Circadian rhythm is an internal regulatory mechanism that allows organisms to adapt to circadian changes in the external environment, and can regulate the body's steady state by affecting the metabolic pathways of multiple organs. When exogenous factors such as eating time, worktime changes, and sleep disturbances cause the body's circadian rhythm to be disrupted, the risk of developing metabolic syndrome is significantly increased. This article explores the relationship between circadian rhythm and body metabolism and summarizes the molecular mechanisms by which circadian rhythm regulates the digestive system, liver and bile acid production, and kidney function. We review research progress on intervention in the circadian rhythm by traditional Chinese medicine and provide a reasonable and valuable basis for follow-up studies on the role of traditional Chinese medicine in research on the molecular mechanisms of regulation of circadian rhythm.

3D printing technology has the advantages of accurate spatial distribution, accurate drug release and personalized drug dosage, which can make up for the shortcomings of traditional pharmaceutical technology. In recent years drop-on powder (DoP) 3D printing technology has been widely used in pharmaceutical preparation. Compared with other types of 3D printing technology, it is more simple, flexible and easy to operate. In 2015, Aprecia Pharmaceuticals announced that the US Food and Drug Administration (FDA) approves the launch of its first instant tablet Spritam^® (levetiracetam) made with DoP 3D printing. After the first 3D printed medicine was launched, people also saw the unique advantages and broad prospects of DoP 3D printing technology platform in pharmaceutical preparation. This review focuses on the technical principles and key factors of DoP 3D printing, its application in the preparation field and its future development challenges.

Reactive nitrogen species (RNS) affects intracellular redox balance and induces post-translational modification of proteins. Moreover, RNS, as the signal molecule, participates in the transduction of cellular signals under physiological conditions. However, excessive RNS can induce nitrosative stress and then damage cells, and thereby may play a role in the tumor initiation and progression. Thus, we discussed the role of RNS under physiological conditions and the tumor microenvironment, which may provide some novel ideas for the development of new drugs and the treatment of diseases.

Characterization of the polysaccharides and monosaccharides of Bupleurum chinense was undertaken to identify differences in the Bupleurum chinense's sugar profiles, so as to provide a basis for the identification of different varieties. High performance liquid chromatography (HPLC) was used to generate chromatograms of the total polysaccharides of Bupleurum using an Evaporation Light Detector (ELSD), and a monosaccharide chromatogram was generated using a UV-detector (UV) following polysaccharide derivatization. The data were analyzed using SIMCA software and SPSS software to distinguish different varieties of Bupleurum. The results show that the yield of polysaccharides from Bupleurum falcatum is the highest, while the yield of polysaccharides from Bupleurum chinense is the lowest. The polysaccharide spectrum shows that the molecular weights of the polysaccharides in different Bupleurum differ, and their percentages of the total peak area are also different. The four Bupleurum polysaccharides are composed of mannose, glucuronic acid, rhamnose, galacturonic acid, glucose, galactose, and arabinose, but differ in length. The ratio of glucose to arabinose in Bupleurum chinense, Bupleurum scorzonerifolium, Bupleurum falcatum and Bupleurum marginatum var. stenophyllum is: 3.0-4.0, 5.5-7.0, 12.0-17.0, 9.0-12.0. In this study, a sugar profile technique was developed to provide a new method for the identification of different varieties of Bupleurum.

In recent years the interaction between host and gut microbiota has attracted increasing attention. However, intestinal flora dysbiosis may lead to many diseases, and there is increasing evidence that the intestinal microbiota in patients with chronic kidney disease (CKD) is associated with the pathophysiological status of the host. "Gut-kidney axis" provides a better explanation of the two-way communication between intestinal flora and CKD. Impaired kidney function leads to dysbiosis of intestinal flora and an altered intestinal flora can damage the intestinal mucosal barrier and facilitate the entry into the bloodstream of harmful bacteria, which can induce chronic inflammation and thus accelerate renal injury. In addition, the accumulation of nephrotoxic metabolites from an altered intestinal flora can aggravate CKD in the "gut-kidney axis". Among them, p-cresol sulfate, indoxyl sulfate and trimethylamine oxide are the most widely studied metabolites of nephrotoxicity, and their renal toxicity has been widely confirmed in basic research and clinical studies. Current studies show that the intestinal microbiota-metabolite network is closely related to the occurrence and development of chronic kidney disease. Thus, intervention in the intestinal microbiota may provide a new approach to the prevention and treatment of chronic kidney disease.

The major challenge in the development of recombinant biologics lies in generating and isolating rare high-producing stable single clone in a short period of time. The selection marker is an essential component of the plasmid vector, it plays an important part in the generation and screening of producing cell lines. Engineering the selection marker to enhance the stringency of selection for high producing cells is one of the most effective approaches to improve the cell line development process. Here, using Chinese hamaster overy (CHO) cells as an example, we introduce the application of selection marker for generation of recombinant biologics producing mammalian cell lines, methods of engineering the selection markers to enhance the selection stringency, and propose considerations on cell substrate stability and selection marker safety, in order to provide references for high-efficiency development of recombinant biologics.

