After two decades of development, transcatheter left atrial appendage closure has emerged as a safe and effective intervention for stroke prevention in patients with atrial fibrillation. In 2024, significant advancements were made in the field of left atrial appendage closure in terms of evidence-based medicine, device research and development, and guideline consensus. The annual report on transcatheter left atrial appendage closure systematically reviews global academic progress in 2024, encompassing newly published clinical evidence, recently developed occlusion devices, and updated international guidelines/consensus statements. In the future, the development direction of transcatheter left atrial appendage closure mainly includes expanding surgical indications, optimizing imaging assistance technology, improving closure device design, and exploring individualized strategies for postoperative antithrombotic therapy.

Objective To analyze the trend of global cellulitis disease burden from 1990 to 2019, and to provide a theoretical basis for the prevention and control of cellulitis disease. Methods The Global Burden of Disease 2021 (GBD2021) data were collected, and data on the incidence, mortality, and disability-adjusted life year (DALY) of cellulitis were analyzed for each country worldwide. The estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trend change of cellulitis from 1990 to 2021. Results The global burden of cellulitis increased significantly in 2021, with 55.96 million cases, 28.9 million deaths and 876.1 million DALYs, respectively. Incidence and mortality rates were generally higher in males than in females. The incidence and DALYs were higher in high SDI regions, with the highest burden observed in South Asia. In contrast, East Asia exhibited the lowest burden and demonstrated a declining trend. There were significant differences between countries, with India having the highest prevalence, the United States having the highest incidence, and Bahrain having the fastest growing rate.In 2021, China had the lowest age-standardised incidence of cellulitis in the world and the fastest declining age-standardised incidence and age-standardised DALYs. Conclusion The global disease burden of cellulitis is increasing from 1990-2021, and cellulitis remains an an important global public health problem. Targeted preventive meausres should be taken in areas with different economical levels. Men, middle-aged and elderly people, and newborns are the key groups in need of attention and health education.

Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

OBJECTIVE: To investigate the inhibitory effect of miR-125b-5p on proliferation and migration of osteosarcoma and the role of RAB3D in mediating this effect. METHODS: The expression level of miR-125b-5p was detected by qRT-PCR in a normal bone cell line (hFOB1.19) and in two osteosarcoma OS cell lines (MG63 and HOS). A miR-125b-5p mimic or inhibitor was transfected in the osteosarcoma cell lines via liposome and the changes in cell proliferation and migration were detected with EDU and Transwell experiments. Bioinformatic analysis was conducted for predicting the target gene of miR-125b-5p, and the expression level of RAB3D in hFOB1.19, MG63, and HOS cells was detected by Western blotting. In the two osteosarcoma cell lines transfected with miR-125b-5p mimic or inhibitor, the expression levels of RAB3D mRNA and protein in osteosarcoma cells were examined with qRT-PCR and Western blotting. The effects of RAB3D overexpression, RAB3D knockdown, or overexpression of both miR-125b-5p and RAB3D on the proliferation and migration of cells were assessed using EDU and Transwell experiments. RESULTS: The two osteosarcoma cell lines had significantly lower expression levels of miR-125b-5p (P < 0.05). Bioinformatic analysis predicted that RAB3D was a possible target gene regulated by miR-125b-5p. In osteosarcoma cells, overexpression of miR-125b-5p significantly lowered the expression of RAB3D protein (P < 0.05); inhibiting miR-125b-5p expression significantly decreased RAB3D expression only at the protein level (P < 0.05) without obviously affecting its mRNA level. Modulation of miR-125b-5p and RAB3D levels produced opposite effects on proliferation and migration of osteosarcoma cells, and in cells with overexpression of both miR-125b-5p and RAB3D, the effect of RAB3D on cell proliferation and migration was blocked by miR-125b-5p overexpression (P < 0.05). CONCLUSION Overexpression of miR-125b-5p inhibits the proliferation and migration of osteosarcoma cells by regulating the expression of RAB3D at the post-transcriptional level.
Humans ; Bone Neoplasms/genetics* ; Cell Proliferation ; MicroRNAs/genetics* ; Osteosarcoma/genetics* ; rab3 GTP-Binding Proteins/genetics* ; RNA, Messenger

Objective: To analyze the clinical characteristics of children with multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 in China, and to improve the understanding of MIS-C among pediatricians. Methods: Case series study.Collect the clinical characteristics, auxiliary examinations, treatment decisions, and prognosis of 64 patients with MIS-C from 9 hospitals in China from December 2022 to June 2023. Results: Among the 64 MIS-C patients, 36 were boys and 28 were girls, with an onset age being 2.8 (0.3, 14.0) years. All patients suffered from fever, elevated inflammatory indicators, and multiple system involvement. Forty-three patients (67%) were involved in more than 3 systems simultaneously, including skin mucosa 60 cases (94%), blood system 52 cases (89%), circulatory system 54 cases (84%), digestive system 48 cases (75%), and nervous system 24 cases (37%). Common mucocutaneous lesions included rash 54 cases (84%) and conjunctival congestion and (or) lip flushing 45 cases (70%). Hematological abnormalities consisted of coagulation dysfunction 48 cases (75%), thrombocytopenia 9 cases (14%), and lymphopenia 8 cases (13%). Cardiovascular lesions mainly affected cardiac function, of which 11 patients (17%) were accompanied by hypotension or shock, and 7 patients (12%) had coronary artery dilatation.Thirty-six patients (56%) had gastrointestinal symptoms, 23 patients (36%) had neurological symptoms. Forty-five patients (70%) received the initial treatment of intravenous immunoglobulin in combination with glucocorticoids, 5 patients (8%) received the methylprednisolone pulse therapy and 2 patients (3%) treated with biological agents, 7 patients with coronary artery dilation all returned to normal within 6 months. Conclusions: MIS-C patients are mainly characterized by fever, high inflammatory response, and multiple organ damage. The preferred initial treatment is intravenous immunoglobulin combined with glucocorticoids. All patients have a good prognosis.
Male ; Child ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Blood Coagulation ; COVID-19 ; China/epidemiology* ; Connective Tissue Diseases ; Coronary Aneurysm ; Fever ; Systemic Inflammatory Response Syndrome/therapy*

[摘 要] 目的：构建负载二氧化锰（MnO2）纳米颗粒的可得然（Cur）复合水凝胶MnO2@Cur（简称MGel），研究其对黑色素瘤B16-F10细胞的杀伤效果。方法：采用热诱导法制备Cur水凝胶（Gel），物理负载MnO2构建MGel，表征其宏观和微观形貌，检测其机械性能、降解性能以及光热转换性能等理化性能，并研究其联合PTT对小鼠皮肤黑色素瘤B16-F10细胞的光热杀伤效果。结果：MGel具有优异的机械和可降解性能，抗拉伸强度达（127.97±3.60）kPa、抗压缩强度达（151.44±5.23）kPa，28 d降解率约58.17%。MGel负载MnO2纳米片（粒径约180 nm）获得优异的光热转换性能，负载1.0 mg/mL MnO2的MGel在1.0 W/cm2的808 nm NIR光照4 min后到达最高温度50 ℃。细胞毒性实验和Calcein-AM/PI荧光双染色实验表明，MGel联合PTT有效杀伤B16-F10黑色素瘤细胞，NIR光照使得MGel组细胞存活率降低至（4.68±0.66）%（P<0.000 1）。结论：MGel复合水凝胶具备优异的机械性能、可降解性能以及光热转换性能，其联合PTT能有效杀伤肿瘤细胞，可能成为一种有效治疗黑色素瘤的新手段。

【Objective】 To analyze the risk factors for intraoperative massive red blood cell (RBC) transfusion in patients with Stanford type A aortic dissection (TAAD), in order to develop a risk-prediction model and validate its predictive effect. 【Methods】 The clinical data of 233 patients with TAAD admitted to our hospital from July 2018 to June 2021 (modeling set) were retrospectively analyzed. They were divided into routine transfusion group (n=128, RBC≤8 U) and massive transfusion group (n=105, RBC>8 U). Risk factors for intraoperative massive RBC transfusion in TAAD patients were analyzed by multivariate logistic regression and a risk prediction model was developed. Calibration curve and receiver operating characteristic (ROC) curve were used to assess the accuracy and discrimination of the model. In addition, 61 TAAD patients admitted to our hospital from July 2021 to May 2022 (validation set) were used for external validation. 【Results】 The rate of intraoperative massive RBC transfusion in 233 TAAD patients was 45.06% (95% CI: 38.59%-51.69%). Logistic analysis showed that women, age >50 years, preoperative Hb≤131.50 g/L, intraoperative bleeding >720 mL, and CPB time >155 min were independent risk factors for massive intraoperative RBC transfusion (P<0.05). The intraoperative risk prediction model formula for massive RBC infusion was: -4.427+ 0.925×gender+ 1.461×age+ 2.081×preoperative Hb+ 1.573×bleeding volume+ 2.823×CPB time. The area under the ROC curve of the modeling set and validation set were 0.904 (95% CI: 0.865-0.943) vs 0.868 (95%CI: 0.779-0.958), and the slopes of the calibration curves all converged to 1, indicating that the model predicted the risk of intraoperative massive RBC infusion in TAAD patients in good consistency with the actual risk of massive infusion. The decision curve shows that the model exhibits a positive net benefit with a threshold probability of 0.15-0.67 and has a high clinical application value. 【Conclusion】 The prediction model constructed based on the risk factors of intraoperative massive RBC infusion in TAAD patients can effectively predict the risk of intraoperative massive RBC infusion with high clinical predictive efficacy.

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

OBJECTIVE To interpret Teacher Training Syllabus for Clinical Pharmacist Training Program （2023 edition） （hereinafter referred as to the “new syllabus”）， and to provide reference and guidance for promoting the implementation of the new syllabus and realizing the quality-improving goal of the reform of the clinical pharmacist teacher training program initiated by China Hospital Association. METHODS From the perspective of the management and based on the position of the designer， the new syllabus was interpreted from four aspects： the background of its compilation and release， the process of its compilation and its characteristics， the key improvements of the program and the points for attention about its subsequent implementation. RESULTS & CONCLUSIONS The development and release of the new syllabus provide a “construction blueprint” for the reform of the clinical pharmacist teacher training program of the China Hospital Association. The whole process of compiling the new syllabus is characterized by four basic features： theory-led， goal-oriented， research-based， and synergistic. Compared with the previous syllabus， in addition to the adjustment of the text structure，the new syllabus presents more complete and clearer competence requirements for clinical teaching competence in terms of training objectives； in terms of training content， it further structures the group of task items， pays attention to the 育。E-mail：zhenjiancun@163.com sequential planning and time arrangement of items， and puts forward both quantitative and qualitative refinement requirements for each specific training task；in terms of training methods， it emphasizes the interaction of lecturing， demonstrating and guiding， and the progression of observation， operation and reflection， with the intention of guiding teacher trainees to “learn how to teach by teaching”. In the subsequent implementation of the new syllabus， it is necessary for the teacher training bases to attach great importance to the guarantee of training conditions and process quality management， and to organize the teacher training team to do a good job in the two training programs of “clinical pharmacist training” and “clinical pharmacist teacher training”. Based on further improving the connection between the two training programs， the teacher training team should continue to explore the scientific model of clinical pharmacist teacher training oriented by clinical teaching competence.