ObjectiveTo elucidate the mechanism by which total flavonoids of Abelmoschi Corolla （TFA） treat immunoglobulin A （IgA） nephropathy （IgAN） through serum metabolomics analysis. MethodsSPF-grade male SD rats were randomly assigned into six groups （n=10）： blank， model， low-dose TFA （TFA-L， 27 mg·kg^-1）， medium-dose TFA （TFA-M， 54 mg·kg^-1）， high-dose TFA （TFA-H， 108 mg·kg^-1）， and losartan potassium （LST， 4.5 mg·kg^-1） groups. The remaining five groups， excluding the blank group， were modeled with bovine serum albumin （BSA）， lipopolysaccharide （LPS）， and carbon tetrachloride （CCl₄）. Specifically， from weeks 1 to 10， BSA was administered via gavage every other day， and a mixture of castor oil and CCl₄ was injected subcutaneously once a week， with LPS injected into the tail vein at weeks 6 and 8. After successful modeling， each intervention group was administrated with the medication prepared with distilled water once daily by gavage for a continuous period of 4 weeks. The levels of 24-hour urinary total protein （24 h UP） and serum creatinine （SCr） were quantified by kits， and the serum IgA level was determined by enzyme-linked immunosorbent assay （ELISA）. Renal pathological changes were observed by hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. Renal IgA deposition was assessed by immunofluorescence （IF）. Endoplasmic reticulum （ER） stress was observed by transmission electron microscopy. Western blot and immunohistochemistry （IHC） were employed to detect the expression of ER stress-related factors. Non-targeted metabolomics was used to screen differential metabolites for analysis， and key metabolites arachidonic acid （AA）， prostaglandin E₂ （PGE₂）， and cyclooxygenase-2 （COX-2） were validated. ResultsCompared with the blank group， the model group showed increased 24-hour urine protein （24 h UP） and serum creatinine （SCr） levels （P<0.01）， obvious renal pathological damage， elevated serum IgA level （P<0.01）， increased renal AA and PGE₂ levels （P<0.01）， and up-regulated protein levels of COX-2， glucose-regulated protein 78 （GRP78）， phosphorylated eukaryotic initiation factor 2α （P-EIF2α）， activating transcription factor 4 （ATF4）， inositol-requiring enzyme 1α （IRE1α）， and spliced X-box binding protein 1 （XBP1s） in the renal tissue （P<0.05， P<0.01）. Compared with the model group， the intervention groups showed reductions in 24 h UP and SCr levels （P<0.05， P<0.01）， alleviated renal pathological injury， decreased serum IgA level （P<0.05， P<0.01）， and reduced renal AA and PGE₂ levels （P<0.01）. Western blot and IHC results showed that TFA reduced the levels of COX-2， GRP78， P-EIF2α， ATF4， IRE1α， and XBP1s in the renal tissue （P<0.05， P<0.01）. Metabolomics results indicated that 51 commonly differential metabolites were found among the normal， model， and TFA-M groups. TFA ameliorated IgAN by affecting metabolic pathways related to the biosynthesis of arachidonic acid and arginine through L-aspartic acid， prostaglandin 2α， leukotriene B₄， leukotriene D₄， among others. ConclusionTFA can regulate the arachidonic acid metabolism pathway， thereby modulating ER stress， reducing renal damage， and ameliorating IgA nephropathy.

Objective: This prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO). Materials and Methods: A total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO. Results: Patients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively;all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001). Conclusion MTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.

Objective To investigate the feasibility and safety of bedside transesophageal echocardiography(TEE)-guided atrial septostomy in patients undergoing extracorporeal membrane oxygenation(ECMO)support.Methods Eight patients(2 females and 6 males)who developed pulmonary edema during VA-ECMO treatment between January 2020 and October 2024 were enrolled.All patients underwent bedside TEE-guided atrial septal puncture,followed by gradual balloon dilation using an Inoue balloon(diameter:18-24 mm).The endpoint for dilation was defined as mean left atrial pressure＜15 mmHg.Post-procedure evaluation included assessment of the septal defect size,mean left atrial pressure,and improvement in bilateral pulmonary edema.Results The mean age of all 8 patients was(43.50±16.84)years old.Atrial septostomy was successfully performed in all patients.The mean balloon dilation diameter was(22.75±2.68)mm,resulting in a mean septal defect size of(6.31±0.37)mm.The mean left atrial pressure significantly decreased from(26.63±1.77)mmHg pre-procedure to(12.75±1.28)mmHg post-procedure(P＜0.001).All patients demonstrated marked improvement in bilateral pulmonary edema,and six patients also showed a significant reduction in the severity of mitral regurgitation following the procedure.No procedure-related complications were observed.Conclusions Bedside TEE-guided atrial septostomy is safe and effective for reducing left heart loading during ECMO support and improving pulmonary edema.

