ObjectiveTo construct a nomogram prediction model for non-valvular persistent atrial fibrillation （PeAF） patients with left ventricular hypertrophy （LVH） ， followed by prognostic analysis through follow-up. MethodsThis study retrospectively enrolled 949 patients with newly diagnosed and hospitalized non-valvular PeAF. Among them， 403 patients presented with LVH. The cohort was randomly stratified into a training set （n=665） and a validation set （n=284）. Univariate and multivariate Logistic regression analyses were employed to identify independent risk factors for PeAF complicated by LVH. A nomogram prediction model was subsequently constructed and evaluated for discriminative ability， calibration， and clinical utility using receiver operating characteristic （ROC） curve analysis， calibration plots， and decision curve analysis （DCA）. ResultsSeven independent risk factors were ultimately identified and included in the prediction model： female sex， hypertension， diabetes， red blood cell distribution width-SD （RDW-SD）， body mass index （BMI）， left atrial diameter （LAD）， and left ventricular ejection fraction （LVEF）. The area under the ROC curve （AUC） in the training set was 0.862 （95% CI： 0.834-0.890）， and in the validation set， it was 0.870 （95% CI： 0.829-0.911）， demonstrating excellent predictive performance. ConclusionIndependent risk factors for LVH in PeAF patients include female， hypertension， diabetes， RDW-SD， BMI， LAD， and LVEF. The prediction model built based on this can help early identification of PeAF patients with high risk of LVH. At the same time， the incidence of major adverse cardiovascular events （MACE） is higher in PeAF patients with LVH. Patients with atrial fibrillation combined with LVH may benefit from catheter ablation.

This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.

Objective·To explore the metabolic profiling and metabolic reprogramming patterns of lung cancer cells with acquired resistance to sotorasib,a specific inhibitor to KRAS.Methods·The H2122 and H358 lung cancer cell models with acquired resistance to sotorasib(H2122-SR and H358-SR cells)were established and validated by CCK-8 assay.Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)was employed to acquire the metabolic profiling of the resistant lung cancer cells and their homologous parental cells.Untargeted metabolomics studies and metabolic characterizations were conducted with multi-dimensional methods,including principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA),to identify differential metabolites associated with acquired resistance to sotorasib.Then these differential metabolites were subjected to pathway enrichment analysis.Heatmap analysis was used to compare the changes in metabolites in major differential metabolic pathways between the resistant and parental cells.Results·The cell models of H2122 and H358 with acquired resistance were successfully constructed,with half-maximal inhibitory concentrations(IC50)of sotorasib being 50 times higher than those of the parental cells.Besides,the metabolic profiling was significantly different between the resistant and parental cells.A total of 48 differential metabolites were identified between H2122-SR and H2122 cells.The top 10 differential metabolites,ranked by VIP values,were uridine,xanthylic acid,indole-3-carboxylic acid,nicotinic acid,xanthosine,xanthine,N-methylnicotinamide,hypoxanthine,trigonelline,and galactonic acid.Between H358-SR and H358 cells,a total of 79 differential metabolites were identified.The top 10 differential metabolites,ranked by VIP values,were glutathione,xanthosine,2-ketoglutaric acid,carboxyethyl lysine,thymidine,purine,riboflavin,3-indoleacrylic acid,indole-3-pyruvic acid,and dihydrouracil.The differential metabolites in the two lung cancer cell lines mainly participated in purine metabolism and glycolysis/gluconeogenesis,and purine metabolism was the most significantly altered metabolic pathway.Heatmap analysis showed that many metabolites in the purine metabolism were elevated in the sotorasib-resistant cells.Conclusion·The lung cancer cells with acquired resistance to sotorasib show enhanced purine metabolism.

