1.Research progress on the association between physical activity and sleep quality in adolescents
WANG Jinxian*, LIU Yuan, WU Jian, WU Huipan, WANG Zhe, ZHANG Yingkun, WANG Yi, YIN Xiaojian
Chinese Journal of School Health 2026;47(1):140-143
Abstract
To promote adolescents active participation in physical activity and improve sleep quality, the article analyzes the relationship of adolescent physical activity with subjective sleep satisfaction, sleep latency, sleep continuity, sleep efficiency, and sleep duration. It explores potential mechanisms underlying the link between physical activity and sleep quality, including physiological mechanisms (circadian rhythms, body temperature, neuroendocrine systems, and immune function), and psychological mechanisms (stress relief, improvement of negative emotions, and promotion of mental relaxation). Based on existing research, it is recommended that adolescents engage in moderate to vigorous physical activity daily to promote improved sleep quality.
2.Expert Consensus on Neurocritical Care Monitoring and Management in Beijing and Tibet(2025)
Drolma PHURBU ; Wenjin CHEN ; Heng ZHANG ; Jian ZHANG ; Xiaomeng WANG ; Guoying LIN ; Wenjun PAN ; Xiying GUI ; Xin CAI ; Chodron TENZIN ; Jianlei FU ; Qianwei LI ; TSEYANG ; Yijun LIU ; Bo LIU ; Tsering DROLMA ; Yudron SONAM ; KYILV ; Samdrup TSERING ; Wa DA ; Juan GUO ; Cheng QIU ; Huan CHEN ; Xiaoting WANG ; Yangong CHAO ; Dawei LIU ; Wenzhao CHAI ; Chenggong HU ; Wanhong YIN ; Shihong ZHU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):59-72
Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.
3.Advances in perioperative nutritional management for patients with esophageal cancer
Zuyu ZHANG ; Bo YANG ; Rong NIU ; Jijun XUE ; Jian CHEN ; Dong LI ; Wentao ZHAO ; Wenfeng HAN ; Yue BAI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):157-162
Esophageal cancer is a prevalent malignant tumor of the digestive tract in China, and radical surgery remains the cornerstone of its comprehensive treatment. However, multifactorial challenges such as postoperative gastrointestinal tract reconstruction, traumatic stress, and tumor-related metabolic disturbances render esophageal cancer patients highly susceptible to malnutrition. Perioperative nutritional support therapy plays a crucial role in enhancing surgical safety, improving clinical outcomes, and elevating patients' quality of life by regulating metabolic homeostasis, preserving organ function, and optimizing the immune microenvironment. This article reviews the mechanisms underlying malnutrition in esophageal cancer, methods for nutritional status assessment, and precision intervention pathways based on multi-omics evaluations. The aim is to strengthen clinicians' awareness of standardized perioperative nutritional management for esophageal cancer patients and promote its clinical implementation, thereby facilitating postoperative recovery and improving long-term quality of life.
4.Effect and mechanism of BYL-719 on Mycobacterium tuberculosis-induced differentiation of abnormal osteoclasts
Jun ZHANG ; Jian GUO ; Qiyu JIA ; Lili TANG ; Xi WANG ; Abudusalamu·Alimujiang ; Tong WU ; Maihemuti·Yakufu ; Chuang MA
Chinese Journal of Tissue Engineering Research 2025;29(2):355-362
BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.