Aim To investigate the effect of tetrameth-ylpyrazine(TMP)on neuroinflammation after cerebral ischemia and hypoxia via mannose-binding lectin(MBL).Methods Patients diagnosed with ischaemic stroke at Shanxi Provincial People's Hospital were in-cluded in the study,and their clinicopathological data,as well as blood and urine samples,were collected with the consent of the patients and their families.Using these biological samples,differential proteins and tar-gets were identified by proteomic analysis and subse-quently verified with animal experiments.The mice were divided into the sham,dMCAO,and TMP(10,20,40 mg·kg-1)treatment groups.After seven days of drug administration,the modified neurological sever-ity score(mNSS)was used to assess the neurological function.TTC staining was used to detect the volume of cerebral infarction.Motor function was evaluated be-haviourally,and ELISA was used to detect MASP1,sC5b-9,TNF-α,IL-6,and IL-1β.Western blot was used to determine the expression of relevant proteins,such as MBL2,MASP2,and C3.Results Compared with the sham group,the dMCAO group exhibited in-creased neurological impairment,which was signifi-cantly ameliorated by TMP treatment.The expression levels of MBL2,C3 and MASP2 were elevated in the dMCAO group and were reduced following TMP treat-ment.Additionally,the dMCAO group showed elevat-ed expression of inflammatory factors IL-1 β,IL-6 and TNF-α,which were then suppressed by TMP treat-ment.Conclusion TMP inhibits the inflammatory re-sponse after ischemia and hypoxia by regulating MBL,thus attenuating brain injury.

Objectives:To investigate the influence of the mild photothermal effect of Au nanorods on the osteogenic differentiation of MC3T3-E1 osteoblast cells.Methods:Surface modification of Au nanorods was performed with bovine serum albumin(BSA)coating.The photothermal effect,photothermal stability and characteristics of AuNRs@CTAB and AuNRs@BSA were analyzed u-sing scanning electron microscopy(SEM),transmission electron microscopy(TEM),and a near-infrared laser.The biocompatibili-ty of AuNRs@BSA was evaluated using live/dead staining and the CCK-8 assay.The influence of the mild photothermal effect of AuNRs@BSA on the osteogenic differentiation of MC3T3-E1 was assessed by ALP staining,alizarin red staining,and semi-quanti-tative analysis.Results:Biocompatible and near-infrared light-responsive AuNRs@BSA were prepared.In vitro experiments dem-onstrated that the mild photothermal effect of AuNRs@BSA increased the ALP activity and mineralization ability of MC3T3-E1(P＜0.000 1).Conclusion:The mild photothermal effect of AuNRs@BSA can promote the osteogenic differentiation of MC3T3-E1 cells.

Objectives:To investigate the influence of the mild photothermal effect of Au nanorods on the osteogenic differentiation of MC3T3-E1 osteoblast cells.Methods:Surface modification of Au nanorods was performed with bovine serum albumin(BSA)coating.The photothermal effect,photothermal stability and characteristics of AuNRs@CTAB and AuNRs@BSA were analyzed u-sing scanning electron microscopy(SEM),transmission electron microscopy(TEM),and a near-infrared laser.The biocompatibili-ty of AuNRs@BSA was evaluated using live/dead staining and the CCK-8 assay.The influence of the mild photothermal effect of AuNRs@BSA on the osteogenic differentiation of MC3T3-E1 was assessed by ALP staining,alizarin red staining,and semi-quanti-tative analysis.Results:Biocompatible and near-infrared light-responsive AuNRs@BSA were prepared.In vitro experiments dem-onstrated that the mild photothermal effect of AuNRs@BSA increased the ALP activity and mineralization ability of MC3T3-E1(P＜0.000 1).Conclusion:The mild photothermal effect of AuNRs@BSA can promote the osteogenic differentiation of MC3T3-E1 cells.

