1.Prevention and Treatment of Cardiovascular-Kidney-Metabolic Syndrome with Traditional Chinese Medicine Based on the Core Pathogenesis Evolution of "Constraint,Heat,Deficiency,Stasis,and Toxin"
Zhichao RUAN ; Jiangteng LIU ; Hua ZHANG ; Weijun HUANG ; Qiang FU ; Shidong WANG ; Jinxi ZHAO
Journal of Traditional Chinese Medicine 2025;66(7):680-684
Traditional Chinese medicine (TCM) offers a rich theoretical foundation and clinical experience for the prevention and treatment of cardiovascular-kidney-metabolic syndrome(CKM), demonstrating unique advantage. Building on previous work in managing diabetes, its complications, and chronic kidney disease, our team has proposed a five-phase evolution theory of "constraint, heat, deficiency, stasis, and toxin" as the core pathogenesis. These phases correspond to the pathological progression of constraint of phlegm-dampness, constraint transforming into heat, heat damaging qi and yin, stasis accumulated in the collateral vessels, and toxin induced by deficiency and stasis. In the prevention and treatment of CKM by TCM, it is emphasized to integrate the concept of "treating disease before it arises" with constitution theory, and incorporate the "2-5-8" prevention and treatment strategy, which combines prevention with treatment, tailors interventions to different phases, and employs comprehensive treatment modalities. Our goal is to leverage TCM's holistic advantages in preventing and treating CKM.
2.Clinical application of "talus home technique" in pronation open ankle fractures.
Zhenhui SUN ; Jinxi HU ; Yanci ZHANG ; Dehang LIU ; Jianyi LEI ; Jianbo GUO
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(5):542-549
OBJECTIVE:
To explore the safety and effectiveness of the "talus home technique (THT) " in the surgery of pronation open ankle fractures (POAF).
METHODS:
A retrospective analysis was conducted on 14 patients with POAF admitted between January 2023 and December 2023 who met the selection criteria. There were 7 males and 7 females; age ranged from 26 to 58 years, with a median age of 53 years. Injury causes included 9 cases of traffic accident injury, 3 cases of fall from hight injury, and 2 cases of crush injury. There were 5 cases of type Ⅱ, 6 cases of type ⅢA, and 3 cases of type ⅢB according to Gustilo classification; and 6 cases of pronation-abduction grade Ⅲ and 8 cases of pronation-external rotation grade Ⅳ according to Lauge-Hansen classification. Emergency first-stage debridement of the ankle joint was performed, followed by second-stage open reduction and internal fixation surgery. The THT was used through a limited incision on the lateral malleolus to restore the height of the lateral malleolus, rotational alignment, and anatomical relationship of the distal tibiofibular syndesmosis (DTFS). Wound healing was observed postoperatively. At 4 months postoperatively, weight-bearing anteroposterior, lateral, and mortise view X-ray films and CT scans of both ankles were reviewed to measure the medial clear space (MCS), tibiofibular clear space (TFCS), distal fibular tip to lateral process of talus (DFTL), and anterior/posterior syndesmosis distances of DTFS, and the quality of reduction of ankle fractures was evaluated. Ankle joint function was assessed using the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and active dorsiflexion/plantar flexion range of motion were recorded at last follow-up.
RESULTS:
After second-stage internal fixation, 8 patients achieved wound healing by first intention, 1 case had skin edge necrosis, 2 cases had local skin necrosis, 1 case had extensive medial soft tissue defect, and 2 cases developed medial wound infection with sinus formation. All 14 patients were followed up 13-24 months (mean, 16.8 months). Postoperative X-ray films showed 1 case of delayed union of the lateral malleolus, which healed after bone grafting at 12 months; the remaining 13 cases achieved clinical union at 12-32 weeks (mean, 21.5 weeks). At 4 months postoperatively, X-ray films and CT examination showed no significant differences in MCS, TFCS, DFTL, and anterior/posterior syndesmosis distances of DTFS between the healthy and affected sides ( P>0.05), with no poor DTFS reduction. AOFAS ankle-hindfoot score ranged from 80 to 95, with an average of 87.7; ankle range of motion ranged from 10° to 25° (mean, 19.6°) in dorsiflexion and from 32° to 50° (mean, 41.2°) in plantar flexion.
