The exploration and pilot studies of applying blockchain to drug supply chain show great potential in promoting information sharing, collaboration competence among the actors, regulatory efficiency, and etc. In the future, with the help of blockchain, the optimization of the entire supply chain for orphan drugs is expected to be realized. However, there is no such exploration in China at present. This paper systematically sorts out the whole process of supply chain for orphan drugs and the existing problems of the chain. The article concludes that at present, blockchain is mainly used in the " circulation" and " use" of the drug supply chain. It helps to improve the traceability of drugs, to cope with the problem of counterfeit drugs, to enable actors of the drug supply chain to form a collaborative network in optimizing resource allocation, and to improve the operation and supervision efficiency of the supply chain. In the future, the application faces challenges such as high costs in system conversion, lack of personnel awareness, and incomplete supporting systems. Based on the three dimensions of technology, practice, and research, this paper also looks into the future and suggests for the future use of blockchain in the supply chain of orphan drugs by constructing a practice model, the so called DI-GIVE (Digital, Intelligence, Government′s supervision, Innovation, Views of variety, Evaluation-based) hoping to innovate the supply chain of orphan drugs and to ensure the drug use for the patients with rare diseases in China.

Radiation-induced injury, a body dysfunction caused by irradiation, is associated with the dose, duration, and speed of radiation and is predominantly derived from radiation therapy for patients with malignant tumors. The current clinical treatment mainly includes amelioration of injury, alleviation of symptoms, and improvements in function restoration of the affected sites because of lack of targeted agents specific to radiation-induced injuries. Research and development of preventive and therapeutic agents against radiation-induced injuries are of great significance to reduce the body damages caused by radiotherapy and improve the quality of life of cancer survivors. This review summarizes the radiation-induced injury and its mechanisms, radioprotectants, and therapeutic agents for radiation, and proposes future development directions, so as to provide a reference for alleviation of radiation-induced injury and improvement in prognosis.

Objective To investigate the effects of different concentrations of morphine in combination with ropivacaine on proliferation,migration,invasion and cell cycle in MDA-MB-231 breast cancer cells.Methods MDA-MB-231 breast cancer cells were inoculated on the culture plate for 24h and randomly divided into 8 groups:Control group(C),ropivacaine 400μg/ml group(R),morphine 3μg/ml group(LM),morphine 30μg/ml group(MM),morphine 300μg/ml group(HM),ropivacaine 400μg/ml group+ morphine 3μg/ml group(R+LM),ropivacaine 400μg/ml+ morphine 30μg/ml group(R+MM),and ropivacaine 400μg/ml+ morphine 300μg/ml group(R+HM).After treaments of MDA-MB-231 breast cancer cells for 24h,these proliferation,migration,invasion and cell cycle were evaluated.Results When using morphine alone,the proliferation inhibitive effect was positively correlated with the concentration of morphine.The proliferation was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the proliferation was significantly inhibited(P<0.05).When using morphine combined with ropivacaine,the high concentration morphine group has a synergistic effect with ropivacaine group on proliferation inhibition(P<0.05).When using morphine alone,the migration rate decreases sequentially with the increase of morphine concentration.The migration rate was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the migration rate was inhibited(P<0.05).When using morphine combined with ropivacaine,the low and medium concentration morphine group have a synergistic effect with ropivacaine group on migration rate(P<0.05).When using morphine alone,the number of cell invasion was decreased with the concentration of morphine increasing(P<0.05).The MM and HM groups inhibited cell invasion ability.When using ropivacaine alone,the invasiveness of cells was also inhibited(P<0.05).When using morphine combined with ropivacaine,the medium and high concentration morphine groups have a synergistic effect with ropivacaine group on inhibiting cell invasion ability(P<0.05).When using morphine alone,the cell cycle progression was inhibited into G2/M Phase(P<0.05).When using ropivacaine alone,the cell cycle progression was inhibited into G2/M phase(P<0.05).The combination of low concentration morphine and ropivacaine has synergistic effect on arresting at G0/G1 and S phase(P<0.05).Conclusion Morphine combined with ropivacaine inhibits the Proliferation,migration and invasion of MDA-MB-231 breast cancer cells in a dose-dependent manner.

