Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

AIM:To explore the protective effect of Xiaoxuming decoction(XXMD)on synaptic plasticity in the context of cerebral ischemia-reperfusion injury following ischemic stroke.METHODS:An oxygen-glucose depriva-tion/reoxygenation(OGD/R)model was employed in vitro using mouse hippocampal neurons(HT22 cells)to simulate ischemia-reperfusion injury.Cell viability was assessed using a CCK-8 assay to determine the optimal XXMD concentra-tion.The HT22 cells were divided into two groups:control and model(OGD/R).Cellular morphological changes were ob-served using an inverted microscope.The levels of IL-1β,IL-6 and TNF-α in the supernatant were quantified by ELISA.Ultrastructural changes were examined by transmission electron microscopy.Immunofluorescence staining was used to de-tect neuron markers NeuN and synaptic proteins NF200 and MAP2.The protein levels of NF200 and MAP2 were analyzed by Western blot.RESULTS:The highest cell survival rate occurred at an XXMD concentration of 100 mg/L(P<0.05).Compared with control group,the cells in model group exhibited round shape and shrinkage,mitochondrial swelling or vacuolization,and a marked decrease in survival rate.There were significant increases in IL-1β,IL-6 and TNF-α levels(P<0.05).Immunofluorescence intensity and protein levels of NeuN,NF200 and MAP2 were notably reduced(P<0.05).Treatment with XXMD improved cell morphology,ultrastructure and survival rate(P<0.05),and decreased in-flammatory factor levels(P<0.05).Compared with model group,the cells in OGD/R+XXMD group showed significantly increased immunofluorescence intensity and protein levels of NeuN,NF200 and MAP2(P<0.05).CONCLUSION:Xiaoxuming decoction may mitigate OGD/R-induced injury,potentially by inhibiting inflammatory responses and enhanc-ing synaptic plasticity.

AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.

Berberine is a natural isoquinoline alkaloid that was initially used as a broad-spectrum antibacterial agent in clinical treatment of enteritis,peptic ulcers,chronic gastritis,pneumonia,and other diseases.In recent years,in-depth study of the pharmacological effects of berberine has provided increasing evidence that berberine has neuroprotective effects on ischemic stroke.In this review,we introduce the effect of berberine on risk factors of ischemic stroke and discuss the neuroprotective effects of berberine on various mechanisms of ischemic stroke in detail to provide a reference for clinical and basic research in this field.

Objective To explore the effects of different acupoints,different target organs,and different interventions on acupoint efficacy based on ACU&MOX-DATA platform;To illustrate and visualize whether the above factors have the characteristics of"specific effect"or"common effect"of acupoint efficacy.Methods The multi-source heterogeneous data were integrated from the original omics data and public omics data.After standardization,differential gene analysis,disease pathology network analysis,and enrichment analysis were performed using Batch Search and Stimulation Mode modules in ACU&MOX-DATA platform under the conditions of different acupoints,different target organs,and different interventions.Results Under the same disease state and the same intervention,there were differences in effects among different acupoints;under the same disease state,the same acupoint and intervention,the responses produced by different target organs were not completely consistent;under the same disease state and acupoint,there were differences in effects among different intervention measures.Conclusion Based on the analysis of ACU&MOX-DATA platform,it is preliminary clear that acupoints,target organs,and interventions are the key factors affecting acupoint efficacy.Meanwhile,the above results have indicated that there are specific or common regulatory characteristics of acupoint efficacy.Applying ACU&MOX-DATA platform to analyze and visualize the critical scientific problems in the field of acupuncture and moxibustion can provide references for deepening acupoint cognition,guiding clinical acupoint selection,and improving clinical efficacy.

Objective To evaluate the bioequivalence of test and reference mirabegron sustained release tablets under fasting/postprandial conditions.Methods A randomized,open,single dose,four cycle,two sequence,self-crossover trial design was used.32 healthy subjects respectively for fasting and fed study were enrolled,who were randomized to a single oral dose of 50 mg of either reference or test preparation of mirabegron sustained release tablets.The plasma concentration of mirabegron in healthy subjects after oral administration was detected by liquid chromatography tandem mass spectrometry,and Phoenix WinNonlin 8.2 software was used to calculate pharmacokinetic parameters and perform bioequivalence analysis.Results Subjects received a single oral dose of the reference and test formulations of mirabegron.The main pharmacokinetic parameters of mirabegron in the fasting study were asfollows:Cmaxwere(43.91±21.40)and(40.82±24.94)ng·mL-1,AUC0-t were(464.45±149.01)and(452.67±157.63)h·ng·mL-1,AUC0-∞were(501.64±162.39)and(488.70±173.81)h·ng·mL-1.The main pharmacokinetic parameters of mirabegron in the fed study were as follows:Cmax were(16.90±8.94)and(16.90±9.66)ng·mL-1,AUC0-t were(247.09±82.53)and(243.22±78.20)h·ng·mL-1,AUC0-∞ were(269.58±86.52)and(265.66±81.89)h·ng·mL-1.The 90％confidence intervals for the geometric means of Cmax,AUC0-t and AUC0-∞ for reference and test preparations in the fasting and fed groups were in the range of 80.00％to 125.00％.Conclusions The test and reference formulation of mirabegron sustained release tablets were bioeguivalence.

