Purpose/Significance The relative positions of causality words are utilized to assist deep learning models to improve cau-sality prediction and mine medical text gain information.Method/Process The relative position information of causality words in medical texts is represented as a relational feature layer embedded in a pre-trained language model,and the baseline model is integrated for enti-ty recognition and relationship extraction.Result/Conclusion The F1 value of the model embedded in the relational feature layer is im-proved by 2.92 percentage points and 6.41 percentage points compared with the baseline models BERT-BiLSTM-CRF and CasRel,re-spectively,with better causal prediction capacity.

Objective:This study aimed to overview the typical practies made by Europe on rare diseases cooperative researches and provide reference for the construction of rare disease research system in China.Methods:Through literature reviews and official website information, this study systematically summarized the contributions and outputs made by the framework of Europe cooperation in rare disease field.Results:Focusing on the needs of patients, the aim of international cooperation was to improve the ability of ″diagnosis, treatment, research and education″. inclnding multi-sourced special funding and project topic screening, expert networks setup and patient impower, research network construction and mutual promotion, information system modernization, etc.Conclusions:The eco-system of rare disease research in China is still under-construction. It is recommended to combine the characteristics of China′s healthcare system, optimize input strategies, empower patients, innovate mechanism, and speed up bioinformation technology.

AIM: To evaluate the clinical effect of Iron Dextran Dispersible Tablets on patients with chronic heart failure who reduced ejection fraction after 24 weeks. METHODS: From January 2020 to June 2022, forty-five patients with heart failure complicated with iron deficiency and reduced ejection fraction were selected as the research objects. According to the random number table, they were randomly divided into control group and observation group.The control group was given routine anti-heart failure treatment such as Sacubitril Calsartan sodium tablets, while the observation group was given iron dextran dispersible tablets 50 mg three times a day on the basis of the anti-heart failure treatment of the control group for 8 weeks. The 6-minute walking distance, Hemoglobin, Serum Ferritin, N-terminal B-type natriuretic peptide precursor, Left Ventricular Ejection Fraction, Left Ventricular end Diastolic Diameter and 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) overall summary score and clinical summary score were compared between the two groups. RESULTS: There was no significant difference in baseline data between the two groups (P > 0.05). After treatment, the 6-minute walking distance in the observation group was longer than that in the control group, while the serum ferritin level in the observation group was higher than that in the control group. The N-terminal pro-B-type natriuretic peptide level in the two groups was lower than that before treatment, and the left ventricular end diastolic diameter was shorter than that before treatment, and the left ventricular ejection fraction, clinical comprehensive score and symptom score were higher than that before treatment. The difference was statistically significant (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). CONCLUSION: Iron Dextran Dispersible Tablets can improve the exercise endurance and quality of life of patients with chronic heart failure who reduced ejection fraction after 24 weeks.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Eubhorbia neriifolia L. is a plant of Euphorbia family.Five known lignans were isolated from the aerial parts of E. neriifolia L. by silica gel for column chromatography and preparative high-performance liquid chromatography (HPLC).Their potential antitumor activities were evaluated in vitro.Compound 2 exhibited proliferation inhibition and cytotoxicity against esophageal squamous cancer cells, especially KYSE-410 and KYSE-450 cells.Further analyses showed that compound 2 could significantly induce apoptosis through the activation of caspase 3/9 and down-regulation of the Bcl-2/Bax protein ratio.These results suggested that compound 2 had a significant inhibitory effect on the esophageal squamous cancer cells, especially KYSE-410, which deserves further research as a potential antitumor agent.

