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

The finite element method(FEM)is a widely employed mathematical technique in mechanical research that divides an object into discrete and interacting finite elements. Medically, finite element analysis(FEA)enables the simulation of biomechanical experiments that are challenging to conduct. Orbital surgery poses significant challenges to ophthalmologists due to its inherent difficulty and steep learning curve. FEM enables the simulation and analysis of the mechanical properties of orbital tissue, offering a novel approach for diagnosing and treating orbital-related diseases. With technological advancements, FEM has significantly matured in the diagnosis and treatment of orbital diseases, becoming a popular area of research in orbital biomechanics. This paper reviewed the latest advancements in orbital FEM, encompassing the development of orbital FEA models, simulation of orbital structure, and its application in orbital-related diseases. Additionally, the limitations of FEM and future research directions are also discussed. As a digital tool for auxiliary diagnosis and treatment, orbital FEA will progressively unlock its potential for diagnosing and treating orbital diseases alongside technological advancements.

Objective:To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.Methods:Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale(NIHSS)score≤3 and a platelet count<100×109/L were obtained from a multicenter register.Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded.Short-term safety outcomes were in-hospital bleeding events,while the long-term safety outcome was a 1-year all-cause death.The short-term neurological outcomes were evaluated by modified Rankin scale(mRS)score at discharge.Results:A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled.Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge(OR=1.657,95%CI:1.253-2.192,P<0.01)and did not increase the risk of intracranial hemorrhage(OR=2.359,95%CI:0.301-18.503,P>0.05),compared with those without antiplatelet therapy.However,dual-antiplatelet therapy did not bring more neurological benefits(OR=0.923,95%CI:0.690-1.234,P>0.05),but increased the risk of gastrointestinal bleeding(OR= 2.837,95%CI:1.311-6.136,P<0.01)compared with those with mono-antiplatelet therapy.For patients with platelet counts≤75×109/L and>90×109/L,antiplatelet therapy significantly improved neurological functional outcomes(both P<0.05).For those with platelet counts(>75-90)×109/L,antiplatelet therapy resulted in a significant improvement of 1-year survival(P<0.05).For patients even with concurrent coagulation abnormalities,mono-antiplatelet therapy did not increase the risk of various types of bleeding(all P>0.05)but improved neurological functional outcomes(all P<0.01).There was no significant difference in the occurrence of bleeding events,1-year all-cause mortality risk,and neurological functional outcomes between aspirin and clopidogrel(all P>0.05).Conclusions:For non-cardioembolic mild stroke patients with thrombocytopenia,antiplatelet therapy remains a reasonable choice.Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.

Objective To observe the effect of preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer on lung function and mRNA expression of GATA-binding protein 3(GATA3)and forkhead protein P3(Foxp3)in peripheral blood.Methods Sixty esophageal cancer patients who underwent modified Ivor-Lewis surgery in our hospital from January 2022 to October 2023 were selected and divided into two groups by simple random method.The control group was given conventional diet before operation,and the observation group was given enteral nutrition support before operation.The two groups were compared in terms of nutritional support.Results Both groups showed significantly decreases in one-second exertion expiratory volume/exertion lung volume(FEV1/FVC)(P<0.05),FVC(P<0.05),FEV1(P<0.05)and the levels of peripheral blood GATA3(P<0.05),Foxp3 mRNA(P<0.05)expression compared with those at admission(P<0.05),but no significant differences in pulmonary function(P>0.05),peripheral blood GATA3(P>0.05),and Foxp3 mRNA(P>0.05)expression between them at 1 week postoperatively.Both groups exhibited significantly lower levels of albumin,prealbumin,haemoglobin,transferrin,PNI and body mass and body mass index at admis-sion as compared to those at one week after surgery(P<0.05).The observation group showed significantly higher levels of albumin,prealbumin,haemoglobin,transferrin,and PNI at 1 week postoperatively(P<0.05),but no significant differences in ventilation time,defecation time,drain retention time,hospitalisation time,and compli-cation rate as compared to the control group(P>0.05).Conclusion Preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer improves postoperative nutritional status,and ren-ders less effect on postoperative lung function and peripheral blood GATA3 and Foxp3 mRNA expression.

