Obesity represents a complex, heritable condition shaped by interactions among genetic, epigenetic, metagenomic, and environmental factors. Nevertheless, the mechanistic contributions of genetic variation and epigenetic regulation to obesity pathogenesis remain incompletely elucidated. Advances in molecular profiling technologies have enabled the identification of numerous biomarkers associated with childhood obesity phenotypes. These discoveries facilitate understanding of obesity etiology and its links to chronic diseases. This review synthesizes current research on genomic and epigenomic biomarkers influencing childhood obesity susceptibility, advances our comprehension of etiological heterogeneity and intervention strategies, and offers conceptual frameworks for precision prevention based on epigenetic mechanisms.

Objective: To explore the association between CDKAL1 rs35261542, FAIM2 rs 3205718, and VGLL4 rs 2574704 polymorphisms with childhood obesity and related metabolic phenotypes to provide evidence for personalized prevention and management strategies. Methods: Based on the 2023 Long term Nutritional Health Effects of Early Childhood Nutrition Package Intervention project, the study enrolled 1 078 children aged 5-7 years from four counties in Henan (Songxian and Ruyang countries) and Guizhou (Guiding and Fuquan countries) provinces. Using BMI Z scores, 87 overweight and obese(OVOB) children were selected and matched by sex, age, and BMI Z score with 117 normal weight controls. Participants were further stratified into four metabolic phenotype groups: metabolically healthy normal weight (MHNW, n =51), metabolically unhealthy normal weight (MUNW, n =66), metabolically healthy obesity (MHO, n =31) and metabolically unhealthy obesity (MUO, n =56) based on four conventional cardiometabolic risk factor (CR) criteria. Data were collected through questionnaires, anthropometric measurements, serum biochemical tests, and KASP genotyping. The distribution of three genetic polymorphisms ( CDKAL1 rs35261542, FAIM2 rs3205718, VGLL4 rs 2574704) across metabolic subgroups was analyzed. Multivariate Logistic regression models assessed associations between these polymorphisms and obesity/metabolic phenotypes. Results: Multivariate Logistic regression analysis showed that Homozygous mutant AA genotype of CDKAL1 rs 35261542 was positively associated with OVOB( OR =3.63), MHO ( OR =11.04), MUO ( OR = 4.88 ) ( P <0.05). Homozygous TT genotype of FAIM2 rs 3205718 increased OVOB risk ( OR =4.44, P <0.05) but showed no association with metabolic phenotypes ( P >0.05). Homozygous mutant TT of VGLL4 rs 2574704 reduced the risks of MHO and MUO ( OR = 0.30, 0.24， P <0.05). Cumulative genetic effects analysis demonstrated carriers of 1 or 2 risk genotypes of rs 35261542 and rs 3205718 had progressively higher OVOB risk ( OR =2.53, 20.79), and the combination of rs 35261542 and rs 2574704 increased risks for both MHO ( OR =8.50) and MUO ( OR =5.00) ( P <0.05). Conclusions The AA genotype of rs 35261542 ( CDKAL1 ) positively correlates with childhood obesity and metabolic abnormalities. The TT genotype of rs 3205718 ( FAIM 2) increases obesity risk but not metabolic phenotypes. The TT genotype of rs 2574704 ( VGLL 4) shows protective effects against metabolic dysfunction. Risk genotypes exhibit dosedependent cumulative effects on obesity and metabolic outcomes.

