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.

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.

Emotional dysregulation(ED)is a common problem in the children with autism spectrum disorder(ASD)and has adverse effects on social interaction,academic achievement,parent-child relationships,and overall functioning.The comorbid ED in the children with ASD is easily confused with or overlooked due to its core symptoms.Assessing the emotional regulation(ER)problems in the children with ASD from multiple perspectives is helpful for the early identification and diagnosis of ED,and can provide the reference for developing intervention methods to improve ED and even the overall prognosis of the children with ASD.Discussing the application of non-pharmacological and pharmacological treatment methods for ED in the children with ASD is helpful for selecting appropriate intervention strategies for ED in different subgroups of the children with ASD,and can also provide the basis for intervention methods more suitable for ED in toddler and preschool-aged children with ASD.Based on relevant research results at home and abroad,this article introduces the research progress in comorbid ED in the children with ASD from the aspects of the current status of emotional dysregulation,assessment methods,and intervention strategies,in order to provide more scientific basis for the early identification,diagnosis,and effective intervention of ED in children with ASD.

BACKGROUND:Monounsaturated fatty acids are mostly recognized as a fatty acid with beneficial effects on human health,and some studies have suggested that they may contribute to non-inflammatory pain at multiple sites in the body.OBJECTIVE:To investigate the effect of monounsaturated fatty acids on the incidence of low back pain and all-cause mortality,thereby providing potential biomarkers and intervention strategies for low back pain management and prevention.METHODS:A Mendelian randomization method was used to analyze the potential association of monounsaturated fatty acids on the incidence of low back pain and all-cause mortality in conjunction with large sample data from the National Health and Nutrition Examination Survey(NHANES)database.Results were validated and sensitivity analyzed using multiple statistical models(e.g.,inverse variance weighting,MR-Egger regression,simple median,weighted median,and weighted median)to enhance the reliability of causal inferences.In the NHANES study,multivariate Cox proportional risk regression models were used to assess the independent predictive values of different fatty acid ratios and to control for confounders.Potential nonlinear relationships between monounsaturated fatty acids and all-cause mortality were assessed using Kaplan-Meier curves,log-rank tests,and restricted cubic spline curves.RESULTS AND CONCLUSION:Elevated monounsaturated fatty acids have been found to be associated with a significantly higher risk of low back pain,suggesting an unfavorable effect of this fatty acid.Also,monounsaturated fatty acids may increase all-cause mortality in patients with low back pain.This provides new insights into the potential effects of monounsaturated fatty acids on low back pain and all-cause mortality,and provides a scientific basis for nutritional interventions for low back pain.The results support the use of dietary modification as one of the strategies for the prevention and management of low back pain in the European population,but further studies are needed to explore the specific biological mechanisms and potential for clinical application,thereby improving guidance for the prevention and treatment of diseases in China.

BACKGROUND:Monounsaturated fatty acids are mostly recognized as a fatty acid with beneficial effects on human health,and some studies have suggested that they may contribute to non-inflammatory pain at multiple sites in the body.OBJECTIVE:To investigate the effect of monounsaturated fatty acids on the incidence of low back pain and all-cause mortality,thereby providing potential biomarkers and intervention strategies for low back pain management and prevention.METHODS:A Mendelian randomization method was used to analyze the potential association of monounsaturated fatty acids on the incidence of low back pain and all-cause mortality in conjunction with large sample data from the National Health and Nutrition Examination Survey(NHANES)database.Results were validated and sensitivity analyzed using multiple statistical models(e.g.,inverse variance weighting,MR-Egger regression,simple median,weighted median,and weighted median)to enhance the reliability of causal inferences.In the NHANES study,multivariate Cox proportional risk regression models were used to assess the independent predictive values of different fatty acid ratios and to control for confounders.Potential nonlinear relationships between monounsaturated fatty acids and all-cause mortality were assessed using Kaplan-Meier curves,log-rank tests,and restricted cubic spline curves.RESULTS AND CONCLUSION:Elevated monounsaturated fatty acids have been found to be associated with a significantly higher risk of low back pain,suggesting an unfavorable effect of this fatty acid.Also,monounsaturated fatty acids may increase all-cause mortality in patients with low back pain.This provides new insights into the potential effects of monounsaturated fatty acids on low back pain and all-cause mortality,and provides a scientific basis for nutritional interventions for low back pain.The results support the use of dietary modification as one of the strategies for the prevention and management of low back pain in the European population,but further studies are needed to explore the specific biological mechanisms and potential for clinical application,thereby improving guidance for the prevention and treatment of diseases in China.

