BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

ObjectiveTo investigate whether Shenmai injection （SMI） improves cisplatin resistance in non-small cell lung cancer （NSCLC） by modulating lipid metabolism and inducing ferroptosis. MethodsHuman lung adenocarcinoma cisplatin-resistant A549/DDP cells were divided into the following groups： Blank group， cisplatin group （23.3 μmol·L^-1 cisplatin）， SMI group （20 g·L^-1 SMI）， cisplatin combined with SMI group （23.3 μmol·L^-1 cisplatin + 20 g·L^-1 SMI）， cisplatin combined with ferroptosis inhibitor/inducer Ferrostatin-1/Erastin group （23.3 μmol·L^-1 cisplatin + 10 μmol·L^-1 Ferrostatin-1/5 μmol·L^-1 Erastin）， and cisplatin combined with SMI and Ferrostatin-1/Erastin group （23.3 μmol·L^-1 cisplatin + 20 g·L^-1 SMI + 10 μmol·L^-1 Ferrostatin-1/5 μmol·L^-1 Erastin）. Network pharmacology， transcriptomics and metabolomics， Cell Counting Kit-8 （CCK-8） assay， transmission electron microscopy （TEM）， colorimetric assays， and Western blot analysis were employed to evaluate the effects of these treatments on A549/DDP cell viability， lipid droplet formation， lipid metabolite levels， mitochondrial function， lipid peroxidation， glutathione （GSH） content， total and ferrous iron content， and effects on ferroptiosis and autophagy related protein expression levels. ResultsSMI improved cisplatin resistance in NSCLC mainly by targeting lipid metabolism-related pathways in A549/DDP cells， affecting tumor cell lipid metabolism via autophagy， ferroptosis， and glycerophospholipid metabolism pathways. Compared with the cisplatin group， the cisplatin combined with SMI group showed significantly decreased cell viability （P<0.01）， increased lipid droplet accumulation （P<0.01）， and reduced mitochondrial maximal respiration， basal respiration， mitochondrial membrane potential， GSH content， total iron， and ferrous iron （all P<0.01）. Mitochondrial reactive oxygen species （ROS） was significantly elevated（P<0.01）， and lipid peroxidation levels were significantly increased. Protein expression analysis showed significant downregulation of solute carrier family 7 member 11 （SLC7A11） and p62 （P<0.05，P<0.01） and upregulation of ferritin heavy chain （FTH） and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） （P<0.05，P<0.01）. Compared with the cisplatin combined with SMI group， addition of Ferrostatin-1 significantly increased cell viability （P<0.05）， decreased mitochondrial ROS levels （P<0.05）， alleviated mitochondrial shrinkage， and reduced lipid peroxidation. Conversely， addition of Erastin further decreased cell viability （P<0.01）. ConclusionSMI improves cisplatin resistance in NSCLC by inducing oxidative stress， which may trigger ferroptosis through upregulation of lipophagy.

Objective To investigate the current distribution of radiotherapy resources in Gansu Province, evaluate the equity of resource allocation, and provide a scientific basis for optimizing regional resource allocation. Methods A questionnaire survey was carried out to assess radiotherapy resources in medical institutions across Gansu Province, China. The equity of radiotherapy resource distribution and associated disparities were assessed using the Gini coefficient, Lorenz curve, and Theil index. Results A total of 23 medical institutions in Gansu Province provided radiotherapy services, comprising 39 radiotherapy devices and 438 professionals, of whom medical physicists accounted for 16.9%. The radiotherapy frequency was 0.47 cases per thousand population. The Gini coefficients for radiotherapy resource distribution ranged from 0.38 to 0.56 by population and from 0.52 to 0.70 by geography. The Theil index for radiotherapy resources ranged from 1.36 to 3.67. Conclusion Radiotherapy resources in Gansu Province were insufficient, and the capacity of radiotherapy service was suboptimal. The equity of radiotherapy resource allocation by geography was worse than that by population. Therefore, it is imperative to address the shortage of radiotherapy resources, strengthen the professional workforce, enhance the capacity radiotherapy service and resource utilization, optimize resource allocation, and promote regional equity in radiotherapy provision in Gansu Province.