Objective:To evaluate the role of NOD-like receptor 3 (NLRP3) inflammasome activation-mediated macrophage polarization in myocardial injury after ischemic stroke in diabetic mice.Methods:Wild-type C57BL/6J mice and NLRP3 -/- mice, aged 4-6 weeks, were fed a high fat diet combined with streptozotocin administration to develop the diabetic model. Twenty-four diabetic wild type C57BL/6J mice and 23 diabetic NLRP3 -/- mice were divided into wild type sham operation group (WT D-SHAM group, n=9) , wild type ischemic stroke group (WT D-MCAO group, n=15) , NLRP3 -/- sham operation group (NLRP3 -/-D-SHAM group, n=9) and NLRP3 -/- ischemic stroke group (NLRP3 -/-D-MCAO group, n=14). The ischemic stroke model was developed by middle cerebral artery occlusion in the animals anesthetized with isoflurane. Echocardiography and electrocardiography were carried out at 3, 7, 14 and 28 days after developing the model. Mice were sacrificed under deep anesthesia, and myocardial tissues were taken at 28 days after surgery for determination of the expression of macrophage marker F4/80 and M2 type macrophage marker CD206 mRNA (by real-time fluorescence quantitative polymerase chain reaction). Results:Compared with WT D-SHAM group, the cardiac output, mass of left ventricle and corrected mass of left ventricle were significantly decreased at 28 days after surgery, and QT interval and QTc interval were prolonged at 14 and 28 days after developing the model in WT D-MCAO group ( P<0.05). Compared with NLRP3 -/-D-SHAM group, the cardiac output, mass of left ventricle and corrected mass of left ventricle were significantly decreased, and QT interval and QTc interval were prolonged at 3 days after surgery in NLRP3 -/-D-MCAO group ( P<0.05). There was no significant difference in CD206 and F4/80 mRNA expression between WT D-SHAM group and WT D-MCAO group and between NLRP3 -/-D-SHAM group and NLRP3 -/-D-MCAO group ( P>0.05). Compared with WT D-MCAO group, the QT interval and QTC interval were significantly shortened at 14 and 28 days after developing the model, and the expression of F4/80 mRNA was down-regulated and the expression of CD206 mRNA was up-regulated at 28 days after developing the model in NLRP3 -/-D-MCAO group ( P<0.05). Conclusions:NLRP3 inflammasome activation-mediated polarization of macrophages to M2 phenotype is involved in myocardial injury after ischemic stroke in diabetic mice.

Objective:To systematically analyze the efficacy of nasal endoscopic transsphenoidal decompression and glucocorticoid pulse therapy for traumatic optic neuropathy (TON).Methods:PubMed, Web of Science, Cochrane Library, ClinicalTrial.gov, CNKI, Wanfang, China Biomedical and other databases were searched to retrieve clinical studies on endoscopic surgery and hormone therapy for TON since their establishment to November 1, 2020.Two researchers screened the literature and evaluated the quality of the included literatures.The improvement of visual acuity before and after treatment was taken as an effective indicator.RevMan 5.3 statistical software was used for meta-analysis.The sensitivity of the results was analyzed atfer literature exclusion.The publication bias of each study was double checked by funnel plot and Begg test.Results:Eight studies were included, including 7 cohort studies and 1 randomized controlled trial.There was no significant difference between the endoscopic decompression group and glucocorticoid group in the efficiency of visual acuity improvement in the treatment of TON [odds ratio ( OR)=1.65, 95% confidence interval ( CI)∶0.75-3.66, P=0.22], neither in TON patients with residual vision before surgery ( OR=2.17, 95% CI: 0.94-4.98, P=0.07). For nasal endoscopic decompression surgery, early surgery (disease course<7 days) was more effective than late surgery (disease course>7 days) ( OR=4.73, 95% CI: 2.55-8.78, P<0.01). Sensitivity analysis suggested that the results of this literature analysis were not robust.The Begg test showed that there was no literature publication bias. Conclusions:There is no significant difference between nasal endoscopic surgery and glucocorticoid therapy in the treatment of TON.Early endoscopic surgery may help improve visual acuity in patients with residual vision.

