Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) block downstream signaling pathways by inhibiting receptor tyrosine kinase activity, consequently suppressing proliferation, invasion and metastasis of tumor cells. EGFR-TKIs have been proven to be highly effective in patients with late non-small cell lung cancer (NSCLC) harboring EGFR sensitive mutations, significantly better than chemotherapy. Third-generation EGFR-TKIs, such as osimertinib, have emerged as the first-line treatment for advanced NSCLC patients with sensitive EGFR mutations. However, there are still some patients who exhibit primary resistance upon initial treatment with EGFR-TKIs. The exact mechanism of primary resistance remains unknown, and may be related to factors such as the structure of EGFR mutation subtypes, concurrent mutations, BIM deletion polymorphism, and high expression of programmed cell death-ligand 1. This review summarizes the molecular mechanisms of primary resistance to EGFR-TKIs and discusses potential therapeutic strategies, with the goal of optimizing precision targeted therapy for NSCLC patients.

ObjectiveThis study aims to construct a reconstituted high-density lipoprotein (rHDL) delivery system loaded with kinsenoside (KD@rHDL), and to systematically evaluate its function in enhancing the phagocytosis of amyloid β-protein (Aβ) by microglia and improving the inflammatory state of microglia, as well as to preliminarily explore its potential application value in the treatment of Alzheimer’s disease (AD). MethodsKD@rHDL was prepared by the film hydration method combined with probe sonication and co-incubation. Its morphology was observed by transmission electron microscopy, and the particle size and Zeta potential were measured by dynamic light scattering. The encapsulation efficiency and drug loading were determined by high-performance liquid chromatography. The affinity between KD@rHDL and Aβ was analyzed by surface plasmon resonance (SPR) to assess its feasibility as a medium for Aβ clearance. At the cellular level, after treating mouse microglial cells (BV-2 cells) with KD@rHDL and adding fluorescently labeled Aβ, the phagocytic efficiency of microglia for Aβ was detected by confocal microscopy. Meanwhile, the CCK-8 method was used to evaluate the effect of KD@rHDL on cell viability to determine its safety. The trans-barrier transport ability of KD@rHDL was detected by Transwell assay. The expression levels of NLRP3 inflammasome and downstream inflammatory factor IL-1β in LPS-induced microglia were detected by Western blot to evaluate the regulatory effect of KD@rHDL on the inflammatory state of cells. ResultsCharacterization results showed that the successfully prepared KD@rHDL presented a typical discoid structure under transmission electron microscopy, with a uniform particle size distribution, an average particle size of approximately (14.4±0.24) nm, and a suitable negative Zeta potential, demonstrating good colloidal stability. The drug content determination results indicated that the encapsulation efficiency of KD@rHDL for kinsenoside was (42.24±1.30)%, and the drug loading was (6.03±0.19)%, indicating a good drug loading capacity. The CCK-8 assay results showed that in the set concentration range, the survival rates of BV2 and HT22 cells in the KD@rHDL treatment group were all above 90%, with no significant difference from the control group, indicating good cell safety of the formulation. The results of the Aβ phagocytosis experiment indicated that, compared with the Aβ oligomers (Aβo) group alone, the fluorescence signal intensity within microglia in the KD@rHDL treatment group was significantly enhanced, and a large amount of fluorescence-labeled Aβ was observed to accumulate intracellularly under a fluorescence microscope. The SPR assay results showed that rHDL had a strong affinity for Aβ, with an affinity constant reaching the nanomolar level. Transwell assay results indicated that KD@rHDL could effectively cross the bEnd.3 cell monolayer barrier and be taken up by BV2 and HT22 cells. Western blot assay results showed that high-dose KD@rHDL treatment could significantly reduce the expression level of NLRP3 protein in LPS-induced microglia and simultaneously down-regulate the maturation and secretion of IL-1β, indicating that KD@rHDL can effectively inhibit the activation of the NLRP3 inflammasome pathway and improve the neuroinflammatory state mediated by microglia. ConclusionThis study successfully constructed a reconstituted high-density lipoprotein delivery system loaded with kinsenoside (KD@rHDL). This nano-delivery system not only significantly enhances the phagocytic clearance ability of microglia towards Aβ, but also effectively inhibits the NLRP3/IL-1β-mediated inflammatory pathway, improving the inflammatory state of microglia. The above results indicate that KD@rHDL has a synergistic effect in promoting Aβ clearance and alleviating neuroinflammation, demonstrating potential therapeutic value for AD and providing new ideas and experimental basis for the development of subsequent AD treatment strategies.