CONCLUSION
THT is safe and effective in POAF surgery. It can restore lateral malleolar height and rotational alignment, enhance DTFS reduction quality, and obtain satisfactory short-term functional recovery of the ankle.
Humans
;
Male
;
Female
;
Middle Aged
;
Ankle Fractures/surgery*
;
Adult
;
Retrospective Studies
;
Fracture Fixation, Internal/methods*
;
Pronation
;
Fractures, Open/surgery*
;
Talus/surgery*
;
Treatment Outcome
;
Debridement/methods*
;
Ankle Joint/surgery*
;
Open Fracture Reduction/methods*
3.Clinical study on reduction of posterior malleolar fractures via modified Rammelt transfibular approach.
Shaozhen JI ; Jianyi LEI ; Jianbo GUO ; Dehang LIU ; Xiangliang GE ; Jinxi HU ; Shixin LIU ; Zhenhui SUN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(11):1441-1446
OBJECTIVE:
To evaluate the safety and effectiveness of reducing posterior malleolar fractures via the modified Rammelt transfibular approach.
METHODS:
A retrospective analysis was conducted on 26 patients with ankle fractures who met the selection criteria and were admitted between September 2023 and May 2024. There were 13 males and 13 females, aged from 14 to 59 years (median, 43.5 years). Causes of injury included traffic accident (1 case), falls (7 cases), and sprains (18 cases). Time from injury to operation ranged from 1 to 13 days (mean, 3.9 days). According to the Lauge-Hansen classification, there were 5 supination-external rotation type Ⅲ fractures and 21 supination-external rotation type Ⅳ fractures. According to the Bartoníček classification for posterior malleolar fractures, there were 12 type Ⅱ fractures, 10 type Ⅲ fractures, and 4 type Ⅳ fractures. During operation, the fracture was exposed via the modified Rammelt transfibular approach; then, the fracture reduction was achieved under direct vision using techniques such as towel clip traction, posterolateral compression, and lifting with a posterior transverse periosteal elevator; finally, the fracture was fixed using anteroposterior cannulated screws or Kirschner wires. The incision healing was observed after operation. At 4 months after operation, X-ray film and CT were reviewed to evaluate the quality of fracture reduction. The medial clear space, tibiofibular clear space, and the anterior/posterior tibiofibular syndesmotic distances were measured. At last follow-up, the ankle function was assessed using the American Orthopaedic Foot & Ankle Society (AOFAS) score and the range of motion.
RESULTS:
The marginal necrosis occurred in 2 lateral malleolar incisions, and superficial infection occurred in 1 lateral malleolar incision; the remaining incisions healed by first intention. All 26 patients were followed up 13-21 months (mean, 15.6 months). X-ray films showed that fractures in 25 patients achieved clinical union within 3-8 months (mean, 5.4 months); 1 case had delayed union of the lateral malleolus. At 4 months after operation, no significant difference was found between the injured and healthy sides in the medial clear space, tibiofibular clear space, or the anterior/posterior tibiofibular syndesmotic distances ( P>0.05). No malreduction of the posterior malleolus or the tibiofibular syndesmosis occurred. At last follow-up, the AOFAS score ranged from 80 to 100 (mean, 91.9). The range of motion ranged from 17° to 22° (mean, 21.0°) in active ankle dorsiflexion and from 40° to 49° (mean, 44.6°) in plantar flexion. Internal fixator was removed in 12 patients at 1 year after operation, with no ankle instability occurring. Ankle joint degeneration was observed in 1 patient at last follow-up.