OBJECTIVE To establish a method for determining the content of multiple components in Astragalus membranaceus,compare the content differences of Astragalus membranaceus in different regions and with different extraction methods in Gansu,and e-valuate the quality of Astragalus membranaceus from different origins of Gansu.METHODS Astragalus membranaceus samples from 40 origins in Gansu were collected on site.The content of Astragaloside Ⅳ,Calycosin-7-O-β-D-glucopyranoside,Ononin,Form-ononetin and Calycosin was determined by HPLC external standard method,and the quality differences of Astragalus membranaceus from 40 origins of Gansu were analyzed by combining bar graphs and line graphs.RESULTS Weiyuan County and Min County of Dingxi City showed high Astragaloside Ⅳ content in both extraction methods,indicating that the Astragalus membranaceus in these two regions has advantages in Astragaloside Ⅳ as an active component;for Calycosin-7-O-β-D-glucopyranoside and Ononin,although the performance of different regions in different extraction methods was different,in general,Weiyuan County and Min County of Dingxi City and Longnan City showed high content in both extraction methods.Water extraction method was more conducive to the extraction of Calycosin-7-O-β-D-glucopyranoside and Ononin,while alcohol extraction method was more conducive to the extraction of Astragalo-side Ⅳ,Calycosin and Ononin.CONCLUSION The content of chemical components of Astragalus membranaceus from different ori-gins is quite different,and the choice of extraction method has a significant effect on the content of active components,while the change trend of different compounds in the two extraction methods is basically the same.The established HPLC multi-component content de-termination method of Astragalus membranaceus is stable and reliable,which can provide a scientific basis for the quality control and comprehensive evaluation of Astragalus membranaceus medicinal materials.

Objective To evaluate the clinical effects of cast post and cores with traction design in coronal extrusion of upper anterior teeth with subgingival fracture.Methods Twenty-five upper anterior teeth with subgingival fracture were treated by root canal therapy,then cast post and cores with traction design and composite resin crown restorations were made for orthodontic extrusion.Position reten-tion and gingival margin modification were performed before crown restoration of these teeth.The correlation between extrusion length and extrusion time was evaluated,as well as the correlation between extrusion length and migration distance in coronal direction about the gingival margin.Crown-root ratio and post-root ratio below the alveolar crest was evaluated after the crown restorations were finished.Evaluation of restoration effects was carried out in 3,6,12 months follow-up period.Results Root resorption began to appear on one tooth at six weeks;the remaining 24 teeth were migrated to target position and prosthesis were finished.There was a positive correlation between the extrusion length(x)and extrusion time(y1),also between the extrusion length(x)and migration distance in coronal di-rection about the gingival margin(y2)by statistical analysis.There was no significant difference(P＞0.05)between the extrusion teeth and compared teeth on crown-root ratio.More than 1/2 of the ratio between the length of post to the length of root below the alveolar crest.The prognostic stability was satisfied in 3,6,12 months follow-up period.Conclusion There are satisfactory clinical application effects of cast post and cores with traction design in coronal extrusion of upper anterior teeth with subgingival fracture.

Objective To investigate the status of hearing impaired children's hearing device independence skills,and to explore the ways to improve their self-use of hearing equipment.Methods This study surveyed 64 re-habilitation teachers and 411 parents of children with hearing impairment aged 0-12 years.Through face-to-face or remote telephone interview,3 good habits(A asking parents for advice before removing the HA,B putting the de-vice into a moisture-proof box after removing it,C bringing batteries to school and knowing where are them)and 3 key abilities[D wearing the device independently,E replacing the battery independently,and F independently handle foreign bodies in the ear mold(Fa)and water vapor(Fb)]was investigated.The age when mastering skills or de-veloping habits difference of hearing impaired children in different groups were compared.Results ① The ratio of ability D in the bilateral CI group and the bilateral HA group of preschool children was 30.97％and 18.57％respec-tively.Among elementary school children,85.29％and 90.70％had this ability respectively.② The ratio of ability E in the bilateral CI group,the bilateral HA group and the bimodel group were 11.50％,15.71％and 16.49％,re-spectively.Among elementary school children,64.71％,53.49％and 68.52％had this ability,respectively.③Among preschool children,there was no statistical difference in age when different equipment groups developed the three good habits and acquired ability D and E(P＞0.05).④ Among primary school children,there was a statisti-cal difference in the age when different equipment groups formed habit A(P＜0.05),and the age when double CI group had this ability was slightly earlier than the double HA group.There was no significant difference in other abilities among age groups(P＞0.05).Conclusion The age at which hearing impaired children develop the three good habits precedes the age at which they master the key skills,which accords with the law of skill acquisition and development of ordinary children.Corresponding teaching process should be based on the age and ability of hearing-impaired children without considering the type of equipment.

Objective·To explore the metabolic profiling and metabolic reprogramming patterns of lung cancer cells with acquired resistance to sotorasib,a specific inhibitor to KRAS.Methods·The H2122 and H358 lung cancer cell models with acquired resistance to sotorasib(H2122-SR and H358-SR cells)were established and validated by CCK-8 assay.Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)was employed to acquire the metabolic profiling of the resistant lung cancer cells and their homologous parental cells.Untargeted metabolomics studies and metabolic characterizations were conducted with multi-dimensional methods,including principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA),to identify differential metabolites associated with acquired resistance to sotorasib.Then these differential metabolites were subjected to pathway enrichment analysis.Heatmap analysis was used to compare the changes in metabolites in major differential metabolic pathways between the resistant and parental cells.Results·The cell models of H2122 and H358 with acquired resistance were successfully constructed,with half-maximal inhibitory concentrations(IC50)of sotorasib being 50 times higher than those of the parental cells.Besides,the metabolic profiling was significantly different between the resistant and parental cells.A total of 48 differential metabolites were identified between H2122-SR and H2122 cells.The top 10 differential metabolites,ranked by VIP values,were uridine,xanthylic acid,indole-3-carboxylic acid,nicotinic acid,xanthosine,xanthine,N-methylnicotinamide,hypoxanthine,trigonelline,and galactonic acid.Between H358-SR and H358 cells,a total of 79 differential metabolites were identified.The top 10 differential metabolites,ranked by VIP values,were glutathione,xanthosine,2-ketoglutaric acid,carboxyethyl lysine,thymidine,purine,riboflavin,3-indoleacrylic acid,indole-3-pyruvic acid,and dihydrouracil.The differential metabolites in the two lung cancer cell lines mainly participated in purine metabolism and glycolysis/gluconeogenesis,and purine metabolism was the most significantly altered metabolic pathway.Heatmap analysis showed that many metabolites in the purine metabolism were elevated in the sotorasib-resistant cells.Conclusion·The lung cancer cells with acquired resistance to sotorasib show enhanced purine metabolism.

Objective:To investigate the impact of the number of examined lymph nodes (ELN) on survival outcomes in gastric cancer patients with postoperative pathological stage pN3b.Methods:This retrospective cohort study included 279 pN3b gastric cancer patients who underwent D2 gastrectomy at Nanfang Hospital, Southern Medical University (September 2008 to April 2023), with 35 patients receiving combination chemotherapy and anti-PD-1 therapy (immunotherapy group) and 244 receiving adjuvant chemotherapy alone (nonimmunotherapy group). Additionally, 422 patients with pN3b from the SEER database (2005 to 2020) were collected as an external validation cohort to determine the optimal cutoff value for the number of lymph nodes examined in the nonimmunotherapy group. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) in the nonimmunotherapy group of the Nanfang Hospital cohort, stratified by whether the number of examined lymph nodes was above or below the ELN optimal cutoff value. These findings were subsequently validated in the SEER cohort.Results:The optimal ELN cutoff value (34 nodes) was determined using X-tile software and by constructing an ELN-HR fitting model with inflection point identification. In the nonimmunotherapy group, patients with ELN >34 exhibited significantly prolonged survival compared to ELN ≤34 (median OS: 25.0 (95%CI:20.5-29.5) to 17.0 (95%CI:12.7-21.3) months, P=0.004; median RFS: 19.0 (95%CI:15.6-22.4) to 13.0 (95%CI:9.5-16.5) months, P=0.048). Multivariate Cox analysis also showed ELN >34 to be an independent protective factor for both OS (HR=0.576, 95%CI: 0.397-0.836) and RFS (HR=0.701, 95%CI: 0.492-0.998). In the SEER cohort, ELN >34 was associated with a 5-month OS extension (19 to 14 months, P=0.065), with multivariate analysis supporting its independent prognostic significance (HR=0.729, 95%CI: 0.580-0.915, P=0.006). Notably, in the immunotherapy group, patients with ELN >34 ( n=30) achieved a median OS of 41 months, but the median OS had not been reached in the ELN ≤34 group ( n=5) (1 death at 48 months). Conclusion:Higher ELN (>34) correlates with improved survival in nonimmunotherapy-treated pN3b gastric cancer patients. However, in pN3b gastric cancer patients treated with immunotherapy, the optimal ELN threshold requires further exploration to determine.

OBJECTIVE To establish a method for determining the content of multiple components in Astragalus membranaceus,compare the content differences of Astragalus membranaceus in different regions and with different extraction methods in Gansu,and e-valuate the quality of Astragalus membranaceus from different origins of Gansu.METHODS Astragalus membranaceus samples from 40 origins in Gansu were collected on site.The content of Astragaloside Ⅳ,Calycosin-7-O-β-D-glucopyranoside,Ononin,Form-ononetin and Calycosin was determined by HPLC external standard method,and the quality differences of Astragalus membranaceus from 40 origins of Gansu were analyzed by combining bar graphs and line graphs.RESULTS Weiyuan County and Min County of Dingxi City showed high Astragaloside Ⅳ content in both extraction methods,indicating that the Astragalus membranaceus in these two regions has advantages in Astragaloside Ⅳ as an active component;for Calycosin-7-O-β-D-glucopyranoside and Ononin,although the performance of different regions in different extraction methods was different,in general,Weiyuan County and Min County of Dingxi City and Longnan City showed high content in both extraction methods.Water extraction method was more conducive to the extraction of Calycosin-7-O-β-D-glucopyranoside and Ononin,while alcohol extraction method was more conducive to the extraction of Astragalo-side Ⅳ,Calycosin and Ononin.CONCLUSION The content of chemical components of Astragalus membranaceus from different ori-gins is quite different,and the choice of extraction method has a significant effect on the content of active components,while the change trend of different compounds in the two extraction methods is basically the same.The established HPLC multi-component content de-termination method of Astragalus membranaceus is stable and reliable,which can provide a scientific basis for the quality control and comprehensive evaluation of Astragalus membranaceus medicinal materials.

Objective To investigate the status of hearing impaired children's hearing device independence skills,and to explore the ways to improve their self-use of hearing equipment.Methods This study surveyed 64 re-habilitation teachers and 411 parents of children with hearing impairment aged 0-12 years.Through face-to-face or remote telephone interview,3 good habits(A asking parents for advice before removing the HA,B putting the de-vice into a moisture-proof box after removing it,C bringing batteries to school and knowing where are them)and 3 key abilities[D wearing the device independently,E replacing the battery independently,and F independently handle foreign bodies in the ear mold(Fa)and water vapor(Fb)]was investigated.The age when mastering skills or de-veloping habits difference of hearing impaired children in different groups were compared.Results ① The ratio of ability D in the bilateral CI group and the bilateral HA group of preschool children was 30.97％and 18.57％respec-tively.Among elementary school children,85.29％and 90.70％had this ability respectively.② The ratio of ability E in the bilateral CI group,the bilateral HA group and the bimodel group were 11.50％,15.71％and 16.49％,re-spectively.Among elementary school children,64.71％,53.49％and 68.52％had this ability,respectively.③Among preschool children,there was no statistical difference in age when different equipment groups developed the three good habits and acquired ability D and E(P＞0.05).④ Among primary school children,there was a statisti-cal difference in the age when different equipment groups formed habit A(P＜0.05),and the age when double CI group had this ability was slightly earlier than the double HA group.There was no significant difference in other abilities among age groups(P＞0.05).Conclusion The age at which hearing impaired children develop the three good habits precedes the age at which they master the key skills,which accords with the law of skill acquisition and development of ordinary children.Corresponding teaching process should be based on the age and ability of hearing-impaired children without considering the type of equipment.