Objective To observe the efficacy of self-guided attention network for detecting responsible lesions related to cerebral palsy(CP)in children with periventricular white matter injury(PVWMI).Methods Totally 383 children with PVWMI were retrospectively enrolled and divided into CP group(n=243)and non-CP group(n=140),while 214 children without obvious brain abnormality on brain MRI were taken as control group.ROI of 4 key anatomical structures related to CP,i.e.centrum semiovale,posterior limb of internal capsule,cerebral peduncle and thalamus were delineated on T1WI,while responsible lesions related to CP within the key anatomical structures were labeled on T2WI,and the images were then registrated and used as input of the networks.ResNet34 network was adopted combined with attention and self-guided networks to train the network for detecting responsible lesions related to CP in children with PVWMI,and their efficacies were evaluated.The optimal network was screened,and its efficacy for segmenting the key anatomical structures was evaluated.Results Self-guided attention network was the optimal network,its area under the curve(AUC)for detecting lesions was 0.794-0.914,and the Dice similarity coefficient for segmenting the key anatomical structures was 0.702-0.764.Conclusion Self-guided attention network could be used for preliminarily detecting responsible lesions related to CP in children with PVWMI.

Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95％CI:0.125-0.327),0.257(95％CI:0.155-0.354),0.179(95％CI:0.074-0.280),and 0.181(95％CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95％CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95％CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.

Objective To elucidate the mechanistic role of ferrostatin-1(Fer-1)in the pathogenesis of diabetic nephropathy(DN).Methods Twenty spontaneous diabetic mice and ten negative control mice were used for in vivo experiments.The for-mer were randomly divided into a model group and a Fer-1 treatment group,with the treatment group receiving intraperitoneal injections of Fer-1(1 mg/kg).Levels of BUN,Scr,glucose,microalbuminuria,GSH,and iron were measured in the mice.Renal histopathological staining was performed to observe renal morphology.Western blot and immunohistochemistry were used to detect the expression of ferroptosis marker proteins,heat shock factor 1(HSF-1),and heme oxygenase-1(HO-1)in renal tis-sues.Human renal cortical proximal tubular epithelial cells(HK-2)were cultured and divided into three groups during in vitro experiments:control group,high glucose group(30 mmol/L),and Fer-1 treatment group(1μmol/L).Levels of GSH,MDA,4-HNE,and iron content were measured.Immunofluorescence experiment was used to assess the level of reactive oxygen species(ROS).Western blot was performed to detect the expressions of ferroptosis marker proteins,kidney injury molecule-1,neutro-phil gelatinase-associated lipocalin,HO-1,and HSF-1 in HK-2 cells.Results In the model group,renal pathological changes,in-cluding glomerular hypertrophy,mesangial matrix expansion,glycogen accumulation,and fibrosis,were observed.Compared with the control group,levels of BUN,Scr,glucose,and urinary microalbumin were increased,GSH content was decreased,and iron level was elevated in the model group(all P＜0.05).The expression of HSF-1 protein in the kidneys of the model group was lower than that in the control group,while HO-1 protein expression was higher.The Fer-1 treatment group exhibited the oppo-site trend.(both P＜0.05).GSH expression was decreased,and iron content,MDA,and 4-HNE levels were increased in the high glucose group(all P＜0.05).Immunofluorescence result revealed that,compared with the control group,ROS level was higher in the high glucose group(all P＜0.05).Additionally,the high glucose group showed increased expressions of KIM-1,NGAL,and HO-1,along with reduced HSF-1 expression,whereas the Fer-1 treatment group exhibited the opposite trend.(all P＜0.05).Conclusion Both in vivo and in vitro experiments have demonstrated that ferroptosis plays a significant role in the de-velopment and progression of DN.Fer-1 may alleviate DN injury by upregulating ferroptosis through the HSF-1/HO-1 signaling pathway.

Objective To observe the efficacy of self-guided attention network for detecting responsible lesions related to cerebral palsy(CP)in children with periventricular white matter injury(PVWMI).Methods Totally 383 children with PVWMI were retrospectively enrolled and divided into CP group(n=243)and non-CP group(n=140),while 214 children without obvious brain abnormality on brain MRI were taken as control group.ROI of 4 key anatomical structures related to CP,i.e.centrum semiovale,posterior limb of internal capsule,cerebral peduncle and thalamus were delineated on T1WI,while responsible lesions related to CP within the key anatomical structures were labeled on T2WI,and the images were then registrated and used as input of the networks.ResNet34 network was adopted combined with attention and self-guided networks to train the network for detecting responsible lesions related to CP in children with PVWMI,and their efficacies were evaluated.The optimal network was screened,and its efficacy for segmenting the key anatomical structures was evaluated.Results Self-guided attention network was the optimal network,its area under the curve(AUC)for detecting lesions was 0.794-0.914,and the Dice similarity coefficient for segmenting the key anatomical structures was 0.702-0.764.Conclusion Self-guided attention network could be used for preliminarily detecting responsible lesions related to CP in children with PVWMI.

