Introduction: Multiple daily insulin injections, while effective for glycemic control, impose considerable costs on healthcare systems and carry inherent risks including hypoglycemia, weight gain, and poor treatment adherence. This study evaluates the glycemic effects of insulin regimen de-escalation from multiple daily injections in poorly controlled type 2 diabetes mellitus (T2DM) patients and explores the predictors of successful insulin de-escalation. Methodology: This is a multi-centred, prospective observational study of adult T2DM patients on multiple daily insulin injections with hemoglobin A1c (HbA1c) 7–12% who underwent de-escalation to one or two injections. Patients were reassessed at 3 months and 6 months. Primary endpoint was change in HbA1c from baseline. Secondary endpoints were changes in body weight, hypoglycemia frequency, treatment adherence and predictors of successful insulin de-escalation defined by at least a 0.3% reduction in HbA1c while on de-escalated regimen. Results: A total of 80 patients were included. HbA1c improved from 9.23 to 8.52% (p <0.001) with total daily insulin dose reduction from 0.81 + 0.35 units per kg to 0.46 + 0.24 units per kg. Symptomatic hypoglycemia decreased from 22.5 to 5.0%. Insulin adherence improved from 50.0 to 92.3%. Body weight decreased by 1.4 kg. Forty-nine patients (61.3%) were successfully de-intensified. Factors associated with successful insulin de-escalation included a high baseline HbA1c, high fasting blood glucose and higher estimated glomerular filtration rate, while increased age, disease duration and being Indian were associated with unsuccessful insulin de-escalation. After adjustment of the confounders, only HbA1c (OR 2.07, 95% CI 1.23–3.46, p = 0.006) and the status of being Indian (OR 0.21, 95% CI 0.05–0.94, p = 0.041) remained as significant positive and negative predictors respectively for successful insulin de-intensification. Conclusion Insulin regimen de-escalation, when combined with optimized oral glucose-lowering agents, improved glycemic control and treatment adherence while reducing hypoglycemia and body weight. These findings support insulin therapy deescalation as a safe, effective strategy for poorly controlled T2DM patients taking multiple daily insulin injections.
Diabetes Mellitus, Type 2 ; Prospective Studies ; Insulins

Objective:To explore the hemodynamic characteristics of the middle cerebral artery (MCA) in atherosclerotic stenosis using four-dimensional flow (4D Flow) MRI, and combining high-resolution magnetic resonance vessel wall imaging (HR VW-MRI) to analyze the relationship between hemodynamics and the degree of stenosis, as well as the morphological characteristics of plaques.Methods:The study was a cross-sectional study. A total of 24 patients with middle cerebral artery(MCA) M1 atherosclerotic stenosis and 10 age and sex matched healthy controls (HC group) were prospectively recruited from September 2018 to March 2021 at Beijing Tiantan Hospital, Capital Medical University. All subjects underwent MRI examination. The hemodynamic of MCA were collected by 4D Flow MRI, and the hemodynamic parameters of proximal and distal MCA stenosis were calculated by blood flow post-processing software, including average blood flow rate (FR avg), average blood flow velocity (V avg), peak blood flow velocity (V pk), time average wall shear stress (TAWSS), minimum wall shear stress (WSS min) and oscillatory shear index (OSI). The differences in hemodynamic parameters among the proximal and distal ends of MCA stenosis and the HC group were compared using one-way ANOVA or Kruskal-Wallis H test. The stenosis rate and characteristics of MCA plaque were analyzed by HR VW-MRI, including remodeling index (RI), normalized wall index (NWI) and plaque length. Pearson or Spearman correlation analysis was used to explore the correlation between stenosis rate and hemodynamic parameters. Taking the stenosis rate as the control variable, partial correlation analysis was used to explore the correlation between plaque morphological characteristics and hemodynamic parameters. Results:There were statistically significant differences in FR avg, V avg, V pk, TAWSS, OSI, WSS min among the proximal and distal stenosis of MCA and HC groups ( P<0.05). The