OBJECTIVE To provide a reference for anticoagulant therapy and vaginal bleeding management during medical abortion in patients with missed abortion after aortic mechanical valve replacement surgery. METHODS Clinical pharmacists conducted pharmaceutical monitoring on a patient with missed abortion after aortic mechanical valve replacement surgery， and analyzed the correlation between warfarin use and abortion. In response to gingival bleeding and an increase in the international normalized ratio （INR） after taking mifepristone， clinical pharmacists recommended discontinuing warfarin based on bleeding risk and INR changes； for the selection of sex hormones after missed abortion， clinical pharmacists suggested that estradiol gel combined with progesterone should be used in sequential treatment， supplemented by Xian yimucao capsules， to accelerate the elimination of residual tissue and congestion in uterine cavity. RESULTS The physician followed the advice of the clinical pharmacist and did not prolong the patient’s hospital stay due to excessive vaginal bleeding during treatment. Warfarin treatment was restarted on the day of discharge， and INR remained stable within the target anticoagulation range after discharge without any adverse events such as thromboembolism. CONCLUSIONS In patients with missed abortion after aortic valve replacement surgery， mifepristone may enhance the anticoagulant effect of warfarin and increase the risk of bleeding during medical abortion. It is recommended to discontinue warfarin before medication. Clinical pharmacists play a crucial role in the development of anticoagulation plans， identification of drug-drug interactions， assessment of bleeding risks， and selection of postoperative sex hormones. Through full pharmaceutical monitoring， they ensure the safety of patients’ medication.

OBJECTIVE To provide a reference for anticoagulant therapy and vaginal bleeding management during medical abortion in patients with missed abortion after aortic mechanical valve replacement surgery. METHODS Clinical pharmacists conducted pharmaceutical monitoring on a patient with missed abortion after aortic mechanical valve replacement surgery， and analyzed the correlation between warfarin use and abortion. In response to gingival bleeding and an increase in the international normalized ratio （INR） after taking mifepristone， clinical pharmacists recommended discontinuing warfarin based on bleeding risk and INR changes； for the selection of sex hormones after missed abortion， clinical pharmacists suggested that estradiol gel combined with progesterone should be used in sequential treatment， supplemented by Xian yimucao capsules， to accelerate the elimination of residual tissue and congestion in uterine cavity. RESULTS The physician followed the advice of the clinical pharmacist and did not prolong the patient’s hospital stay due to excessive vaginal bleeding during treatment. Warfarin treatment was restarted on the day of discharge， and INR remained stable within the target anticoagulation range after discharge without any adverse events such as thromboembolism. CONCLUSIONS In patients with missed abortion after aortic valve replacement surgery， mifepristone may enhance the anticoagulant effect of warfarin and increase the risk of bleeding during medical abortion. It is recommended to discontinue warfarin before medication. Clinical pharmacists play a crucial role in the development of anticoagulation plans， identification of drug-drug interactions， assessment of bleeding risks， and selection of postoperative sex hormones. Through full pharmaceutical monitoring， they ensure the safety of patients’ medication.