BACKGROUND:Our previous studies found that decreased expression of connexin 43 and its Ser368 phosphorylation after myocardial hypothermic ischemia-reperfusion was closely associated with decreased cardiac conduction velocity and reperfusion arrhythmia.OBJECTIVE:To observe the effect of changes in membrane-type matrix metalloproteinase 2,matrix metalloproteinase 2 and collagen type Ⅳ on the expression of connexin 43 and its Ser368 phosphorylation and electrical conduction in the myocardial extracellular matrix after hypothermic ischemia-reperfusion.METHODS:Sixteen Langendorff extracorporeal cardiac perfusion models were successfully established from SD rats and randomly divided into a control group(n=8)and a hypothermic ischemia-reperfusion group(n=8).The control group was balanced perfused with 37 ℃ Krebs-Henseleit solution for 15 minutes and then continued to be perfused with 37 ℃ Krebs-Henseleit solution for 90 minutes.The hypothermic ischemia-reperfusion group was balanced perfused with 37 ℃ Krebs-Henseleit solution for 15 minutes,and then the heart was arrested for 60 minutes by injection of 4 ℃ Thomas solution.During the cardiac arrest,the periphery was protected by 4 ℃ Krebs-Henseleit solution.Half-volume 4 ℃ Thomas solution was reperfused 30 minutes after the arrest.After stopping the arrest,the heart was reperfused with 37 ℃ Krebs-Henseleit solution for 30 minutes.The occurrence of arrhythmias,rebeating time,and the duration of arrhythmias were recorded from the immediate time point to the end of the reperfusion period.Conduction velocity,absolute inhomogeneity,and inhomogeneity index were measured using the Mapping Lab multi-channel electrophysiological mapping system at the time of balanced perfusion for 15 minutes(T1),reperfusion for 15 minutes/continuous perfusion for 90 minutes(T2),and reperfusion for 30 minutes/continuous perfusion for 105 minutes(T3).The relative expression levels of membrane-type matrix metalloproteinase 2,matrix metalloproteinase 2,collagen type Ⅳ,connexin 43,and its Ser368 phosphorylation in ventricular tissue were detected by western blot assay.RESULTS AND CONCLUSION:(1)No arrhythmia occurred in the control group.There were six cases of arrhythmia in the hypothermic ischemia-reperfusion group during reperfusion.Rebeating time and duration of arrhythmias were(25.38+12.02)and(158.67±67.68)seconds,respectively.(2)The conduction sochronal diagrams at T1,T2,and T3 in the control group were uniform and regular in direction,and the conduction velocity at T2 and T3 was not different from that at T1(P＞0.05).The conduction isochronal diagrams at T2 and T3 in the hypothermic ischemia-reperfusion group were uneven and irregular in direction,and the conduction velocity was slower than that at T1(P＜0.01).The conduction velocity at T2 and T3 in the hypothermic ischemia-reperfusion group was slower than that in the control group(P＜0.01).Conduction dispersion was greater in the hypothermic ischemia-reperfusion group than that in the control group at T2 and T3(P＜0.05).(3)Compared with the control group,the protein expressions of membrane-type matrix metalloproteinase 2 and matrix metalloproteinase 2 in the hypothermic ischemia-reperfusion group were increased(P＜0.05 or P＜0.01),and the protein expression levels of type Ⅳ collagen,connexin 43 and its Ser368 phosphorylation were decreased(P＜0.05 or P＜0.01).(4)The results indicate that after hypothermic ischemia-reperfusion,myocardial extracellular matrix remodeling may mediate the downregulation of myocardial connexin 43 and its Ser368 phosphorylation,slowed conduction velocity and increased conduction dispersion,thereby increasing the risk of arrhythmia.