Objective: To construct an evaluation index system of oral health literacy for children's parents, so as to provide an index system for the evaluation of oral health literacy for children's parents in China. Methods: The evaluation index system of oral health literacy for children's parents was designed based on literature review and semi-structured interview. Experts from oral prevention and pediatric oral medicine were invited to participate in two-round Delphi consultations. The indicators were scored and screened according to the importance, and the weight determined using analytic hierarchy process. The effectiveness of the consultation was evaluated by positive coefficient, authority coefficient and coordination coefficient. Results: Twenty-four experts participated in the consultation, including 6 males and 18 females. There were 21 experts with a master degree, 3 experts with a doctor degree, and 20 experts with vice senior professional titles and above. The recovery rates of the two rounds of consultations were 96.00% and 100.00%, the authority coefficients were 0.866 and 0.917, the Kendall's coefficient of concordance were 0.120 and 0.156 (both P<0.05), and the coefficient of variation was 0.15-0.38 and 0.03-0.17, respectively. The final evaluation index system included 3 primary indicators, 11 secondary indicators and 40 tertiary indicators. The primary indicators were basic knowledge and concepts related to oral health, promoting lifestyle and behaviors related to oral health, and maintaining basic skills related to oral health. Conclusion The evaluation index system of oral health literacy for children's parents has been established in this study and needs to be further applied and evaluated.

Progesterone is currently the first-line drug for clinical treatment and prevention of threatened abortion and habitual abortion. However， due to its special chemical structure， its solubility is low， which limits its clinical application. Therefore， the new technology and new dosage form of progesterone solubilization preparation is an important direction of its research and development. In this paper， the research progress of progesterone solubilization preparation technology in recent years is reviewed. It is found that the water solubility of progesterone can be enhanced by solid dispersion technology， inclusion technology， micronization， nanocrystallization （ including nanosuspensions， polymer micelles， nanoparticles， etc. ）， liposome technology， self- emulsification， cocrystal technology， and 3D printing. Eight technologies are used to increase the solubility of progesterone， improve its bioavailability and reduce its toxic and side effects， to serve the clinic better.

ObjectiveTo investigate the possible mechanism of Buzhong Yulin Decoction （补中愈淋汤） in the prevention and treatment of recurrent urinary tract infection. MethodsThe mouse models of recurrent urinary tract infection were established by uropathogenic Escherichia coli （UPEC） strain UTI89 by bladder perfusion， and the successful mouse models were randomly divided into a model group， an antibiotic group， and a low- and high-dose Buzhong Yulin Decoction group， with six mice in each group. In addition， 5 C57BL/6 mice without modelling were taken as blank group. The low- and high-dose Buzhong Yulin Decoction groups received 0.1 ml/10 g of decoction by gavage， with concentrations of 1.3 g/ml and 5.2 g/ml， respectively； the antibiotic group received 0.1 ml/10 g of levofloxacin hydrochloride solution with 5 mg/ml by gavage； the blank and model groups received 0.1 ml/10 g of distilled water by gavage. Each group was gavaged once a day for 7 consecutive days. The total number of urine marks， the number of central urine marks， and the total urine volume of the urine marks were observed by the urine marking test； HE staining was used to observe the histopathological changes in the bladder of mice； serum levels of the inflammatory factors interleukin 1β （IL-1β）， interleukin 6 （IL-6） and tumour necrosis factor α （TNF-α） were detected by ELISA； the morphology of the epithelial cells of bladder was observed by scanning electron microscopy； immunofluorescence assay to detect bladder tissue anti-UroPlakin 3A protein level and UPEC bacterial load； the spread plate method to detect urinary bacterial load and bacterial load of bladder epithelial cells； RT-PCR method to detect Ras-related protein Rab-11A （RAB11A） and Ras-related protein Rab-27B （RAB27B） mRNA level in bladder tissue； immunoblotting to detect microtubule-associated protein 1 light chain3 （LC3） and P62 protein levels in bladder tissue. ResultsCompared with the blank group， the bladder epithelial cell layers were lost and showed abnormal morphology in mice of the model group； bladder tissue UroPlakin 3A protein and RAB11A and RAB27B mRNA levels reduced， the total number of urine marks， the number of central urine marks， bladder tissue UPEC bacterial load， urinary bacterial load， bacterial load in bladder epithelial cells， serum IL-1β， IL-6， and TNF-α levels， and LC3 and P62 protein levels in bladder tissue all elevated （P＜0.05 or P＜0.01）. Compared with the model group， the bladder epithelial cell layers were intact and the morphology of epithelial cells were regular in the low- and high-dose Buzhong Yulin Decoction groups； the average surface area of bladder epithelial cells reduced， the levels of UroPlakin 3A protein and RAB11A and RAB27B mRNA in bladder tissues elevated， and total number of urine marks， the number of central urine marks， bladder tissue UPEC bacterial load， urinary bacterial load， bacterial load in bladder epithelial cells， serum IL-1β， IL-6， and TNF-α levels， and P62 protein levels in bladder tissue all reduced （P＜0.05 or P＜0.01）， but LC3 protein levels showed no statistically significant （P＞0.05）. In the antibiotic group， the bladder epithelial cells were partially missing and the morphology of epithelial cells was abnormal. Compared with the antibiotic group， the average surface area of the bladder epithelial cells in the mice increased in the low- and high-dose Buzhong Yulin Decoction groups， the bacterial load of the bladder epithelial cells decreased， and the P62 protein level of the bladder tissue decreased （P＜0.05）. When comparing between the low- and high-dose Buzhong Yulin Decoction groups， the differences in each index were not statistically significant （P＞0.05）. ConclusionBuzhong Yulin Decoction may prevent and treat recurrent urinary tract infection by repairing the bladder mucosal barrier， increasing RAB11A and RAB27B level and enhancing autophagy in bladder tissues， thereby facilitating bacterial clearance from bladder epithelial cells and reducing the bacterial load of bladder epithelial cells.

