[Application progress on data-driven technologies in intelligent manufacturing of traditional Chinese medicine extraction].

The application of new-generation information technologies such as big data, the internet of things(IoT), and cloud computing in the traditional Chinese medicine(TCM)manufacturing industry is gradually deepening, driving the intelligent transformation and upgrading of the TCM industry. At the current stage, there are challenges in understanding the extraction process and its mechanisms in TCM. Online detection technology faces difficulties in making breakthroughs, and data throughout the entire production process is scattered, lacking valuable mining and utilization, which significantly hinders the intelligent upgrading of the TCM industry. Applying data-driven technologies in the process of TCM extraction can enhance the understanding of the extraction process, achieve precise control, and effectively improve the quality of TCM products. This article analyzed the technological bottlenecks in the production process of TCM extraction, summarized commonly used data-driven algorithms in the research and production control of extraction processes, and reviewed the progress in the application of data-driven technologies in the following five aspects: mechanism analysis of the extraction process, process development and optimization, online detection, process control, and production management. This article is expected to provide references for optimizing the extraction process and intelligent production of TCM.

[Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review].

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.

Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review / 中国中药杂志

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.

[Granulation of Yangxue Qingnao Granules in fluidized bed based on near-infrared spectroscopy].

To realize the real-time monitoring of the production process of Yangxue Qingnao Granules and improve the inter-batch consistency of granule quality in the granulation process, this study established a near-infrared quantitative prediction model of moisture, particle size, bulk density, and angle of repose in the fluidized bed granulation process of Yangxue Qingnao Granules based on near-infrared spectroscopy(NIRS). The near-infrared spectra were collected from 355 samples in 12 batches in the granulation process by integrating the sphere detection module of the near-infrared spectrometer. In combination with the pretreatment methods such as the first derivative, multiplicative scatter correction(MSC), and standard normal variate(SNV), the model was established by partial least squares(PLS) regression. The root mean square error of prediction(RMSEP) of moisture was 0.347 and R_P~2 was 0.935. The RMSEP of the D_(50) particle size model was 38.4 and R_P~2 was 0.980. The RMSEPs of bulk density and angle of repose were 0.018 8 and 0.879, with R_P~2 of 0.085 9 and 0.958. The results showed that the prediction of the PLS quantitative model combined with NIRS was accurate, and this model can be applied to the monitoring of key quality attributes in the fluidized bed granulation of Chinese medicinal granules in the production scale.

[Research on batch-to-batch quality control of compound Danshen extract based on physical characterization and multivariate statistical analysis].

Physical attributes of Chinese herbal extracts are determined by their chemical components, and the physical and chemical attributes jointly affect the preparation process performance and the final product quality. Therefore, in order to improve the quality control of Chinese herbal extracts, we should comprehensively study the batch-to-batch consistency of physical and chemical attributes as well as the correlations between them. This paper first explored the physical attributes affecting the preparation process performance of the compound Danshen extract and developed a method for characterizing the texture attributes. With such main chemical components as water, phenolic acids, saponins, and saccharides and texture, rheology, and other physical attributes taken into consideration, the batch-to-batch quality fluctuation of products from different production lines and time was analyzed by principal components analysis(PCA). Finally, the correlation and partial least squares(PLS) analysis was conducted, and the regression equation was established. The fitting result of the PLS model for dynamic viscosity was satisfying(R~2Y=0.857, Q~2=0.793), suggesting that the chemical components could be adjusted by the component transfer rate in the extraction process, the impurity removal rate in the alcohol precipitation process, and the water retention rate of the concentration process to meet the control of the extract dynamic viscosity. This study clarified the correlations between physical and chemical attributes of the compound Danshen extract and established a method for controlling its physical attributes based on process regulation, which would provide reference for improving the quality control of Chinese herbal extracts.

Cortical ensembles orchestrate social competition through hypothalamic outputs.

Most social species self-organize into dominance hierarchies1,2, which decreases aggression and conserves energy3,4, but it is not clear how individuals know their social rank. We have only begun to learn how the brain represents social rank5-9 and guides behaviour on the basis of this representation. The medial prefrontal cortex (mPFC) is involved in social dominance in rodents7,8 and humans10,11. Yet, precisely how the mPFC encodes relative social rank and which circuits mediate this computation is not known. We developed a social competition assay in which mice compete for rewards, as well as a computer vision tool (AlphaTracker) to track multiple, unmarked animals. A hidden Markov model combined with generalized linear models was able to decode social competition behaviour from mPFC ensemble activity. Population dynamics in the mPFC predicted social rank and competitive success. Finally, we demonstrate that mPFC cells that project to the lateral hypothalamus promote dominance behaviour during reward competition. Thus, we reveal a cortico-hypothalamic circuit by which the mPFC exerts top-down modulation of social dominance.

