OBJECTIVE To evaluate the safety of fondaparinux in pregnancy and provide reference for its rational clinical application. METHODS A search was conducted in databases including CNKI， Wanfang， PubMed， Embase， and Elsevier （the search time was from the construction of the database to December 17， 2024） to collect case report literature on fondaparinux use during pregnancy. Patient demographic information， fondaparinux use during pregnancy， concomitant medications， clinical manifestations， and treatment details were extracted for descriptive statistical analysis. RESULTS A total of 17 case reports regarding the use of fondaparinux during pregnancy were collected， involving 42 patients from 11 countries and 47 pregnancy records. Among these， 20 cases involved the use of fondaparinux for the prevention of pregnancy-related venous thromboembolism （VTE）， while 27 cases were fondaparinux treatment due to related conditions. A total of 29 occurrences of the patients were treated with fondaparinux due to a （family） history of VTE. Nine occurrences of complicated pregnancies were reported， and 35 patients had records of comorbidities or relevant medical histories. The adverse events that occurred during pregnancy with the use of fondaparinux include postpartum hemorrhage （7 cases） and excessive anticoagulation caused by inappropriate dosage （1 case）. Among the 7 cases of postpartum hemorrhage， 3 cases had a blood loss of no less than 1 000 mL （including 2 cases with uterine atony）， 3 cases had a drug discontinuation time of ≤12 h. CONCLUSIONS Based on the existing literature， the safety of fondaparinux during pregnancy is generally manageable， with the main adverse event being postpartum hemorrhage. The dosage， interval between discontinuation，comorbidities/medical history， and concomitant medications of fondaparinux may be the main causes of its adverse events.

This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）. He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever， chills， and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile， soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice， treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids， using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect， particularly in cases where multiple anti-infective treatments have failed.

Objective To prepare polymersomes (PSs) by block copolymers，evaluate their membrane structural stability，investigate the H⁺ transmembrane permeability of PSs and the impact of 1,4-dioxane and establish a foundation for drug encapsulation within polymersomes. Methods PSs were self-assembled by a block copolymer, PEG-PLGA, in a solvent solution. The pH-sensitive fluorescence probe HPTS was employed to examine the H⁺ transmembrane properties of PSs and compare them with PSs prepared using PBD-b-PEO, PS-b-PEO, and liposomes. The effect of varying concentrations of 1,4-dioxane on PSs’ membrane permeability properties was also investigated. Results The fluorescence excitation spectra of HPTS exhibited pH dependency, which showed a linear correlation between extravesicular H⁺ concentration and t^1/2. Significant differences were observed in the membrane permeability capabilities of PSs with different membrane wall thicknesses. Compared to liposomes, the H⁺ transmembrane coefficients for the three types of PSs were reduced by 2.39×10⁴, 3.38×10⁴, and 5.48×10⁸ times, respectively. 1,4-dioxane was found to modulate the permeability of PSs’ membranes, which displayed a concentration-dependent relationship. Conclusion PSs exhibited significantly lower membrane permeability compared to liposomes, indicating superior stability. 1,4-dioxane was identified as a modulator of PSs’ permeability, which offered potential for drug loading and release within PSs.

BACKGROUND:Nano-zirconium dioxide has good application potential in the field of bone tissue repair.Studying the effect of nano-zirconium dioxide on osteogenic differentiation will help to promote the clinical application of nano-zirconium dioxide in the treatment of bone defects. OBJECTIVE:To explore the effect of nano-zirconium dioxide on the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa. METHODS:Ectomesenchymal stem cells derived from rat nasal mucosa were isolated and cultured,and the biotoxicity of nano-zirconium dioxide to the cells was detected by CCK-8 assay.The biosafety concentration was selected according to the cytotoxicity,and the cells were randomly divided into a control group,a nano-zirconium dioxide group,and a nano-hydroxyapatite group.Osteogenic differentiation of cells was directionally induced in each group.On day 7 of induced differentiation,alkaline phosphatase staining was performed.qRT-PCR and western blot assay were used to detect the expression of early osteogenic markers(Runx2 and Osx).On day 21 of induced differentiation,alizarin red staining was conducted.qRT-PCR and western blot assay were utilized to determine the expression levels of late osteogenic markers(OPN and OCN). RESULTS AND CONCLUSION:(1)The median lethal concentration of nano-zirconium dioxide on ectomesenchymal stem cells in nasal mucosa was 0.6 mg/mL.In the experiment,the mass concentration of 200 μg/mL was selected for intervention.Zirconium dioxide had no significant effect on the proliferation of the cells.(2)Compared with the control group,the alkaline phosphatase staining of the cells in the nano-zirconium dioxide group was more obvious and the level of cell mineralization was higher,but there was no significant difference compared with the nano-hydroxyapatite.(3)Compared with the control group,the expression of bone-related genes and proteins increased significantly,but there was no significant difference compared with nano-hydroxyapatite.(4)The results show that nano-zirconium dioxide has good biological safety and can promote the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa.This promoting effect is equivalent to that of nano-hydroxyapatite.