Objective:To evaluate the efficacy of individualized mini-fluid challenge test in determining the fluid responsiveness in the patients undergoing surgery in prone position.Methods:A total of 47 patients of either sex, aged > 18 yr, with boy mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective spinal surgery in prone position, were included. The volume-controlled mode was used for mechanical ventilation, and the tidal volume was set at 8 ml/kg. The hemodynamic parameters were monitored by FloTrac/Vigileo system. The patient was changed to prone position at 5 min after endotracheal intubation (T 1), hydroxyethyl starch 130/0.4 sodium chloride injection 2 ml/kg was intravenously given at 5 min of prone position (T 2), and fluid 3 ml/kg was continuously infused at 1 min after 2 ml/kg fluid infusion (T 3), and both infusion rates were 0.5 ml·kg -1·min -1. A mini-fluid challenge test was performed during T 2-T 3 period, the standard volume therapy (total infusion of liquid 5 ml/kg) was carried out from T 2 to 1 min after infusion of liquid 3 ml/kg (T 4). The rate of change in SV at T 3 time point (ΔSVT 3) was calculated relative to T 2 time point, and the rate of change in SV at T 4 time point (ΔSVT 4) was calculated relative to T 2 time point. Positive fluid responsiveness test was defined as an increase in ΔSVT 4≥10%, and patients were divided into volume response group (Rs group) and non-volume response group (NRs group). ΔSVT 3, ΔSVT 4 and stroke volume variation and pulse pressure variation at T 3 and T 4 time points were selected, the receiver operating characteristic curve predicting fluid responsiveness was generated, and the area under the receiver operating characteristic curve (AUC) was calculated. Results:Forty-one patients were finally enrolled, including 18 cases in Rs group and 23 cases in NRs group. The AUC of ΔSVT 3 determining fluid responsiveness was 0.976, with the sensitivity 0.944 and specificity 0.957. The AUC of ΔSVT 4 determining fluid responsiveness was 0.971, with sensitivity 0.889 and specificity 0.95. The AUC of stroke volume variation at T 3 and T 4 in predicting fluid responsiveness was 0.632 and 0.609, respectively. The AUC of pulse pressure variation at T 3 and T 4 predicting fluid responsiveness was 0.470 and 0.380, respectively. Conclusions:Individualized mini-fluid challenge test (2 mg/kg colloidal solution) can accurately determine the fluid responsiveness in the patients undergoing surgery in prone position.

ObjectiveTo investigate the association of lipid ratios with diabetes and pre-diabetes in residents aged 35-75 years in Changzhou City. MethodsA multistage whole-group random sampling method was used to survey permanent residents aged 35-75 years in Tianning and Wujin districts of Changzhou City， and the study data were obtained by questionnaires， physical examination and laboratory tests. The relationship between lipid ratios and diabetes and pre-diabetes was analyzed by dichotomous logistic regression method. ResultsThe prevalence of diabetes in the surveyed population in Changzhou was 18.69%， and the prevalence of pre-diabetes was 10.53%. In the total population， the risk of pre-diabetes was significantly increased in the highest TC/HDL-C， TG/HDL-C and LDL-C/HDL-C groups， by 68%， 93% and 38%， respectively； the risk of diabetes was also significantly increased in the highest TC/HDL-C， TG/HDL-C and LDL-C/HDL-C groups， by 105%， 149% and 78%， respectively. The risk of diabetes was also significantly increased in the highest TC/HDL-C， TG/HDL-C and LDL-C/HDL-C groups， by 105%， 149% and 78%， respectively. All three lipid ratios increased in women compared to men， leading to a stronger association with increased risk of diabetes and pre-diabetes. ConclusionLipid ratios TC/HDL-C， TG/HDL-C， and LDL-C/HDL-C were correlated with the risk of diabetes and pre-diabetes in people aged 35-75 years， with TG/HDL-C having the strongest association with diabetes and pre-diabetes， and is expected to be a key predictor for assessing the development of diabetes.

