Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

Objective:To explore the relationship between 24-hour movement behavior and anxiety in middle school students.Methods:Totally 2 690 students from 8 middle schools in Hubei Province were selected as research subjects.The Health Behavior in School-aged Children,Pittsburgh Sleep Quality Index and Self-Rating Anxiety Scale were used to assess 24-hour movement behavior[i.e.,moderate to vigorous physical activity(MVPA),screen time(ST),and sleep duration(SD)]and anxiety symptoms.The binary logistic regression analysis was per-formed to examine the relationship between 24-hour movement behavior and anxiety for middle school students.Results:In middle school students,the compliance rate of 24-hour movement behavior was 4.2％,that of MVPA being 15.8％,that of ST being 27.1％,that of SD being 64.2％,and the detection rate of anxiety was 21.7％.The binary logistic regression analysis showed that,compared with the situation when three factors met with the 24-hour movement guidelines,the anxiety risk of middle school students increased when single factor(i.e.,MVPA,ST and SD)and some two factors(i.e.,MVPA+ST and MVPA+SD)met 24-hour guidelines,with odds ratios being respectively 2.62,2.22,2.80,2.62,2.52.Conclusion:The detection rate of anxiety in middle school students was probably negatively correlated with the compliance rate of 24-hour movement behavior.

Objective To investigate the therapeutic effect of Gypenoside L(Gyp-L)on diabetic retinopathy(DR)rats and its effect on the p38 mitogen-activated protein kinase(MAPK)signaling pathway.Methods Rats were divided into 6 groups(n=12):blank group,model group,low,medium,high dose group and combination group.The blank group was normal control rats,and the other groups were DR rat models.Rats in the blank group and model group were intragastrically administered with sodium carboxymethyl cellulose.Rats in the low,medium and high dose group were ga-vaged with 50,100,and 200 mg·kg-1·d-1 of Gypenoside L solution,respectively.Rats in the combination group were gavaged with 200 mg·kg-1·d-1 of Gypenoside L solution,and 2 mg·kg-1·d-1 of p38 MAPK agonist Anisomycin was in-jected into the tail vein.The rats in each group were gavaged with a volume of 2 mL per day for a total treatment period of 4 weeks.After the treatment,fundus photography was performed on the rats in each group,and retinal tissues were stained with hematoxylin and eosin(HE).Fasting blood glucose was measured using a Roche blood glucose meter,and se-rum insulin levels were measured using an ELISA kit.Retinal superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin(IL)-1 β,and IL-6 levels were measured according to the instructions of the kit.Western blot was used to detect the protein levels of p38 MAPK,p-p38 MAPK,p65 nuclear factor-κB(NF-κB),p-p65 NF-κB,inducible nitric oxide synthase(iNOS),and cyclooxygenase(COX-2)in the retina.Results Compared with the model group,the blood glucose level was decreased,the serum insu-lin level was increased,the fundus neovascularization was reduced,the retinal damage was alleviated,the retinal SOD,CAT and GSH-Px levels were increased,the MDA level was decreased,the TNF-α,IL-1β and IL-6 levels were decreased,and the p-p38 MAPK,p-p65 NF-κB,iNOS and COX-2 protein levels were decreased in the low,medium and high dose group(all P＜0.05).Compared with the high dose group,the blood glucose level in the combination group was increased,the serum insulin level was decreased,the fundus neovascularization increased,the retinal damage was aggravated,the ret-inal SOD,CAT and GSH-Px levels were decreased,the MDA level was increased,the TNF-α,IL-1[3 and IL-6 levels were in-creased,and the p-p38 MAPK,p-p65NF-κB,iNOS and COX-2 protein levels were increased(all P＜0.05).Conclusion This study shows that Gypenoside L can reduce inflammation and oxidative stress by blocking the p38 MAPK signaling path-way,thereby playing a role in the treatment of DR.

