BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P＜0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P＜0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P＜0.05),as well as a significant increase in Bax protein expression(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax protein expression(P＜0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

BACKGROUND:The traditional surgical treatment for stromal corneal dystrophy is penetrating keratoplasty.In recent years,more and more doctors are considering using deep lamellar keratoplasty to treat stromal corneal dystrophy.Few studies comparing penetrating keratoplasty and deep lamellar keratoplasty for stromal corneal dystrophy have been reported in China. OBJECTIVE:To compare the clinical efficacy of deep lamellar keratoplasty and penetrating keratoplasty in the treatment of stromal corneal dystrophy. METHODS:Fifty-seven patients(57 eyes)diagnosed with stromal corneal dystrophy and admitted at the General Hospital of Northern Theater Command from January 2000 to January 2018 were selected,including 18 males and 39 females,aged(52.9±20.0)years.They were divided into two groups based on the surgical procedure:21 cases(21 eyes)in the deep lamellar keratoplasty group and 36 cases(36 eyes)in the penetrating keratoplasty group.A 12-month follow-up was conducted to observe the best-corrected visual acuity,corneal endothelial cell density,corneal grafttransparency,intraoperative and postoperative complications,and recurrence of the original disease. RESULTS AND CONCLUSION:Visual acuity at 1,3,6,and 12 months postoperatively was higher than preoperatively in both groups(P<0.05).The postoperative best-corrected visual acuity between the two groups showed no significant difference(P>0.05).With the prolongation of postoperative time,the corneal endothelial cell density gradually decreased in the two groups,and the annual loss rate of corneal endothelial cell density in the penetrating keratoplasty group was higher than that of the deep lamellar keratoplasty group at 6 and 12 months postoperatively(P<0.05),while there was no significant difference in corneal grafttransparency between the two groups at 12 months postoperatively(P>0.05).There were six cases of complications in the deep lamellar keratoplasty group and 14 cases of complications in the penetrating keratoplasty group.There was no recurrence in 57 cases within 12 months after surgery,and the difference in recurrence rates between the two groups at 5 years after surgery was not significant(P>0.05).The graftsurvival rates at 5 years after surgery in the penetrating keratoplasty group and the deep lamellar keratoplasty group were 83%and 86%,respectively,and there was no significant difference between the two groups(P>0.05).To conclude,deep lamellar keratoplasty could be considered as an alternative to penetrating keratoplasty in the treatment of stromal corneal dystrophy.

Objective: To explore the relationship between visual acuity and physical fitness of university freshmen, so as to provide reference for myopia prevention and control for freshmen. Methods: From October to November 2022, 2 160 college freshman without majoring in public safety administration, selected from Guangxi Police College in 2022 by using the stratified cluster random sampling method, were reviewed for the results of visual acuity test and physical fitness scores. The physical fitness indices were evaluated by using the Z scores of physical fitness test scores, and the strength of association between the level of physical fitness index and myopia was analyzed by using Logistic regression model. Results: Among 2 160 college freshman without majoring in public safety administration, 917 (42.5%) students were diagnosed screening myopia, including 66 (3.1%) cases of high myopia, 383 (17.7%) cases of moderate myopia and 468 (21.7%) cases of mild myopia. The differences in the distribution of visual acuity tests among students with different physical fitness indices, body mass index, and gender were statistically significant ( Z/H=54.50, 49.53, 15.51, P <0.01). Low level and low middle level physical fitness indices were associated with screening myopia among freshmen[ OR (95% CI )=2.81(1.93-4.08),1.87(1.38-2.54)], and low level physical fitness indexes were associated with high myopia [ OR (95% CI )=7.22(2.33-22.32)] ( P <0.01). Conclusions Screening myopia among college freshman without majoring in public safety administration is related to physical fitness, and low level and low middle level physical fitness index are risk factors for myopia. Improving the level of physical fitness might be effective in preventing myopia.

