1.Mechanism Investigation of Qi-invigorating and Blood-activating Drug Combination in Yitangkang Compound Against Diabetic Cardiomyopathy Using Multimodal Research Approach
Chenghao YU ; Tingting LI ; Mingbo ZHANG ; Honghe XIAO ; Yufeng YANG ; Yan SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):94-106
ObjectiveThrough multimodal research methods including medication rule mining, network pharmacology, molecular docking and dynamics simulation, and in vivo animal experiments, this study aims to speculate and verify the core composition (Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma) and efficacy (Qi-invigorating and blood-activating) of the drug combination in Yitangkang Compound for improving diabetic cardiomyopathy (DCM), investigate the interaction relationship and binding strength between core active ingredients of the drug combination and key signaling pathway targets, and further explore the mechanism by which the Qi-invigorating and blood-activating drug combination regulates the calcium signaling pathway to improve cardiac function in DCM rats. MethodsThe Ancient and Modern Medical Cases Cloud Platform was used to construct a DCM prescription database, and the "Analysis Method" module of the platform was applied to mine and summarize medication rules, thereby determining the core composition of the Qi-invigorating and blood-activating drug combination in Yitangkang. Drug-active ingredient-signaling pathway-core target-disease analysis and visualization were conducted by combining network pharmacology with the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) database, SwissTargetPrediction platform, GeneCards database, MetaScape database, CytoScape software, etc. Then, molecular docking was performed via the CB-Dock2 platform, and molecular dynamics simulation of the high-binding-strength docking complexes was carried out by Gromacs software. Finally, in vivo animal experiments were carried out. Twenty-eight Sprague Dawley (SD) rats meeting the research criteria were divided into a normal group, a model group, a drug combination group (3.3 g·kg-1), and a Yitangkang group (20 g·kg-1). A type 2 diabetes mellitus (T2DM) rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin (STZ), followed by continuous feeding for eight weeks until the DCM model was successfully established. During this period, the traditional Chinese medicine (TCM) compound and drug combination were administered for prevention and treatment intervention. Meanwhile, changes in blood glucose, body weight, and heart index of each group were monitored. Cardiac function was assessed by echocardiography, and electrophysiological signals were detected by an electrocardiogram. The heart tissue was observed for pathological changes by hematoxylin-eosin (HE) and Masson staining, and the expression of L-type calcium channel (CACNA1C), calmodulin (CALM1), calcium/calmodulin-dependent protein kinase Ⅱδ (CAMK2D), and neuronal nitric oxide synthase (NOS1) proteins in the calcium signaling pathway of myocardial tissue was detected by Western blot. ResultsIn 62 DCM prescriptions, Ginseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma, and Notoginseng Radix et Rhizoma were used most frequently. Their meridian tropism mainly involved the spleen, heart, and lung, and their sweet and warm properties were prominent. The drugs for tonifying or blood-activating and stasis-resolving ranked top. In association rule analysis, (Ginseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma)-Notoginseng Radix et Rhizoma had the highest lift. Network pharmacology obtained 75 active ingredients of the drug combination, 714 drug combination action targets, 2 702 disease targets, and 286 intersection targets. Protein-protein interaction (PPI) network predicted nine interaction component-targets (nine active ingredients and four calcium signaling pathway target genes). Molecular docking showed the four complexes with the lowest binding energy were 2f3z-ginsenoside Re, 1cll-quercetin, 9blh-(6S)-6-(hydroxymethyl)-1,6-dimethyl-8,9-dihydro-7H-naphtho[8,7-g]benzofuran-10,11-dione, and 5vv0-miltionone Ⅱ. Dynamics simulation showed the CALM1-quercetin complex had the strongest binding affinity. The animal experiment results revealed that compared with the normal group, the model group showed significant changes in blood glucose, body weight, myocardial tissue morphology, heart index, cardiac function, electrophysiological indexes, and the expression levels of CACNA1C, CALM1, CAMK2D, and NOS1 proteins (P<0.05, P<0.01). Compared with the model group, the Yitangkang group had a certain improvement effect on the above indexes (P<0.05, P<0.01). Compared with the Yitangkang group, the drug combination group showed no significant difference in improving myocardial tissue morphology, heart index, cardiac function, electrophysiological indexes, and the expression of CACNA1C, CALM1, CAMK2D, and NOS1 proteins, except for blood glucose and body weight. ConclusionGinseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma, and Notoginseng Radix et Rhizoma are the core Qi-invigorating and blood-activating drug combination in Yitangkang Compound. They have a good preventive and therapeutic effect on STZ-induced DCM in rats, and their mechanism of action may be related to the regulation of the calcium signaling pathway.