5.Infiltration resin combined with whitening technique on micro-cracked dental fluorosis
Wenyi ZHANG ; Zhao YIN ; Jian ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(4):686-691
BACKGROUND:Micro-abrasion,at-home whitening combined with infiltration resin have a good effect on dental fluorosis,but the effect of this method on micro-cracks in dental fluorosis is still unclear. OBJECTIVE:To explore the effect of micro-abrasion,at-home whitening combined with infiltration resin on micro-cracked dental fluorosis. METHODS:(1)Clinical research:A total of 23 patients with micro-cracked dental fluorosis,including 255 micro-cracked dental fluorosis,were selected from July 2020 to March 2021 in the Department of Prosthodontics,Stomatology Hospital,Tianjin Medical University.All of them received combined treatment of tooth micro-abrasion,at-home whitening and infiltration resin.The tooth color,tooth sensitivity,and tooth pain threshold were compared before treatment and 1 week and 1 month after treatment.(2)In vitro experiment:60 teeth with fluorosis with at least one crack on the tooth surface were collected and randomly divided into three groups for treatment.The control group was treated without any treatment.The whitening group was treated with micro-abrasion and at-home whitening,and the combined group was treated with micro-abrasion,at-home whitening,and infiltration resin,with 20 teeth in each group.The microhardness of the three groups of teeth samples after treatment was measured. RESULTS AND CONCLUSION:(1)Clinical study:6 months after treatment,among 255 teeth with micro-cracked dental fluorosis,whitening treatment for 207 teeth was significantly effective and whitening treatment for 48 teeth was effective,and the overall treatment efficiency was 100%.With the extension of treatment time,the proportion of moderate and severe dental sensitivity showed a decreasing trend.At 6 months after treatment,255 teeth with dental fluorosis had no severe sensitivity,15 with moderate sensitivity,125 with mild sensitivity,and 115 with no sensitivity,and the difference was significant compared with the sensitivity before treatment(P<0.05).There was no significant difference in the threshold of tooth pain before treatment and 1 week and 6 months after treatment(P>0.05).(2)In vitro experiment:The tooth microhardness of the whitening group was lower than that of the control group and the combined group(P<0.05),but there was no significant difference between the control group and the combined group(P>0.05).(3)The results show that the methods of micro-abrasion,at-home whitening combined with infiltration resin have good clinical efficacy in the treatment of micro-cracked dental fluorosis.
6.Physical factors and action mechanisms affecting osteogenic/odontogenic differentiation of dental pulp stem cells
Yuting SUN ; Jiayuan WU ; Jian ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(7):1531-1540
BACKGROUND:Dental pulp stem cells are one of the stem cells with great potential in oral and maxillofacial tissue engineering.Compared with mesenchymal stem cells,dental pulp stem cells have the advantages of convenient collection,less ethical problems and higher potential of proliferation and differentiation.Currently,except for biochemical factors,physical stimulation also plays a critical role in the osteogenic/odontogenic differentiation of dental pulp stem cells. OBJECTIVE:To review the relevant physical factors and the possible signaling pathway affecting the osteogenic/odontogenic differentiation of dental pulp stem cells to find the optimal induction conditions affecting their differentiation. METHODS:PubMed and CNKI databases were searched for relevant articles using"dental pulp stem cells(DPSCs),osteogenesis differentiation,odontoblastic differentiation,hypoxia,mechanical force,laser therapy,magnetic fields,microgravity"as English and Chinese search terms.Seventy-nine articles regarding physical factors affecting osteogenic/odontogenic differentiation of dental pulp stem cells were selected for the review. RESULTS AND CONCLUSION:(1)Direct or indirect physical signals in the microenvironment have shown broad application prospects in regulating the directed differentiation of stem cells.Many related physical factors,for example,hypoxia,mechanical stimulation(dynamic hydrostatic pressure,mechanical tension,shear force,etc.),laser,microgravity,and magnetic field,have positive influences on the osteogenic/odontogenic differentiation of dental pulp stem cells.Owing to the complex mechanical environment of stomatognathic system,mechanical stimulation is a key physical factor in changing cellular environment and is also a frontier in tissue engineering.It will provide new ideas for investigating the response of dental pulp stem cells to the mechanical environment in the diagnosis and treatment of oral diseases.(2)Because this field is relatively"young",the parameters of equipment have not been unified and the relevant results are not consistent.The optimal induction parameters and conditions of related physical factors should be further explored and optimized.(3)Scaffold material,one of the three elements of tissue engineering,plays a role in promoting the osteogenic/odontogenic differentiation of dental pulp stem cells,and promotes the development of materials science and clinical technology.(4)The signaling pathways involve Notch,Wnt,MAPK,etc.The biological basis of regulating the behavior of dental pulp stem cells is not clear.The specific mechanism will be further explored in the future to provide new ideas for dental pulp regeneration and bone tissue engineering under the influence of physical factors.