Research on batch-to-batch quality control of compound Danshen extract based on physical characterization and multivariate statistical analysis / 中国中药杂志

Physical attributes of Chinese herbal extracts are determined by their chemical components, and the physical and chemical attributes jointly affect the preparation process performance and the final product quality. Therefore, in order to improve the quality control of Chinese herbal extracts, we should comprehensively study the batch-to-batch consistency of physical and chemical attributes as well as the correlations between them. This paper first explored the physical attributes affecting the preparation process performance of the compound Danshen extract and developed a method for characterizing the texture attributes. With such main chemical components as water, phenolic acids, saponins, and saccharides and texture, rheology, and other physical attributes taken into consideration, the batch-to-batch quality fluctuation of products from different production lines and time was analyzed by principal components analysis(PCA). Finally, the correlation and partial least squares(PLS) analysis was conducted, and the regression equation was established. The fitting result of the PLS model for dynamic viscosity was satisfying(R~2Y=0.857, Q~2=0.793), suggesting that the chemical components could be adjusted by the component transfer rate in the extraction process, the impurity removal rate in the alcohol precipitation process, and the water retention rate of the concentration process to meet the control of the extract dynamic viscosity. This study clarified the correlations between physical and chemical attributes of the compound Danshen extract and established a method for controlling its physical attributes based on process regulation, which would provide reference for improving the quality control of Chinese herbal extracts.

Material Attribute Research in Quality Control of Traditional Chinese Medicine Pills： A Review / 中国实验方剂学杂志

As intelligent production of traditional Chinese medicine （TCM） has been inevitable， informatization and automation of the production process have become the precondition for realizing intelligent manufacturing of TCM， of which the accumulation of critical material attribute and the critical quality attribute are the basis. The study of material properties is of great significance to achieve the quality control of the final product in the process， but there is a lack of systematic induction and summary of the research on the attribute of TCM pills. Therefore， the authors analyzed and summarized the attributes of raw materials， excipients and intermediates in the pill unit process according to the classification of powder properties， rheological properties and texture properties. What’s more， the impact of material attributes on the quality of the final product was summarized. Besides， this review summarized the attribute characterization techniques involved in the pill process and provided some suggestions for the characterization of product quality attributes. Finally， based on the concept of quality by design （QbD）， the authors proposed that the study of material attribute should be combined with process analytical technology （PAT）， and the focus of drug quality control should be moved forward to guide equipment upgrading， so as to realize intelligent continuous manufacturing of TCM pills.

The efficacy and safety of modified Gegenqinlian Fomular for advanced colorectal cancer (damp heat accumulation type): A multicenter randomized controlled trial.

INTRODUCTION: CRC, the incidence of the fourth highest among males and the third among females, is one of the malignant tumors that seriously threaten human health. The principle of treatment for advanced stage CRC is a multidisciplinary and comprehensive treatment based on chemotherapy, which always bring significant toxic side effects. CHM has advantages in the treatment of tumors with the effect on improving clinical symptoms and reducing side effects. GGQL formula is mainly used for treating abnormal defecates caused by damp-heat, so we will evaluate the clinical efficacy and safety of modified GGQL formula for patients with advanced CRC with the type of damp-heat in this study. METHODS: Multicenter RCT with two parallel groups in three hospitals planning to recruit 120 CRC patients with the type of damp-heat will be conducted. The control group will be treated by basic antitumor therapy and the treatment group will use modified GGQL formula plus basic antitumor therapy. The primary outcomes will be quality of life, TCM symptom score, PFS and OS, and the secondary outcomes will be performance status, size of tumor, tumor marker in the serum, tumor microenvironment and immune status. All analyses will be based on an intention-to-treat principle. This study was approved by the Human Research Ethics Committee of Shanxi Province Hospital of Traditional Chinese medicine (2021Y-06017). The results will be published in relevant journal. DISCUSSION: The results of this RCT will contribute to Chinese herbal medicine for treating CRC patients with the type of damp heat accumulation. TRIAL REGISTRATION: ChiCTR2100050754 (September 4, 2021).

