ObjectiveTo investigate the association of comprehensive control of multiple metabolic risk factors with the risk of all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease （MASLD） and its quantitative effect. MethodsA retrospective cohort study was conducted based on the data from National Health and Nutrition Examination Survey （NHANES） in 2003—2018. A total of 29 458 participants were enrolled， including 12 528 patients with MASLD and 16 930 non-MASLD controls. The control status of nine risk factors was assessed， i.e.， hypertension， diabetes， liver fibrosis （assessed by fibrosis-4 index ［FIB-4］）， aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio， serum albumin， renal function （assessed by serum creatinine）， systemic inflammation （assessed by neutrophil count）， smoking， and physical activity. According to the status of comprehensive risk factor control， the patients with MASLD were further divided into low-control group with 1 107 patients， moderate-control group with 7 042 patients， and high-control group with 4 379 patients. A total of 397 participants were enrolled in the external validation cohort， among whom there were 266 participants with MASLD and 131 participants without MASLD. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test was used for comparison of categorical data between groups. The Cox proportional hazards model incorporating complex sampling weights for NHANES data were used to investigate the association between the degree of risk factor control and all-cause mortality， and the Kaplan-Meier curve， the log-rank test， restricted mean survival time （RMST）， and population attributable fraction （PAF） were used for further assessment. The robustness of the findings was validated in an independent clinical cohort （n=397）. ResultsThe cohort study based on the NHANES database showed that during the median follow-up time of 6.7 years， 1 171 deaths occurred among the 12 528 patients with MASLD. There was a significant reduction in mortality risk with the increase in the number of risk factors controlled （trend test： χ²=65.06， P<0.001）. Compared with the low-control group， the mortality risk decreased successively in the moderate-control group （hazard ratio ［HR］=0.59， 95% confidence interval ［CI］： 0.51 — 0.69） and the high-control group （HR=0.36， 95%CI： 0.27 — 0.48）， and the mortality risk was reduced by 22% for each additional risk factor controlled （HR=0.78， 95%CI： 0.74 — 0.82）. The PAF analysis showed that AST/ALT ratio control （PAF=19.2%） and physical activity （PAF=18.9%） were the largest contributors. The survival analysis of the sub-cohort constructed based on nearest neighbor matching （with a maximum follow-up time of 13.3 years） showed that there was a significant difference in cumulative survival rate between the MASLD groups with different control levels and the non-MASLD group （P<0.001）. The RMST analysis further quantified the survival benefit of each group， and the high-control group had the longest 10-year RMST （9.88 years）， which was superior to that of the non-MASLD group （9.43 years）， the moderate-control group （9.33 years）， and the low-control group （7.96 years）. The multivariable-adjusted model analysis of the complete cohort showed that compared with the non-MASLD population， the MASLD patients in the low-control group had a significant increase in mortality risk， the moderate-control group had a comparable mortality risk， and the high-control group had a significantly lower mortality risk. The subgroup analysis showed a significant protective effect of comprehensive control in both male and female individuals （P<0.05）， and the interaction analysis suggested a potentially stronger protective effect in female individuals （P_{for interaction}=0.031）. The protective effect was statistically significant in patients aged ≥60 years （P<0.05）. There was a significant difference in protective effect across the groups stratified based on waist circumference （P<0.05）， but there was no significant interaction between groups （P_{for interaction}=0.821）. In the external validation cohort， among the 397 participants， there were 72 cases of all-cause mortality （18.1%）. The survival analysis showed a significant gradient increase in the survival rate of MASLD patients with the increase in the level of control （P=0.022）. The RMST analysis showed that the moderate- and high-control groups had a better RMST than the non-MASLD group at 5 years （4.47 years vs 4.56 years vs 4.40 years）， with a more significant survival advantage at 10 years （8.67 years vs 8.95 years vs 8.44 years）. The Cox regression analysis showed that， with the low-control MASLD group as the reference， there was a significant reduction in mortality risk in the moderate-control group （HR=0.41， 95%CI： 0.21 — 0.81） and the high-control group （HR=0.32， 95%CI： 0.14 — 0.71）； with the non-MASLD population as the reference， there was a significant increase in mortality risk in the low-control group （HR=2.02， 95%CI： 1.03 — 3.95）， with a comparable mortality risk in the moderate-control group （HR=0.83， 95%CI： 0.48 — 1.44） and the high-control group （HR=0.66， 95%CI： 0.30 — 1.38）， and the point estimates of the effects were highly consistent with the main study. ConclusionAmong MASLD patients， better control of metabolic risk factors is associated with a lower mortality risk. Achieving optimal control can eliminate the excess mortality risk associated with MASLD， thereby helping patients achieve a better survival prognosis than the general population.

