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 Based on data mining,analyze the medication rules and formula characteristics for treating cholelithiasis in the national patent database.Methods Search the national patent database of China National Intellectual Property Administration for Chinese medicine compound formulas for treating cholelithiasis since the establishment of the database until January 2024,and used the Traditional Chinese Medicine(TCM)Inheritance Support System(V 2.5)to establish a database of Chinese medicine compound formulas and analyzed them through the platform and SPSS Modeler 18.0 to obtain the frequency of use of the medicines,nature and flavor,channel tropism,the rules of association,the complex network relationship,and the analysis of the complex entropy hierarchical clustering algorithm.Results A total of 305 Chinese medicine compound patents were included,and 478 Chinese medicines were recorded,among which the high frequency(＞50 times)Chinese medicines were Jinqiancao,Yujin,Yinchen,Chaihu,Jineijin,Dahuang,etc..The four qi of Chinese medicines were mainly based on the cold,the five flavors were based on the bitter,sweet,and pungent flavors,and the channel tropism were based on liver meridian,stomach meridian,spleen meridian,and gallbladder meridian.The most commonly used combinations of Chinese medicines were Jinqiancao paired with Yujin,Yinchen,Chaihu,Jineijin,and Dahuang,respectively.The entropy hierarchical clustering algorithm analyzed 4 groups of candidate new group formulas.Conclusion Traditional Chinese medicine for the treatment of cholelithiasis mainly focuses on the effects of clearing heat and promoting diuresis,promoting bile secretion and relieving jaundice,soothe the liver and regulate qi,and treatment should be based on the syndrome differentiation of the disease.The new prescription discovered in this study can provide a more accurate medication plan for the clinical use of cholelithiasis.

OBJECTIVE To analyze the direct economic burden associated with carbapenem-resistant gram-negative bacteria(CRGNB)infections during hospitalization,and to provide reference for relevant policy formulation.METHODS Basic information including ICU admission,International Classification of Diseases(ICD)codes and CRGNB infection of intensive care unit(ICU)inpatients from Sanya Central Hospital(the Third People's Hospi-tal of Hainan Province)in the southern Hainan region from 2019 to 2023 was collected for risk factor analysis.Propensity matching was performed between the CRGNB infection and non-infection subgroups,and the direct economic differences between the two groups were analyzed.RESULTS A total of 164 373 cases were includ-ed.Multifactor logistic regression analysis revealed that ICD codes F00-F99,G00-G99,I00-I99,J00-J99,L00-L99,N00-N99,P00-P96 and S00-T98,ICU admission,hospital-acquired infection,readmission within 90 days and hospitalization exceeding 7 days were risk factors for CRGNB infection,especially,codes J00-J99(respiratory system diseases)were 7.68 to 17.47 folds higer than codes C00-D48(tumors).In the direct economic analysis of CRGNB infection,different matching results yielded consistent findings.In the 1∶1 matching results,a compari-son of total hospitalization costs(yuan)between different groups showed that the infection group had higher total hospitalization costs than the non-infection group.The costs were as follows:CRGNB group(88 421.40 vs.32 475.56),subgroup with two or more CRGNB types(130 984.02 vs.47 367.27),group with CRGNB and oth-er multidrug-resistant bacteria(103 056.35 vs.37 724.78),CRAB group(98 486.01 vs.36 487.98),and CRE group(26 031.38 vs.17 621.82).CONCLUSIONS The direct economic burden of CRGNB infection is greater than that of the non-infection group.Among them,the direct economic burden of carbapenem-resistant gram-negative bacteria infection,carbapenem-resistant gram-negative bacteria co-infected with other multidrug-resistant bacteria and CRAB infection are the highest.

Objective Based on data mining,analyze the medication rules and formula characteristics for treating cholelithiasis in the national patent database.Methods Search the national patent database of China National Intellectual Property Administration for Chinese medicine compound formulas for treating cholelithiasis since the establishment of the database until January 2024,and used the Traditional Chinese Medicine(TCM)Inheritance Support System(V 2.5)to establish a database of Chinese medicine compound formulas and analyzed them through the platform and SPSS Modeler 18.0 to obtain the frequency of use of the medicines,nature and flavor,channel tropism,the rules of association,the complex network relationship,and the analysis of the complex entropy hierarchical clustering algorithm.Results A total of 305 Chinese medicine compound patents were included,and 478 Chinese medicines were recorded,among which the high frequency(＞50 times)Chinese medicines were Jinqiancao,Yujin,Yinchen,Chaihu,Jineijin,Dahuang,etc..The four qi of Chinese medicines were mainly based on the cold,the five flavors were based on the bitter,sweet,and pungent flavors,and the channel tropism were based on liver meridian,stomach meridian,spleen meridian,and gallbladder meridian.The most commonly used combinations of Chinese medicines were Jinqiancao paired with Yujin,Yinchen,Chaihu,Jineijin,and Dahuang,respectively.The entropy hierarchical clustering algorithm analyzed 4 groups of candidate new group formulas.Conclusion Traditional Chinese medicine for the treatment of cholelithiasis mainly focuses on the effects of clearing heat and promoting diuresis,promoting bile secretion and relieving jaundice,soothe the liver and regulate qi,and treatment should be based on the syndrome differentiation of the disease.The new prescription discovered in this study can provide a more accurate medication plan for the clinical use of cholelithiasis.

