The expanded clinical trial system is designed to provide clinical trial drugs for patients suffering from serious or life-threatening diseases for which there is no effective treatment， essentially seeking a balance between the accessibility of drugs to patients and the soundness of the development of the pharmaceutical industry， as well as between the risk of expanding the use of clinical trial drugs and the need to safeguard the rights and interests of patients’ lives and health. Article 23 of China's Drug Administration Law provides only a principled description of the applicable standards and operating procedures for this system， with no implementing regulations， making it difficult for the system to function effectively in practice. The United States， Japan， and Canada have made detailed provisions on the conditions of application， applicants， review subjects and contents， and safeguards of the system through laws， regulations， and guidelines. Based on China's legislative environment and regulatory reality， and considering that the system is still in the initial stage in China， it is recommended that appropriate reference be made to the beneficial experience of foreign countries and that regulations and normative documents be promulgated as soon as possible to clarify the types of expanded clinical trials， applicants， review subjects etc.， and to determine the responsibilities of all the parties involved， to promote the standardization of China’s expanded clinical trial system， to promote the availability of medicines to patients， and to effectively safeguard the rights and interests of patients’ lives and health， and the soundness and safety of the development of the pharmaceutical industry.

Objective:To summarize the relevant evidence of motor rehabilitation of stroke at home and abroad, so as to provide reference for medical staff to carry out motor rehabilitation.Methods:The related evidence on exercise management for patients with stroke in BMJ Best practice, UpToDate, Joanna Briggs Institute (JBI) Evidence-Based Health Care Center Database, National Guideline, American Heart Association/American Stroke Association, European Stroke Organization, National Institute for Health and Care Excellence, Registered Nurses Association of Ontario, Canadian Medical Association, American Association of Critical Care Nurses, National Stroke Foundation, Chinese Stroke Association, Medlive, Cochrane library, PubMed, Web of Science, Embase, OVID, Medline, China National Knowledge Infrastructure, Wanfang, VIP, SinoMed were searched by computer. The retrieval time limit was from 2012 to June 30, 2022. Two to four investigators independently assessed the quality of the included article, and extracted and summarized the evidence that met the quality standards.Results:A total of 22 articles were included, including 5 guidelines, 2 summary of evidence, 2 expert consensus, and 13 systematic evaluations. A total of 42 pieces of evidence related to exercise rehabilitation were extracted and integrated, including 11 aspects such as multidisciplinary teams, exercise goals, exercise timing, exercise evaluation, exercise venue, exercise style, exercise intensity, exercise time and frequency, safety monitoring, exercise behavior maintenance, and health education.Conclusions:The best evidence summarized in this study can provide a reference for clinical medical staff to implement exercise rehabilitation, but in clinical practice, it is necessary to select and apply evidence in a targeted manner in combination with specific circumstances, so as to improve the safety and effect of exercise rehabilitation.

Objective:To investigate the clinical value of endometrial receptivity determination by transvaginal three-dimensional power ultrasound in the prediction of pregnancy outcome after in vitro fertilization and embryo transfer. Methods:A total of 220 infertile patients who underwent in vitro fertilization and embryo transfer in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from July 2018 to July 2021 were included in this study. Before in vitro fertilization and embryo transfer, all patients were tested for endometrial receptivity by transvaginal two-dimensional and three-dimensional power ultrasound. Pregnancy outcomes were followed up. Anatomical indexes (endometrial thickness, endometrial volume, and endometrial morphology) and endometrial blood flow indexes [endometrial blood flow type, pulsation index, resistance index (RI), ratio of peak systolic velocity to end-diastolic velocity (S/D), vascularization index (Vl), blood flow index (FI) and vascular blood flow index (VFI)] were compared between different pregnancy outcomes. Results:There were no significant differences in endometrial thickness, endometrial volume, and endometrial morphology between successful pregnancy and failed pregnancy groups ( t or χ2 = 0.23-0.54, P = 0.523-0.890). There was no significant difference in endometrial blood flow typing between successful pregnancy and failed pregnancy groups ( χ2 = 0.217, P = 0.897). PI, RI, and S/D in the successful pregnancy group were (2.46 ± 0.29), (1.07 ± 0.21), and (0.57 ± 0.10), respectively, which were significantly lower than (2.71 ± 0.34), (1.35 ± 0.24), and (0.66 ± 0.11) in the failed pregnancy group ( t = 4.51, 5.27, 3.43, all P < 0.001). VI, FI, and VFI values in the successful pregnancy group were (23.04 ± 2.95), (32.26 ± 3.17), and (6.59 ± 0.94) respectively, which were significantly higher than (16.85 ± 2.17), (28.42 ± 3.04), and (4.88 ± 0.86) in the failed pregnancy group ( t = 10.94, 6.25, 8.37; all P < 0.001). Conclusion:Endometrial blood flow parameters such as PI, RI, S/D, VI, FI, and VFI determined by transvaginal three-dimensional power ultrasound have a certain predictive value for pregnancy outcomes after in vitro fertilization and embryo transfer. They can be used as sensitive indexes for evaluating endometrial receptivity.

