Objective To systematically summarize the pharmacological characteristics and clinical applications of antithrombotic medications in ischemic stroke， as well as their interactions with drugs used for common comorbidities， and to provide a reference for clinical medication. Methods Based on the UpToDate database and the integration with pharmacokinetic and pharmacodynamic mechanisms， this study systematically analyzed interactions between antithrombotic agents and between antithrombotics and drugs for comorbid conditions. Interactions were categorized and evaluated based on the level of evidence. Results The distinct pharmacological mechanisms of different antithrombotic drugs determine their patterns of drug-drug interactions. Combination antithrombotic therapy produces synergistic antithrombotic effects but increases the risk of hemorrhage. Extensive interactions exist when antithrombotics are co-administered with medications for cardiovascular diseases， metabolic disorders， neuropsychiatric conditions， and infectious diseases. These interactions primarily involve the cytochrome P450 enzyme system and P-glycoprotein pathways， which may compromise therapeutic efficacy or elevate the risk of bleeding and thrombosis. Conclusion Multiple drug interactions are present in antithrombotic therapy for ischemic stroke. In clinical practice， it is essential to consider the impact of pharmacokinetic and pharmacodynamic mechanisms. By integrating tools such as pharmacogenomics and therapeutic drug monitoring， individualized medication strategies should be implemented to achieve an optimal balance between antithrombotic efficacy and safety.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

With the development of artificial intelligence technology and the growing demand for minimally invasive surgery, the intelligentization of minimally invasive surgery has become a current research hotspot. Surgical instrument segmentation is a highly promising technology that can enhance the performance of minimally invasive endoscopic imaging systems, surgical video analysis systems, and other related systems. This article summarizes the semantic and instance segmentation methods of minimally invasive surgical instruments based on deep learning, deeply analyzes the supervision methods of training algorithms, network structure improvements, and attention mechanisms, and then discusses the methods based on the Segment Anything Model. Given that deep learning methods have extremely high requirements for data, current data augmentation methods have also been explored. Finally, a summary and outlook on instrument segmentation technology are provided.
Artificial Intelligence ; Minimally Invasive Surgical Procedures/instrumentation* ; Algorithms ; Deep Learning ; Humans ; Image Processing, Computer-Assisted

Objective:To assess the impact of vaporized hydrogen peroxide (VHP) on the terminal decontamination effectiveness following the spillage of infectious materials in a BSL-3 laboratory.Methods:Within BSL-3 laboratories with volumes of 92.5 m 3 and 218 m 3, two types of Geobacillus stearothermophilus spore strips were used as biological indicators. ATCC7953 was affixed to stainless steel strips, while ATCC12980 was applied to paper strips. The strips were soaked in cell culture medium and chicken embryo egg fluid to simulate minor spill models. While strips continuously immersed in cell culture medium or chicken embryo egg fluid served as major spill models. These were compared against untreated biological indicator strips to evaluate the terminal decontamination efficacy of VHP. Results:After the completion of terminal disinfection, in laboratories of different volumes and at various sampling points, the culture result of both types of bacterial strips from the minor spill models and the untreated control strips were all negative. In the major spill models, the positivity rate of the two types of bacterial strips soaked in cell culture medium was 75%, while the positivity rate of the two types of bacterial strips soaked in chicken embryo egg fluid was 100%.Conclusions:In the event of a large spill of infectious materials in a laboratory, to ensure biosafety, it is recommended to first treat the spilled materials before initiating the terminal disinfection process. Additionally, under the same disinfection conditions, the material of the biological indicator strips does not affect the terminal disinfection outcomes.

Objective:To establish and evaluate the performance of a stable and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of six phytosterols in human plasma.Methods:The methodology was established, evaluated, and applied. A number of 136 healthy subjects were recruited from the Physical Examination Center of Suzhou Municipal Hospital from October 2023 to December 2023, meanwhile plasma phytosterols′ levels were validated in 5 patients with sitosterolemia. Taking deuterium isotope as internal standards, the clear separation was achieved using a Phenomenex C18 (2.1×100 mm, 2.6 μm) column. The mobile phase consisted of water and methanol at a flow rate of 0.4 ml/min with gradient elution, and the column temperature was 25 ℃. The experiments were performed on AB Sciex 6500+triple quadrupole mass spectrometry, and the linearity, limit of quantification, rate of recovery, precision, and stability of the method were evaluated. The testing method was further validated in the sitosterolemia patients.Results:The method had in-run and between-run coefficient of variation ranging 1.8%-12.5% and 2.6%-13.6%, respectively, which accorded with the precision requirements. The rates of recovery were 85.0%-105.1%, which accorded with the accuracy requirements. The samples showed good stability before and after handling stored at 4 ℃ for 72 hours. The plasma levels of sitosterol, campesterol, stigmasterol and cholestanol in sitosterolemia patients were apparently higher compared with those in the healthy group ( P<0.001). Conclusion:LC-MS/MS method for the quantitative measurement of plant sterols in human plasma has been established, which has convenient preprocessing and passed the performance evaluation including linearity, lower limit of quantification, recovery rate, precision and stability, and shown to be suitable for clinical application.

