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.

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 observe the improvement of motor dysfunction and serum levels of C-reactive protein(CRP),blood glucose and blood lipid in post-stroke patients treated with scalp acupuncture at different needle retention time.Methods A total of 120 patients with motor dysfunction after stroke were randomly divided into control group,observation group 1 and observation group 2,with 40 cases in each group.The patients in the 3 groups were treated with scalp acupuncture,body acupuncture and routine rehabilitation exercise,once a day and 6 times a week,lasting for 2 weeks.The control group was given scalp acupuncture with retaining of needles for 30 minutes,the observation group 1 was given scalp acupuncture with retaining of needles for one hour,and the observation group 2 was given scalp acupuncture with retaining of needles for 2 hours.Before and after treatment,the 3 groups were observed in the changes of the scale scores of National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FM A),Berg Balance Scale(BBS)and modified Barthel Index(MBI),and the levels of laboratory indicators of peripheral blood CRP,fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).After treatment,the clinical safety of the three groups was evaluated.Results(1)After treatment,the scale scores of NIHSS in the three groups were lower(P＜0.01)and the scale scores FMA,BBS and MBI were higher than those before treatment(P＜0.05 or P＜0.01).The comparison of post-treatment scale scores showed that the differences among the three groups were statistically significant(P＜0.01).The intergroup comparison showed that the decrease of NIHSS score and the increase of FMA,BBS and MBI scores in the observation group 2 were significantly superior to those in the control group and the observation group 1(P＜0.01);the improvement of FMA score in the observation group 1 was significantly superior to that in the control group(P＜0.01),while the improvement of NIHSS,BBS and MBI scores tended to be superior to that in the control group without statistically significant differences(P＞0.05).The results indicated that the curative effect of scalp acupuncture plus exercise regimen was positively correlated with the duration of needle retention for scalp acupuncture.(2)After treatment,the laboratory indicator levels of CRP and FPG in the peripheral blood of the three groups,the levels of TG and LDL-C in the two observation groups and the level of HDL-C in the observation group 2 were improved compared with those before treatment(P＜0.05 or P＜0.01).Statistically significant differences were presented in the post-treatment levels of CRP and TG in peripheral blood among the three groups(P＜0.05 or P＜0.01).The intergroup comparison showed that the improvement of CRP and TG levels in the observation group 2 was significantly superior to that in the control group,and the improvement of CRP level in the observation group 2 was significantly superior to that in the observation group 1,the differences being statistically significant(P＜0.05 or P＜0.01).The TC level in the three groups after treatment did not differ from that before treatment,and there was no significant difference in TC level after treatment among the three groups either(P＞0.05).(3)During the treatment,no adverse reactions such as fainting,needle breaking and hematoma occurred in the three groups,the vital signs of the patients were stable,and there were no obvious abnormal changes in pulse,blood pressure and respiratory rate.Conclusion Scalp acupuncture can effectively improve the motor function of post-stroke patients in a pasitive time-effect relationship with the needle retention,and better the curative effect can be achieved by retaining of the needle for 2 h.

Objective To analyze the stress changes of thoracic vertebra(T)11-sacrum(S)titanium rods in patients with ankylosing spondylitis after vertebral column decancellation(VCD)osteotomy,and provide reference for the selection and improvement of titanium rods before surgery.Methods The original data of the continuous scanning tomographic images of patients with ankylosing spondylitis after VCD osteotomy were imported into Mimics 21.0 in DICOM format,and T11-S vertebrae,screws and titanium rods were respectively reconstructed.They were imported into 3-Matic to establish a preliminary geometric modeling,and then processed with noise removal,paving,smoothing,etc.The improved model was imported into Hypermesh 10 software for grid division,and the material was imported into ANSYS 19.2 to display the finite element model after attribute assignment,Set the boundary and load conditions,and measure the stress value at the connection between the screw and the titanium rod.Results Under neutral position,forward bending,lateral bending,and axial rotation conditions,the titanium rod had the highest stress at the upper vertebrae(T11)and the lowest stress at the top vertebrae(L3);Under the backward extension condition,the titanium rod has the highest stress at the lower end vertebra(L5).Conclusion In the upper and lower vertebrae,it is possible to consider increasing the diameter of the titanium rod,enhancing its hardness,or changing it to a double rod.

OBJECTIVE: To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome. METHODS: Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2. RESULTS: The proband of pedigree 1 was a fetus at 23⁺⁵ weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign". No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c.812+3G>T and c.1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign". The proband was found to harbor c.485C>G and c.1878+1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c.485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up. CONCLUSION The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.
Female ; Humans ; Pregnancy ; Pedigree ; Cerebellum/abnormalities* ; Abnormalities, Multiple/diagnosis* ; Eye Abnormalities/diagnosis* ; Kidney Diseases, Cystic/diagnosis* ; Phosphoric Monoester Hydrolases/genetics* ; Retina/abnormalities* ; East Asian People ; Mutation

