ObjectiveTo investigate the effects of Huangqi Jianzhongtang （HQJZ） on macrophage polarization and fat consumption in cancer cachexia （CC） mice. MethodsUltra-performance liquid chromatography-quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） was used to control the quality of HQJZ. （1） In vitro experiment： HQJZ-containing serum was prepared， and the optimal concentration was determined by cytotoxicity assay. Mouse monocyte-derived macrophages （RAW264.7） were cultured and randomly divided into six groups， including a blank group， a classically activated macrophages （M1） group， an alternatively activated macrophages （M2） group， a HQJZ + blank group， a HQJZ+M1 group， and a HQJZ + M2 group. The relative expression of macrophage marker genes CD86， inducible nitric oxide synthase （iNOS）， CD206， and arginase-1 （Arg1） was detected by real-time quantitative polymerase chain reaction （Real-time PCR ）. （2） In vivo experiment： Thirty-two BALB/c mice were randomly divided into a control group， a model group， a medroxyprogesterone acetate （MPA） group， and a HQJZ group. Except for the control group， the other mice were injected with CT-26 colon cancer cells to establish a CC model. Mice in the MPA and HQJZ groups were given MPA （0.13 g·kg^-1·d^-1） or HQJZ （13.13 g·kg^-1·d^-1） by gavage， respectively， while mice in the control and model groups were given an equal volume of saline by gavage， with interventions continued for 10 d. Real-time PCR was used to detect the expression of macrophage markers （iNOS， Arg1， CD86， CD206） and fat browning-related genes uncoupling protein 1 （UCP1） and peroxisome proliferator-activated receptor γ （PPARγ） in epididymal adipose tissue. Western blot （WB） was used to detect protein expression levels of UCP1 and PPARγ. Micro-computed tomography （micro-CT） was used to measure residual fat volume， and hematoxylin-eosin （HE） staining was used to assess fat browning and calculate pathological scores. ResultsIn vitro， the dominant effective concentration of HQJZ-containing serum was 12.5%. Real-time PCR results showed that， compared with the blank group， Arg1 expression decreased in the HQJZ+blank group （P<0.05）， CD206 showed a downward trend without statistical significance， while iNOS and CD86 expression were significantly increased （P<0.05）. Compared with the M1 group， Arg1 and CD206 expression decreased in the HQJZ+M1 group （P<0.05）. Compared with the M2 group， CD206 expression decreased in the HQJZ+M2 group （P<0.05）， CD86 expression increased significantly （P<0.01）. In vivo， Real-time PCR results showed that， compared with the control group， CD86 and CD206 expression levels were significantly increased in the model group （P<0.01）. Compared with the model group， CD206 expression in the MPA group was significantly decreased （P<0.01）. In the HQJZ group， CD206 was significantly decreased （P<0.01）. WB results showed that， compared with the model group， protein expression of UCP1 and PPARγ was significantly reduced in the HQJZ group （P<0.05， P<0.01）. micro-CT results showed that the total white fat volume in the HQJZ group was greater than that in the model group （P<0.05）. HE staining results showed that pathological scores in the HQJZ group were lower than those in the model group （P<0.05）. ConclusionHQJZ may inhibit white adipose tissue browning by promoting macrophage M1 polarization and suppressing M2 polarization， thereby delaying fat consumption in CC mice.