2.METTL3/DUXAP8 axis promotes proliferation,migration and invasion of salivary adenoid cystic carci-noma cells
Qi ZHAO ; Wanpeng GAO ; Jiale WANG ; Rong LIU ; Mingrui SHI ; Chenghao REN ; Zihui YANG ; Zhenqing BAI ; Xinjie YANG
Journal of Practical Stomatology 2024;40(3):337-343
Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P<0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P<0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P<0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P<0.05)and enzyme-encoding genes in SACC-LM cells(P<0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P<0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.
3.A Scoping Review of the Application of Large Language Models in Clinical Practice
Chenghao SHI ; Xinyi TU ; Jiawei SHI ; Hongshuang CHEN ; Qinlu WANG ; Haiou ZOU
Journal of Medical Informatics 2024;45(9):19-26
Purpose/Significance The scoping review summarizes the application of large language models in clinical practice,and provides references for their promotion.Method/Process PubMed,Embase,Wanfang and CNKI databases are searched to screen the lit-erature related to the application of large language models in clinical practice,and the content of the included literature is extracted,sum-marized and analyzed.Result/Conclusion Large language models have application value in providing treatment suggestions,assisting disease diagnosis,health education,analyzing text image data,etc.However,their performance in answer accuracy and individualization is not satisfactory.In general,large language models show significant potential in clinical practice,but necessary measures must be taken to control the application risks and confirm the scope of application.
4.Correlation analysis between AIP and vulnerable plaques of coronary CT
Xuankai ZHOU ; Xiaowen HAN ; Guan WANG ; Zhi ZHU ; Shuxin ZHAO ; Fan CUI ; Jiahang SHI ; Chenghao PIAO
China Medical Equipment 2024;21(10):46-50
Objective:To explore the relationship between atherosclerotic index of plasma(AIP)and vulnerable plaque of coronary under computed tomography(CT)based on coronary CT angiography(CCTA).Methods:Data were retrospectively collected on 213 patients with coronary heart disease(CHD)who underwent CCTA examination from January 2021 to February 2024 at the Second Affiliated Hospital of Shenyang Medical College,and they were divided into a vulnerable plaque group(123 cases)and a non-vulnerable plaque group(90 cases)according to whether existed vulnerable plaque of coronary artery.General clinical data such as age,gender,history of smoking,history of alcohol consumption,history of diabetes,and serum indicators such as AIP were collected.The differences in AIP and other factors between the two groups were compared.The independent influencing factors of vulnerable plaque of coronary artery were determined by multifactorial logistic regression analysis,and the predictive value of AIP for vulnerable plaque was assessed by drawing a receiver operating characteristic(ROC)curve.Results:AIP of vulnerable plaque group was 0.22±0.31,which was higher than that 0.05±0.27 of the vulnerable plaque group,and the difference of AIP between two groups was significant(t=4.223,P<0.001).Multifactorial logistic analysis showed there was independent correlation between AIP and vulnerable plaque under CT(OR=7.556,95%CI:2.442~23.385,P=0.002).The ROC curve showed that the best cut-off value of AIP was 0.20 in predicting vulnerable plaque under CT,and the value of area under curve(AUC)was 0.665,and the sensitivity was 55.56%and the specificity was 73.98%.Conclusion:AIP is an independent influencing factor for CHD patients who complicate vulnerable plaques,and it has a certain of predictive value for vulnerable plaques.
5.Incidence of venous thromboembolism in esophageal cancer: a real-world study of 8 458 cases
Kunyi DU ; Xin NIE ; Kexun LI ; Changding LI ; Kun LIU ; Zhiyu LI ; Kunzhi LI ; Simiao LU ; Kunhan NI ; Wenwu HE ; Chenghao WANG ; Jialong LI ; Haojun LI ; Qiang ZHOU ; Kangning WANG ; Guangyuan LIU ; Wenguang XIAO ; Qiang FANG ; Qiuling SHI ; Yongtao HAN ; Lin PENG ; Xuefeng LENG
Chinese Journal of Digestive Surgery 2024;23(1):109-113
Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.