Objective To compare the clinical efficacy between Clamshell incision and bilateral posterolateral incision in the sequential double lung transplantation for end-stage lung disease. Methods Clinical data of 120 recipients undergoing double lung transplantation were retrospectively analyzed. All recipients were divided into bilateral posterolateral incision group (n=108) and Clamshell incision group (n=12) according to different surgical methods. Intraoperative parameters were collected and statistically compared between two groups, including operation time, amount of blood loss, amount of blood transfusion, use of extracorporeal membrane oxygenation (ECMO) or not, cold ischemia time on the first side, and cold ischemia time on the second side. Postoperative parameters were also compared between two groups, including the length of hospital stay, length of intensive care unit (ICU) stay, tracheal intubation duration, ECMO duration, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), incidence of anastomotic stenosis, incidence of bronchopleural fistula, perioperative fatality, and 6-minute walk test for the first time after operation. Results In the Clamshell incision group, the amount of blood loss and blood transfusion was significantly higher than those in the bilateral posterolateral incision group (both P < 0.05). The proportion of ECMO and cold ischemia time on the second side in the Clamshell incision group were significantly lower or shorter than those in the bilateral posterolateral incision group (both P < 0.05). In the Clamshell incision group, the tracheal intubation duration and ECMO duration were significantly shorter compared with those in bilateral posterolateral incision group (both P < 0.05). Conclusions Both Clamshell incision and bilateral posterolateral incision are safe and effective in sequential double lung transplantation. Bilateral posterolateral incision approach can significantly reduce the amount of blood loss and blood transfusion of the recipients without significantly prolonging the operation time. Compared with bilateral posterolateral incision approach, the cold ischemia time of lung graft, tracheal intubation duration and ECMO duration are significantly shortened via the Clamshell incision.

ObjectiveTo observe the clinical efficacy and safety of traditional Chinese medicine （TCM） external therapeutic protocol of enriching pus for tissue growth （EPTG） in the treatment of Wagner 2-3 diabetic foot ulcer. MethodThe randomized controlled trial （RCT） design was adopted. Patients receiving basic treatment were divided into the EPTG group and the control group （debridement and change of nano-silver medical antibacterial dressing）. Ulcer healing rate， ulcer area， ulcer depth， TCM symptom score， visual analogue scale（VAS）， transcutaneous partial pressure of oxygen， wound blood flow， inflammatory factors ［C-reactive protein （CRP）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）］， growth factors ［vascular endothelial growth factor （VEGF）， transforming growth factor-β₁ （TGF-β₁）， and fibroblast growth factor-β （FGF-β）］， adverse events， and outcome events of the two groups before and after treatment were observed. ResultCompared with the conditions before treatment， the ulcer healing rate， ulcer area， ulcer depth， TCM symptom score， VAS score， transcutaneous partial pressure of oxygen， wound blood flow， CRP， IL-6， TNF-α， VEGF， TGF-β₁， and FGF-β were significantly improved （P<0.01）. In terms of the improvement in the ulcer healing rate， ulcer area， ulcer depth， VAS score， transcutaneous partial pressure of oxygen， wound blood flow， CRP， IL-6， TNF-α， VEGF， TGF-β₁， and FGF-β， the EPTG group was superior to the control group （P<0.01）. There were no statistically significant differences in adverse events and outcome events between the two groups. ConclusionThe TCM external therapeutic protocol of EPTG is safe and effective in the treatment of Wagner 2-3 diabetic foot ulcer. It can greatly reduce the area and depth of diabetic foot ulcer， improve the ulcer healing rate and TCM symptom score， relieve the pain of patients， and improve the microcirculatory blood supply in the local ulcer. Its mechanism of action may be related to the reduction of the local inflammatory response of the wound and the improvement of the proliferation of fibroblasts and vascular endothelial cells.