The ethical review of clinical research on rare diseases is crucial in ensuring the scientific validity of the research and the rights and interests of the subjects. Starting from the definition of rare diseases， this paper analyzed the current situation of domestic and international regulations and ethical review in clinical research on rare diseases. It also explored the key elements of ethical review from the two dimensions of scientific and ethical aspects of clinical research， including research objectives， methods， risk and benefit assessment， researcher qualifications， research infrastructure， informed consent process， data security and privacy protection， and protection of vulnerable groups such as children. Regarding the ethical review of clinical research on rare diseases， strategies can be adopted such as strengthening the training of ethics review personnel， conducting multi-center collaborative reviews， and focusing on the long-term safety of trials， to improve the quality of ethical review， protect the safety of the subjects， and ensure the efficiency and quality of clinical research.

Objective The aim of this study was to investigate the prospective association between physical activity (PA),independently or in conjunction with other contributing factors,and osteoporosis (OP) outcomes. Methods The Physical Activity in Osteoporosis Outcomes (PAOPO) study was a community-based cohort investigation. A structured questionnaire was used to gather the participants' sociodemographic characteristics. Bone mineral density (BMD) measurements were performed to assess OP outcomes,and the relationship between BMD and OP was evaluated within this cohort. Results From 2013 to 2014,8,471 participants aged 18 years and older were recruited from Tangshan,China's Jidong community. Based on their PA level,participants were categorized as inactive,moderately active,or very active. Men showed higher physical exercise levels than women across the activity groups. BMD was significantly higher in the very active group than in the moderately active and inactive groups. Individuals aged>50 years are at a higher risk of developing OP and osteopenia. Conclusion The PAOPO study offers promising insights into the relationship between PA and OP outcomes,encouraging the implementation of PA in preventing and managing OP.

Objective To summarize the experience of integrative palliative care at Peking Union Medi-cal College Hospital and provide a reference for promoting the integrative palliative care model.Methods Twenty cases receiving integrative palliative care at Peking Union Medical College Hospital were collected.The clinical characteristics,reasons for initiating integrative palliative care,the process of integrative palliative care,and feedback from these cases were summarized.Results Insomnia(11 cases,55％)and pain(9 cases,45％)were the most common symptoms requiring control in the 20 cases.The integrative palliative care team assisted in medical decision-making for 17 cases(85％),prepared end-of-life for 9 cases(45％),assisted in the transfer for 3 cases(15％),and provided comfort care for all the 20 cases(100％).Conclusions The integrative palliative care model can help alleviate suffering in end-of-life patients and provide support to patients'families and the original medical teams.This model is worth further promotion within class A tertiary hospitals.

ObjectiveThis article aims to investigate the clinical features of portal biliopathy （PB） patients， in order to improve the understanding of PB. MethodsClinical data were collected from 22 patients who were diagnosed with PB in recent years in The First Hospital of Jilin University， and an analysis was performed for their clinical manifestations， liver function， abdominal color Doppler ultrasound， abdominal CT， and hepatobiliary magnetic resonance imaging. The imaging manifestations of biliary tract abnormalities were described， as well as the type of collateral circulation and the location of thrombosis. ResultsAs for the initial symptom in these 22 patients， three were 11 patients with gastrointestinal bleeding， 5 with abdominal distension， 3 with abdominal pain， 1 with fever， 1 with abdominal discomfort， and 1 with gingival bleeding. There were 3 patients with an increase in aspartate aminotransferase， 4 with an increase in alanine aminotransferase， 4 with an increase in gamma-glutamyl transpeptidase， 7 with an increase in alkaline phosphatase， 8 with a reduction in cholinesterase， 9 with a reduction in albumin， 2 with an increase in globulin， and 5 with an increase in total bilirubin. Among the 22 patients， 20 had cavernous transformation of the portal vein， and 2 had portal vein thrombosis without cavernous transformation. All 22 patients had bile duct abnormalities， among whom 2 had extrahepatic bile duct abnormalities alone， 12 had intrahepatic bile duct dilatation alone， and 8 had dilatation of both intrahepatic and extrahepatic bile ducts. Varices at different sites were observed in 20 patients， among whom 19 had esophageal and gastric varices and 1 had peri-gallbladder varices， and no varices was observed in the superior mesenteric vein or the splenic vein. ConclusionThere are no typical clinical symptoms and changes in liver function parameters in patients with PB， but radiological examination may show dilatation， stenosis， or malformation of the bile ducts at different parts. Therefore， it is necessary to expand the sample size to further explore the diagnosis and treatment of PB.