Objective To compare the efficacy and complications of cupric ion electrochemical therapy and selective suprahemorrhoid resection and stapling surgery for the treatment of grade Ⅲ-Ⅳhemorrhoids.Methods 204 patients with grade Ⅲ-Ⅳ mixed hemorrhoids admitted to our hospital from September 2022 to October 2023 were included as the study subjects.They were divided into two groups using numerical method,with 102 cases in each group.The observation group received copper ion electrochemical therapy,while the control group received selective hemorrhoid mucosal resection and stapling surgery.Compare the surgical outcomes,efficacy,pain scores,anal function scores,quality of life index scores,and incidence of complications between two groups.Results There was no statistically significant difference in gender,age,hemorrhoid grade,surgical time,and hospitalization period between the observation group and the control group(P＞0.05),but the intraoperative blood loss in the observation group was less than that in the control group[(11.37±5.32)ml and(26.72±14.24)ml],and the difference between the two groups was statistically significant(P＜0.05).The severity of pain in the observation group was lower than that in the control group on the 1st and 7th day after surgery(P＜0.05);There was no statistically significant difference in the Wexner anal incontinence scores between the two groups at 1 and 8 weeks after surgery(P＞0.05).The observation group had a better gastrointestinal quality of life index(GIQLI)score than the control group at 2 weeks after surgery[(20.92±4.63)and(26.77±5.03)scores,P＜0.05],and there was no statistically significant difference between the two groups at 8 weeks[(4.38±0.90)and(4.68±1.41)mm,P＞0.05].The total incidence of postoperative complications in both groups was statistically significant(8.8％vs 20.6％,P＜0.05).An average follow-up of six months showed no recurrence.Conclusion Cupric ion electrochemical therapy for mixed hemorrhoids is safe,effective,and has no serious complications,providing a more convenient and minimally invasive treatment method.

BACKGROUND:It has also been confirmed that ferroptosis is closely related to a variety of musculoskeletal diseases,such as rheumatoid arthritis,osteosarcoma,and osteoporosis.The pathophysiological mechanisms of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and osteoporosis.It will provide research ideas for the future elucidation of new mechanisms of osteoporosis and the development of new technologies and drugs for the treatment of osteoporosis. OBJECTIVE:To provide an overview of the current status of research on ferroptosis in osteoporosis,to provide a new direction for future research on the specific molecular mechanisms of osteoporosis,and to provide more effective and better options for osteoporosis treatment strategies. METHODS:The first author used the computer to search the literature published from 2000 to 2024 in CNKI,WanFang,VIP,and PubMed databases with search terms"ferroptosis,iron metabolism,osteoporosis,osteoblast,osteoclast,bone metabolism,signal pathway,musculoskeletal,review"in Chinese and English.A total of 68 articles were finally included according to the selection criteria. RESULTS AND CONCLUSION:(1)Ferroptosis is a new type of cell death discovered in recent years,which is usually accompanied by a large amount of iron accumulation and lipid peroxidation during cell death,and its occurrence is iron-dependent.This is distinctly different from several types of cell death that are currently being hotly studied(e.g.,cellular pyroptosis,necrotic apoptosis,cuproptosis,and autophagy).(2)Intracellular iron homeostasis is manifested as a balance between iron uptake,export,utilization,and storage.The body's iron regulatory system includes systemic and intracellular regulation.The main factor of systemic regulation is hepcidin produced by hepatic secretion,and cellular regulation depends on the iron regulatory protein/iron response element system.Of course,intracellular iron homeostasis can be controlled by other factors,such as hypoxia,cytokines,and hormones.(3)Lipid peroxidation causes oxidative damage to biological membranes(plasma membrane and internal organelle membranes),lipoproteins,and other lipid-containing molecules.Polyunsaturated fatty acid-containing phospholipids are important targets of lipid peroxidation.Free polyunsaturated fatty acid is an important substrate for lipid oxidation and can bind to the phospholipid bilayer,leading to over-oxidation and thus triggering lipid apoptosis.(4)Several studies have shown that osteoblasts are overloaded with iron in different ways,resulting in the accumulation of unstable ferrous iron and the generation of reactive oxygen species and lipid peroxides,causing ferroptosis of osteoblasts and ultimately a decrease in bone formation,affecting bone homeostasis and the development of osteoporosis.(5)Osteoclasts are large multinucleated cells formed by the fusion of mononuclear macrophage cell lines or bone marrow mesenchymal stem cells induced by nuclear factor-κB ligand receptor activator,and they have the function of bone resorption.Iron ions can promote osteoclast differentiation and bone resorption through the production of intracellular lipid reactive oxygen species,while iron chelators can inhibit osteoclast formation in vitro and thus affect the occurrence and development of osteoporosis.

