Depression is a heterogeneous mental disorder in which the interaction between genetic susceptibility and environ-mental factors plays a key role in its pathogenesis.Although the specific mechanisms of the disease still need to be thoroughly studied and elucidated,there is now a broad consensus that epi-genetic markers have a central influence on its mechanism of ac-tion.DNA methylation of brain-derived neurotrophic factor(BD-NF)is not only regarded as a promising epigenetic biomarker of pathology,but may also help predict the efficacy of antidepres-sants.In this paper we reviewed the gene structure of BDNF and its DNA methylation regulation mechanism,and also analyzed the changes of DNA methylation of this factor in depression pa-tients and animal models,aiming to provide new ideas and theo-retical support for clinical research.

Objective To observe the mid-and long-term effects of Kegel training combined with Pilates training on urinary conti-nence recovery in different body mass index(BMI)male patients with urinary incontinence after prostatectomy.Methods From May,2023 to June,2024,48 patients in Beijing Bo'ai Hospital were recruited and divided into group A(<25 kg/m2,n=15),group B(25 to 30 kg/m2,n=18)and group C(>30 kg/m2,n=15)according to their BMI.All the groups performed Kegel training combined with Pilates training for two months,and followed up at six months from baseline.They were evaluated with one hour pad test,the number of daily urinary incontinence,In-ternational Consultation on Incontinence Questionnaire-Short Form(ICIQ-SF)and modified Oxford Rating Scale before treatment,and four weeks,eight weeks and six months after treatment.Results The intra-group effect,the inter-group effect and interaction effect were significant in the results of one hour pad test and the daily number of urinary incontinence(F>2.955,P<0.05).Post Hoc test showed that they were worse in group C than in groups A and B(P<0.05),and the number of daily urinary incontinence was more in group B than in group A(P<0.05).There was significant difference in the scores of ICIQ-SF and modified Ox-ford Rating Scale among groups in different time points after treatment(Z>10.476,P<0.05)except the score of ICIQ-SF four weeks after treatment(P>0.05),and they were the worst in group C.BMI(group A=1,group B=2,group C=3)was correlated with the results of one hour pad test(r=0.79,P<0.001),the number of daily uri-nary incontinence(r=0.68,P<0.001),and the scores of ICIQ-SF(r=0.68,P<0.001)and modified Oxford Rating Scale(r=-0.47,P=0.001)six months after treatment.Conclusion Kegel training combined with Pilates training could improve the urinary control in patients with urinary in-continence after prostatectomy.The decrease of BMI can promote the recovery of urinary control,and improve the symptoms of later urinary incontinence in mid-and long-term.

Depression is a heterogeneous mental disorder in which the interaction between genetic susceptibility and environ-mental factors plays a key role in its pathogenesis.Although the specific mechanisms of the disease still need to be thoroughly studied and elucidated,there is now a broad consensus that epi-genetic markers have a central influence on its mechanism of ac-tion.DNA methylation of brain-derived neurotrophic factor(BD-NF)is not only regarded as a promising epigenetic biomarker of pathology,but may also help predict the efficacy of antidepres-sants.In this paper we reviewed the gene structure of BDNF and its DNA methylation regulation mechanism,and also analyzed the changes of DNA methylation of this factor in depression pa-tients and animal models,aiming to provide new ideas and theo-retical support for clinical research.

