ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To develop a scientific,systematic,and operable healthcare quality evaluation system for Nation-al Regional Medical Centers(NRMCs),providing a theoretical basis and practical tool for objectively assessing their construction outcomes and guiding high-quality development.Methods Based on the classic"Structure-Process-Outcome"(SPO)quality management model,and aligned with national policy directives and the functional positioning of regional medical centers,a pre-liminary set of evaluation indicators was screened and an indicator system was constructed through literature review,policy analy-sis,and field investigations.Guangxi Hospital Division of The First Affiliated Hospital,Sun Yat-sen University was selected as the study subject,and cross-sectional data from March 2023 to June 2025 were collected for empirical application.Results A healthcare quality evaluation system for NRMCs was established,comprising 3 first-level dimensions(Structure Quality,Process Quality,Outcome Quality),10 second-level indicators,and 66 third-level indicators.This system covers multiple aspects,inclu-ding resource allocation,healthcare service efficiency,clinical practices,patient outcomes,and social benefits.Empirical results indicated that the center demonstrated a consistent upward trend in key indicators such as"Proportion of Discharged Patients Un-dergoing Level-4 Surgeries"(O1.2)and"DRG-CMI Value"(O2.1),while"Average Length of Hospital Stay"(P3.1)and"Cost Consumption Index"(O2.3)showed a steady decline.The indicator system effectively revealed the center's progress in en-hancing regional influence and operational efficiency.Conclusion The developed healthcare quality evaluation system is well-grounded in theory and practice,combining scientific rigor with policy relevance,and can serve as a decision-support tool for quality assessment and improvement in National Regional Medical Centers.

Objective:To compare the safety and efficacy of transarterial chemoembolization (TACE) combined with donafenib and programmed death protein 1 (PD-1) inhibitors and TACE combined with donafenib in the treatment of unresectable hepatocellular carcinoma (uHCC).Methods:Clinical data of 148 patients with uHCC treated at the First Affiliated Hospital of Zhengzhou University from December 2021 to December 2022 were retrospectively analyzed, including 127 males and 21 females, aged (56.6±9.9) years. Patients were divided into two groups: the TACE combined with donafenib and PD-1 inhibitors group (TACE+ DP, n=73) and TACE combined with single donafenib (TACE+ D, n=75). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and the occurrence of treatment-related adverse events (TRAEs) of the two groups of patients were observed. Kaplan-Meier analysis was used for survival assessment, and the log-rank test was used for comparison. The related factors affecting the prognosis of patients were indentified and analyzed. Results:The median PFS of patients in the TACE+ D group and the TACE+ DP group were 7.2 months (95% CI: 5.7-8.3 months) and 10.5months (95% CI: 8.9-11.3 months), respectively. The median OS was 13.2 months (95% CI: 12.3-13.7 months) and 16.9 months (95% CI: 15.1-19.8 months), respectively. All these differences were statistically significant ( χ2=17.81, 26.92, respectively, both P<0.001). The ORR and DCR of TACE+ DP group were both higher than those in TACE+ D group [53.4% (39/73) vs 36.0% (27/75), χ2=4.55, P=0.031; and 90.4% (66/73) vs 77.3% (58/75), χ2=4.66, P=0.044]. No grade 4 or above adverse events occurred in either the TACE+ DP or the TACE+ D group. The most common treatment-related adverse events in TACE+ D and TACE+ DP group were hand-foot syndrome [46.7% (35/75) vs 49.3% (36/73)], hypertension [26.7% (20/75) vs 30.1% (22/73)], fatigue [22.7% (17/75) vs 24.7% (18/73)], diarrhea [26.7% (20/75) vs 28.8% (21/73)], and thrombocytopenia [25.3% (19/75) vs 28.8% (21/73)]. There was no significant difference in the incidence and severity of TRAEs between the groups ( χ2=0.08, P=0.774). TACE+ DP treatment was a favorable prognostic factor for PFS ( HR=0.33, 95% CI: 0.22-0.49, P<0.001) and OS ( HR=0.19, 95% CI: 0.11-0.33, P<0.001) of patients. Conclusion:Compared to TACE combined with donafenib, TACE combined with donafenib and PD-1 inhibitors, with good efficacy and safety, significantly improved the treatment response and survival in patients with uHCC.

Objective To investigate the safety and efficacy of the radial artery hemostatic device in trans-brachial coronary intervention,and assess its effectiveness.Methods A retrospective analysis was conducted on patients who underwent trans-brachial coronary intervention at Peking University International Hospital from January 1,2018 to December 31,2023.The patients were divided into the radial artery hemostatic device group(170 cases)and the conventional compression group(100 cases)based on the postoperative hemostasis method,and the incidence of complications and clinical characteristics were compared between the two groups.Results A total of 270 patients underwent trans-brachial coronary intervention,with 18 complications occurring.Among them,17 cases were hemorrhage around the puncture site(16 cases were mild and 1 case was severe)and 1 was transient median nerve injury.The overall complication rate was 6.7％,and the incidence of hemorrhage around the puncture site was 6.3％.The hemorrhage rate in the radial artery hemostatic device group was 5.9％,while that in the conventional compression group was 7.0％,with no statistically significant difference between the two groups(P=0.715).Multivariate regression analysis indicated that female was an independent risk factor for hemorrhage around the puncture site(OR 4.57,95％CI 1.40-14.96,P=0.012).With the accumulation of technology,the application of trans-brachial access and radial artery hemostatic devices increased year by year(both P＜0.010).Conclusions The radial artery hemostatic device effectively controls bleeding in trans-brachial coronary interventions and demonstrates satisfactory safety.Its simplicity and efficacy provide a new strategy for hemostatic management in percutaneous trans-brachial access,which may gradually become the new standard in the future.

