OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

Purpose: This study aimed to evaluate the contrast-enhanced ultrasound with Sonazoid (Sonazoid-CEUS) features of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: In this retrospective study, patients who underwent surgical resection and were histopathologically diagnosed with NAFLD or cirrhosis-related HCC were included. All patients received Sonazoid-CEUS examinations within 1 week prior to hepatic surgery. The enhancement patterns of HCC lesions were evaluated and compared between the two groups according to the current World Federation for Ultrasound in Medicine and Biology guidelines. Multivariate logistic regression analysis was used to assess the correlations between Sonazoid-CEUS enhancement patterns and clinicopathologic characteristics. Results: From March 2022 to April 2023, a total of 151 patients with HCC were included, comprising 72 with NAFLD-related HCC and 79 with hepatitis B virus (HBV) cirrhosis–related HCC. On Sonazoid-CEUS, more than half of the NAFLD-related HCCs exhibited relatively early and mild washout within 60 seconds (54.2%, 39/72), whereas most HBV cirrhosis–related HCCs displayed washout between 60 and 120 seconds (46.8%, 37/79) or after 120 seconds (39.2%, 31/79) (P<0.001). In the patients with NAFLD-related HCC, multivariate analysis revealed that international normalized ratio (odds ratio [OR], 0.002; 95% confidence interval [CI], 0.000 to 0.899; P=0.046) and poor tumor differentiation (OR, 21.930; 95% CI, 1.960 to 245.319; P=0.012) were significantly associated with washout occurring within 60 seconds. Conclusion Characteristic Sonazoid-CEUS features are useful for diagnosing HCC in patients with NAFLD.

Diabetic kidney disease （DKD） is a kidney disease caused by hyperglycemia，which is one of the most common microvascular complications of diabetes. Due to the high incidence of diabetes，the incidence of DKD has also increased year by year，and DKD has become a global public health problem. The pathogenesis of DKD is related to mechanisms such as oxidative stress，inflammation，renal fibrosis，and decreased mitophagy activity，which are developed under a variety of complex mechanisms. In traditional Chinese medicine，it is believed that the incidence of DKD is closely related to damp heat. Therefore，it is necessary to grasp the treatment method of clearing heat and removing dampness in clinical medication. Huangkui Capsules （HKC） have the effect of clearing damp heat，detoxifying， and detumescence. Because of its unique curative effect on DKD，HKC is often used in the treatment of DKD. HKC plays a role in the treatment of DKD with a variety of pharmacokinetic and pharmacodynamic processes. In many laboratory studies，it has been found that the specific mechanisms of HKC in the treatment of DKD include increasing mitophagy，reducing mitochondrial damage，reducing renal fibrosis，controlling inflammatory response，and inhibiting oxidative stress，which can achieve the purpose of reducing renal damage and promoting renal function. Some clinical studies have also verified that the application of HKC alone can exert renal protective function through anti-inflammatory，anti-oxidative stress，anti-renal fibrosis effects，as well as reduction of urinary protein. Since DKD is not a single injury of renal function，it is often accompanied by problems in blood pressure，blood lipids，blood circulation，body immunity， and other aspects. Therefore，the combination of HKC with other drugs can often achieve more comprehensive results，improve the advantages of various drugs，and improve the therapeutic effect. The combination of drugs such as antihypertensive，lipid-lowering， vascular circulation improvement，immunity inhibition，and anti-oxidative stress with HKC has achieved good results. In addition，HKC is often used in combination with other Chinese patent medicines in clinics. The application of HKC in the treatment of DKD has made some progress，but there are still many places worthy of further study，and the research on the mechanism of HKC is not comprehensive enough. The research on its long-term effect and safety in clinical application is relatively lacking，and the drug variety is relatively single when combined with certain drugs. These problems deserve further attention. Finally，it is necessary to pay attention to the promotion and application of HKC in clinical practice so that HKC can be better applied in clinical practice and better solve practical problems for patients.