OBJECTIVE: To study incident and clinical characteristics of the coronary microcirculation dysfunction (CMD) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) by myocardial contrast echocardiography (MCE) and to explore the predictive value of CMD for in-hospital acute heart failure event. METHODS: One hundred and forty five patients with AMI who had received PCI and completed MCE during hospitalization in Peking University People' s Hospital from November 2015 to July 2021 were enrolled in our study. The patients were divided into CMD group and normal group according to the coronary microcirculation status detected by MCE. Clinical data and MCE data of the two groups were collected and analyzed. The acute heart failure event during hospitalization was described. A multivariate Logistic regression model was built to analyze the risk of acute heart failure in patients with CMD. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of CMD in predicting acute heart failure event. RESULTS: CMD detected by MCE occurred in 87 patients (60%). Compared with normal group, patients with CMD had higher troponin I (TnI) peak level [52.8 (8.1, 84.0) μg/L vs. 18.9 (5.7, 56.1) μg/L, P=0.005], poorer Killip grade on admission (P=0.030), different culprit vessel (P < 0.001) and more patients had thrombolysis in myocardial infarction (TIMI) flow pre-PCI less than grade 3 in culprit vessel (65.1% vs. 43.1%, P=0.025). Meanwhile, patients with CMD had poorer left ventricular ejection fraction (LVEF) [52% (43%, 58%) vs. 61% (54%, 66%)], poorer global longitudinal strain (GLS) [-11.2% (-8.7%, -14.0%) vs.-13.9% (-10.8%, -17.0%)] and worse wall motion score index (WMSI) (1.58±0.36 vs. 1.25± 0.24) (P all < 0.001). Acute left heart failure happened in 13.8% of the CMD patients, which were significant higher than that in the patients with normal coronary microcirculation perfusion (1.7%, P=0.013). After correcting for the culprit vessel, the TIMI flow pre-PCI in the culprit vessel and the peak TnI value, the risk of acute left heart failure in the patients with CMD was still high (OR=9.120, 95%CI: 1.152-72.192, P=0.036). The area under ROC curve (AUC) was 0.677 (95%CI: 0.551-0.804, P=0.035). CONCLUSION The incidence of CMD detected by MCE in patients with AMI post-PCI was 60%. Patients with CMD have a higher risk of acute left heart failure during hospitalization.
Humans ; Heart Failure/physiopathology* ; Microcirculation ; Percutaneous Coronary Intervention/adverse effects* ; Myocardial Infarction/complications* ; Male ; Female ; Hospitalization ; Middle Aged ; Aged ; Echocardiography ; Coronary Circulation ; Predictive Value of Tests ; Troponin I/blood*

Objective To investigate the multi-target mechanisms of quercetin in treating endometriosis(EMT)through integrative network pharmacology analysis.Methods Active targets of quercetin were collected from the TCMSP database,while EMT-related differentially expressed genes(DEGs)were identified through the Gene Expression Omnibus(GEO)dataset.A comparative analysis was conducted to pinpoint potential therapeutic targets of quercetin for EMT treatment.Functional enrichment analyses were employed to investigate the biological functions associated with these targets,and a protein-protein interaction(PPI)network was conducted to identify core targets.Molecular docking and dynamics simulations were performed to validate the binding characteristics between quercetin and the core targets.The top 2 target protein pairs,HSP90AB1 and AR,exhibiting the lowest binding energy,were selected for subsequent cellular experimental validation.Human EMT-immortalized ectopic endometrial epithelial cell line 12Z(n=6,independent replicates)was subjected,and CCK-8 assay was used to determine ehe effects of quercetin on cell viability and proliferation,and the half-maximal inhibitory concentration(IC50)was calculated at 48 h after treatment.Then the 12Z cells were treated with quercetin at a concentration gradient of 0,30,60 and 90 μmol/L,the migration and invasion abilities were assessed with cell scratch and cell invasion assays.Western blotting was conducted to detect the changes in the expression of HSP90AB1 and AR proteins after different doses of treatment.Results There were 49 potential EMT-related therapeutic targets and 10 core targets identified.Functional enrichment analyses revealed that these targets were significant enriched in inflammation-related signaling pathways,including AGE-RAGE,ErbB and TNF;immune-related pathways,such as Th17 cell differentiation,T/B cell receptor signaling;angiogenesis-related pathways like VEGF;and hormonal regulatory pathways involving estrogen and GnRH.Molecular docking demonstrated that quercetin exhibited favorable binding activity(binding energy<-5 kcal/mol)with all core target proteins,with particularly strong binding energies(<-7 kcal/mol)observed for AR,EGFR,FOS,ERBB2,and HSP90AB1.Molecular dynamics simulations revealed that quercetin forms sustained hydrogen bond interactions with AR and HSP90AB1,facilitating the formation of stable complexes.CCK-8 assay,cell scratch assay,and transwell invasion assay indicated that quercetin inhibited the proliferative activity,and migrative and invasive abilities of 12Z cells in a concentration-dependent manner,with more pronounced inhibitory effects observed at 60 and 90 μmol/L quercetin(P<0.001);Western blotting revealed that treatment of 12Z cells with varying quercetin concentrations for 48 h up-regulated the expression of HSP90AB1 and AR,with the most significant increase observed at 90 μmol/L quercetin(HSP90AB1,P<0.05;AR,P<0.001).The restored expression levels of HSP90AB1 and AR showed positive correlations with the proliferative activity,migrative and invasive abilities of ectopic endometrial cells.Conclusion Quercetin effectively addresses endometriosis through multiple molecular targets and signaling pathways,and stabilization of the HSP90AB1/AR complex and subsequent protein upregulation represents a key therapeutic mechanism.