Objective:To investigate the impact of ginseng alcohol extract(GEE)on improving sleep quality in the aged Drosophila model by regulating the redox balance,and to elucidate its associated mechanism.Methods:Thirty-two male drosophila melanogaster(7-days-old)were randomly selected as young group,while 64 male Drosophila melanogaster flies(35-days-old)were randomly assigned to aged model group(n=32)and GEE group(n=32).The sleep parameters,including total sleep duration,daytime sleep duration,night sleep duration,0-4 h of sleep duration after lights off(ZT0-4 sleep duration),deep sleep duration,sleep episodetimes,sleep fragmentation,and the activity parameters such as the total number of locomotor activity daytime locomotor activity amount and nighttime locomotor activity amount were analyzed using the DAM2 Drosophila behavioral analysis system 7 d after administration.The grouping of the drosophila was as above,and there were 100 drosophila ineach group.The differentially expressed proteins in drosophila brain tissue were screened,identified,and functionally analyzed using two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF/TOF-MS)proteomic methods.The grouping of the drosophila was as above,and there were 100 drosophila in each group.The activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the levels of lipid peroxidation product(MDA)in brain tissue of the drosophila were determined using assay kits.Results:Compared with young group,the total sleep duration daytime sleep duration and night sleep cluration of the drosophila in agaed group were decreased(P<0.05 or P<0.01);and the sleep rhythm amplitude was shortened.Compared with aged group,the total sleep duration and daytime and nighttime sleep durations of the drosphila in GEE group were lengthened(P<0.01).Compared with young group,the ZT0-4 sleep duration deep sleep duration and sleep fragment of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the sleep rhythm amplitude was shortened.Compared with young group,the ZT0-4 sleep duration,deep sleep duration,and single sleep fragment of the drosphila in GEE group were significantly prolonged(P<0.01),and the sleep amplitude was increased.Compared with young group,there was no significant difference in diurnal spontaneous activity or total spontaneous activity of the drosophila in aged group(P>0.05),while the nocturnal spontaneous activity was significantly increased(P<0.05).Compared with aged group,the diurnal spontaneous activity,nocturnal spontaneous activity,and total spontaneous activity of the drosophila in GEE group were significantly decreased(P<0.05 or P<0.01).A total of 47 differentially expressed proteins were selected in the 2D-DIGE electrophoretic mapping.Compared with young group,the expressions of 47 differentially expressed protein sites in aged group were down-regulated mainly including glutathione S-transferase,peroxiredoxin 1 and dihydrolipoic dehydrogenase,which were related to redox balance.Compared with young group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the level of MDA was increased(P<0.01);compared with aged group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosphila in GEE group were increased(P<0.05 or P<0.01),and the MDA level was decreased(P<0.05).Conclusion:GEE has improvement effect on the sleep quality of aged drosophila,and its possible mechanism may be related to upregulating the activities of antioxidant enzymes,inhibiting the accumulation of lipid peroxidation products,and maintaining redox balance.

Under the current situation of "low prevalence and low infection" of schistosomiasis in China, and to provide a basis for achieving the goal of eliminating schistosomiasis by 2030 proposed by the Healthy China Action (2019 - 2030) as scheduled, the Hunan Provincial Corps Hospital of the Chinese People's Armed Police Force established a schistosomiasis monitoring and early warning index system based on the previous studies on schistosomiasis early warning index system and the recent literature analysis, combined with the current potential risk factors affecting the transmission and prevalence of schistosomiasis, and organized two rounds of expert consultation and carried out project promotion meetings. The experts reached a consensus on the comprehensiveness and practicability of the index system, aiming to lay a solid foundation for construction of China's schistosomiasis prevention and control early warning system.

Objective To compare the efficacy and complications of cupric ion electrochemical therapy and selective suprahemorrhoid resection and stapling surgery for the treatment of grade Ⅲ-Ⅳhemorrhoids.Methods 204 patients with grade Ⅲ-Ⅳ mixed hemorrhoids admitted to our hospital from September 2022 to October 2023 were included as the study subjects.They were divided into two groups using numerical method,with 102 cases in each group.The observation group received copper ion electrochemical therapy,while the control group received selective hemorrhoid mucosal resection and stapling surgery.Compare the surgical outcomes,efficacy,pain scores,anal function scores,quality of life index scores,and incidence of complications between two groups.Results There was no statistically significant difference in gender,age,hemorrhoid grade,surgical time,and hospitalization period between the observation group and the control group(P＞0.05),but the intraoperative blood loss in the observation group was less than that in the control group[(11.37±5.32)ml and(26.72±14.24)ml],and the difference between the two groups was statistically significant(P＜0.05).The severity of pain in the observation group was lower than that in the control group on the 1st and 7th day after surgery(P＜0.05);There was no statistically significant difference in the Wexner anal incontinence scores between the two groups at 1 and 8 weeks after surgery(P＞0.05).The observation group had a better gastrointestinal quality of life index(GIQLI)score than the control group at 2 weeks after surgery[(20.92±4.63)and(26.77±5.03)scores,P＜0.05],and there was no statistically significant difference between the two groups at 8 weeks[(4.38±0.90)and(4.68±1.41)mm,P＞0.05].The total incidence of postoperative complications in both groups was statistically significant(8.8％vs 20.6％,P＜0.05).An average follow-up of six months showed no recurrence.Conclusion Cupric ion electrochemical therapy for mixed hemorrhoids is safe,effective,and has no serious complications,providing a more convenient and minimally invasive treatment method.