Diabetic kidney disease （DKD） is a kidney disease caused by hyperglycemia，which is one of the most common microvascular complications of diabetes. Due to the high incidence of diabetes，the incidence of DKD has also increased year by year，and DKD has become a global public health problem. The pathogenesis of DKD is related to mechanisms such as oxidative stress，inflammation，renal fibrosis，and decreased mitophagy activity，which are developed under a variety of complex mechanisms. In traditional Chinese medicine，it is believed that the incidence of DKD is closely related to damp heat. Therefore，it is necessary to grasp the treatment method of clearing heat and removing dampness in clinical medication. Huangkui Capsules （HKC） have the effect of clearing damp heat，detoxifying， and detumescence. Because of its unique curative effect on DKD，HKC is often used in the treatment of DKD. HKC plays a role in the treatment of DKD with a variety of pharmacokinetic and pharmacodynamic processes. In many laboratory studies，it has been found that the specific mechanisms of HKC in the treatment of DKD include increasing mitophagy，reducing mitochondrial damage，reducing renal fibrosis，controlling inflammatory response，and inhibiting oxidative stress，which can achieve the purpose of reducing renal damage and promoting renal function. Some clinical studies have also verified that the application of HKC alone can exert renal protective function through anti-inflammatory，anti-oxidative stress，anti-renal fibrosis effects，as well as reduction of urinary protein. Since DKD is not a single injury of renal function，it is often accompanied by problems in blood pressure，blood lipids，blood circulation，body immunity， and other aspects. Therefore，the combination of HKC with other drugs can often achieve more comprehensive results，improve the advantages of various drugs，and improve the therapeutic effect. The combination of drugs such as antihypertensive，lipid-lowering， vascular circulation improvement，immunity inhibition，and anti-oxidative stress with HKC has achieved good results. In addition，HKC is often used in combination with other Chinese patent medicines in clinics. The application of HKC in the treatment of DKD has made some progress，but there are still many places worthy of further study，and the research on the mechanism of HKC is not comprehensive enough. The research on its long-term effect and safety in clinical application is relatively lacking，and the drug variety is relatively single when combined with certain drugs. These problems deserve further attention. Finally，it is necessary to pay attention to the promotion and application of HKC in clinical practice so that HKC can be better applied in clinical practice and better solve practical problems for patients.

Objective: To explore the effect of YTH domain family protein 1(YTHDF1) on the activation, proliferation and migration of hepatic stellate cells(HSCs) by regulating mitochondrial fission mediated by mitochondrial fission protein 1(Fis1). Methods: The mouse hepatic stellate cell line JS-1 was treated with 5 ng/ml TGF-β1 for 24 h to induce its activation and proliferation, andYTHDF1-siRNA was used to construct aYTHDF1silencing model.The experiment was divided into Control group, TGF-β1 group, TGF-β1+si-NC group and TGF-β1+si-YTHDF1 group.Expression changes ofYTHDF1,Fis1and key indicators of fibrosis, type Ⅰ collagen(CollagenⅠ) and α-smooth muscle actin(α-SMA) were detected through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot; CCK-8 was used to detect cell proliferation ability; Transwell migration assay and cell scratch assay were used to detect cell migration ability; immunofluorescence staining experiment was used to detect the effect ofYTHDF1onFis1-mediated mitochondrial fission; finally, JC-1 staining was used to experimentally detect the effect ofYTHDF1on mitochondrial membrane potential. Results: Compared with the Control group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1increased in the TGF-β1 group(P<0.05,P<0.01;P<0.000 1), as well as the fibrosis markersCollagenⅠand the expression level of α-SMA increased(P<0.01;P<0.001,P<0.000 1); while adding CCK-8, the experimental results showed that the proliferation ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); Transwell experimental results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.01); the cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); the immunofluorescence experiment results showed that the TGF-β1 group Mito-Tracker Red staining andFis1co-localization signal increased(P<0.05); JC-1 staining experiment results showed that the mitochondrial membrane potential increased in the TGF-β1 group(P<0.01). Compared with the TGF-β1+si-NC group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1in the TGF-β1+si-YTHDF1 group was reduced(P<0.01;P<0.001), and fibrosis markers the levels ofCollagenⅠandα-SMAwere reduced(P<0.01;P<0.001,P<0.01).CCK-8 experimental results showed that the proliferation ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); Transwell experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.001); cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); immunofluorescence experiment results showed that the Mito-Tracker Red staining andFis1co-localization signal decreased in the TGF-β1+si-YTHDF1 group(P<0.01); JC-1 staining experiment results showed that mitochondrial membrane potential decreased in the TGF-β1+si-YTHDF1 group(P<0.05). Conclusion YTHDF1promotes the activation, proliferation and migration capabilities of HSCs by positively regulatingFis1-mediated mitochondrial fission. This suggests thatYTHDF1may be a key gene involved in regulating the activation, proliferation and migration of HSCs.