OBJECTIVE: To develop a convenient method for rapid purification of fresh Pheretima proteins and assess the inhibitory effect of these proteins against pulmonary fibrosis. METHODS: The crude extract of fresh Pheretima was obtained by freeze-drying method and then purified by size exclusion chromatography. The composition of the purified proteins was analyzed by mass spectrometry. MRC-5 cells were treated with 5 ng/mL TGF-β1 alone (model group) or in combination with SB431542 (2 μmol/L) or the purified proteins (13.125 μg/mL), and the cytotoxicity of purified proteins and their inhibitory effects on cell proliferation were detected with CCK8 assay. Flow cytometry was used to detect the changes in cell apoptosis, and the cellular expressions of α-SMA, Vimentin, E-cadherin, collagen I, Smad2/3 and P-Smad2/3 were detected using RT-PCR and Western blotting. In the animal experiment, adult male C57BL/6 mice were subjected to intratracheal instillation of bleomycin followed by treatment with the purified proteins (5 mg/mL) for 21 days, after which HE and Masson staining was used to observe the pathological changes in the lung tissue of the mice. RESULTS: We successfully obtained purified proteins from fresh Pheretima protein by size exclusion chromatography. Treatment with the purified proteins significantly inhibited TGF-β1-induced proliferation of MRC-5 cells (P < 0.01), reduced the cellular expressions of α-SMA, Vimentin and collagen I (P < 0.001 or P < 0.01), increased the expression of E-cadherin (P < 0.01), and inhibited the expressions of Smad2/3 and P-Smad2/3 (P < 0.001 or P < 0.01). In male C57BL/6 mice models of bleomycin-induced pulmonary fibrosis, treatment with the purified proteins obviously reduced the number of inflammatory cells and fibrotic area in the lungs. CONCLUSION The purified proteins from fresh Pheretima obtained by size exclusion chromatography can inhibit pulmonary fibrosis in mice by regulating the TGF-β/ Smad pathway.
Animals ; Biological Products/pharmacology* ; Bleomycin/adverse effects* ; Cadherins/metabolism* ; Collagen Type I ; Lung/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Oligochaeta/chemistry* ; Pulmonary Fibrosis/drug therapy* ; Transforming Growth Factor beta1/metabolism* ; Vimentin/metabolism*

In this experiment, ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze and identify chemical constituents of Ginseng-Douchi(GD) compound fermentation, and explore the conversion rules of ginsenosides and soybean isoflavones after compound fermentation. Waters Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was adopted, with 0.1% formic acid aqueous solution(A)-0.1% formic acid acetonitrile solution(B) as mobile phase for gradient elution; electrospray ion source(ESI) was used to collect data in positive and negative ion modes; according to the exact mass number, the secondary spectrum comparison of the database and the existing literature reports, Peakview 2.0/masterview 1.0 software was used to determine the common ion structure formula. Finally, a total of 133 chemical constituents were analyzed and identified from the GD. Ginseng saponins and isoflavone glycosides were significantly converted after fermentation. Among them, peak areas of prototype ginsenosides Rk_3, Rh_1, Rh_2, Rh_3, daidzin, glycitin and genistin decreased significantly; whereas peak areas of se-condary ginsenoside Rb_1, Rb_2, Rk_1, glycitein, genistein and daidzein increased significantly. In this experiment, liquid-mass spectrometry technique was used to investigate the conversion of active ingredients of GD compound fermented products after co-fermentation, so as to provide a scientific basis for elucidating pharmacodynamics material basis and quality control.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Fermentation ; Panax ; Tandem Mass Spectrometry

Animals ; Diethylnitrosamine/toxicity* ; Liver ; Liver Neoplasms/chemically induced* ; Rats

Objective:To discuss clinical effect of addition and subtraction therapy of Wuhutang combined with Qingjin Jianghuotang to community acquired pneumonia (CAP) in children with syndrome of phlegm heat closing lung, and to study the influence to inflammatory factors. Method:One hundred and forty patients were randomly divided into control group (69 cases) and observation group (71 cases) by random number table. Patients in two group of chidren got comprehensive symptomatic treatment measures of anti-infection, antipyretic, expectorant, antiasthmatic and respiratory support of inflammatory factors. The control group was treated with Lingyang Qingfei granules.1 g/time,3 time/day. Patients in observation group added addition and subtraction therapy of Wuhutang combined with Qingjin Jianghuotang, 1 dose/day. The courses of treatment in two groups were 7 days. And temperature, time of antipyretic, time of complete antipyretic and rate of complete antipyretic at the 7^th day after treatment were recorded. And release time and disappearance time of cough, expectoration, disappearance time of pulmonary rales and treatment failure were also recorded. And before and after treatment, scores of syndrome of phlegm heat closing lung were graded, and levels of serum high sensitive C-reactive protein (hs-CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected. Result:Analyzed by rank sum test, effect in observation group was better than that in control group (Z=2.106, P<0.05), and curative effect of traditional Chinese medicine (TCM) syndrome was also better than that in control group (Z=2.119, P<0.05). Time of antipyretic, time of complete antipyretic, release time and disappearance time of cough and expectoration and disappearance time of pulmonary rales were all shorter than those in control group (P<0.01). Rate of complete antipyretic at the 7^th day after treatment in observation group was 96.92%（63/65） higher than 82.81%（53/64） in control group (χ²=7.085, P<0.05). Failure rate of treatment was 9.23%（6/65） lower than 23.44%（15/64） in control group (χ²=4.775, P<0.05). And major symptom, physical sign score, minor symptom score, the total score of syndrome of phlegm heat closing lung and levels of hs-CRP, PCT, TNF-α and IL-6 were all lower than those in control group (P<0.01). Conclusion:On the basis of comprehensive anti-infection treatment, addition and subtraction therapy of Wuhutang combined with Qingjin Jianghuotang can control the clinical symptoms, and the advantages of rapid onset, rapid symptom regression, short course of disease can be found, and it can also reduce the inflammatory reaction, control the progress of the disease. The complete antipyretic rate, disease efficacy and TCM syndrome efficacy are better.