Objective To investigate the changes of serum levels of soluble scavenger receptor 163 (sCD163),angiopoietin-like protein 3 (ANGPTL3) before and after intravenous thrombolysis in patients with acute cerebral infarction (ACI) and their correlation with prognosis. Methods A total of 60 ACI patients accepted by Cangzhou Central Hospital from June 2021 to June 2022 were collected as the ACI group,and another 60 healthy individuals were regarded as the control group. According to the National Institutes of Health Stroke Scale (NIHSS) score after admission,60 patients were divided into mild group (n=10),moderate group (n=38) and severe group (n=12).According to the scores on the modified Rankin scale 90 days after thrombolysis,patients were separated into a good prognosis group (n=42) and a poor prognosis group (n=18). The serum levels of sCD163 and ANGPTL3 were detected using enzyme linked immunosorbent assay (ELISA),and receiver operating characteristic (ROC) curve was applied to analyze the predictive value of serum sCD163 and ANGPTL3 levels for the prognosis of ACI patients after intravenous thrombolysis therapy. Results Compared with the control group,the levels of serum sCD163 (687.55±86.43 ng/ml vs 411.07±58.24 ng/ml) and ANGPTL3 (60.28±10.55 mg/L vs 25.34±5.93 mg/L) in ACI group were significantly increased,and the differences were significant (t=20.549,22.363,all P<0.05). The levels of serum sCD163 (551.65±69.66 ng/ml,668.92±81.12 ng/ml,859.79±117.24 ng/ml) and ANGPTL3 (44.52±8.12 mg/L,58.67±10.37 mg/L,75.34±13.12 mg/L) in mild,moderate and severe groups were gradually increased,and the differences were significant (F=36.011,23.007,all P<0.05). Compared with the good prognosis group,the proportion of time from onset to thrombolysis≥ 3 h,the proportion of NIHSS score>10 at admission,and the serum sCD163 and ANGPTL3 levels before and after thrombolysis were significantly increased in the poor prognosis group,and the differences were statistically significant (t/x2=5.644,4.775,8.982,10.866,10.293,9.702,all P<0.05). ROC results showed that the area under the curves(95％ confidence intervals)[AUC(95％CI)]of serum sCD163 and ANGPTL3 level alone in predicting the prognosis of ACI patients were 0.830 (0.711～0.915) and 0.783 (0.658～0.879),and their sensitivity and specificity were 72.22％ and 85.71％,77.78％ and 85.71％,respectively. The AUC(95％CI)of combined prediction of serum sCD163 and ANGPTL3 in predicting the prognosis of ACI patients[0.950(0.861～0.990)]was obviously greater than the AUC predicted by sCD163 and ANGPTL3 alone (Z=2.378,2.109,P=0.017,0.035). Conclusion sCD163 and ANGPTL3 levels are elevated in the serum of ACI patients,and are related to their severity and prognosis.

Aim To investigate the effect of irisin on endothelial inflammation and atherosclerosis(As)in mice.Methods ApoE-/-mice were randomly divided into control group,As model group,and irisin group(treated with irisin based on the As model),with 10 mice in each group.The carotid tissues were stained using pathological techniques and immunofluorescence.Human aortic endothelial cells(HAEC)were cultured in vitro,treated with irisin,and stimulated with cholesterol crystal(CC).The protein levels of vascular cell adhesion molecule-1(VCAM-1)and intercellular cell adhesion molecule-1(ICAM-1)were then detected by Western blot.The expression of inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6)and chemokine(C-C motif)ligand 2(CCL2)were detected by RT-qPCR.The ad-hesion of monocytes was assessed using cell adhesion assay.Results The carotid plaque area in the mice of As model group was significantly increased compared with that in control group(P＜0.05).In contrast,the plaque area was re-duced in the irisin group compared with the As model group(P＜0.05).Compared with the control group,the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC were increased in the carotid arteries of the As model group(P＜0.05),while irisin could reduce the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC(P＜0.05).At the in vitro level,the expression of VCAM-1 and ICAM-1,as well as the adhesion of monocytes in CC-stimulated HAEC,were increased(P＜0.05).However,irisin could inhibit the increased expression of VCAM-1 and ICAM-1(P＜0.05),as well as the adhesion of monocytes induced by CC(P＜0.05).The mRNA levels of IL-1β,IL-6 and CCL2 in HAEC of CC stimulated group were increased(P＜0.05),while irisin could inhibit the mRNA expressions of IL-1β,IL-6 and CCL2 induced by CC(P＜0.05).Conclusion Irisin can inhibit vascular inflamma-tion,thereby reducing the occurrence and progression of atherosclerosis.

Aim To investigate the effect of irisin on endothelial inflammation and atherosclerosis(As)in mice.Methods ApoE-/-mice were randomly divided into control group,As model group,and irisin group(treated with irisin based on the As model),with 10 mice in each group.The carotid tissues were stained using pathological techniques and immunofluorescence.Human aortic endothelial cells(HAEC)were cultured in vitro,treated with irisin,and stimulated with cholesterol crystal(CC).The protein levels of vascular cell adhesion molecule-1(VCAM-1)and intercellular cell adhesion molecule-1(ICAM-1)were then detected by Western blot.The expression of inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6)and chemokine(C-C motif)ligand 2(CCL2)were detected by RT-qPCR.The ad-hesion of monocytes was assessed using cell adhesion assay.Results The carotid plaque area in the mice of As model group was significantly increased compared with that in control group(P＜0.05).In contrast,the plaque area was re-duced in the irisin group compared with the As model group(P＜0.05).Compared with the control group,the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC were increased in the carotid arteries of the As model group(P＜0.05),while irisin could reduce the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC(P＜0.05).At the in vitro level,the expression of VCAM-1 and ICAM-1,as well as the adhesion of monocytes in CC-stimulated HAEC,were increased(P＜0.05).However,irisin could inhibit the increased expression of VCAM-1 and ICAM-1(P＜0.05),as well as the adhesion of monocytes induced by CC(P＜0.05).The mRNA levels of IL-1β,IL-6 and CCL2 in HAEC of CC stimulated group were increased(P＜0.05),while irisin could inhibit the mRNA expressions of IL-1β,IL-6 and CCL2 induced by CC(P＜0.05).Conclusion Irisin can inhibit vascular inflamma-tion,thereby reducing the occurrence and progression of atherosclerosis.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Acute kidney injury (AKI) is a critical clinical condition characterized by rapid renal function decline, with high morbidity, mortality, and healthcare costs. Traditional Chinese medicine (TCM) has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models. Scutellaria barbata D. Don (SB) and Scleromitrion diffusum (Willd.) R. J. Wang (SD), a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities. Using advanced chromatographic separation technology, we enriched the effective fractions of water extracts from SB-SD, obtaining self-assembled herbal nanoparticles (SB and SD nanoparticles, SSNPs) rich in flavonoids and terpenoids. These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Oral administration of SSNPs in mice resulted in absorption into the bloodstream, formation of a protein corona, reduced macrophage phagocytosis, and enhanced bioavailability and renal targeting. Furthermore, we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids. Kinetic studies and in situ transmission electron microscopy (in situ TEM) revealed that these compounds self-assemble via supramolecular forces like hydrogen bonding and π-π interactions, forming stable nanostructures. This study elucidates the renoprotective effects and mechanisms of SB and SD, and provides a novel approach for the development of TCM-based nanomedicines, highlighting the potential of nano-TCM in AKI treatment.

