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.

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.

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

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

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.

OBJECTIVE: To introduce the design of customized pelvic prosthesis, to evaluate the biomechanical property under three load conditions of customized pelvic prosthesis under three load cinditions. METHODS: A titanium alloy prosthesis for reconstruction of pelvic tumors was designed by CAD software. The strength and stiffness of the custom prosthesis under static and slow gait conditions were analyzed and evaluated by finite element method. RESULTS: The results of the finite element analysis suggested that the maximum von Mises stress in the pelvic under three load conditions were 39.0, 202.8 and 42.4 MPa; the maximum displacement were 0.199, 0.766 and 0.847 mm. The maximum von Mises stress in the prosthesis under three load conditions were 62.3, 318 and 468 MPa. The maximum Von Mises stress in the Ti-alloy prosthesis and pelvic was far smaller than the yield strength of Ti-alloy. CONCLUSIONS The study can design the size and shape of prosthesis accurately according to patient's condition. The finite element method can reduce the bone stress level and fracture risk, prolong the service life of prostheses, and ensure the safety and stability of the postoperative patients under normal gait.
Biomechanical Phenomena ; Finite Element Analysis ; Fractures, Bone ; Gait ; Humans ; Prostheses and Implants ; Prosthesis Design ; Stress, Mechanical

Objective: To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods: A cross-sectional survey was used in this study. Selection of subjects: (1) Domestic public grade III A (provincial and prefecture-level) oncology hospitals or general hospitals possessing the radiotherapy department and the diagnosis and treatment qualifications for colorectal cancer. (2) Surgeons of deputy chief physician or above. Using the "Questionnaire Star" online survey platform to create a questionnaire about cognition, attitude and treatment choice of the "watch and wait" strategy after cCR following nCRT for rectal cancer. The questionnaire contained 32 questions, such as the basic information of doctor, the current status of rectal cancer surgery, the management of pathological complete remission (ypCR) after nCRT for rectal cancer, the selection of examination items for diagnosis of cCR, the selection of suitable people undergoing "watch and wait" approach, the nCRT mode for promotion of cCR, the choice of evaluation time point, the willingness to perform "watch and wait" approach and the treatment choice, and the risk and monitoring of "watch and wait" approach. A total of 116 questionnaires were sent to the respondents via WeChat between January 31 and February 19, 2019. Statistical analysis was performed using Fisher′s exact test for categorical variables. Results: Forty-eight hospitals including 116 surgeons meeting criteria were enrolled, of whom 77 surgeons filled the questionnaire with a response rate of 66.4%. "Watch and wait" strategy was carried out in 76.6% (59/77) of surgeons. Seventy surgeons (90.9%) were aware of the ypCR rate of rectal cancer after preoperative nCRT and 49 surgeons (63.6%) knew the 3-year disease-free survival of patients with ypCR in their own hospitals. Fifty-five surgeons (71.4%) believed that patients with ypCR undergoing radical surgery met the treatment criteria and were not over-treated. Three most necessary examinations in diagnosing cCR were colonoscopy (96.1%, 74/77), digital rectal examination (DRE) (90.9%,70/77) and DWI-MRI (83.1%, 64/77). Responders preferred to consider a "watch and wait" strategy for patients with baseline characteristics as mrN0 (77.9%, 60/77), mrT2 (68.8%, 53/77) and well-differentiated adenocarcinoma (68.8%, 53/77). Sixty-six surgeons (85.7%) believed that long-term chemoradiotherapy (LCRT) with combination or without combination of induction and/or consolidation of the CapeOX regimen (capecitabine + oxaliplatin) should be the first choice as a neoadjuvant therapy to achieve cCR. Forty-one surgeons (53.2%) believed that a reasonable interval of judging cCR after nCRT should be ≥ 8 weeks. Forty-four surgeons (57.1%) routinely, or in most cases, informed patient the possibility of cCR and proposed to "watch and wait" strategy in the initial diagnosis of patients with non-metastatic rectal cancer. Thirteen surgeons (16.9%) would take the "watch and wait" strategy as the first choice after the patient having cCR. Fifty-two surgeons (67.5%) would be affected by the surgical method, that was to say, "watch and wait" approach would only be recommended to those patients who would achieve cCR and could not preserve the anus or underwent difficult anus-preservation surgery. Sixteen surgeons (20.8%) demonstrated that "watch and wait" strategy would not be recommended to patients with cCR regardless of whether the surgical procedure involved anal sphincter. Eleven surgeons (14.3%) believed that the main risk of "watch and wait" approach came from distant metastasis rather than local recurrence or regrowth. Twenty-nine of surgeons (37.7%) did not understand the difference between "local recurrence" and "local regrowth" during the period of "watch and wait". Twenty-six surgeons (33.8%) thought that the monitoring interval for the first 3 years of "watch and wait" strategy was 3 months, and the follow-up monitoring interval could be 6 months to 5 years. Surgeons from cancer specialist hospitals had higher approval rate, notification rate, and referral rate of "watch and wait" strategy than those from general hospitals. Thirty-one surgeons (42.5%) considered that the difficulty and concern of carrying out "watch and wait" approach in the future was the disease progress leading to medical disputes. Twenty-six surgeons (35.6%) demonstrated that their concern was lack of uniform evaluation standard for cCR. Conclusions Chinese surgeons seem to have inadequate knowledge of non-operative management for rectal cancer patients achieving cCR after nCRT and show relatively conservative attitudes toward the strategy. Chinese consensus needs to be formed to guide the non-operative management in selected patients. Chinese Watch & Wait Database (CWWD) is also needed to establish and provide more evidence for the use of alternative procedure after a cCR following nCRT.

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