ObjectiveTo explore the listed varieties and prescription characteristics of Chinese patent medicines for stroke in China， explore the medication rules of Chinese medicine for stroke， and provide guidance for further clinical research and development of Chinese patent medicines. MethodsExcel 2021 and the Ancient and Modern Medical Record Cloud Platform （V2.3.5） were used to systematically mine and analyze the varieties and prescriptions of Chinese patent medicines for stroke in China. ResultsA total of 244 Chinese patent medicines （two for different dosage forms of the same prescription）， 1 736 approval documents for Chinese patent medicines， 792 manufacturers， and 83 varieties of protected Chinese patent medicines were finally included in the database. The top three dosage forms were capsules （75）， pills （53）， and tablets （42）. There were 28 Chinese patent medicines for stroke in the National Essential Drug Catalogue （2018）， 129 in the National Essential Medical Insurance， Industrial Injury Insurance and Maternity Insurance Drug Catalogue （2023）， and 4 in the National Non-prescription Drug Catalogue. Among the 138 prescriptions screened out， Chinese patent medicines mainly treated stroke patients with the syndrome of Qi deficiency and blood stasis. The top three most frequent medicinal herbs were Chuanxiong Rhizoma （63）， Pheretima （47）， and Salviae Miltiorrhizae Radix et Rhizoma （47）. The medicinal herbs used were mainly warm， pungent， with the meridian tropism to the liver meridian. The correlation analysis showed that the herb pair with the highest support was Astragali Radix-Chuanxiong Rhizoma， and that with the highest confidence was Carthami Flos-Chuanxiong Rhizoma. Five herb combinations were identified based on the cluster analysis. ConclusionThe Chinese patent medicines for stroke mainly treat patients with the syndrome of Qi deficiency and blood stasis. The medicinal herbs used in the prescriptions mainly have the functions of activating blood and resolving stasis， extinguishing wind and stopping convulsions. Drug compatibility usually focuses on activating blood and resolving stasis， as well as expelling phlegm and opening orifices. This review of the varieties and prescription characteristics of Chinese patent medicines for stroke helps optimize clinical decision-making， guide drug research and development， promote medical research and scientific progress， and provide more effective support and guarantee for the treatment of stroke patients.

【Objective】 To perform pre-transfusion examination and major crossmatch test using CD47 anti-idiotypic antibody (CD47 AID) (method 1) and reagent lack of anti-IgG4 anti-human globulin(method 2) in patients treated with CD47 monoclonal antibodies, and evaluate the feasibility of method 1 by comparing the transfusion efficacy of patients after cross matching with two methods. 【Methods】 Post-drug samples were collected from 18 clinical subjects treated with CD47 monoclonal antibody in our hospital. Antibody screening and major crossmatch test were performed using method 1 and method 2, and the difference of ΔHb (post-transfusion Hb minus pre-transfusion Hb) was compared after transfusion. The differences in ΔHb after transfusion were analyzed between the test group using method 1 and the control group without CD47 monoclonal antibody using ordinary microcolumn gel method. 【Results】 There was no significant difference in ΔHb between the test group using method 1 and test group using method 2 (8.40±0.71 vs 7.36±0.94, P>0.05). No significant difference was noticed in ΔHb between the test group using method 1 and the control group without CD47 monoclonal antibody (8.40±0.71 vs 6.59±0.77, P>0.05). 【Conclusion】 In the test group, major crossmatch test with method 1 has the same transfusion efficacy as the test with method 2. Method 1 is simple and easy to operate, and the results are objective and accurate. It is recommended to use method 1 for pre-transfusion antibody screening and major crossmatch tests for patients using CD47 monoclonal antibody.

