In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

Background Air pollution exposure has a significant impact on maternal and child health. However, the research on the association between ambient ozone (O₃) exposure during pregnancy and the risk of premature birth in newborns is limited, and the conclusions are inconsistent. Objective To investigate the association of ambient O₃ exposure during pregnancy with the risk of preterm birth in Guangdong Province. Methods Data of pregnant women in Guangzhou from 2013 to 2019 and Foshan from 2018 to 2023 were collected, and O₃ concentrations during different trimesters were assessed according to maternal residential addresses. Bilinear interpolation was used to evaluate the concentrations of air pollution. A cohort study design was adopted in our study. Restricted cubic spline curves were used to evaluate the exposure-response relationship between O₃ exposure and preterm birth risk and explore potential exposure threshold of O₃. Logistic regression models were used to evaluate the association of O₃ exposure with preterm birth. Results A total of 702 924 pregnant women were included in this study, of whom 43 051 (6.12%) were preterm. The average O₃ exposure concentrations of pregnant women during the first, second, third, and whole trimesters were 95.51, 97.51, 100.60, and 97.87 μg·m⁻³, respectively. We observed J-shaped associations between O₃ exposure and preterm birth risk during the second, third, and whole trimesters of pregnancy using restricted cubic spline curves. This study found that there were threshold concentrations between O₃ exposure and preterm birth risk during different gestational periods, and the threshold concentrations in the first, second, third, and whole trimesters were 112.32, 99.83, 111.74, and 112.46 μg·m⁻³, respectively. During the second, third, and whole trimesters of pregnancy, after adjusting for maternal age, baby sex, pre-pregnancy body mass index, mode of delivery, baby birth weight, gestational diabetes, and gestational hypertension, the odds ratios (OR) of preterm birth were 1.02 (95%CI: 1.01, 1.04), 1.02 (95%CI: 1.00, 1.03), and 1.17 (95%CI: 1.13, 1.21) for each 10 μg·m⁻³ increase in O₃ concentration above the O₃ threshold. No significant association was found between O₃ exposure and the risk of preterm birth during the first trimester. Conclusion There is a nonlinear association between the risk of preterm birth and O₃ exposure during pregnancy, and higher concentrations of O₃ exposure during pregnancy are associated with the risk of preterm birth. Above the O₃ threshold concentration during pregnancy, especially during the second, third, and whole trimesters, the risk of preterm birth elevates with the increase of O₃ exposure concentrations.

Background Occupational disease diagnosis appraisal is an appeal procedure initiated when a party disagrees with the occupational disease diagnosis conclusion. It is a legal procedure to safeguard the health rights of employees and the legitimate rights and interests of employers. Objective To analyze the data of occupational disease diagnosis appraisal in Shanghai, identify existing problems, and provide suggestions for improving. Methods Statistical analysis was conducted on basic situation, characteristics of workers and employers, disease classification, and consistency between diagnosis and appraisal conclusions of all occupational disease diagnosis appraisal cases from 2012 to 2024. All diagnosis conclusions were named in accordance with the Classified Catalogue of Occupational Diseases included employers were classified according to the Measures for the Statistical Classification of Large, Medium, Small and Micro Enterprises" and the Notice on Adjusting the Provisions for Classifying Enterprise Registration Types; industry classification followed the Industrial Classification for National Economic Activities (GB/T 4754-2017). Results From 2012 to 2024, a total of 260 cases of occupational diseases diagnosis appraisal were closed. The main diagnosis were 138 cases of ear, nose, throat, and oral diseases (53.1%), chemical poisoning (18.8%), and pneumoconiosis and other respiratory diseases (16.2%). The proportion of ear, nose, throat, and oral diseases gradually increased (2022 excluded). The incidence of annual municipal and provincial cases decreased by 76.3% and 85.0% respectively (2024 vs 2012). The consistency rate of conclusions between appraisal and diagnosis gradually increased. The total consistency rates between final appraisals and diagnostic conclusions were 81.5%, and 79.7%, 87.8%, 100.0%, 85.0% for ear, nose, throat, and oral diseases, chemical poisoning, and pneumoconiosis and other respiratory system diseases, respectively. Specifically, the consistency rates were 80.1% and 80.0% for noise-induced deafness and chronic benzene poisoning. In terms of inconsistency reasons, "inconsistent interpretation of standards and excessive discretion in standard application" accounted for 43.8%, followed by "failure to correctly apply standards" (31.3%) and and "discrepancies in occupational exposure history recognition" (15.6%). Conclusion The revisions and improvements of the legal system for occupational disease diagnosis appraisal have played a positive role in improving the consistency of conclusions between appraisal and diagnosis of occupational diseases in Shanghai. It is suggested to further strengthening the publicity and training of occupational disease diagnosis standards to improve the quality of occupational disease diagnosis.