ObjectiveTo evaluate the predictive value of epicardial adipose tissue （EAT） parameters for microvascular obstruction （MVO） formation in patients with ST segment elevation myocardial infarction （STEMI） using cardiac magnetic resonance quantification. MethodsA total of 139 STEMI patients were included in this study， and various parameters such as EAT thickness， volume， and mass index were measured utilizing cardiac magnetic resonance. All included patients were divided into MVO group and non-MVO group according to whether MVO occurred. Differences in EAT related parameters between two groups were compared and correlation analysis was applied to evaluate the correlation between quantitative indicators of EAT and indicators such as infarct size and ejection fraction. Logistic regression analysis was used to identify the relevant risk factors for MVO formation. Receiver Operating Characteristic （ROC） curve analysis was performed to assess the predictive value of the epicardial adipose tissue （EAT） quality index and other indicators for the occurrence of MVO. ResultsCompared with non MVO group， patients in MVO group presented with higher peak troponin T levels， increase of neutrophil lymphocyte ratio （NLR） and C-reactive protein （CRP）， larger infarct size and compromised left ventricular ejection fraction （LVEF） （P<0.05）. Total EAT volume， EAT mass index， left atrioventricular EAT volume， left atrioventricular EAT mass index and thickness of EAT in the left atrioventricular groove were significantly higher in patients with MVO. Multivariate Logistic regression analysis demonstrated that NLR， peak troponin T levels and left atrioventricular EAT mass index were independent predictors of MVO. The ROC curve suggested that the left atrioventricular EAT mass index had the highest predictive power for MVO formation in STEMI patients. ConclusionThe parameters of EAT quantified by cardiac magnetic resonance serve as imaging biomarkers for predicting MVO formation in STEMI patients. These metrics enable risk stratification post-myocardial infarction and facilitate early identification of high-risk individuals， thereby supporting personalized therapeutic decision-making.

Objective:To improve the awareness of Beh?et′s disease with ventricular neoplasm.Methods:A case with fever, thrombosis, and right ventricular neoplasm was described. The diagnosis and treatment were analyzed and discussed.Results:A young male with genital ulcers and oral ulcers, ocular, skin, and vascular lesions presenting as large venous thrombus, was diagnosed with Beh?et′s disease. Pathological results of space-occupying lesion in right ventricle revealed inflammation and necrotic substance. Endocarditis was considered. Glucocorticoids and cyclophosphamide was given, together with warfarin. During one-year follow-up, the patient remained stable.Conclusion:It is difficult to distinguish between Beh?et′s disease with cardiac neoplasm and infective endocarditis or cardiac tumor based on clinical manifestations and imaging only. Multidisciplinary management is a valuable approach for the diagnosis and treatment.

Objective To investigate the association between single nucleotide polymorphisms(SNP)rs57095329 and rs6864584 of miR-146a gene and cervical intraepithelial neoplasia(CIN).Methods A total of 96 patients diagnosed with CIN were randomly collected as the CIN group,and 225 healthy individuals examined during the same period were selected as the control group using SPSS software.Genotyping of the above SNP loci was performed using the TaqMan probe method,and their correlation with CIN was analyzed.Results The allele and genotype distribution of rs57095329 showed a statistically significant differences compared to the control group,with the frequency of the allele A in the CIN group significantly lower than that in the control group(P<0.001;OR=0.48,95%CI:0.32～0.70).In the dominant model,individuals carrying the G allele(A/G-G/G)had a significantly increased risk of CIN(P<0.001;OR=2.67,95%CI:1.64～4.37).In contrast,no correlation was found between the rs6864584 and the risk of CIN.Conclusion The A allele of the miR-146a gene at the rs57095329 locus may be a protective factor for CIN.

Objective To investigate the correlation between single nucleotide polymorphisms(SNPs)of the EGF gene,including rs11569017(A>T),rs2237051(A>G),rs3733625(C>T),and rs4444903(A>G),and the risk of non-small cell lung cancer(NSCLC)in a Han population of Yunnan.Methods A total of 439 patients with NSCLC and 520 healthy controls were recruited in Yunnan Province between January 2022 and December 2023.Genotyping of four SNP loci in the EGF gene was performed using TaqMan probes,followed by analysis of allele,genotype,genetic model,and haplotype distribution frequencies between NSCLC and control groups.Stratified analyses were further conducted based on NSCLC pathological types and clinical stages.Results The rs2237051 locus showed significant differences in allele(P=0.011)and genotype(P=0.042)frequencies between the squamous cell carcinoma(SCC)group and the control group.The frequency of the A allele was lower in the SCC group than in the control group(OR=0.71,95%CI 0.54～1.85),but there was no difference after Bonferroni correction(P>0.0125).Under the log-additive model,the rs2237051-2G/G+A/G genotype was associated with an increased risk of SCC(P=0.01;OR=1.42,95%CI 1.08～1.86).However,the association lost statistical significance after Bonferroni correction(P>0.0125).The haplotype rs11569017-rs2237051-rs3733625-rs4444903 has no difference between the two groups(P>0.0125).The stratified analysis revealed no significant associations between the genetic loci and different disease stages(P>0.0125).Conclusion In the Yunnan Han population,the individuals carrying the rs2237051-A allele of the EGF gene have a significantly lower risk of squamous lung cancer,but further functional experiments are needed to verify the protective mechanism.

