Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Through consulting the herbs and medical books of past dynasties, combining with modern literature and field investigation, this paper made textual research on the name, origin, producing area, harvesting and processing of Bupleuri Radix used in the Catalogue of Ancient Classical Prescriptions(the first batch).From Han to the Southern and Northern Dynasties, the source of Bupleuri Radix was a mixture of Bupleurum and Peucedanum, it's hard to define the origin of authentic products.In Tang Dynasty, Caryophyllaceae had been used as Bupleuri Radix. In Song Dynasty, it was clear that the genuine production area of Bupleuri Radix was Yinzhou, its origin was B. corzonerifolium and B. yinchowense.After the Ming Dynasty, B. chinense gradually became the mainstream. It has been confirmed that there were differences in the efficacy between Stellaria dichotoma in Caryophyllaceae and Bupleurum in Umbelliferae, however, the use of S. dichotoma is still attributed to Bupleuri Radix. In the Qing Dynasty, S. dichotoma was distinguished from Bupleuri Radix as another medicine. Among the prescriptions containing Bupleuri Radix included in the Catalogue of Classical Prescriptions in Ancient China(the first batch), the mainstream of genuine Bupleuri Radix should be B. scorzonerifolium and B. chinense. It is suggested that the genuine base of Bupleuri Radix should be selected according to the current resources and industrial development of Bupleuri Radix, and it should conform to the Chinese Pharmacopoeia.
Bupleurum/chemistry* ; China ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Plant Roots/chemistry* ; Prescriptions

The quality marker(Q-marker) of traditional Chinese medicine(TCM) is a new concept of TCM quality control proposed in recent years. It is a hot issue in the research of modern Chinese medicine. The TCM efficacy is a high-level summary of the TCM therapeutic effect under the guidance of TCM theory. On this basis, it is of considerable significance to explore the TCM efficacy marker for the TCM modernization. However, the traditional research strategy based on the single herb and decoction piece in macro TCM level, or the drug research strategy based on the biological effect of the targets, is quite different from the characteristics of multiple components of TCM, as well as the weak and low-selective effect of Chinese medicine ingredients on targets. Therefore, how to select representative ingredients to characterize the TCM overall efficacy is a problematic point in establishing TCM efficacy markers. In this paper, the concept and method of Q-marker were introduced into the study of Chinese medicine efficacy. The research method for systematic TCM was used to systematically discuss the connotation of TCM efficacy markers, the principles of discovery and determination, common research ideas and techniques by taking the representative research results as an example. This study provides new ideas for the research and discovery of TCM efficacy markers.
Biomarkers ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Quality Control ; Research Design

Hepatitis B virus (HBV) capsid protein plays an important role in the life cycle, thus becoming an ideal target for drug design. Capsid protein inhibitors can exert a synergistic antiviral effect with nucleoside drugs by inhibiting the replication of HBV. This paper reviews the research progress of capsid protein inhibitors with different structural types from the perspective of medicinal chemistry.

Hepatitis B has become one of the major diseases which seriously affect people's health and social development. Hepatitis B, with high incidence and long disease course, cannot be cured by approved drugs such as the nucleoside analogues. Therefore, the discovery of safe and efficient novel HBV inhibitors is of great significance. From the point of view of medicinal chemistry, we summarized and discussed current endeavours towards the discovery and development of anti-HBV agents of RNase H and other novel target inhibitors with various scaffolds or distinct mechanisms of action, besides the existing capsid protein inhibitors.

Norovirus (NoV) is the main pathogen causing the global acute gastroenteritis in humans and NoV infection has become an important public health problem that threatens human health. Because of the lack of appropriate animal models and in vitro cell culture models, the development of NoV biology and antiviral research has been restricted, and there is currently no effective antiviral drug or vaccine against NoV. In the past few years, considerable progress has been made toward the development of norovirus antivirals. This review selects the most representative research examples and provides an overview of recent advances in anti-norovirus drugs and vaccines.

Objective:To develop a Nurses' Self-Care Scale so as to provide an effective and reliable tool for evaluating Nurses' Self-Care Scale ability.Methods:A draft of the scale was developed through literature review, expert consultation and small sample pre-experiment. By convenience sampling method, a total of 364 nurses from 3 ClassⅢ Grade A hospitals in Beijing from April to June 2019 were selected for questionnaire survey. The scale was revised and its reliability and validity were evaluated.Results:A total of 5 dimensions and 36 items were finally contained in the Nurses' Self-Care Scale. A total of 5 common factors were generated by exploratory factor analysis, namely the generation of self-care consciousness, the mastery of self-care knowledge, the implementation of healthy lifestyle, the satisfaction of inner self and the acceptance of professional self, and the contribution rate of cumulative variance was 72.523%. The r value of Pearson linear correlation analysis among the scores in 5 dimensions was from 0.497 to 0.836 ( P<0.05) , and the r value of the scores in each dimension and the total score of the scale was from 0.705 to 0.934 ( P<0.05) . The Cronbach's α coefficient of the total scale was 0.977, and the Cronbach's α coefficient of the five dimensions was from 0.890 to 0.975. Conclusions:The Nurses' Self-Care Scale has good reliability and validity, which can be used as a tool to evaluate the level of nurses' self-care.