Traditional Chinese Medicine (TCM) is an indispensable carrier of traditional culture for China to embrace the world. During the 14th Five-Year Plan period, the state proposed to "comprehensively promote the building of a healthy China, attach equal importance to TCM and western medicine, and vigorously develop the cultural industry of TCM". Promoting the development of TCM cultural industry needs scientific and innovative approaches. This paper explored how to realize the communication path of TCM culture from the perspective of "Industry-University-Research". Based on the analysis of the current situation of TCM culture communication, taking Shandong University of Traditional Chinese Medicine as an example, this paper integrated technology, human resources, resources, environment and information and other collaborative innovation elements to effectively gather, and explored a new way for the collaborative development of TCM communication with enterprises, schools, scientific research institutions and et al, aiming to further help TCM culture go abroad.

Objective To evaluate the efficacy and safety of fluorouracil and leucovorin and oxaliplatin(FOLFOX)regimen hepatic artery infusion chemotherapy(HAIC)combined with lenvatinib(LEN)and immune checkpoint inhibitors(ICIs)in treating patients with hepatocellular carcinoma(HCC)after the occurrence of transcatheter arterial chemoembolization(TACE)refractoriness.Methods The clinical data of 54 HCC patients who developed TACE refractoriness,were admitted to the Jiangsu Provincial Cancer Hospital of China to receive FOLFOX-HAIC combined with LEN and ICIs therapy between January 2019 and December 2022,were retrospectively analyzed.The modified Response Evaluation Criteria in Solid Tumors(mRECIST)was used to statistically analyze the clinical efficacy,the Common Terminology Criteria For Adverse Events version 5.0(CTCAE 5.0)was adopted to record and evaluate the treatment-related adverse events(TRAEs).The primary endpoints were progression-free survival(PFS)and overall survival(OS),the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and safety.Results The median PFS was 11.7 months(95％CI:8.124-15.276 months),the median OS was 23.1 months(95％CI:19.508-26.692 months),the ORR was 46.3％,and the DCR was 87.0％.The most common TRAE at all levels was elevated alanine aminotransferase(51.9％),and the most common TRAE of grade 3/4 was hypertension(9.3％).No treatment-related death occurred.Conclusion For the treatment of HCC patients who developed TACE refractoriness,FOLFOX-HAIC combined LEN and ICIs is clinically safe and effective.(J Intervent Radiol,2024,33:610-615)