Objective To evaluate the molluscicidal effect and cost of spraying molluscicides with drones against Oncomelania hupensis snails in marshland and lake areas, so as to provide new insights into field snail control in China. Methods A marshland and lake setting measuring approximately 12 000 m² was selected in Wanzhi District, Wuhu City on June 2023 as the test field, and assigned to four groups, of 3 000 m² in each group. Environmental cleaning was not conducted in groups A or B, which were given 5% niclosamide ethanolamine salt granules sprayed with knapsack-type sprayers and drones at a dose of 40 g/m², and environmental cleaning was conducted in groups C and D, which were given 5% niclosamide ethanolamine salt granules sprayed with drones and knapsack-type sprayers at a dose of 40 g/m², respectively. O. hupensis snails were surveyed before chemical treatment and 1, 3, 5, 7, 14 days post-treatment. The uniformity of chemicals was determined on the day of treatment, and the snail mortality, corrected snail mortality and density of living snails were calculated and compared among groups. The cost of molluscicides, labor fees of environmental cleaning and chemical treatment and cost of equipment were calculated, and the cost for a 1% reduction in the mean density of living snails was calculated 14 days post-treatment. Results The mean densities of living snails and mortality rates of snails were 1.82 to 2.85 snails/0.1 m² and 1.41% to 2.94% in groups A, B, C and D before chemical treatment, and the mortality and corrected mortality of snails were 55.75%, 49.32%, 85.94% and 87.50%, and 55.00%, 48.47%, 85.70% and 87.29% in groups A, B, C and D 14 days post-treatment. There was a significant difference in the mortality of snails among the four groups 14 days post-treatment (χ² = 38.735, P < 0.005), and there was a higher snail mortality in Group D than in Group A (χ² = 16.876, P < 0.005), and higher in Group C than in Group B (χ² = 20.508, P < 0.005). The density of living snails reduced by 55.00%, 43.94%, 90.43% and 87.14% 14 days post-treatment relative to pre-treatment in groups A, B, C and D, respectively. The test for uniformity of chemicals showed that the mean dose of molluscicides were 57.34, 55.21, 40.19 g/m² and 32.37 g/m² in groups A, B, C and D, respectively, and the minimal standard deviation (7.07) and coefficient of variation (0.18) of mean doses were seen in Group C. The costs for chemical treatment were 0.33 Yuan in groups A and B and 1.53 Yuan in groups C and D, respectively. The costs for a 1% reduction in the mean density of living snails were 17.82, 22.47, 50.73 Yuan and 52.56 Yuan in groups A, B, C, and D 14 days post-treatment, respectively. Conclusions The molluscicidal effect and cost of spraying 5% niclosamide ethanolamine salt granules with drones are comparable to manual spraying, and chemical treatment with drones are high in uniformity of molluscicides, time- and labor-saving, and feasible for applications in complex environments, which deserves widespread applications in the field of snail control.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

Objective To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus(SLE)and lupus nephritis(LN)in children,as well as their diagnostic value for active SLE and LN.Methods A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital,Central South University from January 2016 to March 2019 as the SLE group,all of whom were tested for anti-C1q antibodies.A control group was formed by collecting 70 hospitalized children with other autoimmune diseases(OAD)during the same period.The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed,and the diagnostic value of anti-C1q in SLE and LN was evaluated.Results The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group(P<0.05).The SLE disease activity index score was positively correlated with anti-C1q antibodies(rs=0.371,P<0.001)and positively correlated with anti-double-stranded DNA antibodies(rs=0.370,P<0.001).The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90%and 53.90%,respectively,with an area under the curve of 0.720(P<0.05)and a critical value of 5.45 U/mL.The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50%and 85.00%,respectively,with an area under the curve of 0.675(P<0.05)and a critical value of 22.05 U/mL.Conclusions Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.