CONCLUSION
The modified Rammelt transfibular approach is a safe and reliable technique. It enables precise reduction under direct vision, improves the quality of reduction for the distal tibial articular surface and the tibiofibular syndesmosis, and provides satisfactory ankle functional recovery in short-term follow-up.
Humans
;
Male
;
Female
;
Adult
;
Ankle Fractures/diagnostic imaging*
;
Middle Aged
;
Retrospective Studies
;
Fracture Fixation, Internal/instrumentation*
;
Adolescent
;
Treatment Outcome
;
Young Adult
;
Bone Screws
;
Ankle Joint/surgery*
;
Fibula/surgery*
;
Range of Motion, Articular
4.Effect of Zuogui Jiangtang Jieyu Formula on hippocampal H3K18la modification in a rat model of diabetes mellitus complicated with depression and prediction of related regulatory genes
Hui YANG ; Wei LI ; Shihui LEI ; Jinxi WANG ; Zhuo LIU ; Pan MENG ; Lin LIU ; Fan JIANG ; Yuhong WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(6):791-801
Objective:
To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la.
Methods:
Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la.
Results:
Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes.
Conclusion
ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.
5.Mechanism of Zuogui Jiangtang Jieyu Prescription in Treatment of Diabetes with Depression Based on GSEA and STEM
Shihui LEI ; Wei LI ; Jinxi WANG ; Jian LIU ; Pan MENG ; Yuhong WANG ; Hui YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):98-106
ObjectiveTo explore and verify the key pathway of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression by means of gene set enrichment analysis (GSEA) and short time-series expression miner (STEM). MethodSD rats were randomly divided into six groups, including a normal group, a model group, high, medium, and low dose groups of Zuogui Jiangtang Jieyu prescription, and a positive drug group. The model of diabetes with depression was established by high-fat feeding, streptozotocin (STZ) injection, and chronic mild unpredictable stress. The high, medium, and low dose groups of Zuogui Jiangtang Jieyu prescription were orally administered at 20.52, 10.26, and 5.13 g·kg-1 respectively. The positive drug group was orally administered 0.18 g·kg-1 metformin and 1.8 g·kg-1 fluoxetine. The rats in the normal group and model group were administered with an equal volume of distilled water. After 28 days, the animals were tested for depressive-like behaviors and cognitive function using the forced swimming test and Morris water maze. Fasting blood glucose was measured using blood glucose test strips. Cholesterol and triglyceride levels were measured using enzyme-linked immunosorbent assay (ELISA). Three hippocampus samples were randomly selected from the normal group, the model group, the high dose group of Zuogui Jiangtang Jieyu prescription for high-throughput transcriptome sequencing. Differential gene analysis, GSEA analysis, and STEM analysis were used to screen the key pathways and target genes of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression. Key target genes were validated using real-time fluorescence quantitative PCR (Real-time PCR). The expression of the signal protein mediated by the target genes was detected by Western blot. ResultCompared with the results in the normal group, the fasting blood glucose, cholesterol, and triglyceride levels in the model group were significantly increased (P<0.01). Moreover, the immobility time in the forced swimming test was significantly increased, while the time to climb the platform was significantly prolonged, and the search distance in the target quadrant was significantly reduced in the Morris water maze test (P<0.05,P<0.01). Compared with the model group, the high dose of Zuogui Jiangtang Jieyu prescription significantly reduced the levels of blood glucose, cholesterol, and triglycerides in rats with diabetes with depression (P<0.05,P<0.01), reduced the immobility time in the forced swimming test, shortened the stage time in the Morris water maze test, and increased the search distance ratio in the target area (P<0.05,P<0.01). Transcriptome sequencing differential analysis showed that the normal group had 1 366 differentially expressed genes compared to the model group, while the model group had 1 149 differentially expressed genes compared to the high dose group of Zuogui Jiangtang Jieyu prescription, with 581 intersecting genes. The GSEA results showed that there were 9 sets of differentially expressed genes between the normal group and the model group, and 43 sets of differentially expressed genes between the model group and the high dose group of Zuogui Jiangtang Jieyu prescription, with 7 intersecting gene sets. STEM analysis showed that according to the analysis order of the normal group, model group, and high dose group of Zuogui Jiangtang Jieyu prescription, two significantly different trend clustering groups were obtained. One key gene set for axonal guidance, as well as key target signal elements Sema3c, Sema7a, Robo3, Epha8, and Epha7, were identified through synthesizing the three analysis results. Real-time PCR validated that compared with the results in the normal group, the mRNA expression of Robo3, Sema7a, and Epha7 in the hippocampus of the model rats was significantly reduced (P<0.05, P<0.01). Compared with the model group, the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the mRNA expression of Robo3, Sema7a, and Epha7 (P<0.05, P<0.01). Western blot results showed that compared with the results in the normal group, the Sema7a, ITGB1, and FAK protein expression in the hippocampus of the model group was significantly reduced (P<0.01). Compared with the model group, the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the protein expression of Sema7a, ITGB1, and FAK in the hippocampus (P<0.05,P<0.01). ConclusionZuogui Jiangtang Jieyu prescription may treat diabetes with depression by regulating axonal guidance based on the Sema7a/ITGB1 signaling pathway.
6.Protective mechanism of Paeoniae Radix Alba against chemical liver injury based on network pharmacology, molecular docking, and in vitro experiments
Shuangqiao Liu ; Xin Liu ; Sijia Jiang ; Min Fu ; Jinxi Hu ; Jiaqi Liu ; Xiaoxu Fan ; Yingtong Feng ; Shujing Zhang ; Jingxia Wang
Journal of Traditional Chinese Medical Sciences 2024;11(1):55-66
Objective:
To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments.
Methods:
Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot.
Results:
Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells.
Conclusion
P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.
7.Study on the Molecular Mechanism of Shema Zhichuan Liquid in the Treatment of Neutrophilic Asthma Based on Network Pharmacology and In Vivo Experiment
Leshen LIAN ; Xingru MENG ; Xiufang HUANG ; Jinxi ZHOU ; Yanxiao XIE ; Hailan TAO ; Ziyun JIANG ; Xiaohong LIU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(2):247-256
Objective To investigate the molecular mechanism of Shema Zhichuan Liquid in the treatment of neutrophilic asthma(NA)based on network pharmacology and in vivo experiments.Methods(1)The TCMSP,literature search and Swiss ADME and Swiss Target Prediction databases were used to search and screen the active components and their targets of Shema Zhichuan Liquid.OMIM,GeneCards,DisGeNET and DrugBank databases were used to search and screen NA disease-related targets.The intersection of the active components and NA disease-related targets of Shema Zhichuan Liquid was obtained through the microbiology platform to obtain the potential targets of Shema Zhichuan Liquid for the treatment of NA(common targets).Cytoscape 3.8 software was used to construct the network of"Chinese medicinals-active components-potential targets".The PPI network of potential targets was established by STRING database,and the core targets were obtained by analysing the built-in Mcode plug-in.The Metascape platform was used to enrich the gene ontology(GO),Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathways for the potential targets.