Background When live working line operators engage in upper limb operations, working for a long time with raising arms and the exposure to adverse ergonomic factors tend to increase muscle load, cause fatigue accumulation, and increase the risk of work-related musculoskeletal disorders (WMSDs). Objective To analyze work posture and associated muscle fatigue during executing breaking/connecting contact terminal, and identify adverse ergonomic factors of the work process. Methods This study recruited 10 volunteers to perform breaking/connecting contact terminal simulation. At a distance of 4.5, 3.5, and 2.5 m from the body to the wire, each performed the task 5 times. Visual 3D was used to analyze the kinematic data from motion capture. The surface electromyography (sEMG) signals of the deltoid, biceps, triceps, and brachioradialis were recorded during the simulation and analyzed for muscle fatigue using root mean square (RMS), median frequency (MF), and jointed EMG amplitude and spectrum analysis (JASA). After completion of each task, Borg scale was used to query the volunteers of their subjective fatigue. A 2-min rest was required between each distance. Results The kinematic data from motion capture showed that in the entire process of the task, the right upper limb was higher when lifting, with the right shoulder joint maintaining flexion and fluctuating periodically between abduction and adduction, external and internal rotation, the right elbow joint maintaining flexion and supination. The frequency of task cycle showed a significant effect on the Borg scale scores (P<0.001, partial \begin{document}$ {\eta }^{2} $\end{document}=0.464); the distance showed no significant effect on the Borg scale scores (P>0.05, partial \begin{document}$ {\eta }^{2} $\end{document}=0.002); their interaction effect was not significant (P>0.05, partial \begin{document}$ {\eta }^{2} $\end{document}=0.020). The results of the sEMG signals showed that at a distance of 4.5 m, the volunteers had the highest percentages of maximal voluntary electrical activation (MVE%) in the deltoid and right brachioradialis and the lowest MF values in the deltoid and left brachioradialis after completing 5 task cycles. The results of JASA showed that fatigue was observed in brachioradialis and deltoid after completing 5 task cycles at a distance of 4.5 m, the right deltoid and right brachioradialis at a distance of 3.5 m, in the brachioradialis, deltoid, and left bicep at a distance of 2.5 m. Conclusion The subjective fatigue of workers who engaged in breaking/connecting contact terminal elevates with more repetitive operations. Based on the sEMG and motion capture analysis, it can be found that improper distance between the workers and the target work area can increase the burden from poor posture and improper use of work equipment, and lead to muscle fatigue; the deltoid and brachioradialis are the key muscles of fatigue in this type of operation; changing the angle of the elbow joint and the shoulder joint during the process of the operation can affect the deltoid and brachioradialis exertion and loading.

Background Power grid is an important component of the national infrastructure. The occupational health issues among the workers in this industry are attracting great concern nationwide. Objective To investigate the prevalence of work-related musculoskeletal disorders (WMSDs) in neck and shoulder among the power distribution workers of power supply enterprises, and analyze the related influencing factors. Method In April 2023, a total of 1244 workers in 50 municipal power supply bureaus were randomly selected from the three provinces under China Southern Power Grid using cluster sampling method. The questionnaire used in the study was based on a revised Musculoskeletal Disorders Questionnaire and added ergonomic load of upper limb work. \begin{document}$ {\chi }^{2} $\end{document} test and logistic regression model were used to explore the influencing factors of neck pain and shoulder pain among the subjects. Results A total of 1244 valid questionnaires were recovered and the effective recovery rate was 90.87%(1244/1369). The positive rates of neck pain and shoulder pain were 45.5% (566 cases) and 36.3% (452 cases) respectively. The logistic regression analysis results showed that more than 20 years working age (OR=2.27, 95%CI: 1.39, 3.96; OR=2.56, 95%CI: 1.53, 4.26), often (OR=2.08, 95%CI: 1.35, 3.20; OR=2.40, 95%CI: 1.50, 3.58)/quite often (OR=2.96, 95%CI: 1.73, 5.04; OR=2.72, 95%CI: 1.49, 4.94) maintaining a forced posture, and working immediately after break (OR=1.72, 95%CI: 1.04, 2.85; OR=2.14, 95%CI: 1.19, 3.88) were associated with a higher positive rate of neck pain and shoulder pain respectively. Feeling sufficient rest (OR=0.61, 95%CI: 0.47, 0.80; OR=0.63, 95%CI: 0.50, 0.83) and opportunity to decide when to take breaks (OR=0.72, 95%CI: 0.53, 0.98; OR=0.62, 95%CI: 0.41, 0.93) were associated with a lower positive rate of neck pain and shoulder pain respectively. Conclusion The positive rates of neck pain and shoulder pain are high among power distribution workers. The main influencing factors included long working age, quite often maintaining a forced posture, and working immediately after break.

Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/10⁵, 95% UI: (1.49/10⁵, 4.07/10⁵)], prevalence [0.64/10⁵, 95% UI: (0.37/10⁵, 1.02/10⁵)], mortality [0.51/10⁵, 95% UI: (0, 1.80/10⁵)] and DALYs rates of VL [33.81/10⁵, 95% UI: (0.06/10⁵, 124.09/10⁵)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/10⁵, 95% UI: (0.45/10⁵, 0.72/10⁵); 0.14/10⁵, 95% UI: (0.11/10⁵, 0.18/10⁵)] than among women [0.27/10⁵, 95% UI: (0.21/10⁵, 0.33/10⁵); 0.06/10⁵, 95% UI: (0.05/10⁵, 0.08/10⁵)], and the highest mortality of VL was found among children under 5 years of age [0.24/10⁵, 95% UI: (0.08/10⁵, 0.66/10⁵)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/10⁵, 0.03/10⁵, 0.02/10⁵ and 1.44/10⁵ in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.

