1.Improvement effects and mechanism of Zhichi suanzaoren decoction on oxidative stress injury of hippocampal neurons in perimenopausal insomnia mice
Yufei LIU ; Zeyu ZHANG ; Yonghua ZHANG ; Linlin HU ; Xin ZHANG
China Pharmacy 2025;36(19):2372-2378
OBJECTIVE To investigate the improvement effects and mechanism of Zhichi suanzaoren decoction (ZSD) on hippocampal oxidative stress injury in hippocampal neurons of mice with perimenopausal insomnia. METHODS The potential targets of active ingredients in ZSD were predicted using TCMSP and TCMIP databases; the targets related to insomnia were searched through GeneCards, OMIM and DisGeNET databases; protein-protein interaction network of intersecting targets of ZSD ingredients and insomnia was constructed; Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted on key targets. Sixty mice were divided into sham operation group, model group, ZSD low-, medium-, and high-dose groups (11, 22, and 33 g/kg), and eszopiclone group (positive control, 1 mg/kg). Except for sham operation group, the perimenopausal insomnia model was constructed by ovariectomy (OVX) in the other groups. After successful modeling, mice in each group were gavaged with normal saline or the corresponding drug solution, once a day, for three consecutive weeks. The sleep status of mice was evaluated through the pentobarbital sodium sleep synergy experiment, and the pathological changes of hippocampal neurons and the expressions of related genes and proteins in mice were observed by HE staining, immunohistochemistry staining, immunofluorescence staining, transcriptome sequencing technology and Western blot. RESULTS The results of network pharmacology showed that there were 296 intersection targets between ZSD and perimenopausal insomnia. Protein kinase B1 (Akt1) was a key target for treating insomnia with ZSD. After administration of ZSD, the sleep latency of mice was shortened, the sleep duration was prolonged significantly, and the mean optical density value of neuron-specific nuclear protein in the hippocampal CA1 region was significantly increased (P<0.01). Additionally, hippocampal neuron damage in OVX mice was significantly alleviated. The results of transcriptome sequencing showed that ZSD significantly upregulated the transcriptional levels of Nfe2l2 gene in hippocampal tissue of OVX mice (P<0.05). After administration of ZSD, protein expressions of nuclear factor E2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in hippocampal tissue of OVX mice, as well as the phosphorylated Akt level, were increased significantly (P<0.01). CONCLUSIONS ZSD can ameliorate hippocampal oxidative stress injury of hippocampal neurons in perimenopausal insomnia mice by activating the Akt/Nrf2/HO-1 signaling pathway.
2.Prognostic impact of adjuvant therapy on patients with esophageal squamous cell carcinoma receiving neoadjuvant therapy plus esophagectomy: A systematic review and meta-analysis
Zihao HU ; Peidong SONG ; Donglai CHEN ; Sukai XU ; Lijie TAN ; Yonghua SANG ; Yongbing CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(10):1505-1513
Objective To investigate whether adjuvant therapy can bring survival benefits to patients with esophageal squamous cell carcinoma (ESCC) who have received neoadjuvant therapy plus esophagectomy. Methods Studies were identified by searching databases including PubMed, EMbase, Web of Science, The Cochrane Library and CNKI from inception to November 2022 to collect studies which conformed to the objective of this study. Clinical outcomes including overall survival (OS) and recurrence-free survival (RFS) were extracted from eligible studies after screening. RevMan 5.4 and Stata 14.0 were used to perform the meta-analysis. Results A total of 9 studies were selected including 1 340 patients. Compared with the neoadjuvant therapy plus surgery (NS) group, the neoadjuvant therapy plus surgery+adjuvant therapy (NS+A) group had no significant benefit in the OS [HR=0.88, 95%CI (0.75, 1.02), P=0.09], but had remarkable benefit in the RFS [HR=0.75, 95%CI (0.58, 0.97), P=0.03]. Subgroup analysis by nodal status showed that adjuvant therapy could improve the RFS of patients with node-positive disease. Prolonged OS was observed in the patients with both positive and negative nodes but not in the patients with only positive nodes. In terms of the subgroup analysis by prescription, it revealed that triple agents exhibited advantages in improving RFS but not OS. However, dual agents did not bring additional survival benefits to the NS+A group compared with the NS group. Subgroup analysis by adjuvant therapy indicated that neither postoperative chemoradiotherapy nor chemotherapy improved OS, whereas postoperative chemoradiation elongated RFS. Conclusion Adjuvant therapy can improve the prognosis of patients with ESCC after neoadjuvant therapy followed by esophagectomy.