ObjectiveThis paper aims to investigate the potential molecular biological mechanism of Buyang Huanwu Tongfeng decoction in treating hyperuricemia and gouty arthritis by network pharmacology and molecular docking technology and preliminarily verify the mechanism through animal experiments. MethodsThe active ingredients and targets in the Buyang Huanwu Tongfeng decoction were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and ETCM databases. The DisGeNET and GeneCards databases were utilized to acquire disease targets associated with hyperuricemia and gouty arthritis. These disease targets were then intersected with drug targets to identify key targets. The R language ClusterProfiler package and Python were employed for conducting gene ontology（GO） enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis. The regulatory network diagram of the drug-key target-function-pathway was visualized using Cytoscape 3.9.1 software， and the protein-protein interaction （PPI） network for key targets was depicted. Finally， the hub gene was determined through topological analysis. Auto Dock， PyMOL， and other software were used for molecular docking to explore the possible therapeutic mechanism of Buyang Huanwu Tongfeng decoction for hyperuricemia and gouty arthritis. In animal experiments， a composite rat model of hyperuricemia induced by intraperitoneal injection of oteracil potassium combined with gouty arthritis induced by the modified Coderre method was established. Through hematoxylin-eosin（HE） staining， uric acid test， enzyme linked immunosorbent assay（ELISA）， Western blot， and real-time polymerase chain reaction（Real-time PCR）， the molecular mechanism and key targets of Buyang Huanwu Tongfeng decoction for treating hyperuricemia and gouty arthritis were observed. ResultsAfter screening and removing duplicate values， 76 active ingredients and 15 key targets were finally obtained. GO enrichment analysis yielded that the treatment of hyperuricemia and gouty arthritis with Buyang Huanwu Tongfeng decoction was significantly associated with acute inflammatory response， astrocyte activation， regulation of interleukin （IL）-8 production， nuclear receptor activity， and binding of growth factor receptor. KEGG pathway enrichment analysis obtained that the key target genes were significantly associated with the IL-17 signaling pathway， advanced glycosylation end/receptor of advanced glycation endproducts（AGE/RAGE） signaling pathway， anti-inflammatory， and other pathways. PPI network indicated that albumin（ALB）， peroxisome proliferator-activated receptor-γ （PPAR-γ）， IL-6， IL-1β， and C-reactive protein（CRP） were the key protein targets. The molecular docking results showed that ALB had the strongest binding force with beta-carotene （β-carotene）. Biochemical results showed that blood uric acid decreased in the Buyang Huanwu Tongfeng decoction groups. HE staining results showed that the low-dose （7.76 g·kg^-1·d^-1）， medium-dose （15.53 g·kg^-1·d^-1）， and high-dose （31.05 g·kg^-1·d^-1） groups of Buyang Huanwu Tongfeng decoction had different degrees of remission， and the remission of the high-dose group was the most obvious. Fibroblastic tissue hyperplasia in synovial joints accompanied with inflammatory cell infiltration， as well as inflammatory cell infiltration in renal tissue of the high-dose group was significantly reduced， followed by the medium-dose and low-dose groups， and the expression of ALB， PPAR-γ， IL-6， IL-1β， and CRP was down-regulated to different degrees. ConclusionBy regulating the targets such as ALB， PPAR-γ， IL-6， IL-1β， and CRP， inhibiting the PPAR-γ/nuclear transcription factor （NF）-κB pathway， and reducing AGEs/RAGE-mediated inflammation， Buyang Huanwu Tongfeng decoction exerts anti-inflammatory and analgesic effects and activates blood circulation and diuresis in the treatment of hyperuricemia and gouty arthritis.