6.Dynamic and static nasolabial muscle anatomy of unilateral cleft lip adult patients based on magnetic resonance imaging data
Kangzhe WANG ; Yuming LI ; Chunchao XIA ; Bing SHI ; Chenghao LI
West China Journal of Stomatology 2024;42(5):636-643
Objective This study aims to obtain a three-dimensional reconstruction model based on magnetic reso-nance imaging(MRI)data of patients with different degrees of unilateral cleft lip and analyze the anatomy and changes in multiple groups of nasolabial muscles under dynamic and static conditions.Methods One normal person and four adult patients with unilateral cleft lip were included,and MRI was performed under static(upper and lower lips closed naturally)and dynamic(pout and grin)conditions.3D Slicer software was used to reconstruct the model and draw the anatomic morphology of nasolabial muscles.The distance between the junction(where the muscle merges into the orbicularis oris)of the levator muscle,zy-gomaticminor muscle,and zygomatic major muscle to the median sagittal plane,the starting point to the junction point,the dynamic and static junction points,and the angle between the connection of dynamic and static junctions and the hori-zontal plane were measured under three kinds of movements,and the ratio was calculated.Results In all patients,un-der dynamic and static conditions,the distance from the muscle junction to the median sagittal plane,their ratios of the cleft side to the non-cleft side were all greater than 1.While the ratios of the distance from the starting point of the mus-cle to the junction point were less than 1.At static conditions,the two ratios of the same muscle increased gradiently with the severity of the cleft,and the ratio of the zygomatic minor muscle was prominent in the same patient.The ratio of the cleft side to the non-cleft side was greater than 1,and the value for comparison was the angle of the line from the static to the dynamic junction and the horizontal plane.Conclusion The symmetry of the insertion site of the orbicularis oris and the linear distance of both sides of the muscle are related to muscle and cleft types.The angle of muscle contraction on the cleft side is greater than that on the non-cleft side.
7.Effect of symmetrical bone repair of nasal alar base on nasal deformity after unilateral cleft lip surgery
Jiaqi JIAN ; Bingshuai JING ; Chao YANG ; Bing SHI ; Chenghao LI
West China Journal of Stomatology 2024;42(6):748-754
Objective This study aimed to compare the impacts of undertaking symmetrical bone repair of the nasal alar base combined with nasolabial deformity repair versus nasolabial deformity repair alone on the improvement in nasal de-formity of patients with unilateral cleft lip and alveolar cleft.Methods Fifty patients presenting with unilateral cleft lip and alveolar cleft were evaluated.Among them,20 underwent nasolabial deformity repair solely(non-bone grafting group),whereas 30 patients received bone repair in conjunction with nasolabial deformity repair(bone-repair group).Preoperative measurements and one-year follow-up results were assessed through photographic anthropometric analysis.According to the Farkas anthropometric standard,the nasal anatomic landmarks were located,and 10 nostril indicators were measured.The operative effects of two groups were compared.Results In contrast to the non-bone-grafting group,the nasal deformity of patients in the bone-repair group demonstrated significant improvement one year post-operation.The symmetry pa-rameters of the nasal columella more closely approximated 1,the columella deviation angle more closely approached 90°,and the sub-alare inclination angle and the inclination angle of the nasal alar were smaller(P<0.05).Conclusion The accomplishment of symmetrical bone repair of the nasal alar base is conducive to enhancing nasal deformity after cleft-lip surgery in patients with unilateral cleft lip and alveolar cleft.This strategy has a positive influence on nasal symmetry,the morphology of the nasal alar,and nasal base deformity.
8.Analysis of high risk factors affecting delayed recovery of patients undergoing radical mastectomy under general anesthesia
Chenghao JIN ; Qiang LIU ; Meiyi ZHAO ; Yijun SHI
Chinese Journal of Endocrine Surgery 2023;17(5):540-544
Objective:To investigate the risk factors affecting the delay of recovery in patients under general anesthesia.Methods:Patients who underwent radical mastectomy for breast cancer in our hospital from Jul. 2020 to Aug. 2022 were selected as the research objects, and the effective data of 80 patients were obtained after screening. The patients were divided into the non-delayed recovery group (54 cases) and the delayed recovery group (26 cases). The general conditions and perioperative data of the two groups were compared, and the high-risk factors affecting delayed recovery from anesthesia were analyzed using the Logistic hazard proportional regression model. Results:In general, there were no significant differences in body mass index, hypertension, diabetes, tumor size, tumor subtype, tumor location, or tumor stage between the non-delayed awakening group and the delayed awakening group (all P>0.05). The