Objective To investigate the factors affecting the prognosis of patients with malignant obstructive jaundice(MOJ)after receiving biliary stent placement combined with intraluminal brachytherapy with 125I seed-strip implantation.Methods The clinical data of 52 patients with MOJ,who received biliary stent placement combined with intraluminal brachytherapy with 125I seed-strip implantation at the Jiangsu Provincial Cancer Hospital of China between January 2019 and January 2023,were retrospectively analyzed.The difference value between preoperative and postoperative number of lymphoid immune cells was recorded as△X.X-tile software was used to calculate the optimal cut-off value of △X,based on which the patients were divided into two groups.Univariate and multivariate analysis were used to determine the risk factors for overall survival(OS).Results The mean survival time of the 52 patients was(201.0±32.1)days.Univariate analysis indicated that postoperative TACE,preoperative ALT,preoperative AST,△lymphocyte cell,△CD3+T cell,△CD8+T cell,△natural killer cell(NK)and △regulatory cell(Treg)were significantly associated with OS,the differences were statistically significant(all P＜0.05).Multivariate analysis revealed that △lymphocyte cell(P=0.007)and △Treg(P=0.038)were the independent risk factors for OS.Conclusion For MOJ patients whose△lymphocyte is ≥0.237 or △Treg is ≥0.21,a longer OS can be expected after receiving the treatment of biliary stent placement combined with intraluminal brachytherapy with 125I seed-strip implantation.

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.

Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9％vs.17.7％,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P＜0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95％CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.

This study was aimed at investigating the effect of lymphocyte activation gene-3(LAG3)on liver B lymphocyte subsets and their functions in WT and LAG3-KO mice infected with Echinococcus multilocularis(E.multilocularis).In a mouse model of E.multilocularis infection,the expression and localization of CD19 and α-SMA in liver were detected by immu nohistochemistry.CD80,CD86 and MHC-Ⅱ molecules expressed on B cells and their subsets in mice liver were detected by flow cytometry.After 12 weeks of infection,the area and percentage of CD19 in LAG3-KO group was slightly higher than that in WT group,but the difference was not statistically(t=-1.241、-1.237,P＞0.05).The area and percentage of a-SMA in LAG3-KO group was higher than that in WT group(t=-3.224、-3.227,P＜0.05).The proportion of CD80 and MHC-Ⅱ molecules expressed on liver B cells in LAG3-KO group was up-regulated(t=-2.379,-3.321,P＜0.05).The percentage of liver B2 cells in LAG3-KO group was higher than that in WT group(t=-2.695,P＜0.05).The expression of CD80 on Blb cells in LAG3-KO group was significantly up-regulated(t=-5.315,P＜0.001).The proportion of CD80 of B2 cells in LAG3-KO group was lower than that in WT group(t=2.806,P＜0.05).The expression of MHC-Ⅱ molecule in B2 cells in LAG3-KO group was up-regulated(t=-4.227,P＜0.01).It is suggested that LAG3 molecules affected the B cell subsets and func-tion of mouse liver in the middle stage of E.multilocularis infection,especially B2 lymphocytes.LAG3 molecule exerted an in-hibitory effect on the activation of B cells and the expression of MHC-class Ⅱ molecules,suggesting that it may be involved in B cell exhaustion caused by E.multilocularis.

Objective:To investigate the frequencies and subset distribution of peripheral helper(Tph)T cells in patients with immune thrombocytopenia(ITP),and explore the pathogenesis of ITP.Methods:A total of 25 newly diagnosed ITP patients treated in The Second Affiliated Hospital of Dalian Medical University from January to December 2022 were selected,and 25 healthy volunteers(age-and sex-matched)were recruited as the control group.Flow cytometry was used to detect the subsets of CD4+T cells and Tph cells.Results:The frequency of effector memory(CCR7-CD45RO+CD4+)T cells in ITP patients was significantly higher than that in healthy controls(P＜0.05).The frequency of Tph cells in ITP patients was also significantly higher than that in healthy controls(P＜0.001),and most of the Tph cells in ITP patients were effector memory T cells.Furthermore,the expressions of T-cell costimulatory molecules in Tph cells,including ICOS and CD84,were similar to those in follicular helper T(Tfh)cells.CXCR3-CCR6-Tph(Tph2)subgroup was dominant in Tph cells,but the frequency of CXCR3+CCR6-Tph(Tph1)cells in ITP patients was much higher than that in healthy controls(P＜0.05).Conclusion:Tph cells,especially Tph1 cells,were abnormally expanded in ITP patients,which may be a potential etiology of ITP.