3.Association between short-term ambient air pollution exposure and arterial stiffness and effect modification of obesity
Yinxi TAN ; Hexiang PENG ; Yi ZHENG ; Siyue WANG ; Yiqun WU ; Xueying QIN ; Jin LI ; Tao WU ; Dafang CHEN ; Mengying WANG ; Yonghua HU
Chinese Journal of Epidemiology 2024;45(12):1639-1648
Objective:To assess the association between short-term ambient air pollution exposure and arterial stiffness and whether obesity modifies these associations.Methods:A cross-sectional study was conducted based on Fangshan family cohort in Beijing. The 24 hours average air pollutant levels on the day cohort participants took baseline survey were calculated as short-term air pollution. A generalized additive model (GAM) with Gaussian links was used to estimate changes in typical carotid artery intima-media thickness (CIMT), brachial-ankle pulse wave velocity (BAPWV), pulse pressure (PP) and ankle-branchial index (ABI) after short-term exposure to each air pollution (PM 2.5, PM 10, SO 2, NO 2, CO). The cross-product terms of each air pollution, body mass index (BMI), and waist-to-hip ratio were included in the GAM model to test the interaction. Further, they conducted a stratified analysis to test their effects on the relationship between short-term exposure to each air pollution and the arterial stiffness indicators. Results:A total of 4 211 individuals were included in the analysis. Individuals' age was (58.9±8.7) years, of which 2 268 (53.9%) were female. Several covariates, including sociodemographic factors, lifestyle behaviors, and history of drugs, were included in the analysis. The results of the GAM analysis showed that an increase in PM 2.5 ( β=2.912×10 -4, 95% CI: 1.424×10 -4-4.400×10 -4, P<0.001), CO ( β=0.027, 95% CI: 0.011-0.043, P<0.001), SO 2 ( β=2.070×10 -3, 95% CI: 7.060×10 -4-3.430×10 -3, P=0.003), and NO 2 ( β=3.650×10 -4, 95% CI: 2.340×10 -5-7.060×10 -4, P=0.036) were associated with an increase in CIMT, while an increase in PM 10 ( β=0.018, 95% CI: 0.002-0.033, P=0.028) was associated with an increase in PP in the study population. Besides, the waist-to-hip ratio had an effect-modification on the correlation of short-term exposure of PM 2.5 (interaction P=0.015), NO 2 (interaction P=0.008), and CO (interaction P=0.044) with CIMT, and the correlation between short-term exposure of PM 2.5 (interaction P=0.002), NO 2 (interaction P=0.010), CO (interaction P=0.029), PM 10 (interaction P<0.001) with PP. The significant association between CIMT, PP, and air pollution concentrations was more visible in people with lower waist-to-hip ratios. Conclusions:Short-term ambient air pollution exposure was associated with arterial stiffness indicators, and there was an effect modification of waist-to-hip ratio on these associations, and lower waist-to-hip ratios may enhance the association between air pollution exposure and indicators.
4.Early prediction of growth patterns after pediatric kidney transplantation based on height-related single-nucleotide polymorphisms
Yi FENG ; Yonghua FENG ; Mingyao HU ; Hongen XU ; Zhigang WANG ; Shicheng XU ; Yongchuang YAN ; Chenghao FENG ; Zhou LI ; Guiwen FENG ; Wenjun SHANG
Chinese Medical Journal 2024;137(10):1199-1206
Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.
5.Associations of short-term ambient particulate matter exposure and MTNR1B gene with triglyceride-glucose index:A family-based study
Huangda GUO ; Hexiang PENG ; Siyue WANG ; Tianjiao HOU ; Yixin LI ; Hanyu ZHANG ; Mengying WANG ; Yiqun WU ; Xueying QIN ; Xun TANG ; Jing LI ; Dafang CHEN ; Yonghua HU ; Tao WU
Journal of Peking University(Health Sciences) 2024;56(3):375-383
Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90%females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95%CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95%CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95%CI:0.004-0.076).The TyG index was 0.079(95%CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.