Through consulting the ancient herbs and medical books,combining with modern literature and field investigation,this paper makes textual research on herbal medicine,and makes textual research on the name,origin,position and changes of collection and processing of the medicinal herbs in Ancient Classical Prescriptions. " Zhu" wasn't distinguished before the Northern and Southern Dynasties,but the efficacy of the techniques recorded in the documents at that time was similar to that of today's Atractylodis Rhizoma.Tao Hongjing put forward the theory of " red and white" in the Northern and Southern Dynasties. " Cangzhu" and " Baizhu" gradually differentiated,but there was no clear distinction between them. Since Song and Yuan Dynasties, " Baizhu" has been respected and classified in the literature. In Ming Dynasty, " Baizhu" was cultivated and differentiated into different quality specifications according to its growth pattern and origin. Maoshan is the genuine production area of " Cangzhu". The quality of wild " Baizhu" produced in Yuqian city is the best. In modern times,the origins of " Cangzhu" and " Baizhu" were defined according to plant taxonomy. " Zhu" before Song Dynasty was close to Atractylodes lancea, " Baishu" had been respected since the Song Dynasty. So when Song people revised the previous literature,they unified " Zhu" into " Baizhu" and used it for later generations. Its safety and effectiveness have been confirmed,and the wild resources of modern atractylodes are scarce. Therefore,it is suggested that when classical famous prescriptions are developed,the prescription recorded as " Baizhu" does not need to be changed in its origin,that is,A. macrocephala at present or can choose the appropriate basis according to the principle of local righteousness.Textual research shows that the origin of " Cangzhu" in the classical prescription should be A. lancea.
Atractylodes/classification* ; China ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Phytotherapy ; Plants, Medicinal/classification* ; Rhizome

Based on the prescription books of herbs and medical books of all dynasties,this article makes a textual research on the name,origin,position,quality,collection,processing and concocting of Acorus tatarinowii used in the classical prescription,and clarifies the relationship between ancient and modern,so as to provide reference and basis for the development and utilization of the classical famous prescription.According to research,A. tatarinowii has many aliases and is often remembered as " Chang pu" when use as medicine; It has a wide distribution of resources in our country,all over the country have produced and mostly wild,its producing areas there is a trend of migration to the southeast; It is recorded in the ancient books of Chinese herbs that most of its medicinal parts are roots,and to root thin,solid quality,dense,aromatic smell,full taste,chewing less slag of high quality; It is harvested in February,May,August and December,and dried in the shade after harvesting; Its concocting methods are more than 20 species have been recorded; Before the Tang Dynasty,the basis of the medicinal A. tatarinowii was relatively chaotic,through textual research,it is concluded that A. tatarinowii should be the mainstream in all dynasties,and that its quality is superior to that of other species in the same genus.It is recommended to be used in " Kaixin san" and " rehmannia drink".
Acorus/chemistry* ; Books ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional

In this paper,the name,origin,producing area,harvesting and processing changes of Paeonia lactiflora used in classical prescriptions were studied by textual research of herbal medicine and field investigation. Chinese herbaceous peony wasn' t distinguished before the Northern and Southern Dynasties; Tao Hongjing proposed that there were two kinds of P. lactiflora in the Northern and Southern Dynasties,but they were not clearly defined; since the Song and Yuan Dynasties,the method of distinguishing P. lactiflora by flower color and root color was proposed. In the Ming Dynasty,people put forward the criteria similar to modern ones,that is,to divide red peony and white peony by means of harvesting and processing,and to continue for future generations. Since modern times,different growth patterns and processing methods have been used to classify red peony and white peony. Paeoniae Radix Alba has gradually formed three major cultivation genuine producing areas: Hangzhou,Sichuan and Bozhou,while Paeoniae Radix Rubra in modern times has praised the wild medicinal materials produced in Inner Mongolia,Toronto and other places. According to textual research,Paeoniae Radix Alba was highly praised in Song Dynasty. When people in Song Dynasty revised the previous literature,they changed " Shaoyao" into " Baishao" and continued to use Paeoniae Radix Alba for future generations. Therefore,the origin of P. lactiflora in classical prescriptions before the Song Dynasty should be determined by the combination of prescription function and prescription meaning evolution; After the Song Dynasty,the origins of " Red Paeonia Root" and " White Paeonia Root" in prescriptions are basically the same as those in today's prescriptions,which should be recorded in ancient prescriptions. For the medicinal flavor of " Paeonia Root" recorded in prescriptions after the Song Dynasty,the origins can be determined by functional domination and the evolution of prescriptions.
China ; Drugs, Chinese Herbal/history* ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, Medieval ; Humans ; Paeonia ; Phytotherapy ; Plants, Medicinal