7.Application of three-dimensional fluid-attenuated inversion recovery sequence using artificial intelligence-assisted compressed sensing technique in intravenous gadolinium contrast-enhanced magnetic resonance imaging of inner ear
Kai LIU ; Jian WANG ; Huaili JIANG ; Shujie ZHANG ; Di WU ; Xinsheng HUANG ; Mengsu ZENG ; Menglong ZHAO
Chinese Journal of Clinical Medicine 2025;32(2):212-217
Objective To investigate the value of artificial intelligence-assisted compressed sensing (ACS) technology for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence. Methods The patients received gadolinium contrast-enhanced magnetic resonance imaging using ACS and united compressed sensing (uCS) 3D-FLAIR at Zhongshan Hospital, Fudan University from January to November 2024 were prospectively enrolled. The repetition time was 16 000 ms, and acquisition time was 6 min 40 s and 10 min 24 s in ACS 3D-FLAIR and uCS 3D-FLAIR, respectively. The images on the two sequences were evaluated independently by two radiologists. The image quality of the two sequences was subjectively evaluated and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the two sequences. The grading consistencies using two sequences and between the two doctors were analyzed. Results There was no statistically difference in subjective score of image quality between the two sequences. SNR and CNR of the ACS 3D-FLAIR sequence were significantly higher than those of the uCS 3D-FLAIR sequence (P<0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops were 0.942 and 0.888 using two sequences (P<0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops using the ACS 3D-FLAIR sequence between the two doctors were 0.784 and 0.831, respectively (P<0.001); the kappa values of grades of cochlear and vestibular endolymphatic hydrops using uCS 3D-FLAIR sequence between the two doctors were 0.725 and 0.756, respectively (P<0.001). Conclusions ACS 3D-FLAIR could provide higher SNR and CNR than uCS 3D-FLAIR, and is more suitable for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear; the endolymphatic hydrops grades using ACS 3D-FLAIR is similar to use uCS 3D-FLAIR.
8.Analysis of Treatment of Diabetic Kidney Disease with Modified Buyang Huanwutang Based on 5hmC-Seal Sequencing Technology
Baixin ZHEN ; Haoyu CHEN ; Duolikun MAIMAITIYASEN ; Xuehui LI ; Hong XIAO ; Xiaxuan LI ; Kuerban SUBINUER ; Lei ZHANG ; Hangyu CHEN ; Jian LIN ; Linlin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):208-217
ObjectiveTo improve the therapeutic effect of Buyang Huanwutang(BYHW) on diabetic kidney disease (DKD) and explore new methods for developing new Chinese medicine decoctions,we utilized 5-hydroxymethylcytosine (5hmC)-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus (DM) patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA (cfDNA) in the patients’ plasma was sequenced. After data processing and screening, we performed temporal clustering analysis to select a DKD 5hmC gene set, which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Encyclopedia of Traditional Chinese Medicine (ETCM), and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction (PPI) network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed on non-common DKD genes, and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes, and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass, random blood glucose, urinary microalbumin (mALB), serum creatinine (Scr), and blood urea nitrogen (BUN) and by hematoxylin-eosin staining, periodic acid-Schiff staining, Masson staining, immunofluorescence assay, and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes, of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 (IL-6), Toll-like receptor 4 (TLR4), lactotransferrin (LTF), lipoprotein lipase (LPL), and sterol regulatory element-binding transcription factor 1 (SREBF1). Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes, among which TBC1 domain family member 5 (TBC1D5), RAD51 paralog B (RAD51B), and proteasome 20S subunit alpha 6 (PSMA6) had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine, glycine, myristicin, serine, and tyrosine, corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus, Ginseng Radix et Rhizoma, Dioscoreae Rhizoma, Rehmanniae Radix Praeparata, Isatidis Radix, Glehniae Radix, Ophiopogonis Radix, Allii Sativi Bulbus, Isatidis Folium, and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory, the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice, with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions, potentially offering new perspectives for the exploration of these prescriptions