Objective To compare the efficacy of stenting in the treatment of idiopathic intracranial hypertension(IIH)complicated by different types of venous sinus stenosis(VSS).Methods The clinical data of 48 patients with IIH complicated by VSS,who received stenting therapy at the First Affiliated Hospital of Zhengzhou University of China from January 2019 to September 2023,were retrospectively analyzed.According to the type of VSS,the patients were divided into intrinsic stenosis group(n=20)and the extrinsic stenosis group(n=28).The improvement of symptoms,Frisén grade of papilledema,lumbar puncture opening pressure(LPOP),trans-stenosis pressure gradient(△P)of VSS,and surgery-related complications were compared between the two groups.Results The mean age of the patients in the intrinsic stenosis group was greater than that of the patients in the extrinsic stenosis group(41.60 years vs.35.25 years,P=0.049).The length of the narrowed segment in the extrinsic stenosis group was 22.5 mm,which was significantly longer than 19.0 mm in the intrinsic stenosis group(P=0.007).The postoperative Frisén grade of papilledema in the extrinsic stenosis group was obviously lower than that in the intrinsic stenosis group(P=0.037).No statistically significant differences in the other clinical data existed between the two groups(all P＞0.05).After stenting,all of the median △P,mean LPOP,and median Frisén grade of papilledema were decreased significantly when compared with their preoperative values(all P＜0.001),and the postoperative 3-day median Frisén grade of papilledema in the extrinsic stenosis group was much lower(P=0.037).The patients were followed up for one year,the clinical symptoms of the patients in both groups were improved to varying degrees.At the time of discharge,the proportion of patients having no symptoms of papilledema in the extrinsic stenosis group was 57.1％,which was higher than 22.2％in the intrinsic stenosis group(P=0.049),and no statistically significant differences in the improvements of other symptoms existed between the two groups(all P＞0.05).There was no significant difference in the incidence of complications between the two groups(P=0.563).Conclusion Venous sinus stenting can effectively treat patients with IIH complicated by different types of VSS.