OBJECTIVE To analyze the direct economic burden associated with carbapenem-resistant gram-negative bacteria(CRGNB)infections during hospitalization,and to provide reference for relevant policy formulation.METHODS Basic information including ICU admission,International Classification of Diseases(ICD)codes and CRGNB infection of intensive care unit(ICU)inpatients from Sanya Central Hospital(the Third People's Hospi-tal of Hainan Province)in the southern Hainan region from 2019 to 2023 was collected for risk factor analysis.Propensity matching was performed between the CRGNB infection and non-infection subgroups,and the direct economic differences between the two groups were analyzed.RESULTS A total of 164 373 cases were includ-ed.Multifactor logistic regression analysis revealed that ICD codes F00-F99,G00-G99,I00-I99,J00-J99,L00-L99,N00-N99,P00-P96 and S00-T98,ICU admission,hospital-acquired infection,readmission within 90 days and hospitalization exceeding 7 days were risk factors for CRGNB infection,especially,codes J00-J99(respiratory system diseases)were 7.68 to 17.47 folds higer than codes C00-D48(tumors).In the direct economic analysis of CRGNB infection,different matching results yielded consistent findings.In the 1∶1 matching results,a compari-son of total hospitalization costs(yuan)between different groups showed that the infection group had higher total hospitalization costs than the non-infection group.The costs were as follows:CRGNB group(88 421.40 vs.32 475.56),subgroup with two or more CRGNB types(130 984.02 vs.47 367.27),group with CRGNB and oth-er multidrug-resistant bacteria(103 056.35 vs.37 724.78),CRAB group(98 486.01 vs.36 487.98),and CRE group(26 031.38 vs.17 621.82).CONCLUSIONS The direct economic burden of CRGNB infection is greater than that of the non-infection group.Among them,the direct economic burden of carbapenem-resistant gram-negative bacteria infection,carbapenem-resistant gram-negative bacteria co-infected with other multidrug-resistant bacteria and CRAB infection are the highest.

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 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 observe the relationship between the response to anti-vascular endothelial growth factor (VEGF) drug treatment and single nucleotide polymorphism (SNP) genotype in patients with wet age-related macular degeneration (wAMD).Methods:A retrospective clinical study. From August 2019 to September 2020, 103 eyes of 103 wAMD patients diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 59 males (57.28%, 59/103) and 44 females (42.72%, 44/103); the average age was 68.74±7.74 years. The standard logarithmic visual acuity chart was used to detect the Best Corrected Visual Acuity of the affected eye and converted to the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. Optical coherence tomography was used to detect the central retinal thickness (CRT) of the affected eye. At the same time, the patient's high-density lipoprotein cholesterol (HDL-C) was tested. All eyes were treated with intravitreal injection of anti-VEGF drugs once a month for 3 months. Before the initial treatment, peripheral venous blood from the patient were collected. Interleukin-8 ( IL-8), complement C3 gene ( C3), complement factor H ( CFH), liver lipase ( LIPC), cholesterol ester transfer protein ( CETP), ATP binding cassette subfamily a member 1 ( ABCA1), lipoprotein lipase ( LPL), fatty acid desaturation gene cluster ( FADS1) SNP. According to gene frequency, genotypes are divided into wild type and mutant type were detected. Qualitative data such as the frequency difference of the genotype distribution in the clinical phenotype and the Hardy-Weinberg equilibrium of the genotype distribution were compared with the Chi-square test or Fisher's exact test. Results:There were fewer CRT responders in IL-8 rs4073 mutant (TA+AA) patients than wild-type (TT) [odds ratio ( OR)=0.310, 95% confidence interval ( CI) 0.106-0.910, P<0.05). Among them, after the drug stratification test, the proportion of patients with IL-8 rs4073 locus TT genotype in the conbercept treatment group was less CRT non-responders ( OR=0.179, 95% CI=0.034-0.960, P=0.033). Patients with LIPC rs2043085 mutant (CT+TT) with BCVA increased ≥0.2 logMAR are more likely than wild-type (CC) ( OR=3.031, 95% CI 1.036-8.867, P<0.05); HDL-C level was significantly lower Compared with wild type (CC), the difference was statistically significant ( t=2.448, P=0.016). There was no significant difference in logMAR BCVA and CRT between IL-8 rs4073, LIPC rs2043085 mutant and wild-type patients before treatment ( IL-8 rs4073: Z=-0.198, -1.651; P=0.843, 0.099; LIPC rs2043085: Z=-0.532, -0.152; P=0.595, 0.879). C3 rs 225066, CFH rs800292, CETP rs708272, ABCA1 rs1883025, FADS1 rs174547, LPL rs12678919 have no correlation with anti-VEGF drug treatment response. Conclusions:Patients with wAMD are treated with anti-VEGF drugs. Those with IL-8 rs4073 locus A genotype may be less responsive to CRT. LIPC rs2043085 locus T genotypes may be relatively more responsive to BCVA.