Objective:To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus.Methods:This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13 3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared.Results:A total of 1 152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences [10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001], but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant ( Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group [1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032]. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group [(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001]. Conclusion:The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.

Objective:To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus.Methods:This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13 3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared.Results:A total of 1 152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences [10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001], but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant ( Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group [1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032]. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group [(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001]. Conclusion:The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.

Clinical research of artificial intelligence (AI) medical devices is one of the most important links in the process of AI medical devices product development. This paper discusses the key elements of the ethical review of clinical research of artificial intelligence medical devices and the four aspects including strengthening the legislative construction and supervision, strengthening the capacity building of the ethics committee, improving the ethical review system and system construction, expanding platform construction and strengthening regional linkage that can improve the quality of ethical review in the future, protect the safety of subjects, and ensure the efficiency and quality of clinical research.

Objective:To evaluate the effect of propofol on right ventricular hypertrophy induced by pulmonary arterial hypertension (PAH) in rats.Methods:Twenty-two clean-grade healthy adult male Wistar rats, weighing 250-280 g, were divided into 3 groups using a random number table method: control group (group C, n=8), PAH group (group PH, n=6) and propofol group (group P, n=8). In PH and P groups, monocrotaline 60 mg/kg was injected intraperitoneally to establish the model of PAH, while the equal volume of normal saline was administered in group C. Propofol 100 mg/kg was injected intraperitoneally twice a week for 6 consecutive weeks starting from 2 weeks after establishment of the model in group P. The weight of rats was measured before establishment of model and after administration, and the weight difference (△BW=weight after administration-weight before administration) was calculated.At the end of administration, the right ventricular end-diastolic dimension (RVEDD), right ventricular wall thickness in diastole (RVWTd), intraventricular septum in diastole (IVSd), left ventricular posterior wall in diastole (LVPWd) and maximal velocity of pulmonic valve (PV) were measured using cardiac ultrasound.The animals were then sacrificed, and the lungs and hearts were removed for examination of the pathological changes (after haematoxylin and eosin staining) and for determination of the degree of myocardial fibrosis in right ventricular (by Masson staining), expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in lung tissues and myocardial tissues of the right ventricle (by immunohistochemistry). Results:Compared with group C, △BW and PV were significantly decreased, RVWTd, IVTd and RVEDD were increased, the thickness of the wall of pulmonary arterioles and myocardial cell penetration area in right ventricular were increased, the expression of IL-6 and TNF-α in lung tissues and myocardial tissues of right ventricle was up-regulated ( P<0.05 or 0.01), inflammatory cell infiltration and structural disorders were found in lung tissues, and intercellular spaces were widened, and the myocardial tissue was extensively fibrotic in group PH.Compared with group PH, △BW and PV were significantly increased, RVWTd, IVTd and RVEDD were decreased, the thickness of the wall of pulmonary arterioles and myocardial cell penetration area (the area of cardiomyocytes in which the nucleus located in the middle) were decreased, the expression of IL-6 and TNF-α in lung tissues and myocardial tissues of right ventricle was down-regulated ( P<0.05 or 0.01), inflammatory cell infiltration, structural disorders, intercellular spaces and degree of fibrosis were improved in group P. Conclusion:Propofol can alleviate right ventricular hypertrophy induced by PAH, and the mechanism is probably related to reduction of inflammatory responses in rats.

Dbait is a small double-stranded DNA molecule that has been utilized as a radiosensitizer to enhance the sensitivity of glioma to radiotherapy (RT). However, there is no effective drug delivery system to effectively overcome the blood-brain barrier (BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles (ch-K(s-s)R8-An) to deliver Dbait into glioma for RT. Angiopep-2 can target the low-density lipoprotein receptor-related protein-1 (LRP1) that is overexpressed on brain capillary endothelial cells (BCECs) and glioma cells. In particular, due to upregulated matrix metalloproteinase 2 (MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2. The results showed that ch-K(s-s)R8-An micelles maintained a reasonable size (80-160 nm) with a moderate distribution and a decreased mean diameter from the cross-linking as well as exhibited low critical micelle concentration (CMC) with positive surface charge, ranging from 15 to 40 mV. The ch-K5(s-s)R8-An/pEGFP showed high gene transfection efficiency , improved uptake in glioma cells and good biocompatibility and . In addition, the combination of ch-K5(s-s)R8-An/Dbait with RT significantly inhibited the growth of U251 cells . Thus, ch-K5(s-s)R8-An/Dbait may prove to be a promising gene delivery system to target glioma and enhance the efficacy of RT on U251 cells.