AIM To establish an HPLC-MS/MS method for the simultaneous content determination of dehydrodiisoeugenol,eugenol,costiolactone,dehydrocostiolactone,quercetin,isorhamnetin,luteolin,caffeic acid,gallic acid,protocatechuic acid,ellagic acid and kaempferol in Anshen Buxin Liuwei Pills,and to make chemical pattern recognition.METHODS The analysis was performed on a 35 ℃ thermostatic Shim-pack GST-HP C18 column(2.1 mm × 100 mm,3 μm),with the mobile phase comprising of methanol-water(containing 0.1％formic acid)flowing at 0.25 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.Subsequently,cluster analysis,principal component analysis and orthogonal partial least square-discriminant analysis were performed.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 95.38％-105.00％with the RSDs of 1.91％-5.14％.Thirteen batches of samples were clustered into 3 types,ellagic acid,dehydrocodenolactone,dehydrodiisoeugenol,protocatechuic acid,gallic acid,quercetin and kaempferol were taken as potential quality differential markers.CONCLUSION This accurate,sensitive,stable and reproducible method can be used for the quality control and evaluation of Anshen Buxin Liuwei Pills.

Objective To observe the mid-and long-term effects of Kegel training combined with Pilates training on urinary conti-nence recovery in different body mass index(BMI)male patients with urinary incontinence after prostatectomy.Methods From May,2023 to June,2024,48 patients in Beijing Bo'ai Hospital were recruited and divided into group A(<25 kg/m2,n=15),group B(25 to 30 kg/m2,n=18)and group C(>30 kg/m2,n=15)according to their BMI.All the groups performed Kegel training combined with Pilates training for two months,and followed up at six months from baseline.They were evaluated with one hour pad test,the number of daily urinary incontinence,In-ternational Consultation on Incontinence Questionnaire-Short Form(ICIQ-SF)and modified Oxford Rating Scale before treatment,and four weeks,eight weeks and six months after treatment.Results The intra-group effect,the inter-group effect and interaction effect were significant in the results of one hour pad test and the daily number of urinary incontinence(F>2.955,P<0.05).Post Hoc test showed that they were worse in group C than in groups A and B(P<0.05),and the number of daily urinary incontinence was more in group B than in group A(P<0.05).There was significant difference in the scores of ICIQ-SF and modified Ox-ford Rating Scale among groups in different time points after treatment(Z>10.476,P<0.05)except the score of ICIQ-SF four weeks after treatment(P>0.05),and they were the worst in group C.BMI(group A=1,group B=2,group C=3)was correlated with the results of one hour pad test(r=0.79,P<0.001),the number of daily uri-nary incontinence(r=0.68,P<0.001),and the scores of ICIQ-SF(r=0.68,P<0.001)and modified Oxford Rating Scale(r=-0.47,P=0.001)six months after treatment.Conclusion Kegel training combined with Pilates training could improve the urinary control in patients with urinary in-continence after prostatectomy.The decrease of BMI can promote the recovery of urinary control,and improve the symptoms of later urinary incontinence in mid-and long-term.

The analysis presented here is based on the blood components of Guanxin Qiwei tablets, the key anti-atherosclerosis pathway of Guanxin Qiwei tablets was screened by network pharmacology, and the anti-atherosclerosis mechanism of Guanxin Qiwei tablets was clarified and verified by cell experiments. HPLC-Q-Exactive-MS/MS technique was used to analyze the components of Guanxin Qiwei tablets into blood, to determine the precise mass charge ratio of the compounds, and to conduct a comprehensive analysis of the components by using secondary mass spectrometry fragments and literature comparison. Finally, a total of 42 components of Guanxin Qiwei tablets into blood were identified. To better understand the interactions, we employed the Swiss Target Prediction database to predict the associated targets. Atherosclerosis (AS) disease targets were searched in disease databases Genecard, OMIM and Disgent, and 181 intersection targets of disease targets and component targets were obtained by Venny 2.1.0 software. Protein interactions were analyzed by String database. The 32 core targets were selected by Cytscape software. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in DAVID database. It was found that the anti-atherosclerosis pathways of Guanxin Qiwei tablets mainly include lipid metabolism and atherosclerosis and AGE-RAGE signaling pathway in diabetic complications and other signal pathways. The core targets and the core compounds were interlinked, and it was found that cryptotanshinone and tanshinone ⅡA in Guanxin Qiwei tablets were well bound to TNF, PPARγ, AKT1, PTG2 and other targets. The lipid metabolism and atherosclerotic pathway was verified using human hl-7702 hepatocytes. This study preliminarily identified the potential pharmacodynamic components of Guanxin Qiwei tablets in the treatment of AS diseases and predicted their pathways of action, and verified the relationship between regulating lipid metabolism and atherosclerosis of Guanxin Qiwei tablets in vitro, providing a reference for the further study of the pharmacodynamic material basis and mechanism of action of this prescription. This experiment was approved by the Medical Ethics Committee of Inner Mongolia Medical University (No. YKD202401262).