Buzhong Tiaogan Formula for delaying colorectal liver metastasis (liver depression spleen deficient type): A multicenter randomized controlled trial: A study protocol.

INTRODUCTION: Colorectal cancer has been ranked third among the most common cancers worldwide and raised to the second leading cause of cancer death with nearly one-tenth of cancer-related deaths globally, and nearly half of colorectal cancer patients present with or develop colorectal cancer liver metastasis (CRLM). Buzhong Tiaogan Formula (BTF) has been proven to treat CRLM in our team, but there are lacking of evidence on its effective in delaying colorectal liver metastasis (liver depression spleen deficiency type), so we will evaluate the efficacy and safety of BTF in preventing the occurrence of CRLM. METHODS: This randomized controlled trial (RCT) will be carried out in 3 different hospitals in Shanxi Province planning to recruit 150 CRLM patients with the type of liver depression spleen deficiency. The control group will be treated by basic antitumor therapy and the treatment group will use BTF plus basic antitumor therapy. The primary outcomes will be quality of life of included patients, the time of occurrence of liver metastasis, the score of traditional Chinese medicine symptom for the type of liver depression spleen deficiency; and the secondary outcomes will include overall survival, progression-free survival, DFS, tumor microenvironment and immune state of the included patient. Safety evaluation will be recorded during the whole study. All data in this RCT will be analyzed by SPSS 23.0 software. This study has been approved by the Clinical Research Ethics Committee of Shanxi Province Hospital of Traditional Chinese medicine (2021Y-06016). DISCUSSION: The results of this RCT will contribute to BTF for delaying colorectal liver metastasis (liver depression spleen deficient type). And the results from this RCT will be published in a relevant journal after finished. TRIAL REGISTRATION: ChiMCTR2100005268 (September 4, 2021).

[Effect of moxibustion combined with Guifu Yuhe decoction on the conversion score of idiopathic constitution, serum total lgE and blood EOS in the patients with allergic acne].

OBJECTIVE: To observe the therapeutic effect of moxibustion combined with Guifu Yuhe decoction on allergic acne and the influence on immunologic function in the patients. METHODS: A total of 60 patients with allergic acne were rando-mized into an observation group (30 cases) and a control group (30 cases).Thirty healthy employees were in the healthy group. In the control group, Guifu Yuhe decoction was prescribed for oral administration, while in the observation group, on the base of the treatment as the control group, moxibustion was exerted at Dazhui (GV14) and Shenque (GV8). The treatment duration was 8 weeks. Before and after treatment, serum IgE, blood EOS, CD4+T cell, CD8+ T cell and CD4+T/CD8+T, as well as the conversion score of idiopathic constitution and the symptom score were compared in the patients of two groups. The clinical therapeutic effect was observed in the two groups. RESULTS: Before treatment, compared with the healthy group, IgE and EOS, CD4+T cell and CD8+T cell all increased (P<0.05), and CD4+T/CD8+T decreased in the two groups (P<0.05). After treatment, IgE, EOS and CD4+T cell and CD8+T cell decreased (P<0.05), and CD4+T/CD8+T increased (P<0.05) in the intra-group comparison in the patients. The changes of IgE, EOS, CD4+T cell and CD8+T cell in the observation group were more larger than those in the control group (P<0.05). After treatment, the conversion score of body constitution and symptom score all decreased in either group (P<0.05) and the scores in the observation group were lower than those of the control group (P< 0.05). The total effective rate of the observation group (29/30, 96.7%) was higher than that of the control group (22/30, 73.3%, P<0.05). CONCLUSION: Moxibustion combined with Guifu Yuhe decoction can significantly improve immune function and body constitution of the patients with allergic acne, which may be related to rectifying idiopathic constitution, improving in lymphocyte subsets dysfunction and inhibiting allergic reaction.

Melatonin supplementation in the subacute phase after ischemia alleviates postischemic sleep disturbances in rats.