Objective:To explore the relationship between 24-hour movement behavior and anxiety in middle school students.Methods:Totally 2 690 students from 8 middle schools in Hubei Province were selected as research subjects.The Health Behavior in School-aged Children,Pittsburgh Sleep Quality Index and Self-Rating Anxiety Scale were used to assess 24-hour movement behavior[i.e.,moderate to vigorous physical activity(MVPA),screen time(ST),and sleep duration(SD)]and anxiety symptoms.The binary logistic regression analysis was per-formed to examine the relationship between 24-hour movement behavior and anxiety for middle school students.Results:In middle school students,the compliance rate of 24-hour movement behavior was 4.2％,that of MVPA being 15.8％,that of ST being 27.1％,that of SD being 64.2％,and the detection rate of anxiety was 21.7％.The binary logistic regression analysis showed that,compared with the situation when three factors met with the 24-hour movement guidelines,the anxiety risk of middle school students increased when single factor(i.e.,MVPA,ST and SD)and some two factors(i.e.,MVPA+ST and MVPA+SD)met 24-hour guidelines,with odds ratios being respectively 2.62,2.22,2.80,2.62,2.52.Conclusion:The detection rate of anxiety in middle school students was probably negatively correlated with the compliance rate of 24-hour movement behavior.

Objective To investigate the therapeutic effect of Gypenoside L(Gyp-L)on diabetic retinopathy(DR)rats and its effect on the p38 mitogen-activated protein kinase(MAPK)signaling pathway.Methods Rats were divided into 6 groups(n=12):blank group,model group,low,medium,high dose group and combination group.The blank group was normal control rats,and the other groups were DR rat models.Rats in the blank group and model group were intragastrically administered with sodium carboxymethyl cellulose.Rats in the low,medium and high dose group were ga-vaged with 50,100,and 200 mg·kg-1·d-1 of Gypenoside L solution,respectively.Rats in the combination group were gavaged with 200 mg·kg-1·d-1 of Gypenoside L solution,and 2 mg·kg-1·d-1 of p38 MAPK agonist Anisomycin was in-jected into the tail vein.The rats in each group were gavaged with a volume of 2 mL per day for a total treatment period of 4 weeks.After the treatment,fundus photography was performed on the rats in each group,and retinal tissues were stained with hematoxylin and eosin(HE).Fasting blood glucose was measured using a Roche blood glucose meter,and se-rum insulin levels were measured using an ELISA kit.Retinal superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin(IL)-1 β,and IL-6 levels were measured according to the instructions of the kit.Western blot was used to detect the protein levels of p38 MAPK,p-p38 MAPK,p65 nuclear factor-κB(NF-κB),p-p65 NF-κB,inducible nitric oxide synthase(iNOS),and cyclooxygenase(COX-2)in the retina.Results Compared with the model group,the blood glucose level was decreased,the serum insu-lin level was increased,the fundus neovascularization was reduced,the retinal damage was alleviated,the retinal SOD,CAT and GSH-Px levels were increased,the MDA level was decreased,the TNF-α,IL-1β and IL-6 levels were decreased,and the p-p38 MAPK,p-p65 NF-κB,iNOS and COX-2 protein levels were decreased in the low,medium and high dose group(all P＜0.05).Compared with the high dose group,the blood glucose level in the combination group was increased,the serum insulin level was decreased,the fundus neovascularization increased,the retinal damage was aggravated,the ret-inal SOD,CAT and GSH-Px levels were decreased,the MDA level was increased,the TNF-α,IL-1[3 and IL-6 levels were in-creased,and the p-p38 MAPK,p-p65NF-κB,iNOS and COX-2 protein levels were increased(all P＜0.05).Conclusion This study shows that Gypenoside L can reduce inflammation and oxidative stress by blocking the p38 MAPK signaling path-way,thereby playing a role in the treatment of DR.

The correspondence between prescription and syndrome is the advantage and characteristic of traditional Chinese medicine(TCM)treatment.However,the pathogenesis of clinical diseases is complex and the condition is changeable,and the clinical application is difficult to achieve the maximum effect under the existing cognition of the correspondence between prescription and syndrome.In this paper,the five categories of physiological characteristics,pathological characteristics,constitution,syndrome,and disease of the longitudinal classification of"TCM state"are introduced into the correspondence of prescription and syndrome.Under the vertical perspective of"TCM state",the theoretical connotation of the correspondence between prescription and syndrome is interpreted as"correspondence between prescription and state",namely correspondence of"prescription-physiological characteristics",correspondence of"prescription-pathological characteristics",correspondence of"prescription-constitution",correspondence of"prescription-syndrome",and correspondence of"prescription-disease".It is hoped to accurately grasp the corresponding connotation of the correspondence between prescription and syndrome,in order to deepen the clinical thinking mode of TCM.