Objective To investigate the effects of Jinfukang on the growth of human lung cancer H358 cell xenografts in nude mice and its regulatory role in the TRIM52-mediated Wnt/β-catenin signaling pathway.Methods Human lung cancer H358 cells were cultured,and a subcutaneous xenograft model was established in nude mice.The mice were randomly divided into four groups:0.9％sodium chloride solution,cisplatin(3 mg·kg-1,intraperitoneal injection every 3 days),Jinfukang(0.4 mL,daily oral administration),and Jinfukang combined with cisplatin.Each group included 6 mice.After 15 days of continuous treatment,the tumor growth inhibition rate was calculated.Hematoxylin and eosin(H&E)staining was performed to observe tumor histopathological changes.TUNEL assay was used to evaluate apoptosis and calculate the apoptotic index.The relative mRNA expression levels and protein expression of TRIM52,PCNA,c-Myc,β-catenin,and Cyclin D1 were assessed by Real-time PCR and western blot,respectively.Results Compared with the saline group,Jinfukang,cisplatin,and Jinfukang combined with cisplatin treatments significantly inhibited tumor growth(P＜0.05).The combination group exhibited the most pronounced anti-tumor effect,slightly better than cisplatin alone,although the difference was not statistically significant(P＞0.05).Histopathological analysis and apoptosis indices revealed that the combination group showed the most severe necrosis and the highest level of apoptosis compared to other groups(P＜0.05).Furthermore,the combination group significantly downregulated the mRNA(P＜0.05)and protein(P＜0.05)expression levels of Cyclin D1,PCNA,TRIM52,β-catenin and c-Myc.Conclusion Jinfukang effectively inhibits the growth of human lung cancer H358 xenografts,disrupts tumor cell structure,and promotes apoptosis.Its anti-tumor effect is further enhanced when combined with cisplatin.The underlying mechanism may involve the downregulation of TRIM52 expression,leading to the suppression of Wnt/β-catenin signaling pathway activity and augmentation of anti-tumor efficacy.

OBJECTIVE To analyze the correlation between styloid process related parameters and symptoms in patients with styloid process syndrome.METHODS A retrospective study was conducted on the 3D reconstruction CT results of the styloid process in 68 patients diagnosed with styloid process syndrome who visited the Department of Otolaryngology Head and Neck Surgery,the Second Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2024.The relationship between parameters such as styloid process length,angle,distance from styloid process tip to pharynx,and specific symptoms in patients with styloid process syndrome was analyzed.RESULTS Among 68 patients with styloid process syndrome,44 had unilateral symptoms and 24 had bilateral symptoms.The length of the styloid process on the symptomatic side of patients with unilateral symptoms(3.86±0.16)cm was significantly longer than that on the asymptomatic side(2.98±0.17)cm(Z=-2.191,P=0.028);The length of the styloid process on the side with severe symptoms in patients with bilateral symptoms(3.98±0.37)cm was also significantly longer than that in patients with mild symptoms(3.37±0.15)cm(t=2.448,P=0.024).Patients with styloid process syndrome mainly present with pharyngalgia(64.71%,44/68).There were no significant differences in the length,inclination angle,anteversion angle,and distance between the styloid process tip and the pharynx among those with unilateral pharyngalgia(n=29),bilateral pharyngalgia(n=15),and non pharyngalgia(n=24)(P>0.05).However,among the 68 patients with styloid syndrome,12 had calcification of the styloid hyoid ligament,while 56 did not.The incidence of unilateral pharyngalgia was significantly higher in patients with calcification of the styloid hyoid ligament than in patients without calcification(66.7%vs.35.7%,χ2=3.909,P=0.048).CONCLUSION The severity of symptoms in patients with styloid process syndrome is related to the length of the styloid process,and those with calcification of the styloid hyoid ligament are more likely to experience pharyngalgia.