BACKGROUND: Sleep disorders are highly prevalent among stroke survivors and impede stroke recovery. It is well established that melatonin has neuroprotective effects in animal models of ischemic stroke. However, as a modulator of endogenous physiological circadian rhythms, the effects of melatonin on poststroke sleep disorders remain unclear. In the present study, we investigated how melatonin delivered intraperitoneally once daily in the subacute phase after stroke onset, influencing neuronal survival, motor recovery, and sleep-wake profiles in rats. METHODS: Transient ischemic stroke in male Sprague-Dawley rats was induced with 30 min occlusion of the middle cerebral artery. Melatonin or vehicle was delivered intraperitoneally once daily in the subacute phase, from 2 to 7 days after stroke. Electroencephalogram and electromyogram recordings were obtained simultaneously. RESULTS: Compared to the effects observed in the vehicle-treated ischemic group, after 6 daily consecutive treatment of melatonin at 10 mg/kg starting at ischemic/reperfusion day 2, the infarct volume was significantly decreased (from 39.6 to 26.2%), and the degeneration of axons in the ipsilateral striatum and the contralateral corpus callosum were significantly alleviated. Sensorimotor performances were obviously improved as evidenced by significant increases in the latency to falling off the wire and in the use of the impaired forelimb. In addition to those predictable results of reducing brain tissue damage and mitigating behavioral deficits, repeated melatonin treatment during the subacute phase of stroke also alleviated sleep fragmentation through reducing sleep-wake stage transitions and stage bouts, together with increasing stage durations. Furthermore, daily administration of melatonin at 9 a.m. significantly increased the nonrapid eye movement sleep delta power during both the light and dark periods and decreased the degree of reduction of the circadian index. CONCLUSIONS: Melatonin promptly reversed ischemia-induced sleep disturbances. The neuroprotective effects of melatonin on ischemic injury may be partially associated with its role in sleep modulation.

[Research on feedforward control method of mixing process for compound Danshen Dripping Pills based on quality by design(QbD)].

The mixing process is one of the key operation units for solid preparation of traditional Chinese medicine. The physical properties such as particle size, density and viscosity of the mixture are key factors that need to be controlled, which will directly affect the performance of the preparation molding process and product quality. Subsequent dripping process performance and appearance qua-lity of dripping pills will be affected by dynamic viscosity of materials in the mixing process. Based on this, with mixing process of compound Danshen dripping pills as the object, a feedforward control method for the dripping pill mixing process was established based on the concept of quality by design(QbD). Firstly, critical quality attribute(CQA)-dynamic viscosity, critical material attributes(CMAs)-the moisture content of compound Danshen extract, average molecular weight of polyethylene glycol 6000 and critical process parameter(CPP)-mixing temperature were identified through the analysis of properties for multiple batches of the raw materials and excipients as well as technological mechanism. Then the Box-Behnken experimental design was used to establish the regression model among CMA, CPP and CMA(R■=0.972 0, RMSE =16.24) to obtain the design space. Finally, through the verification of three batches within the design space, the mixing process temperature was adjusted according to the properties of the raw materials and exci-pients to achieve accurate control of the dynamic viscosity attribute. The relative deviation between the actual dynamic viscosity value and the target value was less than 3.0 %. The feedforward control of the mixing process of compound Danshen dripping pills was rea-lized in this study, which can contribute to improving quality consistency of the mixing process intermediates, simultaneously provide a reference for the research on the process quality control of other Chinese medicine dripping pills.

Research on feedforward control method of mixing process for compound Danshen Dripping Pills based on quality by design(QbD) / 中国中药杂志

The mixing process is one of the key operation units for solid preparation of traditional Chinese medicine. The physical properties such as particle size, density and viscosity of the mixture are key factors that need to be controlled, which will directly affect the performance of the preparation molding process and product quality. Subsequent dripping process performance and appearance qua-lity of dripping pills will be affected by dynamic viscosity of materials in the mixing process. Based on this, with mixing process of compound Danshen dripping pills as the object, a feedforward control method for the dripping pill mixing process was established based on the concept of quality by design(QbD). Firstly, critical quality attribute(CQA)-dynamic viscosity, critical material attributes(CMAs)-the moisture content of compound Danshen extract, average molecular weight of polyethylene glycol 6000 and critical process parameter(CPP)-mixing temperature were identified through the analysis of properties for multiple batches of the raw materials and excipients as well as technological mechanism. Then the Box-Behnken experimental design was used to establish the regression model among CMA, CPP and CMA(R■=0.972 0, RMSE =16.24) to obtain the design space. Finally, through the verification of three batches within the design space, the mixing process temperature was adjusted according to the properties of the raw materials and exci-pients to achieve accurate control of the dynamic viscosity attribute. The relative deviation between the actual dynamic viscosity value and the target value was less than 3.0 %. The feedforward control of the mixing process of compound Danshen dripping pills was rea-lized in this study, which can contribute to improving quality consistency of the mixing process intermediates, simultaneously provide a reference for the research on the process quality control of other Chinese medicine dripping pills.