Objective:To develop the Caregiver Participation Behavior Questionnaire for Elderly Stroke Home Health Management and conduct psychometric evaluation.Methods:Based on the WHO policy framework of active aging, an initial questionnaire pool was constructed through review extensive literature. The initial questionnaire was revised through expert meeting, pilot survey and semantic debugging of the subject. Using multi-stage sampling, 336 caregivers of elderly stroke patients at home in Shanghai were selected from July 2021 to January 2022 to conduct a survey and test the reliability and validity of the questionnaire, and finally a formal questionnaire was formed. A total of 336 questionnaires were distributed. After removing 31 invalid questionnaires that were dropped out of the survey due to personal reasons of some subjects and missing answers, 305 valid questionnaires were recovered, with a valid recovery rate of 90.77% (305/336) .Results:The formal questionnaire included 6 dimensions and 33 items. Exploratory factor analysis extracted 6 common factors, including self-cognition adjustment, community resource utilization, lifestyle change, disease symptom treatment, psychological support, and adherence to rehabilitation exercise. The cumulative variance contribution rate was 81.06%. The item level content validity index was 0.827 to 1.000, and the scale level content validity index was 0.917. The total questionnaire Cronbach's α was 0.887, the split half reliability coefficient was 0.839, and the retest reliability coefficient was 0.812.Conclusions:The reliability and validity of the questionnaire are in line with the statistical test standard, which can be used as a reliable tool to evaluate caregivers' participation behavior in the elderly stroke home health management.

Objective:To investigate the effect of self-made phase-change nanodroplets IR780/FA-Nds-DTX as molecular targeted ultrasound contrast agents for accurate diagnosis and combined targeted therapy of pancreatic cancer.Methods:Pancreatic cancer cell lines were cultured in vitro and 50 tumor bearing nude mouse models were established. The experimental group (IR780/ FA-NdS-DTX) and four control groups[ normal saline, Nds(FITC), FA-Nds (FITC) and IR-780] were divided to verify dual-mode targeted imaging. The imaging using the IVIS Imaging System verified the high-efficiency targeted detection ability and near-infrared fluorescence imaging of IR780/FA-Nds-DTX for tumors in vivo, phase transformation induced by low-intensity focused ultrasound and further contrast-enhanced ultrasound imaging verified the high-efficiency aggregation of IR780/FA-Nds-DTX in local tumors and accurate evaluation of tumor contour. The therapeutic effect was observed in the experimental group (IR780/FA-Nds-DTX) and four control groups (FA-Nds-IR780, FA-Nds-DTX, FA-Nds and normal saline). After low-intensity focused ultrasound irradiation for 30s induced microbubble blasting after phase transformation in each group, 808nm photothermal therapy apparatus was used to irradiate tumor area in each group. Two-dimensional ultrasound was used to monitor the changes in tumor volume in each group before and at 3 d, 9 d, 15 d after treatment, and the changes in tumor volume rate and inhibition in each group were statistically analyzed and compared.Results:The amount of IR780/ FA-Nds-DTX locally targeted aggregation was the largest, and the average fluorescence intensity of tumor in the experimental group was significantly higher than that of the control groups: IR780/ FA-Nds-DTX group compared with Nds(FITC) group[(5.12±0.69)×10 7 vs (1.06±0.23)×10 7, P<0.05], IR780/FA-Nds-DTX group compared with FA-Nds (FITC) group [(5.12±0.69)×10 7 vs (2.98±0.34)×10 7, P<0.05], IR780/FA-Nds-DTX group compared with IR-780 group [(5.12±0.69)×10 7 vs (1.54±0.42)×10 7, P<0.05], and there was no fluorescence in tumor area in saline group. Further contrast-enhanced ultrasound imaging after nanodroplet phase transformation could more accurately locate the tumor boundary. After 15 days of photothermal ablation combined with chemotherapy, the growth rate of tumor volume in the IR780/ FA-Nds-DTX treatment group was significantly lower than that in the control groups: IR780/FA-Nds-DTX group compared with FA-Nds-IR780 group[(0.105±0.075) vs (0.405±0.175), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds-DTX group [(0.105±0.075) vs (1.385±0.035), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds group [(0.105±0.075) vs (2.255±0.105), P<0.05], IR780/ FA-Nds-DTX group compared with normal saline group [(0.105±0.075) vs (2.185±0.155), P<0.05]. And the tumor inhibition rate increased significantly: IR780/ FA-Nds-DTX group compared with FA-Nds-IR780 group [(0.93±0.06) vs (0.48±0.17), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds-DTX group [(0.93±0.06) vs (-0.51±0.105), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds group [(0.93±0.06) vs (-1.63±0.115), P<0.05], IR780/ FA-Nds-DTX group compared with normal saline[(0.93±0.06) vs (-1.35±0.245), P<0.05]. Conclusions:The self-made phase-change ultrasound contrast agents IR780/FA-Nds-DTX have good potential clinical value in targeted detection and combined therapy of pancreatic cancer with small lesions or even metastases.

