In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.

Objective To establish an indirect enzyme-linked immunosorbent assay(ELISA)method for testing the concentration of a monoclonal antibody target tumor necrosis factor-α(TNF-α)in animal serum.Methods The critical parameters of the method including coating concentration of human TNF-α,source,concentration and stability of HRP-labeled goat anti-human immunoglobulin G(IgG)were investigated.The specificity,accuracy,precision,linearity and Limited of Determination of the method were investigated.Results The critical parameters of the method were confirmed as below:TNF-α was coated at 400 ng·mL-1;HRP labeled goat anti-human IgG antibody was diluted at 1:3.0 ×105;the diluted horseradish peroxidase labeled goat anti-human IgG antibody is well stored at 4 ℃ for 3 days.Meanwhile the method was confirmed to have good specificity,the recovery rate ranged from 84.00％to 106.82％,the coefficient of variation of different antibody concentration levels were no more than 10％;the method had a good linearity and the standard curve was y=(-8.37×103-2.37 × 106)/[1+(x/29.80)106]+2.37 × 106(R2=0.999);the limit of quantification was 1 ng·mL-1,all of which met the requirements.Conclusion A accurate and robust ELISA method was developed to test the concentration of anti-TNF-α monoclonal antibody in serum.

This article provides an in-depth analysis of the clinical development process of three non-hormonal drugs,desvenlafaxine extended-release tablets,esmirtazapine tablets and paroxetine capsules,for the treatment of menopausal hot flashes.Both desvenlafaxine extended-release tablets and esmirtazapine tablets were rejected by regulators for poor benefit-risk balance due to inadequate efficacy and safety concerns.In contrast,paroxetine capsules effectively reduced the risk of drug development failure by setting placebo lead-in periods,more conservative sample size estimates,and pre-specifying meta-analyses of key efficacy measures in the two phase Ⅲ trials,not only demonstrating efficacy in the frequency and degree of hot flashes,but also exploring the best-tolerated dose through multiple phase Ⅱ trials,which was finally approved by the U.S.Food and Drug Administration.The development of non-hormonal drugs for the treatment of menopausal hot flashes faces many challenges,including drug safety characteristics that are different from those in patients with psychiatric diseases,weak drug efficacy,weak correlation between preclinical efficacy models and clinical symptom remission,and the need for large sample sizes for dose-finding trials.This case study provides a strategic reference for optimizing trial design and reducing the risk of drug development for subsequent drug development with similar indications.

Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.

Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.

Proprotein convertase subtilisin/kexin type 9(PCSK9)comprised of 692 amino acids is the ninth mem-ber of protease family.It binds to the low-density lipoprotein receptor(LDLR),leading to elevated levels of circulating low-density lipoprotein cholesterol(LDLC),which can lead to a number of cardiovascular diseases,and among then the re-lationship with cardiovascular calcification has recently received attention.Cardiovascular calcification is a kind of ectopic mineralisation in the cardiovascular system,which is mainly characterised by the production of mineral deposits in the vas-cular wall and vascular valves,and its pathogenesis is related to lipoprotein content,platelet activity,matrix vesicle(MV)release and inflammation,through which PCSK9 may be involved in the occurrence of cardiovascular calcification.Therefore,this article reviews the relationship between PCSK9 and cardiovascular calcification,emphasizing the specific role of PCSK9 in affecting cardiovascular calcification through various pathways,assisting in setting up emerging applica-tions of PCSK9 amid vessel biological science and recognize innovative molecular mechanisms for its treatment.

Ichthyosis is a hereditary dyskeratotic skin disease with systemic skin dryness and roughness,mainly manifested by scaly skin,which may be accompanied by ocular abnormalities.At present,there are many studies on skin fungal infection caused by ichthyosis,but only few reports on cases with combined ocular fungal infection.This paper reports a case of X-linked recessive hereditary ichthyosis with recurrent fungal keratitis(FK),which is expec-ted to provide reference for clinical early diagnosis and treatment of this disease.

Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1％vs.0.7％,P=0.030),left main disease(43.9％vs.27.0％,P=0.018),triple vessel disease(90.9％vs.75.5％,P=0.009),and RCA chronic total occlusion disease(60.6％vs.35.5％,P＜0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9％vs.16.7％,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7％vs.9.2％,P=0.031).The rates of 1-month MACE(4.5％vs.2.6％,P=0.435)and 1-year MACE(7.6％vs.7.9％,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95％CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95％CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.

Objective To establish an animal model of lung adenoma in BALB/c mice based on dynamic characterization by micro-computed tomography(CT).Methods Eighty female SPF-grade BALB/c mice were divided randomly into four groups:model low dose group(1 mg/g urethane,iP,once),model medium dose group(1 mg/g urethane,ip,once a week,followed by 2 weeks),model high dose group(1 mg/g urethane,ip,once a week,followed by 4 weeks),and blank group(equal volume of saline).Growth of lung nodules in the mice was monitored regularly using Micro-CT.Three-dimensional images of the lungs were drawn using the Analyze 12.0 system,and lung tissues were taken for histopathological examination(hematoxylin and eosin).Results Lung nodules with round high-density shadows were observed at week 11 in all model groups compared with the findings in the blank group.The rate of nodule formation increased with increasing modeling weeks,with rates of nodule formation in the model high,medium,and low dose groups of 93.8%,93.8%,and 87.5%,respectively,at week 21.Most mice had two to four,followed by one,and one to two nodules,respectively.The average maximum diameter of the lung nodules in the low dose group was significantly higher than the diameters in the medium-and high-dose groups(P＜0.05),but there was no significant difference in lung nodule volume among the three groups.Regarding pathological type,hematoxylin and eosin staining revealed that the tumors in all the model groups were lung adenomas.Conclusions Lung adenomas were successfully induced in all urethane dose groups of mice and growth of the lung nodules could be characterized by micro-CT.The rate of nodule formation was highest in the medium dose group,which developed a moderate number of lung adenomas and provided a stable model,and was thus considered the most suitable model for the study of lung adenomas in mice.

In response to the limitation of some medical image segmentation models for rectal cancer auxiliary diagnosis that are only applicable to single-modality images,a medical image segmentation method based on a cross attention mechanism that is applicable to both CT and MRI modalities is presented.Considering the different feature representations of CT and MRI images,a cross attention mechanism is proposed to unify the feature representations of the two types of images.In view of the small lesions on rectal cancer images,an improved Swin Transformer segmentation network with 3 branches is established,and the cross attention mechanism is incorporated into it,enabling the model to segment lesion areas in both types of images.The proposed method is validated using CT and MRI image data from patients with rectal cancer.Compared with ADDA,CycleGAN,and SIFA methods,the proposed method improves the accuracy by 2.94%,3.05%,0.71%on CT images,and 3.31%,4.55%,1.76%on MRI images,respectively,demonstrating its superior segmentation performance for both types of images.