(2)BALB/C mice were acclimatised and fed for 1 week and randomly divided into a blank group,NA model group,low-dose group(2.5 g·kg-1)and high-dose group of Shema Zhichuan Liquid(10 g·kg-1),and control group of Dexamethasone(1 mg·kg-1);the NA mouse model was replicated by intraperitoneal injection of sensitizer(OVA+CFA)and nebulized inhalation excitation.OVA/CFA(20 μg OVA+75 μg CFA,0.3 mL)was injected intraperitoneally to sensitize on days 0,7 and 14 respectively,and 5%OVA suspension was nebulized on days 21-30(8 mL each time,40 minutes each time,once a day);1 hour before nebulisation,each group was administered by gastric gavage,and the Dexamethasone control group was administered by intraperitoneal injection once a day.The pathological changes of mouse lung tissue were observed by HE staining;IL-8 content in alveolar lavage fluid was detected by ELISA;mRNA expression levels of NLRP3 and CXCR2 were detected by RT-qPCR;and p-mTOR protein expression levels was detected by immunohistochemistry.Results(1)A total of 826 active component targets and 154 NA disease-related targets were obtained,and 51 potential targets(common targets)for the treatment of NA were obtained from the intersection of the active component and the NA disease-related targets of Shema Zhichuan Liquid.Through the network analysis of"Chinese medicinals-active components-potential targets",quercetin,lignocerotoxin,kaempferol,stigmasterol,naringenin and other key active components were obtained.The PPI network analysis of potential targets yielded 29 core targets,including AKT1,IL6,TNF,EGFR,NLRP3,RELA,MIF,CXCR2,VEGFA,etc..The GO functional enrichment analysis yielded 882 biological process entries,33 cellular component entries,and 61 molecular function entries;KEGG analysis yielded 142 signaling pathways,mainly involving TNF signaling pathway,influenza A signaling pathway,Toll-like receptor pathway,MAPK signaling pathway,mTOR signaling pathway and so on.(2)Results of animal experiments:compared with the blank group,mice in the NA model group showed obvious damage to the airway mucosa,structural disorders,a large number of inflammatory cells infiltration,mucosal congestion,oedema,obvious thickening of the alveolar wall,and narrowing of the alveolar lumen;the level of the inflammatory factor IL-8 in the alveolar lavage fluid was significantly elevated(P<0.05);the mRNA expressions of NLRP3 and CXCR2 in the lung tissues of the mice were significantly up-regulated(P<0.01),and the protein expression of p-mTOR was significantly increased.Compared with the NA model group,the structural arrangement of bronchial epithelial cells in the mice in the low-and high-dose groups of Shema Zhichuan Liquid was slightly disordered,with a small amount of inflammatory cell infiltration around the airways and blood vessels,and the congestion and edema of the bronchial mucosa were significantly reduced;the mRNA expression of CXCR2 in the lung tissues of the mice was significantly down-regulated(P<0.01),and the level of expression of p-mTOR protein was significantly reduced.The IL-8 level in the vesicular lavage fluid of mice in the high-dose group was significantly reduced(P<0.05);the mRNA expression of NLRP3 in the lung tissue of mice in the low-dose group was significantly down-regulated(P<0.05).Conclusion The therapeutic effect of Shema Zhichuan Liquid on NA may be achieved through the key active components,such as quercetin,lignocerol and kaempferol,acting on the core targets,such as NLRP3 and CXCR2,and regulating the key signaling pathways,such as the TNF signaling pathway,the MAPK signaling pathway,the Toll-like signaling pathway,and the mTOR pathway.