The chemical constituents of Commiphora myrrha was investigated by column chromatography on silica gel, ODS, Sephadex LH-20, and semi-preparative HPLC. Their structures were elucidated by comprehensive spectroscopic methods including UV, IR, MS, NMR, as well as ECD calculation. Seven compounds were isolated from the dichloromethane-soluble fraction of C. myrrha and their structures were identified as(1S,2R,4S,5R,8S)-guaiane-2-hydroxy-7(11),10(15)-dien-6-oxo-12,8-olide(1), commipholide E(2), myrrhterpenoid H(3), myrrhterpenoid I(4), myrrhterpenoid E(5), 2α-methoxy-8α-hydroxy-6-oxogermacra-1(10),7(11)-dien-8,12-olide(6), 8,12-epoxy-1α,9α-hydroxy-eudesma-7,11-diene-6-dione(7). Compound 1 was a new compound and named myrrhterpenoid P. Compound 7 was isolated from Commiphora genus for the first time. Compounds 2, 5, and 6 significantly inhibited nitric oxide(NO) production in LPS-stimulated RAW264.7 cells, with IC_(50) values of(49.67±4.16),(40.80±1.27),(47.22±0.87) μmol·L~(-1), respectively [indomethacin as the positive control, with IC_(50) value of(63.92±2.60) μmol·L~(-1)].
Commiphora/chemistry* ; Animals ; Mice ; Resins, Plant/chemistry* ; Sesquiterpenes/isolation & purification* ; Molecular Structure ; Nitric Oxide ; Macrophages/metabolism* ; RAW 264.7 Cells ; Drugs, Chinese Herbal/pharmacology*

The chemical components of Carthami Flos were investigated by using macroporous resin, silica gel column chromatography, reversed-phase octadecylsilane(ODS) column chromatography, Sephadex LH-20, and semi-preparative high-performance liquid chromatography(HPLC). The planar structures of the compounds were established based on their physicochemical properties and ultraviolet-visible(UV-Vis), infrared(IR), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), and nuclear magnetic resonance(NMR) spectroscopic technology. The absolute configurations were determined by comparing the calculated and experimental electronic circular dichroism(ECD). Six flavonoid C-glycosides were isolated from the 30% ethanol elution fraction of macroporous resin obtained from the 95% ethanol extract of Carthami Flos, and identified as saffloquinoside F(1), 5-hydroxysaffloneoside(2), iso-5-hydroxysaffloneoside(3), isosafflomin C(4), safflomin C(5), and vicenin 2(6). Among these, the compounds 1 to 3 were new chalcone C-glycosides. The compounds 1, 2, 4, and 5 could significantly increase the viability of H9c2 cardiomyocytes damaged by oxygen-glucose deprivation/reoxygenation(OGD/R) at a concentration of 50 μmol·L~(-1), showing their good cardioprotective activity.
Glycosides/pharmacology* ; Flowers/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Carthamus tinctorius/chemistry* ; Chalcones/pharmacology* ; Animals

Based on the target recognition ability of split aptamer and intelligent analytical capability of molecular logic gate,in this work,two split aptamers were integrated into"AND"logic gate to construct a novel ortho-nucleic acid fluorescence sensor for simultaneous detection of thrombin and myoglobin.When there was one target,the response of the signal was only a single fluorescence output signal,which was used as an evaluation standard for early low-risk judgment.When two targets coexisted,the split aptamer bound to the target to form a ternary complex and led to the head and tail ortho-nucleic acid effect respectively,and triggered the G4 chain to enhance the fluorescence signal of thioflavin T and the fluorescence signal quenching of Cyanine 3,which could be used as an evaluation criterion for early high-risk judgement.Under the optimal conditions,the linear range for detection of thrombin was 3-200 nmol/L,with a correlation coefficient of 0.9931 and a detection limit of 0.97 nmol/L,and the linear range for detection of myoglobin was 6-400 nmol/L,with a correlation coefficient of 0.9933,and a detection limit of 2.14 nmol/L.The method was applied to simultaneous determination of thrombin and myoglobin in clinical serum samples,and the recoveries were 85.4%-118.3%and 85.8%-119.9%,respectively,with relative standard deviations of less than 6.5%.Compared with the standard method,the relative error range was from-8.8%to 5.6%.In addition,the logical diagnosis results of 4 serum samples were high-risk of acute myocardial infarction in 2 cases and low-risk in 2 cases.The ″AND″ logic gate ortho-nucleic acid fluorescence sensing method showed many advantages such as high selectivity,rapidity,accuracy and simultaneous detection,which offered important reference for early diagnosis of acute myocardial infarction,and also provided a general detection design strategy and platform for simultaneous detection of biomarkers.