Objective To elucidate the mechanistic role of ferrostatin-1(Fer-1)in the pathogenesis of diabetic nephropathy(DN).Methods Twenty spontaneous diabetic mice and ten negative control mice were used for in vivo experiments.The for-mer were randomly divided into a model group and a Fer-1 treatment group,with the treatment group receiving intraperitoneal injections of Fer-1(1 mg/kg).Levels of BUN,Scr,glucose,microalbuminuria,GSH,and iron were measured in the mice.Renal histopathological staining was performed to observe renal morphology.Western blot and immunohistochemistry were used to detect the expression of ferroptosis marker proteins,heat shock factor 1(HSF-1),and heme oxygenase-1(HO-1)in renal tis-sues.Human renal cortical proximal tubular epithelial cells(HK-2)were cultured and divided into three groups during in vitro experiments:control group,high glucose group(30 mmol/L),and Fer-1 treatment group(1μmol/L).Levels of GSH,MDA,4-HNE,and iron content were measured.Immunofluorescence experiment was used to assess the level of reactive oxygen species(ROS).Western blot was performed to detect the expressions of ferroptosis marker proteins,kidney injury molecule-1,neutro-phil gelatinase-associated lipocalin,HO-1,and HSF-1 in HK-2 cells.Results In the model group,renal pathological changes,in-cluding glomerular hypertrophy,mesangial matrix expansion,glycogen accumulation,and fibrosis,were observed.Compared with the control group,levels of BUN,Scr,glucose,and urinary microalbumin were increased,GSH content was decreased,and iron level was elevated in the model group(all P＜0.05).The expression of HSF-1 protein in the kidneys of the model group was lower than that in the control group,while HO-1 protein expression was higher.The Fer-1 treatment group exhibited the oppo-site trend.(both P＜0.05).GSH expression was decreased,and iron content,MDA,and 4-HNE levels were increased in the high glucose group(all P＜0.05).Immunofluorescence result revealed that,compared with the control group,ROS level was higher in the high glucose group(all P＜0.05).Additionally,the high glucose group showed increased expressions of KIM-1,NGAL,and HO-1,along with reduced HSF-1 expression,whereas the Fer-1 treatment group exhibited the opposite trend.(all P＜0.05).Conclusion Both in vivo and in vitro experiments have demonstrated that ferroptosis plays a significant role in the de-velopment and progression of DN.Fer-1 may alleviate DN injury by upregulating ferroptosis through the HSF-1/HO-1 signaling pathway.

OBJECTIVE To analyze the homology and drug resistance characteristics of clinical carbapenem-resistant Klebsiella pneumoniae(CRKP)isolates from the children and adults in Kunming area so as to provide guidance for prevention and control of CRKP strains.METHODS Totally 41 strains of clinical CRKP isolates were collected from the children in 4 hospitals of Kunming area in 2023,and 54 strains were collected from the adults.The ho-mology of the strains was analyzed by means of repetitive extragenic palindromic-polymerase chain reaction(REP-PCR);the phenotypes of carbapenemases and the genes in the strains were detected.RESULTS The 95 strains of CRKP were divided into 30 genotypes.There was clustering of genotypes in some strains.The type A enzyme was most common among the strains from the adults(47 strains,87.04％),while the type A enzyme(18 strains,43.90％)and the type B enzyme(23 strains,56.10％)were both detected in the strains from the children.A-mong the strains producing type A enzyme,the strains carrying with KPC gene were both dominant among the strains isolated from the adults(44 strains,81.48％)and the strains isolated from the children(18 strains,43.90％).Among the strains producing type B enzyme,the strains carrying with NDM gene were dominant a-mong the strains from the children(22 strains,53.66％).CONCLUSIONS There is colonization and inter-hospital transmission of CRKP strains in the hospitals of Kunming area.It is necessary for the clinical departments of the children's hospitals to strengthen the active screening of the transferring children and carefully carry out the cleaning and disinfection of nosocomial environment so as to reduce the probability of the CRKP infection among the children.Mean-while,the clinicians of the pediatrics department should comprehensively take all the factors into accounts such as the type of enzyme,formulate the appropriate medication regimens and raise the cure rate of the children with CRKP infection.