The research and development of monoclonal antibodies (mAbs) is a rapidly developing field. From the first generation of murine mAbs to the fourth generation of fully human mAbs, the efficacy and safety of mAbs in the treatment of various diseases have been continuously improved. In order to regulate the development and evaluation of mAbs, drug regulatory agencies and pharmacopeias of America and China have tried to issue feasible test procedures and acceptance criteria for quality evaluation of mAbs and biosimilars. Mass spectrometry (MS) technique with high sensitivity, resolution, selectivity, and specificity has become an important tool to evaluate the quality characteristics of monoclonal antibody-related products or specify mAb quality. The research of MS-based monoclonal antibody study involves structure characterization, impurity analysis, pharmacokinetics/pharmacodynamics (PK/PD), etc. This review focuses on the current quality control requirements of mAb related products and the development of MS technique for mAb quality characterization and specification. It is expected to provide information and references for evaluating the quality of monoclonal antibodies under research and development.

The scientific world has witnessed multiple outstanding breakthroughs in the field of traditional Chinese medicine and natural product derived drugs during 2015-2020. The research by Prof. Tu Youyou on artemisinin gained her as one of the winners of Nobel Prize in Physiology or Medicine in 2015, has also aroused profound impetus in the investigation of traditional Chinese medicine and natural product drugs. Mori ramulus alkaloids tablets and GV-971 capsules have been approved by National Medical Products Administration (NMPA) for clinical application. Some of the important research findings were selected as "Top 10 major medical advances" in China, and a plenty of research articles were accepted by world top publications such as Nature, Science, New England Journal of Medicine, as well as Lancet, etc. The current review summarized and commented on the research highlights of traditional Chinese medicine and natural drugs published in world top journals from 2015 to 2020, including the major progresses in the sub-divided areas of chemistry, molecular pharmacognosy, pharmacology and toxicology, as well as pharmaceutics. This report aims to follow and review the leading research and hot spots in fields of traditional Chinese medicine and natural drugs, and to provide prospects and inspirations in the interdisciplinary areas based on our preliminary analyses.

The goal of this work was to establish a population pharmacokinetics (PPK) model of tacrolimus in idiopathic membranous nephropathy (IMN) patients and to identify potential covariates that influence pharmacokinetic of tacrolimus. A total of 610 data points on the blood concentration of tacrolimus were collected from 96 IMN patients in routine clinical settings. Nonlinear mixed-effect modeling (NONMEM) was used to investigate the effects of CYP3A5 genotype, age, gender, weight, laboratory tests and co-therapy medications on the pharmacokinetic of tacrolimus. The PPK model was evaluated by the goodness-of-fit (GOT), bootstrap and prediction corrected visual predictive check (pc-VPC). The pharmacokinetic of tacrolimus was described by a one-compartment model. The apparent clearance (CL/F) of CYP3A5*1/*3 and *1/*1 were 1.57 and 1.86 times of that of *3/*3, respectively. The CL/F of tacrolimus was 73.6% in patients undergoing co-therapy with Wuzhi capsules, and 1.2 times than that of the patients undergoing co-therapy with Jinshuibao capsules. The evaluation of the model shows that the model is stable and has satisfactory predictive performance. The clinical trial was approved by the Society of Ethics and conducted in Binzhou Medical University Hospital. The established PPK model can describe the pharmacokinetic characteristics of tacrolimus in Chinese patients with IMN, and can facilitate individualized therapy with tacrolimus.

We used the network pharmacology to explore the active ingredients and mechanism of action of Danqi tablets in the treatment of coronary heart disease, providing a theoretical basis for the treatment of clinical coronary heart disease. The TCMSP database was used to screen for active ingredients and targets in Danqi tablets; the predicted targets of coronary heart disease were screened through the GeneCards database; then, the intersection of the two targets was mapped; we used STRING database to construct a protein interaction network map and identified 65 cores targets; then, the DAVID database was used for enrichment analysis of gene ontology (GO) biological processes and KEGG signaling pathways, and finally the Cytoscape-3.6.2 software was used to construct a network diagram of traditional Chinese medicine-active ingredient-key targets-pathway. The H₂O₂-induced H9C2 cells injury model was used for experimental verification. The results suggest that Danqi tablets act on inflammatory factors and apoptosis-related pathways through quercetin, luteolin, tanshinone ⅡA, and other active ingredients, and improve proinflammatory or anti-inflammatory imbalances in the body and protect cardiomyocytes. This study confirms the multi-component and multi-target effects of Danqi tablets in the treatment of coronary heart disease, and provides an objective basis for their use in further experimental research and the clinical diagnosis and treatment of coronary heart disease.