Objective:To investigate the relationship between SET domain bifurcated 1(SETDB1)expression and trefoil factor 1(TFF1)gene methylation,along with its clinical significance.Methods:Fifty-five lung adenocarcinoma samples and normal tissues of distant cancer were collected from the Affiliated Hospital of Chengde Medical College Hebei Province.TFF1 gene methylation levels were measured by pyrosequencing,relative TFF1 mRNA expression was assessed using quantitative real-time polymerase chain reaction(qRT-PCR),and TFF1 and SETDB1 protein expression were quantified via immunohistochemistry.The clinical significance and correlation between TFF1 methyla-tion levels and SETDB1 protein expression were analyzed statistically.In vitro,SETDB1 siRNA or negative control siRNA was transfected into A549 cells.Following transfection,SETDB1 mRNA expression was analyzed using qRT-PCR,and SETDB1 protein expression was evaluated via Western blot.TFF1 methylation was reassessed via pyrosequencing.Results:In lung adenocarcinoma and normal tissues of distant cancer,TFF1 gene methylation rates were(70.16±6.32)%and(12.46±2.22)%,respectively.TFF1 mRNA relative expression levels were 0.56±0.17 for cancer tissues and 1.56±0.22 for the normal tissues of distant cancer.All detected differences were statistically significant(all P<0.05).TFF1 protein expression rates were 29.09%(16/55)for cancer tissues and 65.45%(36/55)for the normal tissues of distant cancer.Additionally,relative positivity rates for SETDB1 protein expression were 74.55%(41/55)and 23.64%(13/55),respectively,and all differences were stat-istically significant(all P<0.05).Western blot analysis showed that SETDB1 protein expression was significantly higher in cancer tissues(72.89±5.27)%,compared to normal tissues of distant cancer(24.27±2.37)%.In contrast,TFF1 protein expressed was markedly lower in can-cer tissues(15.38±2.33)%than in normal tissues of distant cancer(72.72±4.48)%.All differences were statistically significant(all P<0.05).TFF1 methylation and SETDB1 expression were associated with lung adenocarcinoma(r=0.486,P<0.05).Both TFF1 methylation and SETDB1 expression were closely associated with tumor TNM stage,tissue differentiation,and lymph node metastasis(P<0.05).Furthermore,TFF1 methylation increased following SETDB1 downregulation(P<0.05).Conclusions:During lung adenocarcinoma progression,SETDB1 expres-sion correlates with TFF1 methylation,and the highly expressed SETDB1 may play a role in catalyzing TFF1 methylation.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To develop a scientific,systematic,and operable healthcare quality evaluation system for Nation-al Regional Medical Centers(NRMCs),providing a theoretical basis and practical tool for objectively assessing their construction outcomes and guiding high-quality development.Methods Based on the classic"Structure-Process-Outcome"(SPO)quality management model,and aligned with national policy directives and the functional positioning of regional medical centers,a pre-liminary set of evaluation indicators was screened and an indicator system was constructed through literature review,policy analy-sis,and field investigations.Guangxi Hospital Division of The First Affiliated Hospital,Sun Yat-sen University was selected as the study subject,and cross-sectional data from March 2023 to June 2025 were collected for empirical application.Results A healthcare quality evaluation system for NRMCs was established,comprising 3 first-level dimensions(Structure Quality,Process Quality,Outcome Quality),10 second-level indicators,and 66 third-level indicators.This system covers multiple aspects,inclu-ding resource allocation,healthcare service efficiency,clinical practices,patient outcomes,and social benefits.Empirical results indicated that the center demonstrated a consistent upward trend in key indicators such as"Proportion of Discharged Patients Un-dergoing Level-4 Surgeries"(O1.2)and"DRG-CMI Value"(O2.1),while"Average Length of Hospital Stay"(P3.1)and"Cost Consumption Index"(O2.3)showed a steady decline.The indicator system effectively revealed the center's progress in en-hancing regional influence and operational efficiency.Conclusion The developed healthcare quality evaluation system is well-grounded in theory and practice,combining scientific rigor with policy relevance,and can serve as a decision-support tool for quality assessment and improvement in National Regional Medical Centers.

Objective To investigate the effect and mechanism of long non-coding RNA(lncRNA)NRON on myocardial fibrosis in mice with myocardial infarction(MI).Methods Thirty-two C57/BL6 mice were randomly assigned to a Sham group,MI group,MI+shNRON group or MI+NC group,with eight mice in each group.The expression level of lncRNA NRON in myocardial tissue of mice was detected by real-time quantitative PCR.Hematoxylin and eosin staining,Masson's trichrome staining,and immunohistochemistry were used to detect the degree of myocardial injury,myocardial fibrosis,and the expression level of collagen Type Ⅰ(col Ⅰ).Western blotting was used to detect the protein expression levels of TGF-β1,p-Smad2,and p-Smad3 in myocardial tissue of the mice.Results Compared with the Sham group,the expression of NRON,col Ⅰ,TGF-β1,p-Smad2,and p-Smad3 proteins were increased in the MI group.Compared with the MI group,the expression of NRON,the degree of myocardial damage and fibrosis,the expression of col Ⅰ,TGF-β1,p-Smad2,and p-Smad3 proteins were decreased in the MI+shNRON group.Conclusion Down-regulation of lncRNA NRON can alleviate myocardial injury and inhibit myocardial fibrosis in mice with MI,and the molecular mechanism may be related to inhibition of the TGF-β/Smad signaling pathway.