proximal end of the MCA stenosis had significantly higher FR avg, V avg, TAWSS and WSS min than those of the distal end of the stenosis ( P<0.01). The FR avg, V avg, V pk, TAWSS, and WSS min in the distal end of MCA stenosis were lower than those in the HC group, while the OSI was higher than that in the HC group ( P<0.01). The correlation analysis results showed that the MCA proximal V pk ( r=-0.425, P=0.027) and distal V pk ( r=-0.538, P=0.004) were negatively correlated with the diameter stenosis rate. When the stenosis rate was taken as the control factor, in the MCA proximal stenosis, V avg ( r=0.553, P=0.003), TAWSS ( r=0.543, P=0.004) and WSS min ( r=0.547, P=0.004) were positively correlated with RI, proximal OSI was negatively correlated with RI ( r=-0.492, P=0.011), and was positively correlated with the plaque length ( r=0.437, P=0.026). At the distal end of the stenosis, V pk was negatively correlated with NWI ( r=-0.556, P=0.003), OSI was negatively correlated with RI ( r=-0.511, P=0.008), NWI ( r=-0.390, P=0.049). TAWSS was positively correlated with RI ( r=0.393, P=0.047). Conclusions:The 4D Flow MRI demonstrates characteristic hemodynamic changes in the proximal and distal ends of the stenotic MCA. The local hemodynamic characteristics of the stenotic MCA are correlated with plaque morphological parameters, including lumen stenosis, plaque load, and RI. It suggests an interaction between the occurrence and development of MCA plaque and local hemodynamic changes.

Purpose To explore the characteristics of gray matter(GM)volume changes in migraine patients using 7T MRI and voxel-based morphometry(VBM).Materials and Methods This prospective study enrolled 30 migraine patients and 41 age-and gender-matched healthy controls from Beijing Tiantan Hospital,Capital Medical University between November 2023 and November 2024.All participants underwent 7T MRI with 3D T1-weighted magnetization-prepared two rapid gradient-echo(MP2RAGE)sequences for structural brain imaging.VBM analysis was performed to quantify GM,white matter,cerebrospinal fluid and total brain volumes,followed by calculations of their relative percentages.The difference in GM volume between the two groups was compared to identify brain regions with characteristic GM volume changes in migraine patients.And the correlation between these characteristic GM volume alterations and clinical scales was analyzed.Results Migraine patients exhibited significantly lower total GM volume compared to healthy controls(t=2.096,P=0.040),while no group differences were observed in white matter or cerebrospinal fluid volumes(t=0.980,0.151;P=0.330,0.880).VBM analysis revealed reduced GM volume in the left orbitofrontal cortex(t=4.301,P=0.022),left hippocampus(t=5.226,P=0.006)and left parahippocampal gyrus(t=3.960,P=0.040)in the migraine group.Negative correlations were identified between:left orbitofrontal cortex GM volume and headache duration(r=-0.506,P=0.008),left hippocampal GM volume and patient health questionnaire-9 scores(r=-0.620,P=0.003),and left parahippocampal GM volume and visual analogue scale scores(r=-0.449,P=0.019).Conclusion VBM analysis based on 7T MP2RAGE data demonstrates characteristic GM volume reductions in the left orbitofrontal cortex,left hippocampus and left parahippocampal gyrus in migraine patients,with these structural alterations significantly correlate with depressive symptoms and headache burden.The observed microstructural abnormalities may reflect underlying pathophysiological mechanisms related to pain processing,emotional regulation and long-term disease burden in migraine.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Objective To investigate the intervention effect of Xiao'er Zhixiao Pingchuan Granules(XEZXPCG)on ovalbumin(OVA)-induced airway remodeling in asthmatic mice and its potential mechanism by regulating macrophage migration inhibitory factor(MIF)and inhibiting the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods A total of 96 SPF-grade male BALB/c mice were randomly divided into blank,model,XEZXPCG low/medium/high-dose groups(2.05,4.10,and 8.20 g/kg),adeno-associated virus(AAV)NC shRNA,AAV MIF shRNA(MIF gene silencing),and LY294002(PI3K/Akt inhibitor,1 mg/kg)groups(12 mice in each group).Asthma