6.Single nucleotide polymorphism heritability of non-syndromic cleft lip with or without cleft palate in Chinese population
Enci XUE ; Xi CHEN ; Xueheng WANG ; Siyue WANG ; Mengying WANG ; Jin LI ; Xueying QIN ; Yiqun WU ; Nan LI ; Jing LI ; Zhibo ZHOU ; Hongping ZHU ; Tao WU ; Dafang CHEN ; Yonghua HU
Journal of Peking University(Health Sciences) 2024;56(5):775-780
Objective:To delve into the intricate relationship between common genetic variations across the entire genome and the risk of non-syndromic cleft lip with or without cleft palate(NSCL/P).Methods:Utilizing summary statistics data from genome-wide association studies(GW AS),a thorough investigation to evaluate the impact of common variations on the genome were undertook.This involved assessing single nucleotide polymorphism(SNP)heritability across the entire genome,as well as within specific genomic regions.To ensure the robustness of our analysis,stringent quality control measures were applied to the GWAS summary statistics data.Criteria for inclusion encompassed the absence of missing values,a minor allele frequency≥1%,P-values falling within the range of 0 to 1,and clear SNP strand orientation.SNP meeting these stringent criteria were then meticulously included in our analy-sis.The SNP heritability of NSCL/P was calculated using linkage disequilibrium score regression.Addi-tionally,hierarchical linkage disequilibrium score regression to partition SNP heritability within coding re-gions,promoters,introns,enhancers,and super enhancers were employed,and the enrichment levels within different genomic regions using LDSC(v1.0.1)software were further elucidated.Results:Our study drew upon GWAS summary statistics data obtained from 806 NSCL/P trios,comprising a total of 2 418 individuals from the Chinese population.Following rigorous quality control procedures,490 593 out of 492 993 SNP were deemed suitable for inclusion in SNP heritability calculations.The observed SNP heritability of NSCL/P was 0.55(95%CI:0.28-0.82).Adjusting for the elevated disease pre-valence within our sample,the SNP heritability scaled down to 0.37(95%CI:0.19-0.55)based on the prevalence observed in the general Chinese population.Notably,our enrichment analysis unveiled significant enrichment of SNP heritability within enhancer regions(15.70,P=0.04)and super enhan-cer regions(3.18,P=0.03).Conclusion:Our study sheds light on the intricate interplay between common genetic variations and the risk of NSCL/P in the Chinese population.By elucidating the SNP heritability landscape across different genomic regions,we contribute valuable insights into the genetic basis of NSCL/P.The significant enrichment of SNP heritability within enhancer and super enhancer re-gions underscores the potential role of these regulatory elements in shaping the genetic susceptibility to NSCL/P.This paves the way for further research aimed at uncovering novel genetic pathogenic factors un-derlying NSCL/P pathogenesis.
7.Research on Construction of Test Environment for Assessment of RF-Induced Heating Effects of Implants
Yonghua LI ; Lingfeng LU ; Jing WANG ; Chengling LI ; Pengfei YANG ; Zhichao WANG ; Dajing WU ; Xun LIU ; Sheng HU
Chinese Journal of Medical Instrumentation 2024;48(3):281-284,297
In magnetic resonance examination,the interaction between implants and the radio frequency(RF)fields induces heating in human tissue and may cause tissue damage.To assess the RF-induced heating of implants,three steps should be executed,including electromagnetic model construction,electromagnetic model validation,and virtual human body simulations.The crucial step of assessing RF-induced heating involves the construction of a test environment for electromagnetic model validation.In this study,a hardware environment,comprised of a RF generation system,electromagnetic field measurement system,and a robotic arm positioning system,was established.Furthermore,an automated control software environment was developed using a Python-based software development platform to enable the creation of a high-precision automated integrated test environment.The results indicate that the electric field generated in this test environment aligns well with the simulated electric field,making it suitable for assessing the RF-induced heating effects of implants.