【Objective】 To explore the feasibility of blood transfusion compatibility testing for multiple myeloma(MM) patients treated with anti-CD38 monoclonal antibody daratumumab (DARA) after DARA-Fab fragment blocking, and to evaluate the transfusion efficacy by comparing with dithiothreitol(DTT) method. 【Methods】 After DARA was prepared into DARA-Fab fragments using PierceFab preparation kit, the neutralization effects of different volumes (5, 10, 15, 30 μL) on screening cells and panel cells were confirmed. DARA-Fab fragments and screening cells with specific antigens and corresponding monoclonal antibody reagents were used as the experimental group and the control group with the same volume of saline for incubating and centrifugin.Twenty MM patients treated with DARA were selected for cross-matching with DARA-Fab and DTT respectively, and the laboratory indexes before and after transfusion were statistically analyzed, and the two blood matching methods were compared. 【Results】 After incubating and centrifuging, the results of DARA-Fab fragments(15, 30 μL) with screening cells and serum mixed with DARA were negative, while those of DARA-Fab(5, 10 μL) were positive. 15μL DARA-Fab treated antibody identification cells (2, 3, 4, 5, 7, 9, 11) were negative, antibody identification cells (1, 6, 8, 10, 12) were negative after 30 μL DARA-Fab fragments treatment; the results of MNS, Duffy, Kidd, Kell, Lewis, Rh blood group system of the experimental group were consistent with those of the control group; the hemoglobin (Hb) (g/L) of 20 patients after infusion of RBC (73.90±1.90) was significantly higher than that before transfusion (63.60±1.58), P<0.01. There was no significant difference in total bilirubin(TBil)(μmol/L)(16.25±3.54 vs 17.87±3.57), direct bilirubin(DBIL)(μmol/L)(6.31±2.32 vs 7.10±2.80)and indirect bilirubin(I-Bil)(9.94±1.38 vs 10.77±1.22) before and after infusion(P>0.05).And no statistical difference was noticed in Hb (10.75±1.04 vs 10.30±0.98), TBil (3.31±1.47 vs 3.31±0.55), DBIL(2.76±1.24 vs 2.60±0.83), and I-Bil(1.97±0.40 vs 2.82±0.53) between the DTT treatment method and the DARA Fab fragment treatment before and after transfusion(P>0.05). 【Conclusion】 DARA-Fab can remove the interference of RBC on cross matching by blocking CD38 antigen. This method has no effect on the antigens of common RBC blood group systems, and shows significant blood transfusion efficacy as that of DTT method.

This article combs and summarizes the entire process of rare disease selection and priority theme determination,including the application and preliminary review of rare diseases,standardization of disease theme information,the evaluation methods of evidence sorting and disease selection for priority se-lection of disease themes,and other aspects of the content were analyzed in depth.It is expected to provide reference for the subsequent selection of rare diseases,improve the fairness,rationality and scientificity of rare disease selection,and further promote research and decision-making in China's rare disease-related fields.

Objective To investigate the relationships of serum levels of human fractalkine (CX3CL1) and chitinase-3-like protein 1 (YKL-40) with early cognitive impairment in elderly patients with Alzheimer's disease (AD). Methods A total of 110 AD patients in the Second Affiliated Hospital of Xinxiang Medical University from February 2021 to December 2023 were selected as AD group, and 50 healthy individuals with physical examination during the same period were selected as control group. Clinical materials and serum levels of CX3CL1 and YKL-40 were compared between the two groups, and multivariate Logistic regression models were used to analyze the influencing factors of cognitive impairment in AD patients. Based on the Mini-Mental State Examination (MMSE) score, the 110 AD patients were divided into mild cognitive impairment group (n=47), moderate cognitive impairment group (n=36), and severe cognitive impairment group (n=27). Spearman correlation analysis was performed to explore the relationships of serum CX3CL1 and YKL-40 with MMSE score, Addenbrooke's Cognitive Examination-Ⅲ (ACE-Ⅲ) score, and Montreal Cognitive Assessment (MoCA) score. Results The AD group had higher proportions of patients aged over 80 years, with an education level of primary school or below, smoking history, alcohol consumption history, diabetes mellitus, hypertension, AD family history, and living alone as well as higher serum levels of CX3CL1 and YKL-40 compared to the control group; conversely, the AD group had a lower proportion of patients engaging in no physical exercise/labor, and lower MMSE, ACE-Ⅲ, and MoCA scores, with significant between-group differences (P < 0.05). Advanced age, diabetes mellitus, and high serum levels of CX3CL1 and YKL-40 were independent risk factors for cognitive impairment in AD patients (P < 0.05), while an education level of college or above was a protective factor (P < 0.05). Compared with the mild cognitive impairment group, the moderate and severe cognitive impairment groups had higher serum levels of CX3CL1 and YKL-40, and the severe cognitive impairment group had higher serum levels of CX3CL1 and YKL-40 than the moderate group, with significant between-group differences (P < 0.05). Spearman correlation analysis revealed that serum CX3CL1 and YKL-40 were negatively correlated with MMSE, ACE-Ⅲ, and MoCA scores (P < 0.05). Conclusion Serum CX3CL1 and YKL-40 are highly expressed in elderly AD patients, and are closely related to early cognitive impairment in elderly AD patients.

Pharmacoeconomic evaluation is the essential supporting information for the inclusion of rare disease drugs into medical insurance in China. The accurate measurement of the health state utility of rare diseas is of practical significance to the development of rare disease pharmacoeconomic evaluation. Based on the review of pharmacoeconomic evaluation requirements for rare diseases in some countries/regions, we systematically retrieved the published studies on the measurement of health state utility for 121 rare diseases in China and other countries and regions. We identified 17 591 papers in the initial review, and later selected 230 after screening. We also made a comprehensive analysis of the quality of literature, evaluation content and use of tools for measuring health state utility in rare diseases in China. Finally, we analyzed the challenges in measurement in terms of population, instruments use, and application of results and made recommendations based on analysis, hoping to provide reference for the development of rare disease health state utility measurement studies in China.

We have analyzed the current status of recognization and qualification of orphan drugs in China and abroad, looking at the aspects of the authority institutions, identification and qualification process, and the number of orphan drugs identified and available in the market. By comparing and analyzing horizontally the differences in orphan drugs identification between representative developed countries vs. some developing countries, we discuss the inadequacy of orphan drugs supervision in China. We introduce the advanced experience from the developed countries and some developing countries to provide suggestions for the identification and management of orphan drugs, hoping to speed up the process of development and market availability of orphan drugs and to maximize patient's accessibility to treatment in China.

Objective To investigate the clinical efficacy and safety of ziprasidone mesylate injection on the acute agitation symptom in mental retardation. Methods The total of 80 patients of mental retardation with acute agitation symptoms were randomly divided into two groups:the treatment group (40 patients) were intra-muscarly given with ziprasidone mesylate injection at the initial dose of 10 mg, 20 mg 4 h later, and 30 mg once on the second day and third day. And the control group (40 patients) were treated with haloperidol injection. The volume dose of haloperidol was 20 mg everyday. Other antipsychotic drugs, antimanic drugs and benzodiazepines were not allowed to be used during the observation, neither does the prophylactic use of drugs against parkinson's disease. Before and 1, 2, 4, 6, 8, 12, 24, 48, 72 h after treatment, the positive and negative scale ( PANSS) reduction rate, the end of the clinical global impression scale ( CGI) were assessed. By the end of the treatment, the adverse reactions symptom, cale ( TESS) was assessed for the safety. Results By the end of treatment PANSS reduction rate was 46. 31% in the test group and 48. 81% in the control group, the clinical improvement rate was 80. 00% in the treatment group and 82. 50% in the control group. No statistically significant difference on efficacy was found between two groups. The side reaction rate in the treatment group was 27. 5%, that in the control group was 40. 0%, there was significant difference ( P<0. 05) between two groups, but the extrapyramidal reaction in the control group was significantly more than that in the treatment group(P<0. 05). Conclusion Ziprasidone mesylate injection is effective on treating the symptoms of mental retardation, in corresponding to the effect of haloperidol injection,and with less extrapyramidal reactions.

Objective To evaluate bacteriophage therapy for gut-derived sepsis caused by Acinetobacter baumannii in mice.Methods Lyric phages of Acinetobacter baumannii were isolated from environment by using double-layer agar method.A murine model of gut-derived sepsis was established by oral administration of ampicillin-resistant Acinetobacter baumannii and injection of ampicillin and cyclophosphamide into peritoneal cavities of mice.Bacteriophage therapy were given 1 d before infection (group 1),2 d(group 2) and 6 d(group 3) after infection.The survival of the mice was observed,mice without bacteriophage therapy were as control.Independent-sample t test was performed to compare inflammatory cytokines levels in peripheral blood and liver,number of bacteria in liver and spleen between mice with and without bacteriophage therapy.Results The minimal lethal dose of Acinetobacter baumannii for mice with gut-derived sepsis was 1 × 107 CFU/mL.The survival of the mice in group 2 (4/6 survived),which were treated with bacteriophage 2 d after inoculation of Acinetobacter baumannii,was higher than those of group 1 (2/6 survived),group 3 (3/6 survived) and the control group (phage-untreated,0/6 survived).Interleukin (IL)-1 β,tumor necrosis factor (TNF)-α and IL-6 in peripheral blood in mice with bacteriophage therapy were (105 ±6) ng/L,(105 ± 11) ng/L and (104 ± 12)ng/L,which were lower than those in control group (t =5.04,9.05 and 9.33,P ＜ 0.01) ; IL-1 β and TNF-α in liver of mice with bacteriophage therapy were (104 ± 9) ng/L and (104 ± 11) ng/L,which were lower than those in the controls (t =13.70 and 12.80,P ＜0.01),but IL-6 levels were not of statistical difference between therapy and control groups (t =1.06,P ＞ 0.05).Number of bacteria in liver and spleen in mice with bacteriophage therapy were (2.9 ± 1.3) × 103CFU/g and (8.3 ±7.6) × 102 CFU/g,which were also lower than those in control group (t =9.16 and 8.96,P ＜ 0.01).Conclusions Bacteriophage therapy can be effective against gut-derived sepsis caused by Acinetobacter baumannii.