models were established through OVA sensitization and challenge.Airway resistance and the proportions of inflammatory cells(eosinophils and macrophages)in bronchoalveolar lavage fluid(BALF)were detected.Serum inflammatory factor(OVA-IgE,interleukin[IL]-1β,IL-6,tumor necrosis factor-alpha,and interferon-gamma)levels and BALF were quantified.Hematoxylin and eosin,Masson,and periodic acid-Schiff staining were used to evaluate airway wall thickness(Wat/Phm),smooth muscle area(Wam/Phm),collagen deposition,and goblet cell metaplasia.Western blotting,immunofluorescence,and real-time fluorescence-qPCR were used to detect MIF protein and mRNA expressions,as well as activation markers of the PI3K/Akt pathway and cell cycle-related proteins(including cyclin-dependant kinase 6[CDK6],Cyclin D1,Cyclin D3,and p21),in lung tissues.Results Compared to the model group,a XEZXPCG medium or high-dose significantly reduced airway resistance(P<0.05),improved the imbalance of eosinophil and macrophage proportions in BALF,and decreased inflammatory factor levels in serum and BALF(P<0.05).XEZXPCG medium or high-dose alleviated airway epithelial damage,goblet cell hyperplasia,and collagen fiber deposition,and reduced the Wat/Phm and Wam/Phm(P<0.05),with effects comparable to those of the AAV MIF shRNA and LY294002 groups.XEZXPCG medium and high-inhibited MIF protein/mRNA expression(P<0.05),downregulated Akt phosphorylation(P<0.05),upregulated p21 protein expression,and downregulated Cyclin D1,Cyclin D3,and CDK6 expressions(P<0.05).Conclusion XEZXPCG alleviates airway inflammation and improves airway remodeling in OVA-induced asthmatic mice by inhibiting MIF expression,downregulating the PI3K/Akt signaling pathway,and regulating cell cycle progression.XEZXPCG enhances airway remodeling through MIF-mediated PI3K/Akt pathway regulation.

Objective To investigate the intervention effect of Xiao'er Zhixiao Pingchuan Granules(XEZXPCG)on ovalbumin(OVA)-induced airway remodeling in asthmatic mice and its potential mechanism by regulating macrophage migration inhibitory factor(MIF)and inhibiting the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods A total of 96 SPF-grade male BALB/c mice were randomly divided into blank,model,XEZXPCG low/medium/high-dose groups(2.05,4.10,and 8.20 g/kg),adeno-associated virus(AAV)NC shRNA,AAV MIF shRNA(MIF gene silencing),and LY294002(PI3K/Akt inhibitor,1 mg/kg)groups(12 mice in each group).Asthma models were established through OVA sensitization and challenge.Airway resistance and the proportions of inflammatory cells(eosinophils and macrophages)in bronchoalveolar lavage fluid(BALF)were detected.Serum inflammatory factor(OVA-IgE,interleukin[IL]-1β,IL-6,tumor necrosis factor-alpha,and interferon-gamma)levels and BALF were quantified.Hematoxylin and eosin,Masson,and periodic acid-Schiff staining were used to evaluate airway wall thickness(Wat/Phm),smooth muscle area(Wam/Phm),collagen deposition,and goblet cell metaplasia.Western blotting,immunofluorescence,and real-time fluorescence-qPCR were used to detect MIF protein and mRNA expressions,as well as activation markers of the PI3K/Akt pathway and cell cycle-related proteins(including cyclin-dependant kinase 6[CDK6],Cyclin D1,Cyclin D3,and p21),in lung tissues.Results Compared to the model group,a XEZXPCG medium or high-dose significantly reduced airway resistance(P<0.05),improved the imbalance of eosinophil and macrophage proportions in BALF,and decreased inflammatory factor levels in serum and BALF(P<0.05).XEZXPCG medium or high-dose alleviated airway epithelial damage,goblet cell hyperplasia,and collagen fiber deposition,and reduced the Wat/Phm and Wam/Phm(P<0.05),with effects comparable to those of the AAV MIF shRNA and LY294002 groups.XEZXPCG medium and high-inhibited MIF protein/mRNA expression(P<0.05),downregulated Akt phosphorylation(P<0.05),upregulated p21 protein expression,and downregulated Cyclin D1,Cyclin D3,and CDK6 expressions(P<0.05).Conclusion XEZXPCG alleviates airway inflammation and improves airway remodeling in OVA-induced asthmatic mice by inhibiting MIF expression,downregulating the PI3K/Akt signaling pathway,and regulating cell cycle progression.XEZXPCG enhances airway remodeling through MIF-mediated PI3K/Akt pathway regulation.