Objective:To explore the effects of different titanium(Ti)surfaces on mitochondria metabolism and polarization of mac-rophages.Methods:The anodic oxidation method prepared nanotubes with distinct morphologies(NT5 and NT20 groups)on smooth titanium surfaces(P group)were characterized by scanning electron microscopy(SEM).After 24 hours of culturing RAW264.7 cells on the samples,SEM was employed to observe the morphology of the cells of all groups.Levels of mitochondria ATP and ROS,as well as the activity of hexokinase(HK),were measured by fluorescence probes and luciferase assays.The expression of iNOS,Arg-1,TNF-α and CD206 mRNA was evaluated by RT-qPCR.Changes in mitochondria metabolism and macrophage polarization were studied following inhibition of cellular glycolysis by using 2-deoxy-D-glucose(2-DG)in groups P*and NT20*.Results:Compared with the P group,the NT5 group showed no significant changes in mitochondria ATP,ROS levels and HK activity,but an upregula-tion in M2-associated gene expression was observed.In the NT20 group,mitochondria ATP and ROS levels were increased,HK ac-tivity was elevated,and M1-associated gene expression was upregulated.After glycolysis inhibition,there was no significant differ-ence in mitochondria ATP,ROS levels,HK activity and polarization-related gene expression levels between the P*and NT20*groups compared with the P group.Conclusion:Large-diameter nanotubes may promote macrophage M1 polarization by regulating the metabolic reprogramming that occurs in macrophage mitochondria.

Objective To investigate the feasibility and safety of bedside transesophageal echocardiography(TEE)-guided atrial septostomy in patients undergoing extracorporeal membrane oxygenation(ECMO)support.Methods Eight patients(2 females and 6 males)who developed pulmonary edema during VA-ECMO treatment between January 2020 and October 2024 were enrolled.All patients underwent bedside TEE-guided atrial septal puncture,followed by gradual balloon dilation using an Inoue balloon(diameter:18-24 mm).The endpoint for dilation was defined as mean left atrial pressure＜15 mmHg.Post-procedure evaluation included assessment of the septal defect size,mean left atrial pressure,and improvement in bilateral pulmonary edema.Results The mean age of all 8 patients was(43.50±16.84)years old.Atrial septostomy was successfully performed in all patients.The mean balloon dilation diameter was(22.75±2.68)mm,resulting in a mean septal defect size of(6.31±0.37)mm.The mean left atrial pressure significantly decreased from(26.63±1.77)mmHg pre-procedure to(12.75±1.28)mmHg post-procedure(P＜0.001).All patients demonstrated marked improvement in bilateral pulmonary edema,and six patients also showed a significant reduction in the severity of mitral regurgitation following the procedure.No procedure-related complications were observed.Conclusions Bedside TEE-guided atrial septostomy is safe and effective for reducing left heart loading during ECMO support and improving pulmonary edema.

Aim To investigate the effect of tetrameth-ylpyrazine(TMP)on neuroinflammation after cerebral ischemia and hypoxia via mannose-binding lectin(MBL).Methods Patients diagnosed with ischaemic stroke at Shanxi Provincial People's Hospital were in-cluded in the study,and their clinicopathological data,as well as blood and urine samples,were collected with the consent of the patients and their families.Using these biological samples,differential proteins and tar-gets were identified by proteomic analysis and subse-quently verified with animal experiments.The mice were divided into the sham,dMCAO,and TMP(10,20,40 mg·kg-1)treatment groups.After seven days of drug administration,the modified neurological sever-ity score(mNSS)was used to assess the neurological function.TTC staining was used to detect the volume of cerebral infarction.Motor function was evaluated be-haviourally,and ELISA was used to detect MASP1,sC5b-9,TNF-α,IL-6,and IL-1β.Western blot was used to determine the expression of relevant proteins,such as MBL2,MASP2,and C3.Results Compared with the sham group,the dMCAO group exhibited in-creased neurological impairment,which was signifi-cantly ameliorated by TMP treatment.The expression levels of MBL2,C3 and MASP2 were elevated in the dMCAO group and were reduced following TMP treat-ment.Additionally,the dMCAO group showed elevat-ed expression of inflammatory factors IL-1 β,IL-6 and TNF-α,which were then suppressed by TMP treat-ment.Conclusion TMP inhibits the inflammatory re-sponse after ischemia and hypoxia by regulating MBL,thus attenuating brain injury.