Objective:To assess the performance of liver and spleen stiffness measured by MR elastography (MRE) and their combined model in diagnosing liver fibrosis.Methods:From November 2018 to November 2019, 104 patients with chronic liver disease were prospectively enrolled in Beijing Friendship Hospital, all patients underwent MRE scans. Liver and spleen stiffness were measured from MRE elastograms. Liver biopsy was used to identify fibrosis stage (F0—F4). The differences among different fibrosis stages were analyzed by one-way ANOVA or independent samples t test. The Spearman rank correlation analysis was used to evaluate the correlation with fibrosis stages. Liver and spleen stiffness combined model was established by logistic regression. The ROC curve was used to evaluate the performance of the liver, spleen stiffness and combined model in staging fibrosis (≥F1), significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4).The area under the ROC curve(AUC) was compared using Delong test. Results:The liver and spleen stiffness both showed significant differences among the 5 fibrosis stages ( F=64.058, 32.890, both P<0.001). The liver and spleen stiffness were positively associated with fibrosis stage ( r s=0.89, 0.69, both P<0.001). The AUC of liver stiffness in staging ≥F1, ≥F2, ≥F3 were 0. 91, 0.97, 0.93, respectively. The corresponding AUCs of the spleen stiffness were 0.81, 0.82, 0.85, respectively, which were statistically lower than those of liver stiffness ( Z=2.283, 4.085, 2.314, P=0.022,<0.001, 0.021). In diagnosing F4, the AUCs of liver and spleen stiffness were both 0.95. The AUCs of the liver and spleen combined model were 0.92, 0.97, 0.93, 0.96 in diagnosing ≥F1, ≥F2, ≥F3 and F4, with no significantly differences from liver stiffness (all P>0.05). Conclusions:The liver stiffness measured with MRE have better diagnostic performance than spleen stiffness in staging fibrosis. Parameters combined model slightly improves diagnostic value but without significant difference with liver stiffness in staging early fibrosis. Spleen stiffness evaluation is feasible in detecting cirrhosis.

Objective: To investigate the current basic situation of ultrasound machines of ultrasound departments in Shanghai medical institutions, and to provide the basis for making management policy in order to promote medical quality. Methods: Questionnaire surveys about ultrasound machines and service ability including producing countries of ultrasound machines, the number of ultrasound machines, using years of ultrasound machines, yearly workload and the yearly number of patients that each ultrasound machine accepted were made in 2013 and 2018, respectively. Statistical results were compared between the two surveys. Results: Compared with 2013, the share of imported ultrasound machines declined in 2018 (82% vs 91%). Compared with 2013, the number of ultrasound machines in Shanghai medical institutions had increased by 31% in 2018 (2 123 vs 1 617). The occupancy rate of ultrasound machines in tertiary hospitals was the highest (tertiary hospitals 40%, secondary hospitals 25%, primary grade hospitals 20%, and private hospitals 15%). Compared with 2013, the proportion of ultrasound machines that have been used for more than 10 years increased (9% vs 4%), the yearly workload of ultrasound examination had increased by 46% (19.82 million person-time vs 13.59 million person-time). Tertiary hospitals bored the highest proportion of the workload (tertiary hospitals 51%, secondary hospitals 35%, primary grade hospitals 4%, and private hospitals 10%). Currently, the number of ultrasound machines per 10, 000 people in Shanghai was 1.14. The yearly number of patients that each ultrasound machine accepted had increased by 11% (9300 person-time vs 8400 person-time in 2018). Conclusions The scale of ultrasound departments in Shanghai medical institutions has been developing. Brand localization of ultrasound machines is improving. However, the renewal ability of ultrasound machines still needs to be improved. The workload of ultrasound department is getting heavier. Hierarchical diagnosis and treatment is unbalanced.

