OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

ObjectiveTo explore the optimal construction method and the biological basis for establishing a mouse model of ischemic heart disease（IHD） with Qi and Yin deficiency syndrome by intraperitoneal injection of isoproterenol（ISO）. MethodsA total of 144 male C57BL/6J mice were randomly assigned into three normal groups and nine model groups according to body mass， with 12 mice in each group. The model groups 1， 4， and 7 were administered ISO via intraperitoneal injection at a dose of 5 mg·kg^-1·d^-1 for four consecutive days， the model groups 2， 5， and 8 received ISO at a dose of 10 mg·kg^-1·d^-1 for seven consecutive days， while the model groups 3， 6， and 9 were given ISO at a dose of 15 mg·kg^-1·d^-1 for 14 consecutive days. The normal groups were administered an equivalent volume of normal saline via intraperitoneal injection. After the modeling process， body mass， 24-hour food and water intake， grip strength， and spontaneous activity of the mice were measured. Cardiac function was assessed using echocardiography， the serum levels of norepinephrine（NE）， cyclic adenosine monophosphate（cAMP）， and cyclic guanosine monophosphate（cGMP） were determined via enzyme-linked immunosorbent assay（ELISA）. The content of adenosine triphosphate（ATP） in myocardial tissue was measured by biochemical analysis， while histopathological changes in myocardial tissue were observed via hematoxylin-eosin（HE） staining. An orthogonal experimental design was applied for intuitive analysis and variance analysis to screen the optimal modeling conditions of the mouse model of IHD with Qi and Yin deficiency syndrome. A data-dependent acquisition（DDA） proteomic technique was employed to quantitatively detect differentially expressed proteins in myocardial tissue between the optimal model group and the normal group. And bioinformatics analysis was conducted to explore the potential biological mechanisms underlying the Qi and Yin deficiency model of IHD. ResultsOrthogonal results showed that the injection cycle had a great influence on model establishment， and the optimal modeling condition was identified as intraperitoneal injection of ISO at 15 mg·kg^-1·d^-1 for 14 consecutive days. Under this condition， compared with the normal group， the model group demonstrated significant reductions in body mass， food intake， water intake， grip strength， total distance and average speed of exercise， ejection fraction（EF）， fractional shortening（FS）， serum levels of NE and cGMP， and myocardial ATP content（P<0.01）， while immobility time， cAMP level， and the cAMP/cGMP value were significantly increased（P<0.05， P<0.01）. HE staining results revealed that myocardial tissue in the model group had disordered cell arrangement， inflammatory cell infiltration， myocardial fiber rupture， and fibrous tissue proliferation. Proteomic analysis identified 141 differentially expressed proteins in the model group compared with the normal group， with 52 up-regulated and 89 down-regulated. Gene Ontology（GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis indicated that the cellular components（CC） were mainly related to mitochondria and the inner mitochondrial membrane， the biological processes（BP） were associated with complement activation， platelet activation， and responses to metal ions， suggesting that the potential functional pathways involved the complement and coagulation cascade， as well as porphyrin metabolism. ConclusionContinuous intraperitoneal injection of ISO at a dose of 15 mg·kg^-1 for 14 days successfully establishes a mouse model of IHD with Qi and Yin deficiency syndrome， and the underlying mechanisms may be related to the regulation of iron ions by complement C3， C5 and Cp， and plays a role in the regulation through the BP of complement activation， platelet activation， and responses to metal ions， and the signaling pathways of the complement and coagulation cascade and porphyrin metabolism.