Purpose To explore the characteristics of gray matter(GM)volume changes in migraine patients using 7T MRI and voxel-based morphometry(VBM).Materials and Methods This prospective study enrolled 30 migraine patients and 41 age-and gender-matched healthy controls from Beijing Tiantan Hospital,Capital Medical University between November 2023 and November 2024.All participants underwent 7T MRI with 3D T1-weighted magnetization-prepared two rapid gradient-echo(MP2RAGE)sequences for structural brain imaging.VBM analysis was performed to quantify GM,white matter,cerebrospinal fluid and total brain volumes,followed by calculations of their relative percentages.The difference in GM volume between the two groups was compared to identify brain regions with characteristic GM volume changes in migraine patients.And the correlation between these characteristic GM volume alterations and clinical scales was analyzed.Results Migraine patients exhibited significantly lower total GM volume compared to healthy controls(t=2.096,P=0.040),while no group differences were observed in white matter or cerebrospinal fluid volumes(t=0.980,0.151;P=0.330,0.880).VBM analysis revealed reduced GM volume in the left orbitofrontal cortex(t=4.301,P=0.022),left hippocampus(t=5.226,P=0.006)and left parahippocampal gyrus(t=3.960,P=0.040)in the migraine group.Negative correlations were identified between:left orbitofrontal cortex GM volume and headache duration(r=-0.506,P=0.008),left hippocampal GM volume and patient health questionnaire-9 scores(r=-0.620,P=0.003),and left parahippocampal GM volume and visual analogue scale scores(r=-0.449,P=0.019).Conclusion VBM analysis based on 7T MP2RAGE data demonstrates characteristic GM volume reductions in the left orbitofrontal cortex,left hippocampus and left parahippocampal gyrus in migraine patients,with these structural alterations significantly correlate with depressive symptoms and headache burden.The observed microstructural abnormalities may reflect underlying pathophysiological mechanisms related to pain processing,emotional regulation and long-term disease burden in migraine.