9.Characteristic Expression of Multiple Neurotransmitters Oscillation Imbabance in Brains of 1 028 Patients with Depression
Anqi WANG ; Xuemei QING ; Yanshu PAN ; Pingfa ZHANG ; Ying ZHANG ; Jian LI ; Cheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):278-286
ObjectiveTo analyze the characteristic expression patterns of six neurotransmitters including 5-hydroxytryptamine (5-HT), dopamine (DA), acetylcholine (ACh), norepinephrine (NE), inhibitory neurotransmitter (INH), and excitatory neurotransmitter (EXC) in the whole brain and different brain regions of depression patients by Search of Encephalo Telex (SET), providing new ideas for the study of heterogeneous etiology of depression. Methods(1) A retrospective study was conducted on supra-slow signals of EEG fluctuations in 1 028 patients with depression. The SET system was used to obtain the expression information of six neurotransmitters in the whole brain and 12 brain regions: left frontal region (F3), right frontal region (F4), left central region (C3), right central region (C4), left parietal region (P3), right parietal region (P4), left occipital region (O1), right occipital region (O2), left anterior temporal region (F7), right anterior temporal region (F8), left posterior temporal region (T5), and right posterior temporal region (T6). The expression information of each neurotransmitter was compared with the normal model, and it was found that single neurotransmitter was in one of three states: increased, decreased, or normal expression. The simultaneous expression states of six neurotransmitters in the brain space were referred to as the expression pattern of multiple neurotransmitters. (2) A MySQL database was established to analyze the actual expression patterns of different neurotransmitters in the whole brain of patients with depression. (3) Factor analysis was conducted to further analyze the characteristic rules of 78 variables of neurotransmitters in the whole brain and 12 brain regions in depression patients. Results(1) The expression of single neurotransmitters in the whole brain and different brain regions of the total depression population showed one of three expression states (increased/decreased/normal), being normal in the majority. The decreased and increased expression of 5-HT, ACh, DA, INH, EXC, and NE in the whole brain occurred in 6% and 25%, 31% and 17%, 36% and 9%, 15% and 31%, 32% and 14%, and 22% and 22%, respectively. (2) The antagonizing pairs of neurotransmitters (EXC/INH, DA/5-HT, and ACh/NE) showed significant antagonistic relationships in the whole brain and different brain regions, with a strong negative correlation between EXC and INH (P<0.01, |r| values ranging from 0.69 to 0.76), a strong negative correlation between DA and 5-HT (P<0.01, |r| values ranging from 0.83 to 0.90), and a moderate negative correlation between ACh and NE (P<0.01, with |r| values ranging from 0.56 to 0.66). Meanwhile, non-antagonizing pairs of neurotransmitters in the whole brain and different brain regions also showed correlations, with DA/NE (P<0.01, |r| values ranging from 0.38 to 0.46) and NE/EXC (P<0.01, |r| values ranging from 0.56 to 0.61) showing weak and moderate negative correlations, respectively, and DA/EXC showing a weak positive correlation (P<0.01, |r| values ranging from 0.38 to 0.47). (3) The six neurotransmitters in the 1 028 patients with depression presented a total of 170 expression patterns in the whole brain. The top 30 expression patterns were reported in this paper, with a cumulative rate of 60.60%, including patterns ① INH+/5-HT-/ACh+/DA+/NE-/EXC- (9.05%), ② INH+/5-HT-/ACh↓/DA+/NE-/EXC- (4.57%), and ③ INH+/5-HT-/ACh+/DA+/NE↓/EXC- (3.31%). That is, the proportion of depression patients with normal levels of all the six neurotransmitters was 9.05%, and the patients with at least one neurotransmitter abnormality accounted for 91.95%. (4) The factor analysis extracted 22 common factors from 78 variables in the whole brain and different brain regions. These common factors showed the absolute values of loadings ranging from 0.32 to 0.86 and the eigenvalues (F) ranging from 1.03 to 13.43, with a cumulative contribution rate of 76.82%. The characteristic expression patterns included ① AChP3↓/AChW↓/AChC3↓/AChF3↓/AChO1↓/AChT5↓/AChF7↓/NEP3↑/NEW↑/NEC3↑/NEF3↑/NEO1↑/NET5↑/NEF7↑ (F=13.43, whole brain), ② 5-HTO2↑/DAO2↓/5-HTP4↑/DAP4↓/5-HTW↑/DAW↓/5-HTC4↑/DAC4↓ (F=5.94), and ③ EXCF4↓/DAF4↓/NEF4↑/INHF4↑/5-HTF4↑/AChF4↓ (F=5.33). ConclusionThe actual 170 expression patterns of 6 neurotransmitters in the whole brain of 1 028 depression patients indicate that depression is a heterogeneous disease with individualized characteristics. The 22 characteristic expression patterns in the whole brain and 12 brain regions verify the pathogenesis hypothesis of multi-neurotransmitters oscillation imbalance in brains of depression patients. In summary, this study provides new guidance for the etiology, diagnosis, and treatment of depression and establishes a methodological foundation for the effectiveness evaluation of individualized treatment of depression by traditional Chinese medicine based on the objective biological markers.
10.Analysis of Treatment of Diabetic Kidney Disease with Modified Buyang Huanwutang Based on 5hmC-Seal Sequencing Technology
Baixin ZHEN ; Haoyu CHEN ; Duolikun MAIMAITIYASEN ; Xuehui LI ; Hong XIAO ; Xiaxuan LI ; Kuerban SUBINUER ; Lei ZHANG ; Hangyu CHEN ; Jian LIN ; Linlin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):208-217
ObjectiveTo improve the therapeutic effect of Buyang Huanwutang(BYHW) on diabetic kidney disease (DKD) and explore new methods for developing new Chinese medicine decoctions,we utilized 5-hydroxymethylcytosine (5hmC)-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus (DM) patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA (cfDNA) in the patients’ plasma was sequenced. After data processing and screening, we performed temporal clustering analysis to select a DKD 5hmC gene set, which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Encyclopedia of Traditional Chinese Medicine (ETCM), and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction (PPI) network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed on non-common DKD genes, and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes, and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass, random blood glucose, urinary microalbumin (mALB), serum creatinine (Scr), and blood urea nitrogen (BUN) and by hematoxylin-eosin staining, periodic acid-Schiff staining, Masson staining, immunofluorescence assay, and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes, of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 (IL-6), Toll-like receptor 4 (TLR4), lactotransferrin (LTF), lipoprotein lipase (LPL), and sterol regulatory element-binding transcription factor 1 (SREBF1). Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes, among which TBC1 domain family member 5 (TBC1D5), RAD51 paralog B (RAD51B), and proteasome 20S subunit alpha 6 (PSMA6) had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine, glycine, myristicin, serine, and tyrosine, corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus, Ginseng Radix et Rhizoma, Dioscoreae Rhizoma, Rehmanniae Radix Praeparata, Isatidis Radix, Glehniae Radix, Ophiopogonis Radix, Allii Sativi Bulbus, Isatidis Folium, and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory, the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice, with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions, potentially offering new perspectives for the exploration of these prescriptions


Result Analysis
Print
Save
E-mail