Multi-Frequency Ultrasonic Extraction of Anthocyanins from Blueberry Pomace and Evaluation of Its Antioxidant Activity.

BACKGROUND: A large amount of blueberry pomace is discarded and wasted. OBJECTIVE: To make full use of blueberry pomace and extract anthocyanins. METHOD: Multi-frequency ultrasound was used to extract anthocyanins from blueberry pomace. The effects of different extraction conditions on the anthocyanin yields were studied. The antioxidant activity of anthocyanins was evaluated, and the main anthocyanin components were identified by HPLC-electrospray ionization (ESI)-MS/MS. RESULTS: The optimal anthocyanin extraction conditions were as follows: dual-frequency ultrasound of 40 + 80 kHz, ultrasonic power of 350 W, extraction temperature of 50°C, and extraction time of 40 min. Compared with single frequency (25 kHz) and tri-frequency ultrasound (25 + 40 + 80 kHz), the anthocyanin yield with dual-frequency ultrasound increased by 15.26% and 5.45% respectively. Furthermore, the antioxidant activities (DPPH, hydroxyl radical scavenging ability, and reducing power) of anthocyanins extracted with dual-frequency ultrasound were all higher than those without ultrasound. Seven kinds of anthocyanins were identified by HPLC-ESI-MS/MS. CONCLUSIONS: Dual-frequency ultrasound had a higher extraction yield than single frequency ultrasound, tri-frequency ultrasound, and no ultrasound. HIGHLIGHTS: Dual-frequency ultrasonic technology provides an effective approach for improving the extraction yield of anthocyanins from blueberry pomace.

[Study of intelligent manufacturing quality digitalization of traditional Chinese medicine and practice on Compound Danshen Dripping Pills].

China healthcare industry has gradually developed the consumer-centric integrated service model. To satisfy consumers' increasing demands on pluralistic, personalized and transparent healthcare services, pharmaceutical manufacturing enterprises must provide high-quality, precise and flexible medicines. This can be achieved by accelerating implementation of intelligent manufacturing, which is the core competitiveness of pharmaceutical manufacturing enterprises. According to the authors' intelligent manufacturing projects in a traditional Chinese medicine(TCM) factory, study and industrial practice on intelligent manufacturing were presented in this paper. First, the quality digitalization-based intelligent manufacturing methodology of TCM was proposed in this paper. The methodology mainly included three digitalized technologies in process and quality design, manufacturing process control and product batch evaluation. Next, the architectural design of intelligent manufacturing systems in one TCM factory was introduced, and the functional modules and data transmission relationships covering seedling, cultivation, herbal slices, preparation, storage and quality management systems were described. Finally, these technologies were fully used, and an integrated quality digitalization system was successfully established in the production workshop of a TCM product Compound Danshen Dripping Pills. The actual operation and application of process analyzers, supervisory control and data acquisition(SCADA), manufacturing execution system(MES), data analysis system, and enterprise resource planning system(ERP) were introduced. This paper provides reference for technical path planning and systematic architecture of TCM intelligent manufacturing.

Discovery of novel 2,4-disubstituted pyrimidines as Aurora kinase inhibitors.

In order to explore novel Aurora kinase inhibitors, a series of novel 2,4-disubstituted pyrimidines were designed, synthesized and evaluated their in vitro anti-proliferative activities against a panel of cancerous cell lines (A549, HCT-116 and MCF-7). Among them, compound 12a showed the moderate to high anti-proliferative activities against A549 (IC50 = 12.05 ± 0.45 µM), HCT-116 (IC50 = 1.31 ± 0.41 µM) and MCF-7 (IC50 = 20.53 ± 6.13 µM) cells, as well as the Aurora A and Aurora B inhibitory activities with the IC50 values of 309 nM and 293 nM, respectively. Furthermore, compound 12a induced apoptosis by upregulated the pro-apoptotic proteins Bax and decreased the anti-apoptotic protein Bcl-xl in HCT-116 cells. Moreover, the molecular docking study showed that compound 12a had good binding modes with Aurora A and Aurora B and the bioinformatics prediction discovered that compound 12a exhibited good drug likeness using SwissADME. Taken together, these results indicated that 12a may be a potential anticancer compound that was worthy of further development as Aurora kinase inhibitor.

Application Progress of Texture Analyzer in Pharmaceutical Preparation Research / 中国实验方剂学杂志

Texture analyzer is a multifunctional physical property analyzer. Through a variety of test modes such as compression， puncture， shearing and stretching， hardness， adhesion， elasticity， cohesiveness and other physical property parameters are characterized. The results are objective， sensitive， and accurate， which can provide theoretical basis and reference for interpretation of basic theoretical， optimization of prescription technology and quality control research of pharmaceutical preparations. Firstly， the principles， test modes， measurement indexes and measurement data analysis methods of texture analyzer were summarized in this paper. Secondly， the application progress of texture analyzer in solid preparations， semi-solid preparations， liquid preparations， traditional Chinese medicine decoction pieces and their intermediates was described in detail， and compared with the commonly used measurement methods of physical property indicators. Finally， the application prospects of texture analyzer and its research contents to be improved were reviewed， so as to facilitate the use of texture analyzer by pharmaceutical researchers to promote the development of related fields of pharmaceutics， and to provide new ideas and methods for the research and development of pharmaceutical preparations.

Recent research progress in key technologies of Chinese materia medica manufacturing process quality control / 中草药

The development of Chinese materia medica (CMM) has risen to the level of national strategy. Under the new situation that the pharmaceutical industry implements the "Made in China 2025" strategy, quality control of the production process of CMM is one of the key areas in which the CMM industry needs to accelerate its breakthrough. The key common issues in process design, analysis and detection, process modeling, and manufacturing equipment and other aspects in the field of quality control of CMM production processes was analyzed in the paper. The progress in the three aspects of process understanding, real-time analysis method development and process control strategy establishment in the quality control system of CMM production process was reviewed. Combined with the author's corporate research practices, this paper introduces the application progress of key technologies such as quality by design (QbD), process analytical technology (PAT), experimental design (DOE), and multivariate statistical analysis in the above three research directions, and analyzes the difficulties problems in practical industrial application. The application prospect is prospected. The purpose of this article is to provide reference for CMM enterprises to apply and improve the quality control technology in the production process.

[Diterpenoids as PPARγ agonists from Siegesbeckia pubescens and their anti-inflammatory effects in vitro].

This study aims to investigate the PPARγ agonists isolated from the aqueous extract of Siegesbeckia pubescens( SPA) and their anti-inflammatory activities in vitro. The 293 T cells transfected transiently with PPARγ recombinant plasmid were used as a screening model to guide the isolation of PPARγ activitating components,and then PPARγ activities were measured by double luciferase reporter gene assay. The chemical structures were identified by chromatography or spectroscopic techniques. Furthermore,a UC inflammatory model in vitro was established on HT-29 cells by stimulating with TNF-α． The mRNA levels and secretion of proinflammatory cytokines on HT-29 cells,such as IL-1ß,TNF-α,IL-8,were detected by RT-PCR and ELISA. The results showed that five diterpenoids were obtained from the fraction D_(50) with the strongest PPARγ activity among others in SPA,and determined as kirenol( 1),darutigenol( 2),enantiomeric-2-ketone-15,16,19-three hydroxypinomane-8( 14)-ene-19-O-ß-D-glucoside( 3),darutoside( 4),enantiomeric-2-ß,15,16,19-four hydroxypinomane-8( 14)-ene-19-O-ß-D-glucoside( 5),respectively. All the compounds exhibited active effects on PPARγ in a concentration-dependent manner( P<0. 01). In addition,compound 1 significantly inhibited the expression of IL-1ß mRNA and secretion of IL-8 on HT-29 cells inflammation model( P<0. 001); both compounds 2 and 3 effectively inhibited the expression of IL-1ß,TNF-α,IL-8 mRNA and secretion of IL-8( P<0. 01 or P<0. 001),although at different extent; compound 4 significantly inhibited the expression of IL-1ß and TNF-α mRNA( P<0. 01 or P<0. 001),while compound 5 inhibited the expression of IL-1ß mRNA obviously( P<0. 001). In conclusion,the diterpenoids 1-5 isolated from S. pubescens have the PPARγ activation activities and potential effects of anti-UC in vitro.