Objective:To explore the hemodynamic characteristics of the middle cerebral artery (MCA) in atherosclerotic stenosis using four-dimensional flow (4D Flow) MRI, and combining high-resolution magnetic resonance vessel wall imaging (HR VW-MRI) to analyze the relationship between hemodynamics and the degree of stenosis, as well as the morphological characteristics of plaques.Methods:The study was a cross-sectional study. A total of 24 patients with middle cerebral artery(MCA) M1 atherosclerotic stenosis and 10 age and sex matched healthy controls (HC group) were prospectively recruited from September 2018 to March 2021 at Beijing Tiantan Hospital, Capital Medical University. All subjects underwent MRI examination. The hemodynamic of MCA were collected by 4D Flow MRI, and the hemodynamic parameters of proximal and distal MCA stenosis were calculated by blood flow post-processing software, including average blood flow rate (FR avg), average blood flow velocity (V avg), peak blood flow velocity (V pk), time average wall shear stress (TAWSS), minimum wall shear stress (WSS min) and oscillatory shear index (OSI). The differences in hemodynamic parameters among the proximal and distal ends of MCA stenosis and the HC group were compared using one-way ANOVA or Kruskal-Wallis H test. The stenosis rate and characteristics of MCA plaque were analyzed by HR VW-MRI, including remodeling index (RI), normalized wall index (NWI) and plaque length. Pearson or Spearman correlation analysis was used to explore the correlation between stenosis rate and hemodynamic parameters. Taking the stenosis rate as the control variable, partial correlation analysis was used to explore the correlation between plaque morphological characteristics and hemodynamic parameters. Results:There were statistically significant differences in FR avg, V avg, V pk, TAWSS, OSI, WSS min among the proximal and distal stenosis of MCA and HC groups ( P<0.05). The proximal end of the MCA stenosis had significantly higher FR avg, V avg, TAWSS and WSS min than those of the distal end of the stenosis ( P<0.01). The FR avg, V avg, V pk, TAWSS, and WSS min in the distal end of MCA stenosis were lower than those in the HC group, while the OSI was higher than that in the HC group ( P<0.01). The correlation analysis results showed that the MCA proximal V pk ( r=-0.425, P=0.027) and distal V pk ( r=-0.538, P=0.004) were negatively correlated with the diameter stenosis rate. When the stenosis rate was taken as the control factor, in the MCA proximal stenosis, V avg ( r=0.553, P=0.003), TAWSS ( r=0.543, P=0.004) and WSS min ( r=0.547, P=0.004) were positively correlated with RI, proximal OSI was negatively correlated with RI ( r=-0.492, P=0.011), and was positively correlated with the plaque length ( r=0.437, P=0.026). At the distal end of the stenosis, V pk was negatively correlated with NWI ( r=-0.556, P=0.003), OSI was negatively correlated with RI ( r=-0.511, P=0.008), NWI ( r=-0.390, P=0.049). TAWSS was positively correlated with RI ( r=0.393, P=0.047). Conclusions:The 4D Flow MRI demonstrates characteristic hemodynamic changes in the proximal and distal ends of the stenotic MCA. The local hemodynamic characteristics of the stenotic MCA are correlated with plaque morphological parameters, including lumen stenosis, plaque load, and RI. It suggests an interaction between the occurrence and development of MCA plaque and local hemodynamic changes.

Objective:To explore therapeutic effect of sacubitril valsartan sodium combined with Wenxin granule in the treatment of hypertension complicated with paroxysmal atrial fibrillation(AF)and its effect on cardiac electro-physiological structure.Methods:A total of 116 patients with hypertension and paroxysmal atrial fibrillation treated in our hospital from Oct 2021 to Nov 2022 were consecutively selected.According to random number table,they were divided into Wenxin granule group(received Wenxin granule treatment based on routine antihypertensive ther-apy)and combined treatment group(received sacubitril valsartan sodium combined Wenxin granule therapy based on routine antihypertensive therapy)with 58 cases in each group,and both groups were consecutively treated for six months.Clinical symptom score,AF burden,P wave duration,P wave dispersion,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd)and left ventricular ejection fraction(LVEF)were compared between two groups before and after treatment.Results:After treatment,compared with Wenxin granule group,there were significant reductions in clinical symptom score[(1.66±0.69)scores vs.(1.40±0.53)scores],AF burden[4.43(1.65)％vs.1.62(3.50)％],P wave duration[(112.17±6.46)ms vs.(109.29±8.59)ms],P wave dispersion[(32.47±8.11)ms vs.(29.02±7.49)ms]and LAD[(34.83±3.41)mm vs.(33.40±3.74)mm]in combined treatment group(P＜0.05 or＜0.01).There were no significant difference in LVEDd and LVEF between two groups,P＞0.05 both.Conclusion:Sacubitril valsartan sodium combined with Wenxin granule can significantly im-prove clinical symptoms and atrial fibrillation burden,reduce the susceptibility to atrial fibrillation,and inhibit atrial electrical remodeling and structural remodeling in patients with hypertension complicated with paroxysmal atrial fi-brillation.

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.