Objective:To get comprehensive understanding of the registration characteristics of global clinical trials of coronavirus disease 2019(COVID-19) based on the ClinicalTrials. gov and the Chinese Clinical Trial Registry (ChiCTR).Methods:The clinical trials of COVID-19 in the ClinicalTrials.gov and ChiCTR were retrieved. The search start time was unlimited, with deadlines of 14 December, 2020 and 19 March, 2021, respectively. The registration numbers, registration submitted time, country/region distribution, recruitment status, study types, number of recruits, research phases, and other aspects were analyzed by using bibliometric methods.Results:As of March 19, 2021, there were 775 clinical trials in ChiCTR. As of December 14, 2020, there were 4 137 clinical trials in the ClinicalTrials.gov, and 3 157(76.31%) of the clinical trials recruited subjects who were aged≥18 years old. There were 2 347 intervention trials and 1 759 observational trials. The intervention measures mainly included drugs, biologics and medical devices. The numbers of recruits were 110(48, 308) cases for interventional studies, and 300(100, 1 000) cases for observational trials. The interventional research phases were mainly phaseⅡ (570 items) and phase Ⅲ (358 items). Totally, 50.33%(2 082/4 137) of the clinical trials were under recruitment, 13.10%(542/4 137) had been completed. Among the interventional studies, 729(31.06%) were multi-center studies, with the center numbers of 5(2, 15).Conclusions:At present, there are a large number of clinical trials with various intervention measures in the world. However, the number of recruits is unreasonable, and multi-center study with multi-agency cooperation is insufficient.

Objective:To preliminary explore the changes in blood system in pyrrolizidine alkaloids (PAs)-related liver damage.Methods:General situation, liver function, biochemical blood test, routine blood test, coagulation function markers, etc., of 77 cases with drug-induced liver damage admitted to the Zhongshan Hospital Affiliated to Fudan University from 2012 to 2019 were retrospectively analyzed. Patients’ were divided into PA group, other traditional Chinese medicine group and Western medicine group according to their medication history. Simultaneously, the changes in liver function were observed in the established mice model of monocrotaline-induced liver damage. Liver tissues HE staining and blood routine indexes were observed.Results:24 cases received PA, 24 cases received other traditional Chinese medicine, and 29 cases received western medicine. Alanine aminotransferase was lower in PA group than the other two groups ( P < 0.05), and the total bilirubin and direct bilirubin were significantly lower than the other traditional Chinese medicine group ( P < 0.05). The peripheral platelet count of the PA group was (84.11 ± 26.91) ×10 9/L, which was significantly lower than the lower limit of normal, and had statistically significant difference with other traditional Chinese medicine and western medicine group ( P < 0.01). Thrombocytocrit, mean platelet volume and platelet indices of PA group were statistically different from the other two groups ( P < 0.05). The D-dimer level in patients with PA group was (2.62 ± 1.93) mg/L, which was higher than the upper limit of normal, and significantly higher than the D-dimer level of the other two groups of patients ( P < 0.01). Meanwhile, prothrombin time was longer in PA group than that of the other two groups ( P < 0.01), and platelets count were decreased significantly in the mouse model of monocrotaline-induced liver damage after alanine aminotransferase and aspartate aminotransferase elevation ( P < 0.01). Conclusion:PA-related liver damage has lower peripheral platelet counts, and the peripheral platelet counts of these patients are lower than other types of drug-induced liver damage. In addition, increased D-dimer in patients with PA-related liver damage indicate a potential risk of thrombosis.