Objective:To study the protective effects and mechanism of Melastoma sanguineum Sims fruit extract (MSE) on chronic chemical liver injury induced by ethanol, acetaminophen and carbon tetrachloride in mice; To discuss it mechanism.Methods:Totally 96 mice were divided into normal control group, ethanol model group, ethanol+bifendate control group and ethanol+MSE high-, medium- and low-dosage groups, APAP model group, APAP+bifendate control group and APAP+MSE high-, medium- and low-dosage groups, CCl 4 model group, CCl 4+bifendate control group and CCl 4+MSE high-, medium- and low-dosage groups, with 6 mice in each group. Except for the normal control group, the other groups were respectively prepared for the ethanol model, the APAP model and the CCl 4 model. The mice in the MSE high-, medium- and low-dosage groups were intragastrically administrated with 10, 5 and 2.5 g/kg of MSE, respectively; the bifendate control group was intraperitoneally injected with 15 mg/ml bifendate solution at 75 mg/kg; the normal control group was intraperitoneally injected with equal volume of normal saline/peanut oil solution once a day for 25 consecutive days. The levels of GPT, GOT and total bilirubin (TBIL) in serum were detected; the activities of SOD and GSH-Px and the content of MDA in liver tissue were detected; the mRNA expressions of TNF-α, IL-6, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were detected by qRT-PCR; the protein expressions of cytochrome P450 CYP1A1, CYP1A2, and CYP3A in liver tissue were detected by Western blot; the pathological changes of the liver tissue were observed by HE staining. Results:Compared with the corresponding ethanol, APAP and CCl 4 model groups, the serum GPT, GOT and TBIL levels of mice in the ethanol+bifendate control group and ethanol+MSE high- and medium-dosage groups, the APAP+bifendate control group and APAP+MSE high- and medium-dosage groups, and the CCl 4+bifendate control group and CCl 4+MSE high- and medium-dosage groups decreased ( P<0.01 or P<0.05), the activities of SOD and GSH-Px in the liver tissue increased ( P<0.01 or P<0.05), and the MDA level decreased ( P<0.01 or P<0.05), and the mRNA levels of IL-6 and TNF-α decreased ( P<0.01); the mRNA levels of ADH and ALDH in the ethanol+MSE high-, medium-, and low-dosage groups decreased ( P<0.01). Compared with the APAP model group, the expressions of CYP1A1 and CYP1A2 in the APAP+MSE groups increased ( P<0.01), and the expression of CYP3A protein decreased ( P<0.05); compared with the CCl 4 model group, the expressions of CYP1A1, CYP1A2 and CYP3A proteins in the CCl 4+MSE groups decreased ( P<0.05). Conclusion:MSE has a protective effect on chronic chemically-induced liver injury induced by ethanol, APAP, and CCl 4 in mice, and its mechanism may be related to antioxidant stress, inhibition of inflammatory response, and regulation of the expression of cytochrome P450-related enzymes.