Objective: To investigate and understand the causes of partial disorder in health care market of traditional Chinese medicine in recent years and put forward relevant countermeasures and suggestions. Methods: A multi-stage stratified random sampling method was used to investigate 410 medical staff and 535 patients in 10 traditional Chinese medicine medical institutions in Beijing. Self-filling questionnaires were used to obtain relevant data on their views on partial disorder of health care services in traditional Chinese medicine. Statistical software SPSS22.0 was used to analyze the data. Results: Firstly, both doctors and patients believed that "unclear functions of supervision department" was the main cause of some disorder in health care industry of TCM. Secondly, medical staff were more inclined than patients to think that the main causes were "lack of access threshold for institutions and personnel", "unclear functions of supervision department"and "lack of basis for law enforcement". Thirdly, 63.0％ of medical staff said that the legal system most needed to promote the healthy development of health care industry in traditional Chinese medicine was "industry standard system". Conclusion: According to the results of the survey, this paper holds that the healthy development of health care services in traditional Chinese medicine should be ensured by standardizing the supervision system of health care in traditional Chinese medicine, strengthening the construction of industry standards, establishing the self-regulatory mechanism of the industry, standardizing the media propaganda of health care in traditional Chinese medicine, and strengthening the ethical constraints of practitioners.

Different from Western medicine theory, Traditional Chinese Medicine knowledge is tacit knowledge, and the Traditional Chinese Medicine knowledge system also is a complete system independent from the Western medicine system. But the protection for Traditional Chinese Medicine knowledge nowadays still mainly stems from the Western intellectual property system. The current intellectual property system is in a dilemma in the protection of Traditional Chinese Medicine due to its limitations, and it urgently needs to build a special knowledge protection system that is specially applicable to traditional knowledge;while using genetic resources protection system and benefit sharing system of traditional knowledge from Convention on Biological Diversity to protect Traditional Chinese Medicine has its advanced nature and rationality. In the premise of clarifying the definition of "intellectual property right of Traditional Chinese Medicine", this paper proposed 5 countermeasures and suggestions, including establishing the legal content of Traditional Chinese Medicine intellectual property, promoting the legislative coordination of existing intellectual property law and the Law of the People' s Republic of China on TCM, strengthening the institutional coordination of the Law of the People' s Republic of China on TCM, the Law of Intangible Cultural Heritage and the Law of the People' s Republic of China on Drug Administration, promoting the institutional innovation at the local legislation level, and building a benefit sharing mechanism for the holders of Traditional Chinese Medicine knowledge.

Based on the questionnaire survey among 10 Traditional Chinese Medicine medical institutions in Beijing , this paper found that 65 . 2％ of the medical staffs and 82 . 0％ of the patients agreed to include the medical expertise into Traditional Chinese Medicine service system;37 . 3％ of the medical staffs believed that there was a certain risk of relaxing access of Traditional Chinese Medicine clinics, and 38. 4％ of the patients showed that they would choose private clinics to see a doctor. Most medical staffs considered that the current risks of Traditional Chinese Medicine diagnosis and treatment focused on standardized use of toxic decoction pieces and overdose of drugs. Medical staffs were most concerned about the risk of"diagnosis and treatment" on the Internet, were least worried about the risk of "distribution". The clinic registration system of the Law of the People ' s Republic of China on TCM, the registration system of the processed concocted decoction pieces, and the unclear scope of diagnosis and treatment technology posed challenges to future risk management, and it need to adopt the following countermeasures to respond:establishing a new multiple and multi-level risk management mechanism, exploring differentiated supervision, perfecting the technical norms and application scope of Traditional Chinese Medicine diagnosis and treatment, establishing a special system for regulating Traditional Chinese Medicine health care services, and establishing and improving a flexible supervision and law enforcement model to protect the legitimate rights and interests of relatives.