Objective:The objective of this research is to study the prevalence and risk factors of psychosocial and behavioral problems in children and adolescents of different ages and genders to provide a scientific foundation for more targeted psychological interventions and social support in the future.Methods:From April 21 to May 31, 2023, a cross-sectional survey was conducted using a stratified random sampling method in five cities (Beijing City, Changchun City, Baicheng City, Shenyang City, Hohhot City) across four provinces in Northern China (Beijing, Jilin, Liaoning, Inner Mongolia). The study was conducted using an online questionnaire among children and adolescents aged 6-16 years. Self-made social and life characteristics questionnaire and Achenbach Child Behavior Check List (CBCL) (for parent) was utilized to investigate the prevalence of psychosocial and behavioral problems and relative influencing factors. Using stepwise regression analysis to screen potential factors affecting the psychosocial and behavioral health of children and adolescents and logistic regression analysis was employed to analyze the risk factors associated while controlling for confounding variables.Results:A total of 10 492 questionnaires were distributed in this study. Among the 8 593 valid questionnaires collected, there were 4 385 males (51.03%) and 4 208 females (48.97%). The sample consisted of 3 348 children aged 6-11 years old and 5 245 children aged 12-16 years old. Out of these participants, 688 individuals (8.01%) were detected positive. In the 6-11 age group, 1 762 boys were assessed, revealing 142 positive cases (8.06%), while 1 586 girls were assessed, with 84 positive cases (5.30%). In the 12-16 age group, 2 623 boys were evaluated, resulting in 237 positive cases (9.04%), and 2 622 girls were evaluated, with 225 positive cases (8.58%). Overall, boys had a higher prevalence rate than girls did, with older age groups showing higher rates compared to younger ones. Logistic regression analysis identified six significant risk factors: parent-child conflict ( OR=4.207, 95% CI: 3.583-4.940), irregular diet patterns( OR=1.862, 95% CI: 1.566-2.213), parental mental illness history( OR=5.381, 95% CI: 2.673-10.83), sleep disorders( OR=4.664, 95% CI: 4.194-5.187), and excessive screen exposure( OR=1.863, 95% CI: 1.577-2.200) were found to be risk factors; whereas having more close friends ( OR=0.510, 95% CI: 0.431-0.603) acted as a protective factor. Conclusions:Psychosocial and behavioral problems in children and adolescents will change with social conditions, with continuous attention required to prevent risk factors. Precise intervention and integral support should be implemented by families, schools and society to provide more accurate protection for children and adolescents.

Background:The burden of Crohn's disease(CD)is rising globally,and the efficacy and safety of ustekinumab(UST)in treatment of CD need to be further verified.Aims:To assess the short-term efficacy and safety of UST in CD patients.Methods:A single-center retrospective observational study was conducted in the First Affiliated Hospital of Kunming Medical University.The clinical data of CD patients treated with UST from January 2020 to December 2023 were analyzed retrospectively.The clinical activity and endoscopic severity of the disease were assessed using Crohn's disease activity index(CDAI)and simple endoscopic score for Crohn's disease(SES-CD),respectively.The primary outcomes were clinical response(CDAI score decreased≥70 points,or CDAI score decreased<70 points but the total score<150)and clinical remission(CDAI score<150),while the secondary outcomes included endoscopic response(SES-CD decreased≥50%),endoscopic remission(SES-CD≤2),changes of inflammatory and nutritional indicators,and the adverse events.Results:Twenty-seven CD patients were included,of which,16 were males,and 11 were females,with median disease duration of 3.00 years.After treatment with UST,the median CDAI score decreased from 213.00(178.83,302.98)at baseline to 129.83(89.67,151.33)at week 16/20 and 95.07(67.45,178.34)at week 32(all P<0.017).The clinical response rate and remission rate at week 16/20 were 92.6%and 70.4%,respectively,and those at week 32 were 95.5%and 72.7%,respectively.When patients were stratified as biologic na?ve and exposure,or as with and without dose optimization,no significant differences were found in clinical response and remission rates among various subgroups.Seventeen patients reviewed endoscopy at week 16/20,the SES-CD decreased significantly from baseline(5.47±4.53 vs.9.88±4.58,P<0.05),with the endoscopic response rate and remission rate of 35.3%and 23.5%,respectively.C-reactive protein decreased significantly from baseline at week 16/20 and week 32 of treatment(all P<0.017),while the platelet count,hemoglobin,albumin and body mass index only showed insignificant improving trends.No serious adverse events were observed during the medication period.Conclusions:UST can improve the clinical symptoms,endoscopic manifestations,and systemic inflammation effectively in CD patients in short-term follow-up,and represents a good safety profile.

Objective To investigate the relationship between interleukin 1 receptor a(IL-1Ra)gene polymorphism and different outcomes in asymptomatic bacterial vaginosis(aBV)patients with the aim of grouping and managing aBV patients.Methods In study on the natural attribution of aBV patients,all patients were enrolled and a sam-ple of venous blood and vaginal lavage fluid were separately frozen.After 4 months at the end of the clinical study,patients who completed the study were divided into three groups based on clinical outcomes:self-healing,progres-sive,and unchanged.The IL-1Ra gene polymorphism,the concentration of IL-1 β and IL-1Ra were tested,and the differences in the above indicators among three groups of patients with different outcomes were compared.Results 1 014 Chinese Han female patients were enrolled,and 984 patients completed clinical follow-up and obtained clini-cal outcome data.13 specimens were unusable during testing,with a total of 971 specimens completed the test.IL-1Ra gene was detected in all patients,with three genotypes:A1/A1,A1/A2,and A2/A2.Most population had a genotype of A1/A1,with the rarest genotype being A2/A2.No rare genotype of female was found.The frequency of A2 alleles in the progression group was significantly higher than that in the self-healing group(P＜0.05).IL-1 βand IL-1Ra were detected in all vaginal lavage fluid samples.Compared with the progression group,IL-1 β in the self-healing group was significantly lower(P＜0.05).When carrying the A2 allele,IL-1 β in progression group was relatively low,while the level of IL-1Ra was relatively high.The values of the unchanged group were middle.Con-clusion The polymorphism characteristics of the IL-1Ra gene in aBV patients are related to the IL-1Ra content in vaginal secretions.Carrying allele A2 is related to the elevation of IL-1Ra,the decrease of IL-1 β in vaginal secre-tions.Carrying allele A2 may affect the clinical outcome of aBV by some potential mechanism.