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 investigate the contents of natural radionuclides in agricultural soils in some of Gansu Hexi area to accumulate the relevant basic data.Methods:A stratified sampling method was used to collect 146 soil samples in the area. ORTEC P-type HPGE gamma spectrometry system was used to measure radionuclides. The measurement data were collated and analyzed.Results:The activity concentrations measured were 232Th 18.94-108.39 Bq/kg, 226Ra 14.37-79.20 Bq/kg and 40K 440.03-1 358.18 Bq/kg, in turn with the mean values of (68.22±16.32), (47.90±11.12) and (763.90±133.93) Bq/kg, respectively. The difference in activity concentrations of 232Th, 226Ra and 40K in agricultural soils in different areas was statistically significant( H=50.87, 45.14, 40.28, P<0.05). Conclusions:The study on the activity concentrations of natural radionuclides in agricultural soils provides basic information for the transfer of radionuclides to crops, which needs further investigation, monitoring and analysis.

Genomic imprinting refers to the phenomenon of differential expression of two alleles due to their different parental origins. Genes that produce genomic imprinting are usually called imprinted genes. The genetic effect caused by the presence of imprinted genes is called parent-of-origin effect. Parent-of-origin effect and genomic imprinting play important roles in the pathophysiological mechanism and occurrence and development of cardio-metabolic diseases. In-depth exploration of the law and potential roles of imprinted genes and parent-of-origin effects will help to better understand the mechanism of cardio-metabolic diseases, and also provide important theoretical basis for the precise treatment of diseases related to imprinted genes.

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.

Objective To evaluate the therapeutic effects of ticagrelor combined with traditional Chinese medicine(TCM)in patients with microvascular angina.Methods A retrospective analysis was conducted on 356 patients diagnosed with microvascular angina who were hospitalized in the Department of Cardiology at the First Hospital of Hebei Medical University between January 1,2022,and January 1,2024.Patients were assigned to a conventional treatment group or a combined TCM-Western medicine treatment group.The conven-tional treatment group received standard Western medicine therapy,whereas the combined treatment group received ticagrelor and TCM based on syndrome differentiation.After four weeks of treatment,coronary flow reserve(CFR),Canadian Cardiovascular Society(CCS)angina classification,and incidence of adverse drug reactions were compared between the two groups.Results The combined TCM-Western medicine treatment group had significantly better outcomes in CFR and CCS angina classification than the conventional treat-ment group(P＜0.05).Conclusion The combination of ticagrelor and TCM is safe and effective for treating patients with microvascular angina.

Objective:To establish and validate the diagnostic model of acute pulmonary embolism (APE) based on clinical and laboratory variables.Methods:This retrospective analysis was conducted on patients with suspected APE who underwent CT pulmonary angiography at the First Affiliated Hospital of Henan University of Chinese Medicine between February 2015 and December 2023. The patients were randomly divided into a training set and a validation set at a ratio of 7∶3. Clinical and laboratory data of the enrolled patients were collected, and patients were divided into an APE group and a non-APE group according to CT pulmonary angiography results. In the training set, univariate and multivariate logistic regression as well as Lasso regression were used to identify risk factors for APE, and a diagnostic model was developed and validated. Receiver operating characteristic curves were plotted, and calibration and decision curves were used to assess the performance of the diagnostic model. The diagnostic efficacy of the model was compared with that of the Wells score and the revised Geneva score using the DeLong test.Results:A total of 752 patients were enrolled, aged (64±15) years, including 417 (55.5%) males. The training set included 526 patients and the validation set included 226 patients. The incidence of APE in this cohort was 48.7% (366/752), with 366 cases in the APE group and 386 in the non-APE group. Multivariable logistic regression analysis showed that cyanosis ( OR=8.88, 95% CI 2.04-49.11), elevated neutrophil count ( OR=1.82, 95% CI 1.06-3.15), elevated creatine kinase isoenzyme ( OR=3.45, 95% CI 1.76-6.91), decreased partial pressure of carbon dioxide ( OR=12.88, 95% CI 7.64-22.34), elevated age-adjusted D-dimer ( OR=2.53, 95% CI 1.10-6.20), prolonged thrombin time ( OR=4.08, 95% CI 2.06-8.33), and positive lower limb venous ultrasound for thrombus ( OR=4.39, 95% CI 2.59-7.58) were risk factors associated with APE. The area under the curve ( AUC) of the diagnostic model was 0.92 (95% CI 0.90-0.94) in the training set and 0.92 (95% CI 0.89-0.95) in the validation set. The diagnostic efficacy of this model was superior to that of the Wells score ( AUC: 0.92 vs. 0.63, P<0.01) and the revised Geneva score ( AUC: 0.92 vs. 0.59, P<0.01). Conclusion:The diagnostic model for acute pulmonary embolism constructed based on clinical and laboratory parameters demonstrates excellent diagnostic performance and may facilitate rapid and accurate screening in clinical practice.

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.