Objective:To investigate the cost-effectiveness of Helicobacter pylori ( H. pylori) antimicrobial susceptibility testing-guided therapy versus an effective empiric modified bismuth quadruple therapy for first-line H. pylori treatment. Methods:This cost-effectiveness analysis was based on the data from a multicenter prospective randomized controlled clinical trial (NCT02935010), which included 382 patients with H. pylori infection. Among them, 286 cases were in the antimicrobial susceptibility testing group, which were diagnosed by biopsy under endoscopy. And according to the results of antimicrobial susceptibility testing of H. pylori, patients were treated with triple or quadruple therapy of eradicating H. pylori for 14 days. A total of 96 patients were in empirical therapy group, which were diagnosed by biopsy under endoscopy (96 cases, endoscopy empirical group), who were treated with 14-day empiric bismuth quadruple therapy. At the same time, based on the patients of empirical group, a simulated 13C-urea breath test (UBT) empirical group (UBT empirical group) was set up (96 cases, H. pylori infection was first diagnosed by 13C-UBT examination) and in the cost accounting the expenses related to endoscopy, biopsy and drug sensitivity test were removed and the expense of 13C-UBT was added. The information of patients of endoscopy empirical group was kept. Taking the eradication rate of H. pylori as an effectiveness indicator, the cost, cost-effective ratio (CER), incremental cost-effective ratio (ICER) among antimicrobial susceptibility testing group, endoscopy empirical group and UBT empirical group were compared by intention-to-treat (ITT) analysis and per-protocol (PP) analysis. Sensitivity analysis was conducted based on the results of ITT analysis to evaluate the reliability of the research results. Results:The results of ITT analysis indicated that the cost of antimicrobial susceptibility testing group, endoscopy empirical group and UBT empirical group were (1 747.41±149.30), 1 032.71 and 657.71 Yuan, respectively. The cost of antimicrobial susceptibility testing group was (714.70±149.30) and (1 089.70±149.30) Yuan higher than that of the endoscopy empirical therapy group and UBT empirical therapy group, respectively. The CER of antimicrobial susceptibility testing group, endoscopy empirical group and UBT empirical group were (19.08±1.49), 12.09 and 7.70 Yuan/%, respectively. ICER of antimicrobial susceptibility testing group was (115.27±1.49) and (175.76±1.49) Yuan /% in comparison with the endoscopy empirical group and the UBT empirical therapy group. Compared with that of empirical group, the ICER of antimicrobial susceptibility testing group was more likely to be affected by H. pylori eradication rate and the cost of antimicrobial susceptibility testing. When the H. pylori eradication rate decreased in the empirical group, the ICER of the antimicrobial susceptibility testing group also decreased; when the H. pylori eradication rate increased in antimicrobial susceptibility testing group, the ICER decreased, and vice versa. When the cost of antimicrobial susceptibility test was upregulated or downregulated by 20%, for every 1% increase in the eradication rate of H. pylori in comparison with that of the endoscopy empirical group, the cost of the antimicrobial susceptibility testing group increased by 99.15 and 131.40 Yuan; in comparison with that of the UBT empirical group, the cost of the antimicrobial susceptibility testing group increased by 159.63 and 191.89 Yuan. Conclusions:For patients diagnosed with H. pylori infection by 13C-UBT and without indications for endoscopy examination, the empirical quadruple therapy is the first choice. For patients intended to do endoscopy to confirm H. pylori infection, with additional affordability of 115.27 Yuan for every 1% increase in the eradication rate of H. pylori, antimicrobial susceptibility testing can be conducted and personalized. H. pylori eradication therapy can be carried out based on the results of antimicrobial susceptibility test. Reduced cost of the antimicrobial susceptibility test will be more conductive to the promotion of personalized treatment after antimicrobial susceptibility test.

Objective To analyze the management experience of Swedish medical research funding,and provide reference for further rationalization of medical research investment management in China.Methods Literature research method,descriptive statistics and other methods were used to systematically sort out the source of Swedish medical research funding,and specifically analyze the capital investment and distribution in medical fields in the past ten years.Results The Swedish government 's budget in the UO9 (health,medical and social care) field is steadily increasing.The annual average budget accounts for 7.14％ of the total government budget.There are scientific management methods for fund allocation.The appropriation projects are mainly divided into three main directions including public health categories,health care and social care.Conclusions Taking into account of the problems existing in the investment and distribution of medical research funds in China,this paper proposes to explore the capital investment mode suitable for China's national conditions,enhance the targeted investment of funds in medicine,and establish a scientific and efficient fund investment management mechanism.

Objective The paper aims to analyze the effectiveness and problems of health personnel construction in China since 2012,provide reference for promoting the construction of health professionals.Methods Using national data from China health statistics yearbook,adopted the methods of descriptive statistics and literature research and so forth.Results The construction of health personnel has been continuously strengthened in China,the structure and distribution of health personnel have been further optimized,the medical service capabilities have been improved.However,there are still inappropriate or imbalanced situations.Conclusions The construction of key personnel such as primary health personnel and urgently needed personnel need to be further strengthened;promote the construction of health service personnel to meet new health needs;continue to improve the construction of high-level and management personnel to play a leading role.