ObjectiveTo learn the density and seasonal variation of adult mosquitoes in Pudong New Area of Shanghai, and to explore the influence of meteorological factors on the density of adult mosquitoes. MethodsFrom April to November in 2017‒2021, adult mosquito density in Pudong New Area was monitored every ten days a time by using CO₂ trapping light method. Meteorological data were collected during the same time, and Pearson correlation analysis and multiple linear regression model were used to investigate the correlation between adult mosquito density and meteorological factors. ResultsThe seasonal variation of adult mosquito density showed a single-peak pattern, with the peak of 7.09 mosquitoes·(set·time)^-1 in July. The adult mosquito density was positively correlated with the monthly average temperature, monthly maximum temperature, monthly minimum temperature, and monthly average relative humidity (r=0.813, 0.793, 0.820, 0.617, all P<0.05), but negatively correlated with monthly average air pressure (r=-0.738, P<0.05). The regression equation of the adult mosquito density and monthly minimum temperature in Pudong New Area of Shanghai was Y=0.066 X₃-0.884, with a corrected R² of 0.673, indicating a good model fitting. ConclusionThe overall seasonal variation of adult mosquito density in Pudong New Area showed a single-peak pattern. The density of adult mosquitoes was correlated with the monthly average temperature, monthly maximum temperature, monthly minimum temperature, monthly average relative humidity, and monthly average air pressure, and linearly correlated with monthly minimum temperature.

Epilepsy is a chronic neurological disease caused by abnormal synchronous discharge of the brain, which is characterized by recurrent and transient neurological abnormalities, mainly manifested as loss of consciousness and limb convulsions, and can occur in people of all ages. At present, anti-epileptic drugs (AEDs) are still the main means of treatment, but their efficacy is limited by the problem of drug resistance, and long-term use can cause serious side effects, such as cognitive dysfunction and vital organ damage. Although surgical resection of epileptic lesions has achieved certain results in some patients, the high cost and potential risk of neurological damage limit its scope of application. Therefore, the development of safe, accurate and personalized non-invasive treatment strategies has become one of the key directions of epilepsy research. In recent years, photobiomodulation (PBM) has gained significant attention as a promising non-invasive therapeutic approach. PBM uses light of specific wavelengths to penetrate tissues and interact with photosensitive molecules within cells, thereby modulating cellular metabolic processes. Research has shown that PBM can enhance mitochondrial function, promote ATP production, improve meningeal lymphatic drainage, reduce neuroinflammation, and stimulate the growth of neurons and synapses. These biological effects suggest that PBM not only holds the potential to reduce the frequency of seizures but also to improve the metabolic state and network function of neurons, providing a novel therapeutic avenue for epilepsy treatment. Compared to traditional treatment methods, PBM is non-invasive and avoids the risks associated with surgical interventions. Its low risk of significant side effects makes it particularly suitable for patients with drug-resistant epilepsy, offering new therapeutic options for those who have not responded to conventional treatments. Furthermore, PBM’s multi-target mechanism enables it to address a variety of complex etiologies of epilepsy, demonstrating its potential in precision medicine. In contrast to therapies targeting a single pathological mechanism, PBM’s multifaceted approach makes it highly adaptable to different types of epilepsy, positioning it as a promising supplementary or alternative treatment. Although animal studies and preliminary clinical trials have shown positive outcomes with PBM, its clinical application remains in the exploratory phase. Future research should aim to elucidate the precise mechanisms of PBM, optimize light parameters, such as wavelength, dose, and frequency, and investigate potential synergistic effects with other therapeutic modalities. These efforts will be crucial for enhancing the therapeutic efficacy of PBM and ensuring its safety and consistency in clinical settings. This review summarizes the types of epilepsy, diagnostic biomarkers, the advantages of PBM, and its mechanisms and potential applications in epilepsy treatment. The unique value of PBM lies not only in its multi-target therapeutic effects but also in its adaptability to the diverse etiologies of epilepsy. The combination of PBM with traditional treatments, such as pharmacotherapy and neuroregulatory techniques, holds promise for developing a more comprehensive and multidimensional treatment strategy, ultimately alleviating the treatment burden on patients. PBM has also shown beneficial effects on neural network plasticity in various neurodegenerative diseases. The dynamic remodeling of neural networks plays a critical role in the pathogenesis and treatment of epilepsy, and PBM’s multi-target mechanism may promote brain function recovery by facilitating neural network remodeling. In this context, optimizing optical parameters remains a key area of research. By adjusting parameters such as wavelength, dose, and frequency, researchers aim to further enhance the therapeutic effects of PBM while maintaining its safety and stability. Looking forward, interdisciplinary collaboration, particularly in the fields of neuroscience, optical engineering, and clinical medicine, will drive the development of PBM technology and facilitate its transition from laboratory research to clinical application. With the advancement of portable devices, PBM is expected to provide safer and more effective treatments for epilepsy patients and make a significant contribution to personalized medicine, positioning it as a critical component of precision therapeutic strategies.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

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