8.Investigation of Coupling Effect for Adjacent Orthopedic Implants on MRI Radio-Frequency Heating
Ran GUO ; Zhichao WANG ; Jing WANG ; Chengling LI ; Yonghua LI ; Sheng HU
Chinese Journal of Medical Instrumentation 2024;48(5):478-485
This paper investigates the mechanism of radio-frequency(RF)heating that occurs when two adjacent orthopedic implants are present together under magnetic resonance imaging(MRI)at 1.5 Tesla and 3.0 Tesla.When a patient has multiple implants close to each other,interactions between the implants may increase RF heating.Typical generic interlocking plate and antibiotic nail implants are adopted as examples.To analyze the effect of adjacent implants,the amplitude and direction of incident and scattering vector electric fields at the hot spot position are calculated and extracted using numerical simulation based on Huygens principle.It is shown that a strong coupling effect occurs due to the existence of both the incident field and a strong scattering field.Huygens principle can be used to obtain the first and second order scattering fields generated between implants.If the first-and second-order electric field terms are summed within a certain region,the RF-induced heating of this dual-implant system increases.
9.Discussion on Magnetic Resonance Compatibility of Implantable Brain-Computer Interface Devices
Kaixiang JIN ; Xun LIU ; Sheng HU ; Yonghua LI ; Yuetong WU ; Jiaxing LI ; Chenghuai MO
Chinese Journal of Medical Instrumentation 2024;48(5):486-492
Brain-computer interface(BCI)devices are crucial tools for neural stimulation and recording,offering broad prospects in the diagnosis and treatment of neurological disorders.Furthermore,magnetic resonance imaging(MRI)is an effective and non-invasive technique for capturing whole-brain signals,providing detailed information on brain structures and activation patterns.Integrating the neural stimulation/recording capabilities of BCI devices with the non-invasive detection function of MRI is considered highly significant for brain function analysis.However,this combination imposes specific requirements on the magnetic and electronic performance of neural interface devices.The interaction between BCI devices and MRI is initially explored.Subsequently,potential safety risks arising from their combination are summarized and organized.Starting from the source of these hazards,such as the metallic electrodes and wires of BCI devices,the issues are analyzed,and current research countermeasures are summarized.In conclusion,the regulatory oversight of BCI's magnetic resonance safety is briefly discussed,and suggestions for enhancing the magnetic resonance compatibility of related BCI devices are proposed.
10.Discussion on the Experiences in Treating Multiple-Dream Disorder Using ZHANG Yonghua's Emotion Syndrome Differentia-tion Theory Based on the Association Between Dreams and Emotional States
Linlin HU ; Xin ZHANG ; Yonghua ZHANG
Journal of Zhejiang Chinese Medical University 2024;48(7):813-817
[Objective]To summarize Professor ZHANG Youhua's clinical experience in treating multiple-dream disorder based on the emotion syndrome differentiation theory.[Methods]By sorting out,reviewing and analyzing Professor ZHANG's medical cases related to the treatment of multiple dream disorder,this paper summarized Professor ZHANG's academic experience in the treatment of multiple-dream disorder from the aspects of etiology,pathogenesis,treatment principles and methods of traditional Chinese medicine understanding the association between dreams and emotional states,and listed one medical case for vevification.[Results]In the treatment of multiple dream disorder,Professor ZHANG emphasizes the importance of the emotional experience in dreams rather than the content of the dreams themselves.Therefore,the use of emotion syndrome differentiation method is deemed appropriate.According to the emotional experience in dreams,multiple-dream disorder is divided into five basic types:thinking,panic,anger,sad sorrow and joy syndromes.The three core pathogeneses of"Qi,phlegm and fire"are addressed through methods such as eliminating phlegm,regulating Qi and clearing fire.The medical case cited was multiple-dream disorder with panic syndrome,"phlegm stagnation and fire hyperactivity"was the main pathogenesis,the treatment of clearing fire and eliminating phlegm,calming the heart and tranquilizing the mind was adopted,and the prescription was based on Qinlian Wendan Decoction,added and subtracted according to the syndrome,and achieved a significant effect.[Conclusion]Professor ZHANG Yonghua's approach to treating multiple-dream disorder is based on the theory of emotional syndrome differentiation theory.He emphasizes the importance of emotional experiences in dreams,and his unique experience has shown remarkable clinical results.This approach is worth considering,learning from and promoting.

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