Objective To assess stromal fibrosis in epidermal growth factor receptor(EGFR)mutant lung adenocarcinoma and its association with resistance to targeted therapy and patient prognosis.Methods Medical records of 207 patients diagnosed with EGFR-mutant advanced lung adenocarcinoma who received treatment at a hospital between January 2021 and December 2022 were reviewed.A total of 86 patients were ultimately included based on their prognosis and survival duration.These patients were categorized into a resistance group(32 cases)and a non-resistance group(54 cases),depending on whether they developed resistance to targeted therapy within one year.Additionally,patients were classified into mild,moderate,and severe fibrosis groups according to the extent of fibrosis observed.Clinical and pathological characteristics,as well as fibrosis levels,were compared between the two groups.Factors influencing the development of resistance to targeted therapy in patients with EGFR-mutant lung adenocarcinoma were analyzed,and the survival outcomes of patients with varying degrees of fibrosis were evaluated during follow-up.Results In the resistance group,the prevalence of EGFR exon 20 insertion mutations,elevated CA125 levels,and the presence of moderate-to-severe fibrosis were significantly higher compared to the non-resistance group(P<0.05).Multivariate logistic regression analysis revealed that EGFR exon 20 inser-tion mutation(OR=3.691,95%CI:1.043～13.057),elevated CA125 levels(OR=4.104,95%CI:1.160～14.517),and moderate-to-severe fibrosis(OR=3.959,95%CI:1.410～11.115)were independent risk factors associated with resistance to targeted therapy among patients with EGFR-mutant lung adenocarcinoma(P<0.05).The Cox proportional hazards model demonstrated a C-index of 0.72(95%CI:0.65～0.79),with area under the curve(AUC)values for 1-year and 2-year survival predictions of 0.781 and 0.734,respectively.EGFR exon 20 insertion mutation(HR=3.691),moderate-to-severe fibrosis(HR=3.959),and elevated CA125 levels(HR=4.104)were identified as independent prognostic factors for overall survival in these patients following targeted therapy.The median progression-free survival(PFS)for patients with mild,moderate,and severe fibrosis was 10.5 months,7.2 months,and 3.9 months,respectively,while the median overall survival(OS)was 21.4 months,16.1 months,and 11.5 months,respectively.Statistically significant differences in both PFS and OS were observed across the three fibrosis severity groups.(P<0.05).Conclusion The extent of stromal fibrosis in EGFR-mutant lung adenocarcinoma influences resistance to targeted therapy,and the progression of fibrosis is correlated with an unfavorable prognosis.

Objective To assess stromal fibrosis in epidermal growth factor receptor(EGFR)mutant lung adenocarcinoma and its association with resistance to targeted therapy and patient prognosis.Methods Medical records of 207 patients diagnosed with EGFR-mutant advanced lung adenocarcinoma who received treatment at a hospital between January 2021 and December 2022 were reviewed.A total of 86 patients were ultimately included based on their prognosis and survival duration.These patients were categorized into a resistance group(32 cases)and a non-resistance group(54 cases),depending on whether they developed resistance to targeted therapy within one year.Additionally,patients were classified into mild,moderate,and severe fibrosis groups according to the extent of fibrosis observed.Clinical and pathological characteristics,as well as fibrosis levels,were compared between the two groups.Factors influencing the development of resistance to targeted therapy in patients with EGFR-mutant lung adenocarcinoma were analyzed,and the survival outcomes of patients with varying degrees of fibrosis were evaluated during follow-up.Results In the resistance group,the prevalence of EGFR exon 20 insertion mutations,elevated CA125 levels,and the presence of moderate-to-severe fibrosis were significantly higher compared to the non-resistance group(P<0.05).Multivariate logistic regression analysis revealed that EGFR exon 20 inser-tion mutation(OR=3.691,95%CI:1.043～13.057),elevated CA125 levels(OR=4.104,95%CI:1.160～14.517),and moderate-to-severe fibrosis(OR=3.959,95%CI:1.410～11.115)were independent risk factors associated with resistance to targeted therapy among patients with EGFR-mutant lung adenocarcinoma(P<0.05).The Cox proportional hazards model demonstrated a C-index of 0.72(95%CI:0.65～0.79),with area under the curve(AUC)values for 1-year and 2-year survival predictions of 0.781 and 0.734,respectively.EGFR exon 20 insertion mutation(HR=3.691),moderate-to-severe fibrosis(HR=3.959),and elevated CA125 levels(HR=4.104)were identified as independent prognostic factors for overall survival in these patients following targeted therapy.The median progression-free survival(PFS)for patients with mild,moderate,and severe fibrosis was 10.5 months,7.2 months,and 3.9 months,respectively,while the median overall survival(OS)was 21.4 months,16.1 months,and 11.5 months,respectively.Statistically significant differences in both PFS and OS were observed across the three fibrosis severity groups.(P<0.05).Conclusion The extent of stromal fibrosis in EGFR-mutant lung adenocarcinoma influences resistance to targeted therapy,and the progression of fibrosis is correlated with an unfavorable prognosis.