ObjectiveTo explore the optimal construction method and the biological basis for establishing a mouse model of ischemic heart disease（IHD） with Qi and Yin deficiency syndrome by intraperitoneal injection of isoproterenol（ISO）. MethodsA total of 144 male C57BL/6J mice were randomly assigned into three normal groups and nine model groups according to body mass， with 12 mice in each group. The model groups 1， 4， and 7 were administered ISO via intraperitoneal injection at a dose of 5 mg·kg^-1·d^-1 for four consecutive days， the model groups 2， 5， and 8 received ISO at a dose of 10 mg·kg^-1·d^-1 for seven consecutive days， while the model groups 3， 6， and 9 were given ISO at a dose of 15 mg·kg^-1·d^-1 for 14 consecutive days. The normal groups were administered an equivalent volume of normal saline via intraperitoneal injection. After the modeling process， body mass， 24-hour food and water intake， grip strength， and spontaneous activity of the mice were measured. Cardiac function was assessed using echocardiography， the serum levels of norepinephrine（NE）， cyclic adenosine monophosphate（cAMP）， and cyclic guanosine monophosphate（cGMP） were determined via enzyme-linked immunosorbent assay（ELISA）. The content of adenosine triphosphate（ATP） in myocardial tissue was measured by biochemical analysis， while histopathological changes in myocardial tissue were observed via hematoxylin-eosin（HE） staining. An orthogonal experimental design was applied for intuitive analysis and variance analysis to screen the optimal modeling conditions of the mouse model of IHD with Qi and Yin deficiency syndrome. A data-dependent acquisition（DDA） proteomic technique was employed to quantitatively detect differentially expressed proteins in myocardial tissue between the optimal model group and the normal group. And bioinformatics analysis was conducted to explore the potential biological mechanisms underlying the Qi and Yin deficiency model of IHD. ResultsOrthogonal results showed that the injection cycle had a great influence on model establishment， and the optimal modeling condition was identified as intraperitoneal injection of ISO at 15 mg·kg^-1·d^-1 for 14 consecutive days. Under this condition， compared with the normal group， the model group demonstrated significant reductions in body mass， food intake， water intake， grip strength， total distance and average speed of exercise， ejection fraction（EF）， fractional shortening（FS）， serum levels of NE and cGMP， and myocardial ATP content（P<0.01）， while immobility time， cAMP level， and the cAMP/cGMP value were significantly increased（P<0.05， P<0.01）. HE staining results revealed that myocardial tissue in the model group had disordered cell arrangement， inflammatory cell infiltration， myocardial fiber rupture， and fibrous tissue proliferation. Proteomic analysis identified 141 differentially expressed proteins in the model group compared with the normal group， with 52 up-regulated and 89 down-regulated. Gene Ontology（GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis indicated that the cellular components（CC） were mainly related to mitochondria and the inner mitochondrial membrane， the biological processes（BP） were associated with complement activation， platelet activation， and responses to metal ions， suggesting that the potential functional pathways involved the complement and coagulation cascade， as well as porphyrin metabolism. ConclusionContinuous intraperitoneal injection of ISO at a dose of 15 mg·kg^-1 for 14 days successfully establishes a mouse model of IHD with Qi and Yin deficiency syndrome， and the underlying mechanisms may be related to the regulation of iron ions by complement C3， C5 and Cp， and plays a role in the regulation through the BP of complement activation， platelet activation， and responses to metal ions， and the signaling pathways of the complement and coagulation cascade and porphyrin metabolism.

Based on copper death, this study investigates the effect and mechanism of Shenmai Injection on isoproterenol(ISO)-induced myocardial fibrosis(MF) in rats. SPF-grade male SD rats were randomly divided into a normal group, model group, captopril(5 mg·kg~(-1)) positive control group, and Shenmai Injection low(6 mL·kg~(-1)), medium(9 mL·kg~(-1)), and high(12 mL·kg~(-1)) dose groups. Except for the normal group, the rats in the other groups were subcutaneously injected with ISO(5 mg·kg~(-1)) once a day for 10 consecutive days to establish an MF model. Starting from the second day after successful modeling, intraperitoneal injections of the respective treatments were administered for 28 consecutive days. Hematoxylin-eosin(HE) and Masson staining were used to observe pathological changes and fibrosis levels in the myocardial tissue. Colorimetry was employed to detect serum Cu~(2+) concentration in rats. The levels of inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), as well as mitochondrial energy metabolites adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in serum were measured using enzyme-linked immunosorbent assay(ELISA). Western blot was performed to detect the expression of collagen Ⅰ(Col-Ⅰ), collagen Ⅲ(Col-Ⅲ), and copper death-related proteins dihydrolipoamide acetyltransferase(DLAT), ferredoxin 1(FDX1), lipoic acid synthetase(LIAS), and heat shock protein 70(HSP70) in myocardial tissue. Immunofluorescence was used to detect the expression of DLAT, FDX1, and HSP70, while immunohistochemistry was conducted to examine the expressions of DLAT, FDX1, LIAS, and HSP70. The results showed that, compared to the model group, the myocardial structure disorder and collagen fiber deposition in the drug treatment groups were significantly improved, the cardiac index level was reduced, serum Cu~(2+), IL-6, IL-1β, IL-18, TNF-α, ADP, and AMP levels were significantly decreased, ATP levels were significantly increased, and the expressions of Col-Ⅰ, Col-Ⅲ, and HSP70 proteins in myocardial tissue were significantly reduced, while the expressions of DLAT, FDX1, and LIAS proteins were significantly elevated. In conclusion, Shenmai Injection effectively alleviates myocardial structure disorder and interstitial collagen fiber deposition in ISO-induced MF rats, promotes copper excretion, and reduces copper death in the ISO-induced rat MF model.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Myocardium/metabolism* ; Drug Combinations ; Fibrosis/metabolism* ; Copper/blood* ; Cardiomyopathies/genetics* ; Humans

Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals ; Ginsenosides/pharmacology* ; Diabetic Retinopathy/physiopathology* ; Mice ; YAP-Signaling Proteins ; Humans ; Male ; Signal Transduction/drug effects* ; Cell Movement/drug effects* ; Adaptor Proteins, Signal Transducing/genetics* ; Mice, Inbred C57BL ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Panax notoginseng/chemistry* ; Endothelial Cells/metabolism* ; Transcription Factors/genetics* ; Angiogenesis

OBJECTIVE: To investigate the clinical characteristics, curative effect and prognostic factors of patients with multiple myeloma (MM) complicated with light chain myocardial amyloidosis (AL-CA). METHODS: The data of 38 patients diagnosed with MM complicated with AL-CA in our hospital from January 2018 to December 2023 were retrospectively analyzed, and the data were comprehensively screened by multiple methods such as positive two-dimensional spot tracking echocardiography (2D-STE). Survival analysis was performed using the Kaplan-Meier method. Cox regression models were used to screen for independent prognostic factors. RESULTS: Among the 38 MM patients with AL-CA, 23 were male and 15 were female, with a median age of 60(50,75) years. The 1-year survival rate was 71.05%. Patients who underwent transplantation had significantly better survival outcomes than those who did not (P < 0.01). Additionally, the median survival time of patients with all-negative FISH results at the first visit was statistically different compared to patients with other mutations (P < 0.05). Multivariate Cox regression analysis showed that all negative FISH results at the first visit and the absence of autologous hematopoietic stem cell transplantation (ASCT) were not independent risk factor for the prognosis of patients with MM and AL-CA (P >0.05). CONCLUSION ASCT may improve the prognosis of MM patients with AL-CA, and negative FISH results may indicate poor prognosis, but the results still need to be verified by larger samples.
Humans ; Multiple Myeloma/complications* ; Retrospective Studies ; Aged ; Female ; Male ; Middle Aged ; Prognosis ; Hematopoietic Stem Cell Transplantation ; Amyloidosis/complications* ; Survival Rate ; Proportional Hazards Models

Objective To explore the correlation between tongue features of type 2 diabetes patients with coronary heart disease and glycosylated hemoglobin,liver function,blood lipids,C-reactive protein,so as to provide reference for related research.Methods Using the TFDA-1 tongue imaging device to collect patients'tongue images,experts will interpret the tongue images and extract objective parameters of the tongue images through the intelligent auxiliary diagnosis system of traditional Chinese medicine tongue diagnosis;Record patient laboratory indicators and use SPSS statistical software to analyze the correlation between tongue image distribution characteristics,tongue image parameter characteristics,and laboratory indicators using Spearman method.Results 702 patients with type 2 diabetes and coronary heart disease were included.In terms of glycated hemoglobin indicators,bruising parameters are positively correlated with HbA1c,while tongue tip RGB values are negatively correlated with HbA1c.In terms of liver function indicators,tongue edge redness,tongue tip and tongue texture R value are positively correlated with ALT and AST;Red tongue tip,tooth marks on the tongue,etc.are positively correlated with ALT;Fat tongue is positively correlated with AST.In terms of blood lipid indicators,parameters such as tooth mark tongue and tooth mark are positively correlated with TG;The parameters of white coating and tongue coating area are positively correlated with LDL-C;Thin coating is positively correlated with HDL-C,while thick coating is negatively correlated with HDL-C;Red tongue is negatively correlated with TCHO.In terms of C-reactive protein,red tongue,tip red,and edge red are positively correlated with CRP;The GB value of tongue root and tongue substance is negatively correlated with CRP.Conclusion Type 2 diabetes patients with coronary heart disease have tongue picture distribution,tongue shape parameters,tongue color parameters,coating color parameters and HbA1c,ALT,AST,TCHO,TG,HDL-C,LDL-C,CRP indicators in varying degrees of correlation.The combination of patients'tongue picture and laboratory indicators is helpful to clarify the diagnosis and prognosis of type 2 diabetes with coronary heart disease.

Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.

Graves'ophthalmopathy(GO)is a specific autoimmune disease occurring in orbital tissues and is closely related to hyperthyroidism caused by Graves'disease(GD).Its disabling and disfiguring features significantly impact the quality of life of patients.The exact mechanism of GO still remains to be fully elucidated.In recent years,gene sequencing and medical microbiology studies have shown that changes in the gut microbiota may play a role in the development and progression of GO,with gut dysbiosis altering immune system regulatory signals and causing immune damage to organs.Clarifying the correlation between gut microbiota and GO helps to understand the disease's pathogenic mechanism and provides a theoretical basis for the diagnosis and treatment of GO.This review summarizes the impact of gut microbiota dysbiosis in the pathogenesis of GO and promising therapeutic approaches,including research progress in aspects such as gut microbiota experiments,case studies,pathogenesis,and treatment strategies.

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies