A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

OBJECTIVES: To investigate the mechanism through which N-acetylneuraminic acid (Neu5Ac) exacerbates hypoxia/reoxygenation (H/R) injury in rat cardiomyocytes (H9C2 cells). METHODS: H9C2 cells were cultured in hypoxia and glucose deprivation for 8 h followed by reoxygenation for different durations to determine the optimal reoxygenation time. Under the optimal H/R protocol, the cells were treated with 0, 5, 10, 20, 30, 40, 50, and 60 mmol/L Neu5Ac during reoxygenation to explore the optimal drug concentration. The cells were then subjected to H/R injury followed by treatment with Neu5Ac, Fer-1 (a ferroptosis inhibitor), or both. The changes in SOD activity, intracellular Fe²⁺ and lipid ROS levels in the cells were evaluated, and the cellular expressions of Nrf2, GPX4, HO-1, FSP1, and xCT proteins were detected using Western blotting. RESULTS: Following hypoxia and glucose deprivation for 8 h, the cells with reoxygenation for 6 h, as compared with other time lengths of reoxygenation except for 9 h, showed the lowest expression levels of Nrf2, GPX4, HO-1, and FSP1 proteins (P<0.001). Neu5Ac treatment of dose-dependently decreased the viability of the cells with H/R injury with an IC₅₀ of 30.07 mmol/L. Reoxygenation for 3 h with normal glucose supplementation and a Neu5Ac concentration of 30 mmol/L were selected as the optimal conditions in the subsequent experiments. The results showed that Neu5Ac could significantly increase SOD activity, Fe²⁺ and lipid ROS levels and reduce Nrf2, GPX4, HO-1, and FSP1 protein expressions in H9C2 cells with H/R injury, but its effects were significantly attenuated by treatment with Fer-1. CONCLUSIONS Neu5Ac exacerbates ferroptosis of myocardial cells with H/R injury by inhibiting the Nrf2 axis to promote the production of ROS and lipid ROS.
Ferroptosis/drug effects* ; Myocytes, Cardiac/cytology* ; Animals ; NF-E2-Related Factor 2/metabolism* ; Rats ; N-Acetylneuraminic Acid/pharmacology* ; Cell Hypoxia ; Reactive Oxygen Species/metabolism* ; Cell Line ; Myocardial Reperfusion Injury/metabolism*

Objective : To explore the effect and mechanism of CD151 on vascular permeability by regulating vesicle internalization and recycling. Methods: Wild-type mice and CD151 knockout mice were divided into WT-con group, WT-model group, KO-con group and KO-model group, with 6 mice in each group. WT-model group and KO-model group were intraperitoneally injected with LPS to prepare sepsis ALI model, and WT-con group and KO-con group were intraperitoneally injected with phosphate buffer saline(PBS) as a control. 24 h after modeling, pulmonary vascular permeability was measured by Miles test. The siRNA silencing CD151 expression(si-CD151) and negative control si-NC were transfected into EA.hy 926 cells. The permeability of endothelial cell layer to FITC-dextran at different time points was observed under basic conditions and vascular endothelial growth factor-A(VEGF-A) stimulation conditions. Transcriptome sequencing of endothelial cells in si-CD151 group and si-NC group; the distribution and internalization of CD151 in each group were measured using immunofluorescence. Western blot and real-time quantitative RT-qPCR were used to detect the expression of VE-cadherin in si-CD151 groupand other groups. The distribution and internalization of VE-cadherin in each group were measured using immunofluorescence. Results : Miles experiment results indicated that dye exudation in lung tissue of WT-model group was significantly higher than that of WT-con group(P<0.01). The dye exudation in the lung tissue of KO-model group increased compared with WT-model group(P<0.05). The results of endothelial cell layer permeability test showed that the permeability of FITC-dextran in si-CD151 group was significantly higher than that in control group after VEGF-A stimulation for 30, 60 and 120 min(P<0.05). Transcriptome sequencing results suggested that CD151 in endothelial cells was closely related to vesicle-mediated transport. Compared with other groups, protein and mRNA levels of VE-cadherin in CD151 knockdown endothelial cells was significantly lower(allP<0.01). The immunofluorescence assay demonstrated that after VEGF-A stimulation, the decrease of CD151 expression significantly impaired the expression of VE-cadherin at cell-cell contacts and reduced the CD151-VE-cadherin colocalization in the perinuclear region compared with other groups. Conclusion The absence of CD151 affects the internalization and recycling of endothelial cell vesicles, affects the expression and internalization of VE-cadherin, and then influences vascular permeability.

With the extensive application of surgical robots represented by Da Vinci in minimally invasive surgical procedures, robotic technology has gradually extended to the field of flexible endoscopic surgery like digestive endoscopy. Many studies have shown that surgical robots can also improve the operational efficiency and safety of flexible endoscopic surgery and optimize the learning curve. However, due to the narrow and tortuous lumen of digestive tract, the development and design of flexible digestive endoscopic surgical robot is relatively more difficult. In this paper, the research and development characteristics of the flexible digestive endoscopic surgical robot are introduced from the aspects of carrier length, flexibility and ergonomics, and its future clinical application is prospected, with a view to facilitating the application of the flexible surgical robot in the minimally invasive surgical procedures of natural passages such as digestive, respiratory and urinary tract.