Objective Olanzapine has a significant effect in the treatment of mental illness,so its use has been increasing year by year,and poisoning cases have occurred from time to time.Weight gain is a common side effect,and predicting it can be used as a warning to reduce the occurrence of olanzapine poisoning.In this paper,we screened out the differential metabolites between the olanzapine administration rats whose body weight significantly increased and no significantly changed weight.,therefore established an early diagnosis model for predicting olanzapine-induced weight gain in rats.Methods Thirty rats were randomly divided into the control group and olanzapine administration group,which were given continuously gavage with gthe normal saline and olanzapine for 28 days respectively.Blood was taken from the medial canthal vein on the first day after administration,and serum was collected for metabolomics analysis.The olanzapine group was divided into weight gain group and weight unchanged group by comparing with control group.The metabolic group data of the two groups were compared and the differential compounds were screened out between the two groups,Further then an early diagnosis model was established.Results There were 26 differential compounds between the weight gain group and the weight unchanged group after olanzapine administration for 28 days,including 10 lipids,which were involved in the metabolism of α-linolenic acid,the biosynthesis of unsaturated fatty acids,the biosynthesis of primary bile acids,and the synthesis of steroid hormones.Combined with the random forest algorithm,a early diagnosis model was established and the accurate rate was 80％.Conclusion Olanzapine administration would cause changes in the metabolome of rats,mostly concentrated in lipids,and the model based on 26 differential metabolites could be a candidate method for the early forensic determination of olanzapine poisoning.

There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

Objective Olanzapine has a significant effect in the treatment of mental illness,so its use has been increasing year by year,and poisoning cases have occurred from time to time.Weight gain is a common side effect,and predicting it can be used as a warning to reduce the occurrence of olanzapine poisoning.In this paper,we screened out the differential metabolites between the olanzapine administration rats whose body weight significantly increased and no significantly changed weight.,therefore established an early diagnosis model for predicting olanzapine-induced weight gain in rats.Methods Thirty rats were randomly divided into the control group and olanzapine administration group,which were given continuously gavage with gthe normal saline and olanzapine for 28 days respectively.Blood was taken from the medial canthal vein on the first day after administration,and serum was collected for metabolomics analysis.The olanzapine group was divided into weight gain group and weight unchanged group by comparing with control group.The metabolic group data of the two groups were compared and the differential compounds were screened out between the two groups,Further then an early diagnosis model was established.Results There were 26 differential compounds between the weight gain group and the weight unchanged group after olanzapine administration for 28 days,including 10 lipids,which were involved in the metabolism of α-linolenic acid,the biosynthesis of unsaturated fatty acids,the biosynthesis of primary bile acids,and the synthesis of steroid hormones.Combined with the random forest algorithm,a early diagnosis model was established and the accurate rate was 80％.Conclusion Olanzapine administration would cause changes in the metabolome of rats,mostly concentrated in lipids,and the model based on 26 differential metabolites could be a candidate method for the early forensic determination of olanzapine poisoning.

Objective To evaluate two methods measuring alveolar bone loss by micro computed tomography (micro-CT)based on periodontitis model in mice.Methods The silk ligatures were tied around the right maxillary second molars of mice to induce periodontitis model.The right half maxillaries of mice model were harvested for micro-CT analysis.Three dentists were recruited for the measurement with two different methods:Modified tomography (T) method and reconstruction (R) method.Accuracy and consistency of each method were estimated by standard deviation (SD).Results The SDs of R method managed by the same operator (measurement for 3 times) or different operators (3 operators) were 34.87μm and 35.67 μm respectively,while that of T method was 7.82 μm and 14.24 μm respectively.The SDs of T method were significantly lower than those of R method (both P＜0.05).Conclusion T method is more accurate and consistent than R method for evaluating alveolar bone loss in mice periodontitis model.

Objective To explore the results of non-compliance of fluid intake in maintence hemodialysis patients.Methods The qualitative phenomenological research method was adopted in this study.Self-structured in-depth interviews were conducted with 13 maintenance hemodialysis patients.Data were analyzed by content analysis.Result Four themes were extracted including allotrigeusia,have a smattering of fluid intake knowledge,self-condemned and guilty,muddling along.Conclusions Fuild restriction is the most difficuilt prescribed treatment schedule among maintence hemodialysis patients.Nurses should pay attention to those people and provide multilevel,continual,individual and comprehensive measures.