average age of patients in the wake-up delay group was (53.28±11.01), the proportion of anemia was 42.30% (11/26), and the proportion of ASA Ⅱ patients was 76.92% (20/26) compared with the average age of the non-wake-up delay group (46.89±6.91) ( t=3.17, P=0.002), the proportion of anemia was 20.37% (11/54) ( χ2=3.17, P=0.040), the proportion of ASA Ⅱ patients was 27.78% (15/54) ( χ2=17.22, P<0.001), which was significantly increased. In the perioperative data, there was no statistical significance in the intraoperative combined epidural anesthesia between the non-delayed recovery group and the delayed recovery group (all P>0.05). The data of the patients in the delayed recovery group, including average intraoperative blood loss (234.14±32.28), operation time (229.47±29.84), anesthesia time (246.14±35.64) and intraoperative compound sevoflurane inhalation accounted for 69.23% (18/26) ,which were significantly increased compared with the data of non-delayed recovery group following, including the average intraoperative blood loss (215.48±29.54) ( t=2.57, P=0.012), operation time (206.35±27.41) ( t=3.43, P=0.001), anesthesia time (215.61±28.54) ( t=4.13, P<0.001), intraoperative compound sevoflurane inhalation (44.44%, 24/54). Through Logistic hazard ratio regression analysis, it was found that age ( OR=1.15, 95% CI: 1.05-1.30, P=0.008), ASA Ⅱ grade ( OR=9.49, 95% CI: 2.05-60.94, P=0.008), intraoperative bleeding volume ( OR=1.04, 95% CI: 1.01-1.08, P=0.012), operation time ( OR=1.05, 95% CI: 1.01-1.08, P=0.009), and anesthesia time ( OR=1.04, 95% CI: 1.02-1.07, P=0.004) were high-risk factors affecting the delayed recovery from anesthesia. Conclusion:Increasing age, high grade of ASA, heavy intraoperative blood loss, long operation time and anesthesia time are independent risk factors affecting delayed recovery from anesthesia.
9.Two-stage alveolar bone grafting for nasal floor reconstruction in adult cleft patients.
West China Journal of Stomatology 2023;41(2):129-133
Alveolar cleft is one of the key links of cleft lip and palate reconstruction due to its close relationship with tooth and jaw coordination and nasolabial deformity. The alveolar bone graft repairs the hole in the gum ridge and stabilizes the bone arch, providing better support for the base of the nose and new bone for the roots of the developing teeth to grow into. Unfortunately, bone graft failure in the traditional way, even among minor clefts, bony hypoplasia, or absence that affects the nasal base and piriform rim, is common. Two-stage alveolar bone grafting, which has advantages in addressing the underlying skeleton and deficiency, could be an optional surgical procedure for nasal floor reconstruction in adult patients with a broad alveolar cleft.
Humans
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Adult
;
Alveolar Bone Grafting/methods*
;
Cleft Lip/surgery*
;
Cleft Palate/surgery*
;
Treatment Outcome
;
Nose/abnormalities*
;
Bone Transplantation/methods*
10.Effectiveness of iliac cancellous bone grafting in alveolar cleft repair and analysis of factors affecting it.
Bingshuai JING ; Bing SHI ; Qian ZHENG ; Chenghao LI
West China Journal of Stomatology 2023;41(3):284-289
OBJECTIVES:
To review the effectiveness of secondary alveolar bone grafting using iliac cancellous bone in patients with unilateral complete alveolar cleft and to investigate the factors influencing it.
METHODS:
A retrospective study of 160 patients with unilateral complete alveolar clefts who underwent iliac cancellous bone graft repair at the Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, was conducted. Eighty patients in the young age group (6-12 years) and 80 in the old age group (≥13 years) were included. Bone bridge formation was determined using Mimics software, and the volume was measured to calculate the iliac implantation rate, residual bone filling rate, and resorption rate. The factors that affected bone grafting in both subgroups were investigated.
RESULTS:
Using bone bridge formation as the clinical success criterion, the success rate for the entire population was 71.25%, with a significant difference of 78.75% and 63.75% for the young and old age groups, respectively (P=0.036). The gap volume in the latter was significantly larger than that in the former (P<0.001). The factors that influenced bone grafting in the young group were the palatal bone wall (P=0.006) and history of cleft palate surgery (P=0.012), but only the palatal bone wall affected the outcome in the old age group (P=0.036).
CONCLUSIONS
The results of alveolar bone grafting for the old age group were worse than those for the young age group. The palatal bone wall was an important factor that affected alveolar bone grafting, and alveolar bone grafting in the young patients was influenced by the history of cleft palate surgery.
Humans
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Child
;
Adolescent
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Cleft Palate/surgery*
;
Cleft Lip/surgery*
;
Retrospective Studies
;
Cancellous Bone
;
Treatment Outcome
;
Alveolar Bone Grafting/methods*
;
Bone Transplantation/methods*

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