Objective To investigate the relationship between the expression level of miRNA Let-7 and the deletion of DNA mismatch repair(dMMR)proteins in endometrial carcinoma(EC).Methods A total of 74 patients with EC who underwent radical surgery at Lianyungang Maternal and Child Health Hospital in Jiangsu Province from May 2016 to December 2022 were selected.Immunohistochemistry was used to detect the expression of dMMR proteins(including MLH1,PMS2,MSH2,and MSH6),while real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was performed to measure the relative expression levelof miRNA Let-7.According to the expression of dMMR proteins,EC patients were divided into the complete expression group(n=43)and the absent expression group(n=31).Logistic multivariate regression analysis was conducted to identify risk factors associated with dMMR protein deficiency,and receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of relevant factors.Results In 74 cases of EC,the expression level of miRNA Let-7 was higher in the myographic infiltration＜1/2 group than in the myographic infiltration ≥ 1/2 group,and the difference was significant(t=1.79,P=0.04).The deletion rate of dMMR protein expression was 41.89％,the deletion rate in patients aged＜55 years and miRNA Let-7 low expression group(＜0.715)were higher than those in ≥ 55 years and miRNA Let-7 high expression group(≥ 0.715),with significant differences(x2=3.92,4.50,all P＜0.05).Logistic regression analysis revealed that miRNA Let-7 expression level was an independent risk factor for dMMR expression deletion(P=0.012).Spearman correlation analysis demonstrated a negative correlation between miRNA Let-7 expression level and dMMR protein deletion(r=-0.247,P=0.034).ROC curve analysis indicated that the expression level of miRNA Let-7 had a certain predictive value for dMMR protein deletion in EC patients,with an AUC of 0.737,an optimal critical value of 0.77,a sensitivity and a specificity of 0.651 and 0.806,respectively.Conclusion The expression level of miRNA Let-7 was correlated with the deletion of dMMR proteins in patients diagnosed with EC.Moreover,it served as a potential risk factor for dMMR protein deficiency.It may offer valuable insights into predicting dMMR expression deletion.

Objective:To investigate the feasibility and clinical diagnostic value of rapid arterial spin labeling (ASL) imaging in brain glioma.Methods:Patients with glioma admitted to Beijing Tiantan Hospital, Capital Medical University from May 2021 to December 2022 were prospectively enrolled. All patients received MR rapid ASL (scan time: 1 min) and conventional ASL (scan time: 4 min 30 s), where the cerebral blood flow (CBF) perfusion maps were obtained. The qualitative analysis of CBF signal intensity and quantitative analysis of average CBF values from both tumor solid and edema regions were conducted by two radiologists independently. Kappa test and intraclass correlation coefficient ( ICC) were used to analyze the consistency of qualitative and quantitative results, respectively. Results:A total of 30 patients with brain glioma were included. The 2 physicians used rapid ASL to determine low perfusion, isoperfusion, and hyperperfusion in the tumor area in 1, 6, 23 cases and 0, 5, and 25 cases, respectively; and used conventional ASL to determine low perfusion, isoperfusion, and hyperperfusion in the tumor area in 0, 9, and 21 cases, respectively. The results of qualitative analysis of rapid ASL and conventional ASL were highly consistent within and between groups ( Kappa was 0.830 and 0.850 respectively). The results of quantitative analysis of rapid ASL and conventional ASL were highly consistent within and between groups ( ICC 0.940—0.994). Conclusion:Rapid ASL with shorter scanning time could be applied in assessing tissue perfusion in brain glioma and contribute to the clinical diagnosis of gliomas.

Objective:To design an assisted lip retraction breathing exercise tool and observe its application in home-based pulmonary rehabilitation of patients with chronic obstructive pulmonary disease(COPD). Method:A total of 116 COPD patients treated at our hospital from January 2020 to January 2021 were select-ed as study subjects and divided into the control group(n=58)and the observation group(n=58)using a ran-dom number table method.The control group was given conventional inhalation medication and lip retraction breathing training instruction,and the observation group was given an assisted lip retraction breathing exercise tool to assist lip retraction training on the basis of the control group.The pulmonary function,arterial blood gas,6-minute walk distance(6MWD),modified British medical research council(mMRC),body mass in-dex,obstruction,dyspnea,exercise capacity index(BODE index)and patient satisfaction were compared be-tween the two groups at l month,3 months,and 6 months after discharge from the hospital. Result:After 3 and 6 months of exercise,the pulmonary function(FVC,FEV1)of the observation group were better than those of the control group(t=2.196,2.613,3.022,4.200 P＜0.05),and arterial blood gas(PaCO2,PaO2)were better than the control group(t=5.223、11.536、2.086、2.223 P＜0.05),6MWD was higher than the control group(t=10.725,11.620 P＜0.05),mMRC was lower than the control group(t=10.110,22.567 P＜0.05),BODE index grade 1(17.24％,34.48％)and grade 2 rates(37.93％,48.28％)were higher than the control group(10.34％,6.90％,25.86％,27.59％),and grade 3(25.86％,17.24％)and grade 4 rates(18.97％,0)were lower than the control group(31.03％,34.48％,32.76％,31.03％)(Z=-2.060,35.273 P＜0.05),the satisfaction rate of patients in the observation group was 91.38％(53/58)at 1 month of exercise,96.55％(56/58)at 3 months,and 100％(58/58)at 6 months. Conclusion:The assisted lip retraction breathing exercise tool can improve the home-based pulmonary rehabilita-tion,enhance exercise endurance,reduce the severity of dyspnea,and improve patient satisfaction.