Objective:To analyze and explore the effect of dapagliflozin on cardiac function,mitogen activated protein ki-nase(MAPK),inducible nitric oxide synthase(iNOS)and extracellular regulated protein kinase 1/2(ERK1/2)in patients with severe heart failure(SHF).Methods:A total of 122 SHF patients treated in our hospital were selected,randomly and equally divided into routine treatment group(received diuretic vasodilation-dominant basic therapy)and dapagliflozin group(received dapagliflozin based on routine treatment group).After three-month treatment,therapeutic effect,cardi-ac function,coronary hemodynamic indexes and therapeutic safety were compared between two groups.Results:The total effective rate of dapagliflozin group was significantly higher than that of routine treatment group(91.80％vs.77.05％,P=0.025).Compared with routine treatment group after treatment,there were significant rise in left ventricular ejection fraction(LVEF),stroke volume(SV),diastolic peak velocity(DPV),systolic peak velocity(SPV)and coronary blood flow(CBF),and significant reductions in QT interval dispersion(QTd),left ventricular end-diastolic diameter(LVEDd),coronary resistance(CR)and levels of MAPK[(46.79±7.02)ng/L vs.(39.38±5.82)ng/L],iNOS[(88.93±10.02)μmol/L vs.(79.61±9.04)μmol/L]and ERK1/2[(27.03±5.83)ng/L vs.(21.62±4.18)ng/L]in dapagliflozin group,P=0.001 all.There was no significant difference in incidence rate of adverse reactions between two groups,P=0.408.Conclusion:Dapagliflozin combined with diuretic and vasodilator therapy has a significant therapeutic effect on patients with severe heart failure,which can improve cardiac function and coronary hemodynamics,reduce the levels of MAPK,iNOS,and ERK1/2 with good safety.

Objective To formulate a pharmaceutical service pathway to standardize the pharmacists'whole process of pharmaceutical services for breast cancer patients in medical institutions,promote the standardization of pharmacists'work and improve the rationality of drug use for breast cancer patients in medical institutions.Methods The editorial committee aimed at several challenging problems in the whole process of pharmaceutical services for breast cancer patients in medical institutions through systematic search,referring to the latest domestic and international guidelines and expert consensus of breast cancer and under the relevant drug administration regulations in China,collected and sorted out the professional opinions of doctors,pharmacists,and methodological experts,developed questionnaires and held two rounds of expert argumentation meetings,and finally screened out the most valuable results.The whole process management pathway of pharmaceutical care for breast cancer patients was formulated,and the referral principles of hospitals at different levels and the contents of pharmacist training and assessment were clarified.Results The whole process management pathway of pharmaceutical services for breast cancer patients was developed,including information collection,analysis,evaluation,development implementation of intervention plans,and follow-up.Conclusion This pharmaceutical service pathway can standardize and guide pharmacists in hospitals at different levels to carry out pharmaceutical services for breast cancer patients,achieve the whole process of monitoring drug use,and ensure rational drug use and treatment effectiveness for patients.

For patients with abnormal thyroid function,the detection of peripheral blood coagulation indicators may be irregular,and there is a potential risk of thrombosis or bleeding.Patients with hyperthyroidism have significant endothelial dysfunction and risk of thrombosis.However,the reports on the effect of hypothyroidism on coagulation function are still controversial.The potential risk of abnormal thyroid function to the coagulation system may interfere with the safety of anticoagulant therapy,and the interaction between thyroid disease treatment drugs and anticoagulant drugs also affects the safety of the patient's medication.Therefore,this article is based on previous research literature,analyzes the correlation between abnormal thyroid function and coagulation function,and evaluates and discusses the impact of abnormal thyroid function on the coagulation system and related therapeutic drug interactions.It is expected to provide a reference for diagnosing and treating patients with thyroid dysfunction and abnormal coagulation function.

In January 2023,the American Heart Association(AHA)released A Scientific Statement:Cancer Therapy Related Hypertension,provided an overview of the mechanisms and clinical management of anticancer therapy related hypertension.Contemporary anticancer drugs are mostly at the expense of cardiovascular toxicities,one of the most common side effects is hypertension,especially vascular endothelial growth factor inhibitors,as well as tyrosine kinase inhibitors and proteasome inhibitors.Cancer therapy related hypertension is often dose limiting,and is usually reversible after interruption or discontinuation of treatment.The exact molecular mechanisms underlying hypertension are unclear,recent discoveries indicate an important role for decreased nitric oxide,increased endothelin-1,endothelial dysfunction,increased sympathetic outflow,and microvascular rarefaction.Based on the International Cardio Oncology Society(IC-OS),this article provides an interpretation of the diagnosis and management of hypertension related to cancer treatment.Insufficient evidence exists supporting an antihypertensive medication strategy specific to patients with anticancer therapy induced hypertension,therefore,antihypertensive management should follow current guidelines for the general population..Multidisciplinary cooperation is needed to optimize management to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.

Patients with gastric cancer are at high risk for venous thromboembolism(VTE)and bleeding,and patients who develop VTE are often associated with poor outcomes,making it clinically challenging to identify and manage the risk of thrombosis in patients with gastric cancer.Risk factors for VTE in gastric cancer patients include age,obesity,surgery,chemotherapy,etc.It is essential to identify high-risk patients and adopt aggressive prevention strategies.The main strategy to prevent and treat VTE is the use of anticoagulant drugs.This article discusses guidelines and recent studies for the prevention and treatment of VTE in patients with gastric cancer to help clinicians make individualized decisions for their patients and maximize clinical outcomes for their patients.

Patients with primary membranous nephropathy(PMN)tend to develop thrombosis,especially in the early phase of the disease.The pathogenesis of thrombosis is multifactorial,with hypoalbuminemia being widely regarded as an inde-pendent risk factor.Other factors include proteinuria,M-type phospholipase A2 receptor antibody,and D-dimer.Although prophy-lactic anticoagulation therapy is frequently used in clinical practice to prevent thrombosis in PMN patients,there are still many un-resolved issues regarding the optimal prevention of thrombosis in this condition.The timing of prophylactic anticoagulation,the threshold of serum albumin level,and the choice of treatment regimen are still lacking consensus.This article reviewed the relevant literature on these topics,aiming to establish a standard for thrombosis prevention and treatment for this population in the future and provide guidance for clinical practice.