With the extensive application of surgical robots represented by Da Vinci in minimally invasive surgical procedures, robotic technology has gradually extended to the field of flexible endoscopic surgery like digestive endoscopy. Many studies have shown that surgical robots can also improve the operational efficiency and safety of flexible endoscopic surgery and optimize the learning curve. However, due to the narrow and tortuous lumen of digestive tract, the development and design of flexible digestive endoscopic surgical robot is relatively more difficult. In this paper, the research and development characteristics of the flexible digestive endoscopic surgical robot are introduced from the aspects of carrier length, flexibility and ergonomics, and its future clinical application is prospected, with a view to facilitating the application of the flexible surgical robot in the minimally invasive surgical procedures of natural passages such as digestive, respiratory and urinary tract.

Objective To establish an automatic review plan for coagulation tests with image recognition function,and evaluate the correctness and effectiveness of the plan.Methods Artificial intelligence software and hardware were combined to establish an image recognition system that could automatically determine the characteristics of specimens,blood volume and hematocrit.The correctness of the determination results of specimen character was compared with the visual method,the correctness of the determination results of blood volume was compared with the manual measurement method,and the correctness of hematocrit was compared with the hematology analyzer.According to the flow chart,reference interval,medical decision level,critical value range,relevant literature,work experience and historical data,the autoverification rules of coagulation tests were formulated.The autoverification rules were manually verified,and the autoverification pass rate,true positive rate,true negative rate,false positive rate,and false negative rate were calculated.The change of turnaround time in the laboratory after the implementation of the autoverification scheme was evaluated.Re-sults The accuracy rate of sample trait determination in the image recognition system was 96.72％,and the false negative rate of judging hemolytic,jaundice,and lipoid blood samples as normal samples was 0.04％.The image recognition system was compared with the blood volume data of two groups of specimens measured manually,P=0.4881.The image recognition method was not inferior to the manual measurement method.Comparing the two sets of hematocrit data from the image recognition system and the blood cell analyzer,P=0.1130,the image recognition system was not inferior to the blood cell analyzer.A total of 61 automatic re-view rules for coagulation tests had been established,including numerical abnormalities,logical abnormalities,Delta Check,sample quality abnormalities,reaction curve abnormalities,etc.The automatic review pass rate was 76.19％,true positive rate was 23.77％,true negative rate was 76.19％,false positive rate was 0.04％,and false negative rate was 0.00％.After implementing the automatic audit plan,the turnaround time of sam-ples in each quantile was shortened,with an average shortening time of 13.66 min.Conclusion The applica-tion of image recognition technology in the automatic review of coagulation tests makes the automatic review function more automated and scientific,standardizes specimen quality judgment,improves the accuracy of test results,effectively improves work efficiency and saves manpower.

This study adopted the policy text analysis method,review the historical background of the enactment,aimed to comparatively analyze the international pharmaceutical trade policies of the BRICS countries.The main objectives of the BRICS countries'international pharmaceutical trade policies included ensuring stable and accessible drug supply,expanding exports of domestic products and creating a favorable political environment.For these purposes,Brazil,Russia,and South Africa all ensure drug supply through substantial imports.However,they have also taken measures such as compulsory patent licensing and promoting localization of production by foreign companies to reduce import dependence.India,on the other hand,protects its domestic industry by resisting drug imports to ensure drug supply while simultaneously promoting the export of pharmaceutical products.China continually optimizes approval and data monitoring procedures to align with international standards,creating a favorable trade environment and expanding exports.China should further refine its international pharmaceutical trade policies while ensuring the autonomy of domestic drug research and supply,fostering stronger collaboration within BRICS nations and promoting global access to public healthcare products.

Hepatic ascites is one of the common and difficult complications in the decompensated stage of liver cirrhosis， and its incidence is increasing. In clinical practice， the prognosis of patients with hepatic ascites after surgery is worse， and the disease is recurrent. Traditional Chinese medicine （TCM） has certain advantages in treating hepatic ascites. However， there is no uniform standard for the preparation of animal models of hepatic ascites in accordance with TCM evidence. Therefore， this paper summarized the literature on animal models of hepatic ascites and analyzed the existing animal models of hepatic ascites based on the clinical diagnostic criteria of hepatic ascites in TCM and western medicine. The results show that the commonly used modeling methods for hepatic ascites mainly include the single-factor method， composite factor induction method， surgical method， and immunization method. Most of them are guided by western medicine theories， and their pathogenic mechanisms are mostly consistent with those of western medicine and are different from TCM evidence. Therefore， it is suggested that TCM intervening factors should be imposed in the process of model preparation， so as to prepare an animal model of hepatic ascites that meets the clinical evidence characteristics of TCM and western medicine.