Objective To compare the clinical efficacy of medication and stenting in treating patients with idiopathic intracranial hypertension complicated by venous sinus stenosis.Methods The clinical data of 74 patients with idiopathic intracranial hypertension complicated by venous sinus stenosis,who were admitted to the First Affiliated Hospital of Zhengzhou University of China from January 2020 to June 2023,were retrospectively analyzed.The patients were divided into medication group(n=35,receiving drug therapy)and stenting group(n=39,receiving stent implantation therapy).Before and after treatment,lumbar puncture and fundus examinations were performed,and the postoperative improvements in intracranial pressure and papillary oedema were evaluated.The changes in the median papillary oedema Frisén grade and the average opening pressure of lumbar puncture were compared between the two groups during hospitalization period.The improvement degrees of the clinical symptoms determined at discharge,as well as at the 6 months and 12 months after discharge were compared between the two groups.The incidence of complications during the follow-up period in the two groups was recorded.Results The time interval from onset to treatment in the stenting group was longer than that in the medication group(2 months vs.one month,P=0.021),and the differences in the other baseline data between the two groups were not statistically significant(all P＞0.05).After treatment,different degrees of improvement were obtained in both groups(all P＞0.05).At the time of discharge,the degree of median papillary oedema in the stenting group was Frisén grade I,which was lower than Frisén grade Ⅱ in the medication group(P=0.011);the average opening pressure of lumbar puncture in the stenting group was 205.26 mm H2O,which was lower than 248.14 mm H2O in the medication group(P=0.002).The proportions of patients having no symptom or showing symptom improvement in the stenting group and in the medication group at the time of discharge were 74.4％and 45.7％respectively(P=0.017),which at the time of 6 months after discharge were 84.6％and 48.6％respectively(P=0.001)and at the time of 12 months after discharge were 87.2％and 57.1％respectively(P=0.004).No statistically significant difference in the incidence of complications existed between the two groups(10.3％and 8.6％respectively,P=1.000).Conclusion For the treatment of patients with idiopathic intracranial hypertension complicated by venous sinus stenosis,stent implantation therapy is superior to medication therapy in quickly and effectively relieving papillary oedema,decreasing lumbar puncture opening pressure,and improving their corresponding symptoms and signs,with satisfactory patient's prognosis and clinical safety.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Uterine arteriovenous fistula (UAVF), a relatively rare vascular anomaly, may lead to life-threatening hemorrhage and poses diagnostic and management challenges for primary hospitals during initial encounters. This article reports four cases of UAVF treated with Drospirenone and ethinyl estradiol tablets at Department of Gynaecology, Zhuji Maternal and Child Health Hospital between 2023 and 2024. Combined with literature review, we systematically analyzed the etiological mechanisms, clinical characteristics, and diagnostic-therapeutic strategies of this condition, with particular focus on evaluating the efficacy and safety of conservative pharmacological management. By summarizing case features and individualized treatment protocols, this study aims to provide clinical references for early identification, accurate diagnosis, and rational intervention of UAVF, thereby reducing risks of massive hemorrhage and long-term complications while improving patient prognosis.

Objective To compare the efficacy of anticoagulation treatment(AT)alone and combining mechanical thrombectomy(MT)for cerebral venous sinus thrombosis(CVST).Methods Totally 150 patients with CVST were collected,including 90 underwent only AT(AT group)and 60 underwent MT+AT(combined group).The rate of venous sinus recanalization at discharge,the prognosis at discharge and 6,12 months after discharge(modified Rankin scale[mRS]score of 0 to 2 was considered as good prognosis)were compared between groups,and relative complications were recorded.Results At discharge,the rate of complete and partial recanalization of venous sinuses in combined group were both higher than that in AT group(both P＜0.001).No significant difference of the rate of good prognosis at discharge was found between groups(P=0.191),while 6 and 12 months after discharge,the rate of good prognosis in combined group were both higher than that in AT group(P=0.046,0.028).During the treatment and follow-up period,no significant difference of the incidence of complications was found between groups(5.00%[3/60]vs.11.11%[10/90],P=0.245).Conclusion Compared with AT alone,AT combining with MT could improve revascularization rate and prognosis of CVST without increasing the risk of complications.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Systemic sclerosis（SSc）is a chronic autoimmune disease，and cardiac related complication is one of the leading causes of death of systemic sclerosis patients. Nevertheless，by the time cardiac complications become clinically evident，irreversible myocardial damage has usually already occurred. As a novel echocardiographic technique for assessing myocardial function，speckle-tracking technology can be used for the early identification of subclinical cardiac dysfuction in patients with systemic sclerosis，playing a vital role in the early clinical treatment intervention and prognostic evaluation. This article reviewed the current research status and the latest progress of speckle-tracking technology in cardiac damage in patients with systemic sclerosis.