8.Effects of Zuogui Jiangtang Jieyu Formula (左归降糖解郁方) on Dendritic Spines of Hippocampal Dentate Gyrus and Wnt5a/RhoA Signaling Pathway in Diabetic with Depression Model Rats
Hui YANG ; Wei LI ; Shihui LEI ; Fan JIANG ; Jian LIU ; Jinxi WANG ; Yi YANG ; Yuhong WANG
Journal of Traditional Chinese Medicine 2024;65(5):520-528
ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Jieyu Formula (左归降糖解郁方, ZJJF) for diabetic rats with depression. MethodsSixty rats were randomly divided into normal group, model group, wingless MMTV integration site family member 5a (Wnt5a) agonist group, ZJJF group, and ZJJF plus Wnt5a inhibitor group, with 12 rats in each group. Except for the normal group, the rats were fed with high-fat chow, streptozotocin injection, and chronic mild unpredictable stress combination, to establish model of diabetes mellitus complicated with depression. After successful modelling, rats in the Wnt5a agonist group were given bilateral hippocampal stereotactic injections of Wnt5a agonist Foxy-5 with 5 μl each for 7 consecutive days; rats in ZJJF group were given 20.52 g/(kg·d) of ZJJF by gavage; rats in ZJJF plus Wnt5a inhibitor group were given the drug by gavage, and bilateral hippocampal stereotactic injections of Wnt5a inhibitors Box5, with the same dosage and injection method as above. The normal group and model group were given 10 ml/(kg·d) of normal saline by gavage. All groups were gavaged for 4 consecutive weeks. At the end of the intervention, the depression-like behaviour of rats was evaluated using the forced swimming experiment (immobility time) and the absent field experiment (number of activities); the blood glucose and insulin levels of rats were measured and the insulin resistance index was calculated; the dendritic morphology of dentate gyrus neurons in the hippocampus was observed using Golgi staining; the level of dentate gyrus neuron proliferation was measured using 5-bromodeoxyuracil nucleoside (Brdu) injection and immunofluorescence; RT-qPCR and Western blot were used to detect the mRNA and protein expression of Wnt5a, Ras homologue genomic member A (RhoA) and Rho homologue-associated coiled-coil protein kinase 1 (ROCK1) in the dentate gyrus. ResultsCompared with the normal group, rats in the model group had significantly higher blood glucose, insulin and insulin resistance indices, longer immobility time, fewer activities, lower Brdu integral optical density values and Wnt5a, RhoA, ROCK1 protein and mRNA expression in the dentate gyrus of the hippocampus (P<0.05 or P< 0.01); the dendritic branches of rat hippocampal dentate gyrus neurons could be seen to be significantly reduced or broken, and their length shortened. Compared with the model group, the blood glucose, insulin and insulin resistance indices of rats in ZJJF group and the ZJJF plus Wnt5a inhibitor group significantly reduced (P<0.05 or P<0.01); the immobility time of rats in the Wnt5a agonist group and ZJJF group was significantly shortened, the number of activities increased, the Brdu integral optical density values elevated, and the Wnt5a, RhoA, ROCK1 protein and mRNA expression elevated (P<0.05 or P<0.01), and the number of dendritic branches of hippocampal dentate gyrus neurons significantly increased, the length lengthened, and the complexity of dendrites increased. Compared with the Wnt5a agonist group, rats in the ZJJF group showed significant decrease in blood glucose, insulin and insulin resistance indices, prolongation of immobilisation time, reduction in the number of activities, and reduction in the Brdu integral optical density value; except for the Wnt5a mRNA in ZJJF group, Wnt5a, RhoA, ROCK1 protein and mRNA expression reduced in both ZJJF group and ZJJF plus Wnt5a inhibitor group (P<0.05 or P<0.01). Compared with ZJJF group, Wnt5a, RhoA, ROCK1 protein and mRNA expression were reduced in ZJJF plus Wnt5a inhibitor group (P<0.05 or P<0.01). ConclusionZJJF can improve hyperglycemia and depressive-like behaviours in rat models of diabetes with depression, and its antidepressant effects may be related to the activation of hippocampal Wnt5a/RhoA signaling and promotion of dentate gyrus neuron dendritic growth.
9.Predictive value of von Willebrand factor for venous thromboembolism in critically ill patients based on propensity score matching
Jinxi YUE ; Linjun WAN ; Gang WANG ; Ruiling ZHANG ; Xiaoran ZHANG ; Ouya LIU ; Xiaofan YU ; Qingqing HUANG ; Zongfang REN
Chinese Critical Care Medicine 2024;36(1):73-77
Objective:To analyze the predictive value of von Willebrand factor (vWF) for venous thromboembolism (VTE) of patients in intensive care unit (ICU) by using propensity score matching (PSM).Methods:Patients admitted to ICU of the Second Affiliated Hospital of Kunming Medical University from December 2020 to June 2022 who stayed in ICU for ≥72 hours and underwent daily bedside vascular ultrasound screening were included. Baseline data such as age, gender, primary disease, and chronic comorbidities were collected. Coagulation indexes before admission to ICU and 24 hours and 48 hours after ICU admission were collected, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fib), fibrin monomer (FM), vWF, D-dimer, antithrombin Ⅲ (ATⅢ), etc. Patients were divided into VTE group and non-VTE group according to whether they had VTE or not [diagnosis of VTE: patients underwent daily ultrasound screening of bedside blood vessels (both upper and lower limbs, visceral veins), and those suspected of having thrombosis were confirmed by ultrasonographer or pulmonary angiography]. Using PSM analysis method, the VTE group was used as the benchmark to conduct 1 : 1 matching of age, whether there was malignant tumor, whether there was infection, whether there was diabetes, and coagulation indicators before admission to ICU. Finally, the cases with balanced covariates between the two groups were obtained. The risk factors of VTE were analyzed by multivariate Logistic regression analysis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of vWF in the occurrence of VTE in critically ill patients.Results:A total of 120 patients were enrolled, of which 18 (15.0%) were diagnosed with VTE within 72 hours after admission to ICU, and 102 (85.0%) were not found to have thrombus in ICU. Before PSM, there were significant differences in age, gender, proportion of malignant tumor and infection, and coagulation indexes between VTE group and non-VTE group. After PSM, 14 pairs were successfully matched, and the unbalanced covariables between the two groups reached equilibrium. Multivariate Logistic regression analysis showed that vWF was an independent risk factor for VTE at 48 hours after ICU admission in critically ill patients [odds ratio ( OR) = 1.165, 95% confidence interval (95% CI) was 1.000-1.025, P = 0.004]. ROC curve analysis showed that the area under the ROC curve (AUC) of vWF at 48 hours after ICU admission for predicting VTE was 0.782, 95% CI was 0.618-0.945, P = 0.007. When the optimal cut-off value was 312.12%, the sensitivity was 67.7% and the specificity was 93.0%. Conclusion:Dynamic monitoring of vWF is helpful to predict the occurrence of VTE in ICU patients, and vWF at 48 hours after ICU admission has certain value in predicting the occurrence of VTE.
10.Pathogenesis and Treatment of Stomach Exuberance and Spleen Deficiency in Metabolic Disease
Wenxuan LUO ; Jinxi ZHAO ; Jinyan WEI ; Jiangteng LIU ; Zhichao RUAN ; Kaitong ZHANG ; Le WANG ; Weijun HUANG ; Yonghua XIAO
Journal of Traditional Chinese Medicine 2024;65(19):2041-2044
Stomach exuberance and spleen deficiency are common pathogenesis of many metabolic diseases. Through analyzing the pathogenesis of stomach exuberance and spleen deficiency, it is believed that its essence is stomach heat and spleen deficiency. Stomach heat includes gastrointestinal heat, spleen and stomach damp-heat, and spleen deficiency is divided into deficiency of spleen yin, deficiency of spleen qi , and deficiency of spleen yang. It is suggested that the metabolic diseases of stomach-exuberance and spleen-deficiency syndrome can be divided into three categories,i.e. stomach-heat and spleen yin-deficiency, stomach-heat and spleen qi-deficiency, and stomach-heat and spleen yang-deficiency, and the main treatment methods are clearing and draining heat, nourishing yin and moistening intestine, clearing dampness and heat, strengthening spleen and qi, clearing dampness and heat, strengthening spleen and warming yang, respectively, with prescriptions as Maziren Pills (麻子仁丸), Qinlian Pingwei Powder (芩连平胃散), and Jiawei Lianli Decoction (加味连理汤) accordingly.


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