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To analyze ethnic differences in mutations of the PIK3CA and TP53 genes among breast cancer patients from the Han, Tibetan, and Hui ethnic groups in Qinghai, China, and their associations with clinicopathological characteristics. Methods A total of 382 breast cancer tissue samples were retrospectively collected from surgical patients (Jan 2020−Dec 2022), comprising 200 Han, 93 Tibetan, and 89 Hui ethnicity. Mutations in PIK3CA (E542K, H1047R, and E545K) and TP53 (R273H and R175H) were detected by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Correlations between mutations and clinicopathological parameters were analyzed. Results Significant differences were observed in pTNM stage, lymph node metastasis, molecular subtypes, and PR status among the three ethnic groups. The overall mutation rate of PIK3CA and TP53 was 48.95%. The PIK3CA-p.E542K mutation rate in Tibetan cohort was significantly higher than those in Han and Hui cohort, whereas the detection rate of the PIK3CA-p.E545K mutation was lower in Tibetan cohort than that in Han cohort. The PIK3CA-p.E542K mutation was associated with an increased risk of lymph node metastasis. The TP53-p.R175H mutation was significantly correlated with advanced pTNM stage, vascular invasion, and triple-negative breast cancer. The PIK3CA-H1047R and E545K mutations were enriched in the luminal A subtype of breast cancer. Conclusion Considerable ethnic disparities exist in breast cancer mutation profiles in Qinghai, with the high-frequency PIK3CA-p.E542K mutation in Tibetan population potentially serving as a region-specific therapeutic target. Mutations are closely linked to tumor aggressiveness and molecular subtypes, highlighting the value of PIK3CA/TP53 mutation detection for early risk stratification and personalized treatment of breast cancer in high-altitude populations.

Liquiritigenin(LG)is a flavone of pharmacological importance,however,its application potential is severely limited due to its poor water solubility.LG could be disassociated slightly in water to form phenolate anion,therefore,better solubilization effect is expected by inclusion with cationic cyclodextrins(CCDs).In this work,four kinds of CCDs modified with amino groups at the primary face were synthesized,and their solid inclusion complexes with LG were successfully prepared by preparing their saturated solutions.The formation of the solid inclusion complexes was confirmed by scanning electron microscopy(SEM)and powder X-ray diffraction(PXRD),and their supramolecular binding behavior in solution was studied using multiple techniques.A 1∶1 inclusion stoichiometry of inclusion complexation was defined using Job plot by ultraviolet-visible(UV-vis)spectroscopy,and their binding stability constants(Ks)were determined as 2862.77,3494.70,6521.85 and 9599.48 L/mol using UV-vis spectroscopic titration,far more superior to that of nativeβ-CD(Ks=236.79 L/mol).This indicated that the amino side chains on CCDs could actively participate in the inclusion complexation through anion-cation interactions,significantly strengthening the host-guest binding between CCDs and LG.The inclusion modes were further elucidated based on proton and two-dimensional rotating-frame overhauser enhancement spectroscopy(2D-ROESY)nuclear magnetic resonance(NMR)experiments and molecular docking.Water solubility of LG was dramatically promoted up to 4.9 mg/mL,which was 70-fold higher than that of native LG.This study could draw inspiration for the binding and solubilization of phenols such as flavones by design of cationic macrocyclic molecules.

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis