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 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 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 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.

Promoting the modernization of TCM can facilitates the modernization of nation,the development of national social economy,and the construction of a"healthy"China;industrially,it improves of the quality and efficiency,achieving qualitative innovation and development;for the general public,it ameliorates the lifestyle and the perception of the people on being healthy.This article focuses on TCM industry,whilst executing the policies of the State Council.Based on the current stage of development,the modernization of TCM and its essential philosophy,strategic background and pathway,basic principles,this article strives to explore the most appropriate methods to modernize TCM in terms of healthcare,technology,education,industry,culture and management system.

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 To investigate the current status of infection management quality control centers in county-level hospitals in Guangdong Province,providing reference for the development of quality control management programs for county-level infection control centers by provincial infection control centers,and exploring corresponding management strategies.Methods A survey was conducted using the QuestionStar questionnaire platform to investigate county-level quality control centers established in Guangdong Province before December 31,2023.The survey covered the establishment time,personnel structure,level of in-formatization,management,quality control,and training of hospital infection management professional quality control centers.Results There are 68 county-level infection control centers in Guangdong Province,with a coverage rate of 50.37%,and 95.59%of them have been established within the past five years.Experts mainly come from clinical and nursing backgrounds(accounting for23.75%and62.97%respectively),and the majority have a bachelor's degree(71.06%).Only 13%have operational funding.Among them,39 have established hospital infection informatization monitoring,23 have not been equipped,and 6 are under construction.Twenty centers have conducted quality control supervision and issued quality control reports,ac-counting for 29.41%,while 41 have organized training,accounting for 60.29%.Conclusion The coverage rate of county-level infection management quality control centers in Guangdong Province is steadily increasing,but not all counties and districts are covered.There is a lack of policy and funding support,insufficient personnel allocation,and inadequate professional coverage.The health administrative departments and county-level infection control centers need to unify monitoring standards,quality con-trol specifications,and evaluation programs,improve infection control capabilities,and enhance the"four-level"management and training system to effectively promote the quality and safety management level of primary healthcare institutions.

Objective:To investigate the effect of myopia on retinal vascular geometry in young subjects.Methods:A retrospective cross-sectional study. From June 2018 to December 2018, 235 participants (235 eyes) who took part in routine physical examination in Huadong Sanatorium were included. There were 94 males and 141 females; age was (34.89±6.15) years old; equivalent spherical refraction (SE) was (-3.78±3.25) D. 59 (25.11%, 59/235) were divided into high myopia group (SE≤-6.0 D), along with 131 (55.74%, 131/235) low to moderate myopia group (-0.5 D> SE>-6.0 D), and 45 (19.15%, 45/235) emmetropia group (0.5 D≥SE≥-0.5 D). Retinal vascular geometric measurements, including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), fractal dimension arteriole (FDa), fractal dimension venule (FDv), curvature tortuosity arteriole (CTORTa), curvature tortuosity venule, branch angle arteriole (BAa), branch angle venule, branch coefficient arteriole and branching coefficient venule, were extracted by using a validated computer program. One-way analysis of variance and analysis of covariance were performed to compare the measurements across the high myopia, low to moderate myopia, and emmetropia groups. Linear regression analysis was used to explore the relationship between SE and retinal vascular geometric parameters.Results:The differences in CRAE ( F=65.11), CRVE ( F=61.52), FDa (F=14.26), FDv ( F=8.31), CTORTa ( F=5.07) and BAa (F=6.51) among eys of high myopia group, low to moderate myopia group and emmetropia group remained significant ( P<0.05) after adjusting for age, glycosylated hemoglobin, mean arterial pressure, body mass index, and intraocular pressure. CRAE and CRVE were linearly correlated with the SE ( P<0.05). FDa, FDv, cTORTa and BAa decreased with the decrease of SE in high myopia ( P<0.05). Conclusions:Myopia is associated with the change of the retinal vascular geometric characteristics. With the deepening of myopia, the change of retinal vascular geometric characteristics gradually worsens.

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.

Objective:To explore the different functional connectivity of right caudate nucleus between adults with high myopia and normal vision controls.Methods:The resting-state functional magnetic resonance imaging(fMRI) data were collected from twenty-five high myopia(HM group) and twenty-seven normal vision subjects(NC group). Right caudate nucleus and their subregions(anterior and posterior subregions included) were used as seeds to perform seed-based functional connectivity (FC)analyses at group level under three different frequency bands: convention (0.010~0.080 Hz), slow-5(0.010~0.027 Hz) and slow-4(0.027~0.073 Hz).Results:(1)Compared with NC group, FC of right caudate nucleus with left middle occipital gyrus(MNI: x=-48, y=-84, z=9), left fusiform gyrus(MNI: x=-30, y=-63, z=-12), and right middle frontal gyrus(MNI: x=39, y=12, z=39) were stronger in HM group(all P<0.05, Alphasim Corrected). (2)In HM group, these changed FC were mainly detected in the anterior subregion of right caudate nucleus.(3)The increased FC of right caudate nucleus and its anterior subregion with left middle occipital in HM group were mainly reflected in the frequency band of slow-4(all P<0.05, Alphasim Corrected). Conclusion:The right caudate nucleus in adults with high myopia may play compensatory roles in visual perception and visual attention by enhancing its functional connectivity with visual and visual attentional brain areas.