples of Huagan Decoction, and the peak attribution and the similarity range in the characteristic spectrum were clarified. The ranges of paste-forming rate, content, and transfer rate of the index components including geniposide, paeonol, and paeoniflorin were analyzed. The key quality attribute of the reference samples of Huagan Decoction was defined. The results showed that the 15 batches of the reference samples of Huagan Decoction had good similarities in the characteristic spectrum, which were all higher than 0.9. According to the information of characteristic peak, there were 18 characteristic peaks in the whole prescription, including seven common characteristic peaks from green tangerine peel and dried tangerine peel, four characteristic peaks from tree peony root bark(three of them were common characteristic peaks from tree peony root bark and red peony root), five characteristic peaks from cape jasmine fruit, one characteristic peak from paniculate bolbostemma, and one characteristic peak from oriental waterplantain rhizome.The paste-forming rate of the 15 batches of reference samples was 14.73%-18.83%. The content of geniposide was 1.68%-2.87%, with the average transfer rate of 70.05%±11.13%. The content of paeonol was 0.10%-0.16%, with the average transfer rate of 9.38%±1.78%. The content of paeoniflorin was 1.94%-2.74%, with the average transfer rate of 36.69%±4.63%. This study analyzed the quality value transfer of the reference samples of Huagan Decoction by the evaluation mode of combining the characteristic spectrum, the paste-forming rate, and the content of index components. The findings of this study initially established a stable and feasible standard decoction evaluation method and provided references for the quality control and the subsequent development of relevant preparations of Huagan Decoction.

[Quality value transfer of substance benchmarks in Sanpian Decoction].

According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.

[Analysis on quality value transmitting of substance benchmark of Houpo Wenzhong Decoction].

By preparing 15 batches of lyophilized powder samples of substance benchmark in Houpo Wenzhong Decoction,the fingerprint,index component content and extract rate were determined,and the characteristic peaks,the range of similarity with the reference map,the content range and transfer rate range of magnolol,hesperidin,glycyrrhizic acid and pinocembrin,the extract rate range and the change range were clarified. The results showed that the similarity between the fingerprint of substance benchmark and the reference map R generated from the 15 batches of substance benchmark samples was higher than 0. 90. The assignment of the characteristic peaks in the full prescription's fingerprint of the herbs except Poria cocos was clarified. Nineteen characteristic peaks were assigned,and 12 characteristic peaks were assigned by the reference substance,of which 4 were from Magnolia ocinalis Cortex,5 from Exocarpium Citri Rubrum,2 from Radix aucklandiae,3 from Glycyrrhiza Radix et Rhizoma,4 from Semen Alpiniae Katsumadai,and one from Rhizoma Zingiberis and Zingiber officinale Roscoe. The index component content range and transfer rate range were 0. 80%-1. 14% and 20. 25%-39. 61% for hesperidin,0. 49%-0. 79% and 23. 09%-33. 87%for glycyrrhizic acid,0. 03%-0. 07% and 3. 55%-10. 09% for pinocembrin,0. 15%-0. 38% and 8. 08%-24. 35% for magnolol. The extract rate range and the change range were22. 60%-25. 57% and 12. 67%-23. 68% respectively. In this study,we introduced the concepts of index component content,fingerprint,extract rate,explored the transfer relation of quality value transmitting of substance benchmark in Houpo Wenzhong Decoction,and initially established the quality standard of Houpo Wenzhong Decoction,all of which would provide ideas for the development and research of similar prescriptions.

Cost-sharing and horizontal compensation scheme of regional sulfur dioxide treatment: Evidence from China.

Establishing a reasonable cost-sharing and compensation mechanism for air pollution control is a prerequisite for realizing inter-regional cooperative treatment. Taking inter-provincial sulfur dioxide (SO2) emissions in China from 2005 to 2019 as the research object, this paper proposes a data-driven approach to establish a cost-sharing index system of regional SO2 treatment in four dimensions and construct a cost-sharing and compensation scheme using the entropy-TOPSIS method. The results revealed that there are significant spatial and temporal differences in the treatment cost of SO2 emission, and the total SO2 treatment costs at the national level increased first and then decreased during the study period, meanwhile, the regional SO2 treatment costs are much higher in the less economically developed regions such as the central and western regions than in economically developed eastern coastal regions. The design of the cost-sharing and compensation mechanism of SO2 treatment should consider the regional differences in abatement capacity, abatement potential, abatement responsibility, and development demands. The economically developed regions should share higher treatment costs according to their historical cumulative abatement responsibilities, and provide economic compensation and technical support to the less economically developed regions. Specifically, the marginal abatement cost in the more economically developed eastern region is much higher than that in the less economically developed central and western areas due to their large abatement responsibility and strong reduction capacity but insufficient abatement potential, so the eastern regions can transfer part of their abatement responsibility to the central and western regions using economic compensation. Reasonable cost sharing and horizontal compensation can help promote regional cooperation and synergistic management in air pollution abatement. Finally, corresponding policy recommendations are given to provide a decision basis for cross-regional cooperation in air pollution control.