AIM: To observe the changes of retinal nerve fiber layer(RNFL)thickness and radial peripheral capillary(RPC)density in patients with unilateral branch retinal vein occlusion(BRVO), and further analyze the correlation between RPC density and RNFL thickness.METHODS: Observational study. Totally 37 patients with unilateral BRVO diagnosed at the ophthalmology department of First Hospital of Qinhuangdao from October 2020 to January 2022 were selected, the 37 affected eyes were the unilateral BRVO group, and 37 fellow healthy eyes were the contralateral unaffected group, and 35 healthy individuals(35 right eyes were selected)without ocular diseases during the same period were selected as the normal control group. The best corrected visual acuity, intraocular pressure, anterior segment, fundus and optical coherence tomography angiography(OCTA)were examined in both eyes of all BRVO patients and healthy individuals. The central macular thickness(CMT), the RNFL thickness, and the optic disc-AV crossing distance(DAVD)were measured by built-in software of the OCTA equipment. The optimized U-net algorithm was used to eliminate the large blood vessels, and then the RPC density was calculated. The CMT, RNFL thickness and RPC density were compared among the three groups. And the correlations of the RPC density with the CMT, RNFL thickness, and the DAVD were investigated.RESULTS: Compared with the contralateral unaffected group and the normal control group, the CMT and the RNFL thickness were significantly thickened in the unilateral BRVO group(all P<0.05); there were no statistical differences in the CMT and the RNFL thickness between the contralateral unaffected group and the normal control group(all P>0.05). The RPC density in the unilateral BRVO group increased compared with the contralateral unaffected group and decreased compared with the normal control group, but there was no statistically difference(all P>0.05). However, the RPC density in the contralateral unaffected group decreased compared with the normal control group(P<0.05). The RPC density in the unilateral BRVO group was not correlated with the CMT(P=0.960), but positively correlated with the RNFL thickness(r=0.401, P=0.014)and negatively correlated with the DAVD(r=-0.339, P=0.040).CONCLUSION: The RNFL thickened significantly and the RPC density did not change significantly in the optic disc area of BRVO patients. The RPC density is positively correlated with the RNFL thickness, indicating that the RNFL thickness can be used as a monitoring indicator to analyze and study the damage degree of the RPC density.

ObjectiveTo investigate the mechanism by which Wendantang regulates the silent information regulator 3 （SIRT3）/peroxisome proliferator-activated receptor-gamma coactivator-1α （PGC-1α） pathway to influence energy metabolism and thereby prevent and treat myocardial ischemia （MI） in a rat model of hyperlipidemia （HL）. MethodsThirty SD rats were randomly assigned into five groups： control， model， low-dose （3.702 g·kg^-1·d^-1） Wendantang， high-dose （7.404 g·kg^-1·d^-1） Wendantang， and positive control （trimetazidine， 0.006 g·kg^-1·d^-1）， with six rats in each group. The control group was fed normally， while the other groups were fed with a high-fat diet for six weeks for the modeling of HL. Subsequently， the drug intervention groups were administrated with corresponding drugs by gavage， and the control and model groups received an equivalent volume of normal saline for 14 days. One hour after the last gavage， the other groups except the control group were injected intraperitoneally with posterior pituitary hormone （30 U·kg^-1） to induce MI. Electrocardiography （ECG） was employed to detect changes in the electrocardiogram. Hematoxylin-eosin staining was performed to observe cardiac pathological changes. Enzyme-linked immunosorbent assay was employed to measure the serum levels of cardiac troponin I（cTnI）， myoglobin （MYO）， and creatine kinase-MB （CK-MB）. Colorimetry was used to determine the levels of total cholesterol （TC） and triglycerides （TG） in the serum and ATP， malondialdehyde （MDA）， and superoxide dismutase （SOD） in the myocardial tissue. Western blot was employed to determine the protein levels of SIRT3， PGC-1α， adenosine monophosphate-activated protein kinase （AMPK）， and phosphorylated AMPK （p-AMPK） in the myocardial tissue. Real-time PCR was employed to measure the mRNA levels of SIRT3， PGC-1α， and AMPKα in the myocardial tissue. ResultsCompared with the control group， the model group showed significant J-point deviation and elevation in the ECG image， increased heart rate， disarrangement of myocardial fibers with unclear boundaries， elevated levels of CK-MB， cTnI， MYO， TC， and TG （P<0.05， P<0.01）， declined levels of SOD and ATP （P<0.01）， down-regulated mRNA levels of SIRT3， PGC-1α， and AMPK （P<0.05）， and down-regulated protein levels of SIRT3， PGC-1α， and p-AMPK （P<0.05）. Compared with the model group， the low-dose and high-dose Wendantang groups and the trimetazidine group showed inhibited J-point deviation and elevation in the ECG image， slowed heart rate， reduced inflammatory cell infiltration， alleviated disarrangement of myocardial fibers， declined levels of CK-MB， cTnI， MYO， TC， and TG （P<0.05， P<0.01）， elevated level of SOD （P<0.01）， up-regulated mRNA levels of SIRT3， PGC-1α， and AMPK （P<0.05， P<0.01） and up-regulated protein levels of SIRT3， PGC-1α， and p-AMPK （P<0.05， P<0.01）. ConclusionWendantang can effectively intervene in HL-associated MI in rats by reducing oxidative stress in myocardial cells， alleviating lipid metabolism disorders， and improving myocardial energy metabolism via the SIRT3/PGC-1α signaling pathway.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.