A Co-Module Regulated by Therapeutic Drugs in a Molecular Subnetwork of Alzheimer's Disease Identified on the Basis of Traditional Chinese Medicine and SAMP8 Mice.

There are currently no approved effective therapies for Alzheimer's disease (AD). AD is a classic, multifactorial, complex syndrome. Thus, a polypharmacological or multitargeted approach to AD might provide better therapeutic benefits than monotherapies. However, it remains elusive which biological processes and biomolecules involved in the pathophysiologic processes of AD would constitute good targets for multitargeted therapy. This study proposes that a co-module, consisting of biological processes, cellular pathways and nodes, in a molecular subnetwork perturbed by different therapeutic drugs may be the optimal therapeutic target for an AD multitarget-based intervention. Based on this hypothesis, genes regulated in the hippocampus and cortex of senescence-accelerated mouse prone-8 (SAMP8) mice by traditional Chinese medicine (TCM) prescriptions with different constituents and the same beneficial effects on AD, including the decoctions Liu-Wei-Di-Huang (LW), Ba-Wei-Di-Huang (BW), Danggui-Shaoyao-San (DSS), Huang-Lian-Jie-Du (HL) and Tiao-Xin-Fang (TXF), were investigated via cDNA microarray, and the perturbed subnetworks were constructed and interpreted. After comparing 15 perturbed subnetworks based on genes affected by LW, BW, HL, DSS and TXF, the results showed that the most important common nodes perturbed by these interventions in the brains of SAMP8 mice were RPS6KA1 and FHIT, and that other important common nodes included UBE2D2, STUB1 and AMFR. These five drugs simultaneously and significantly disturbed the regulation of apoptosis and protein ubiquitination among biological processes. These nodes and processes were key components of the co-module regulated by therapeutic drugs in a molecular subnetwork of AD. These results suggest that targeting candidate regulator of apoptosis and protein ubiquitination might be effective for AD treatment, and that RPS6KA1, FHIT, UBE2D2, STUB1 and AMFR might be optimal combinational targets of an AD multitarget-based therapy.

[Changes of Th1/Th2/Th17 in patients received non-myeloablative haploidentical hematopoietic stem cell transplantation detected by flow cytometric bead array].

This study was purposed to investigate the changes of Th1/Th2/Th17 in patients received non-myeloblastic haploidentical hematopoietic stem cell transplantation (NAHSCT). The levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ, as well as IL-17 level were determined by flow cytometric bead array (CBA) in samples from 18 patients underwent allo-peripheral NAHSCT at different time points before and after transplantation. The results showed that all cytokines changed obviously after transplantation, and their serum levels were higher than that before transplantation. The expression levels of IL-2, IL-4 and IL-17 changed early, and their obviously up-regulation was found after transplantation. The expression levels of IL-6, IL-10 and TNF-α changed significantly, and were high as compared with that before transplantation. The change of INF-γ serum level was observed late, its rising occurred at week 4 after transplantation. The expression of all cytokines kept increasing during 4 weeks after transplantation and peaked at week 4. It is concluded that the serum levels of all cytokines from the patients after NAHSCT increased significantly, in which the levels of IL-2, IL-4 and IL-17 increased early, but the level of INF-γ changed late. The detection of cytokines is helpful for deep understanding the pathophysiologic mechanism of transplant-related complications.

[Different changes of serum cytokines following HLA-identical and HLA haploidentical non-myeloablative allogeneic hematopoietic stem cell transplantation].

This study was aimed to investigate the expression difference of serum cytokines in 20 patients receiving HLA-identical nonmyeloablative allogeneic hematopoietic stem cell transplantation (iNAHSCT) and HLA-haploidentical nonmyeloablative allogeneic hematopoietic stem cell transplantation (hiNAHSCT). IL-2, IL-4, IL-6, IL-10, TNF-α, γ-IFN and IL-17 were detected by flow cytometric bead array before and on week 1, 2, 4 after transplantation respectively. The results showed that the IL-2 level was found to be up-regulated at week 1 and 2 after transplantation in iNAHSCT group and in hiNAHSCT group respectively, but there was no difference between these two groups (P > 0.05). The γ-IFN levels was up-regulated at week 4 after transplantation in above-mentioned two groups, but no difference was found between these two groups. The IL-4 level increased at week 2 and 1 after transplantation in iNAHSCT and hiNAHCT groups respectively, but the IL-4 level in iNAHSCT group was higher than that in hiNAHSCT group. The IL-6 level rose at week 1 and 2 after transplant in above mentioned groups respectively, and reached to peak level at week 4 after transplantation, but IL-6 level in hiNAHSCT was higher than that in iNAHSCT group (P < 0.02). The IL-10 level was up-regulated at week 1 and 2 in iNAHSCT and hiNAHSCT groups respectively, but the IL-10 level in iNAHSC was higher than that in hiNAHSCT group. The TNF-α level was up-regulated at week 1 in hiNAHSCT group, but at week 2 in iNAHSCT group after transplantation. The TNF-α level in hiNHASCT group was higher than that in iNAHSCT group (P < 0.01). The IL-17 level was up-regulated at week 1 and week 4 after transplantation in hiNAHSCT and iNAHSCT groups respectively, the IL-17 level in hiNAHSCT group was high as compared with that in iNAHSCT group. It is concluded that the serum cytokine levels are obviously up-regulated in iNAHSCT and hiNHASCT groups, and reach to peak level at week 4 after transplantation. The IL-6, TNF-α and IL-17 level up-regulated significantly in hiNAHSCT group, but the IL-4 and IL-10 level up-regulated significantly in iNAHSCT.

Nodes and biological processes identified on the basis of network analysis in the brain of the senescence accelerated mice as an Alzheimer's disease animal model.

Harboring the behavioral and histopathological signatures of Alzheimer's disease (AD), senescence accelerated mouse-prone 8 (SAMP8) mice are currently considered a robust model for studying AD. However, the underlying mechanisms, prioritized pathways and genes in SAMP8 mice linked to AD remain unclear. In this study, we provide a biological interpretation of the molecular underpinnings of SAMP8 mice. Our results were derived from differentially expressed genes in the hippocampus and cerebral cortex of SAMP8 mice compared to age-matched SAMR1 mice at 2, 6, and 12 months of age using cDNA microarray analysis. On the basis of PPI, MetaCore and the co-expression network, we constructed a distinct genetic sub-network in the brains of SAMP8 mice. Next, we determined that the regulation of synaptic transmission and apoptosis were disrupted in the brains of SAMP8 mice. We found abnormal gene expression of RAF1, MAPT, PTGS2, CDKN2A, CAMK2A, NTRK2, AGER, ADRBK1, MCM3AP, and STUB1, which may have initiated the dysfunction of biological processes in the brains of SAMP8 mice. Specifically, we found microRNAs, including miR-20a, miR-17, miR-34a, miR-155, miR-18a, miR-22, miR-26a, miR-101, miR-106b, and miR-125b, that might regulate the expression of nodes in the sub-network. Taken together, these results provide new insights into the biological and genetic mechanisms of SAMP8 mice and add an important dimension to our understanding of the neuro-pathogenesis in SAMP8 mice from a systems perspective.

[Clinical study of bortezomib for treating multiple myeloma with renal impairment].

This study was purposed to analyze the clinical characteristics of multiple myeloma (MM) patients with and without renal impairment (RI) and to investigate the effect of bortezomib (Bor) on MM with RI. Clinical data of 39 MM patients (15 cases with RI, 24 cases without RI) received treatment of Bor in department of hematology in our hospital from Jan 2007 to Aug 2011 were collect and analyzed in term of clinical characteristics, curative efficacy, outcome of renal impairment and toxic reaction associated to chemotherapy. The results showed that (1) the obvious difference of the disease type, the creatinine, uric acid, serum calcium and ß2-microglobulin levels existed in patients with and without RI, while there were no significant difference in hemoglobin and globin levels; (2) there were no significant difference in overall reaction rate and overall survival rate between MM patients with and without RI, however the median survival time of patients without RI was longer than that of patients with RI; (3) the RI could be reversed after the treatment with Bor, and the effect was most obvious after the first cycle. 20% MM patients with RI had recovered from RI after the first cycle; and the recovery rate from RI got up to 38.4% after the second cycle. The decline of creatinine levels had no difference between MM patients with or without RI after the second cycle. (4) The adverse events included gastrointestinal symptoms, peripheral neuropathy, thrombocytopenia and infection. There was also no difference between the 2 groups. It is concluded that Bor-based regimens for the MM patients with RI are effective and safe, and the renal function would be reversed after 2 cycle of Bor-based regimen.