Objective To explore the enhancement effect of N-trimethyl chitosan(TMC) on transdermal absorption of 8-methoxypsoralen-loaded liposomal(LMOP) gels in vitro.Methods TMC with quaternization degree of 60％ (TMC60) as the enhancer,the LMOP gels were prepared with free TMC60 or TMC60-coating.The enhancement of free TMC60 or TMC60-coating was studied by using Franz diffusion,cells with LMOP gels as the negative control and LMOP gels including 1％ Azone + propylene glycol as the positive control.Results Compared with the negative control,enhancement and drug amount in skin of LMOP gels with enhancer all showed significant difference (x2 =8.65,P ＜ 0.05),and the free TMC.60 was the best.Conclusion TMC can enhance the transdermal penetration of LMOP gels in vitro and is valuable to be studied further.

Objective:To study the effect of mesalazine hydroxyl-propyl-β-cyclodextrin inclusion compound ( MSZ-HP-β-CD) liq-uid suppositories on ulcerative colitis ( UC) in rats. Methods:Dextran sulfate sodium was used to induce UC in rats. The marketed MSZ suppositories were applied as the positive control, and the changes in morphology and histopathology of the UC rats were observed after the treatment with MSZ-HP-β-CD liquid suppositories. Results:The results of morphology study showed that CMDI was decreased in the two MSZ preparation groups when compared with that in the model group (P<0. 01), and that in MSZ-HP-β-CD liquid supposi-tories group was the lowest (P<0. 05). The results of histopathology study showed that with the treatment of the marketed MSZ sup-positories and MSZ-HP-β-CD liquid suppositories, the ulcer and damage were improved, and the improvement in the MSZ-HP-β-CD liquid suppositories group was more significant. Conclusion: MSZ-HP-β-CD liquid suppositories exhibit better effect on UC in rats when compared with the marketed MSZ suppositories, which is worthy of further studies.

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is un-known.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the acti-vation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphory-lation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by acti-vating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

Methods:From February 2018 to January 2022, the clinical data of 1 123 patients who underwent Starclose vascular closure device, Angio-Seal and Exoseal vascular occlusion devices and Perclose ProGlide vascular suture device at femoral artery puncture hemostasis after neuro-intervention, in the Department of Interventional Radiology (Eastern District), The First Affiliated Hospital of Zhengzhou University, were retrospectively analyzed. The patients were divided into three groups based on the intervention method: the closure group (Starclose, n=271), the occlusion group (Angio-Seal, n=327 and Exoseal, n=352) and the suture group (ProGlide, n=173). Next, the hemostatic efficacy and complications associated with the three devices were analyzed and compared. Additionally, regression analysis was conducted to identify any relevant factors that may contribute to complications. Results:Three vascular hemostatic devices demonstrated effective hemostasis and the success rate were 92.6% in the closure group (Starclose), 93.4% in the occlusion group (Angio-Seal 93.0% and Exoseal 93.8%) and 89.6% in the suture group (ProGlide). There was no statistically significant difference( χ2=3.026, P=0.388). Single or multiple complications were observed in 102 patients (9.1%), including local oozing (16 cases in the closure group, 39 cases in the occlusion group, 13 cases in the suture group), local hematoma (14 cases in the closure group, 31 cases in the occlusion group, 11 cases in the suture group), pseudoaneurysm (13 cases in the closure group, 35 cases in the occlusion group, 10 cases in the suture group), local infection (2 cases in the closure group, 3 cases in the occlusion group, 1 case in the suture group). There were no statistically significant differences ( P>0.05). Moreover, serious complications such as femoral artery occlusion, embolus shedding and permanent nerve injury weren′t observed in the three groups. Multivariate logistic regression analysis revealed that overweight ( OR=1.562,95% CI 1.023—2.385, P=0.039), femoral artery with calcified plaque ( OR=1.934,95% CI 1.172-3.189, P=0.010), combined use of multiple antiplatelet drugs ( OR=1.769,95% CI 1.103—2.839, P=0.018), use of an 8F sheath( OR=2.824,95% CI 1.406—5.671, P=0.004) and the operator′s proficiency ( OR=0.508,95% CI 0.328—0.788, P=0.002) were the independent factors influencing complications, of which the first four were identified as risk-promoting factors for complications while the operator′s rich experience and high proficiency were the protective factors. Conclusions:Three hemostatic devices demonstrate effective hemostasis and comparable rates of complications at femoral artery puncture hemostasis after neuro-intervention. Overweight, femoral artery with calcified plaque, combined use of multiple antiplatelet drugs, use of an 8 F sheath and the operator′s proficiency were independent factors influencing complications.Ojective:To investigate the efficacy and complications associated with vascular suture, closure and occlusion devices at femoral artery puncture hemostasis after neuro-intervention.

Objective:To explore the degradation property of novel magnesium alloy stents in Bama mini-pig models of carotid artery stenosis, and evaluate the feasibility of observing their dynamic and continuous process by high-resolution C-arm CT.Methods:Twelve Bama mini-pigs were selected; carotid artery stenosis models were established by large balloon over-dilation and high-fat and high-salt diet in Bama pigs; 24 weeks after that, self-made braided degradable magnesium alloy stents were inserted into the carotid artery stenosis models (confirmed by DSA) by balloon dilation. Degrees of stent patency and in-stent restenosis were examined by DSA immediately after procedure and on the 30 th, 60 th and 90 th d of procedure. Four experimental pigs were sacrificed on the 30 th, 60 th and 90 th d of procedure, respectively; the degradation property of the novel magnesium alloy stents was observed according to results of high-resolution C-arm CT in the inserted-stent areas and staining results of specimens in the stenosis areas, and stent imaging features during degradation were summarized. Results:Twelve Bama mini-pig models of carotid artery stenosis were established and 12 magnesium alloy stents were successfully inserted with a technical success rate of 100%. Both immediate postoperative and follow-up angiography showed patency of the vascular lumens without obvious in-stent restenosis. High-resolution C-arm CT and pathological examination showed homogeneous stent lumens and clear delineation of the stent meshes, with slightly degraded stent on the 30 th d of procedure; the stent lumen was blurred and some magnesium alloy wires were fractured with developed degradation of the stent on the 60 th d of procedure; and the stent meshes and stent strut could not be visualized due to severe degradation of the stent on the 90 th d of procedure. Conclusion:Magnesium alloy degradable stent is almost completely degraded within 90 th d of procedure in Bama mini-pig models of carotid artery stenosis, and high-resolution C-arm CT can be used to dynamically monitor the degradation of the stent in vivo.

Objective:To explore the stent apposition and safety of Neuroform EZ and Enterprise 2 stents in treatment of symptomatic intracranial atherosclerotic stenosis (sICAS), and their influencing factors for in-stent restenosis.Methods:A total of 143 sICAS patients treated by Enterprise 2 stents (implanted 143 Enterprise 2 stents, E2 group) and 202 patients treated by Neuroform EZ stents (implanted 202 Neuroform EZ stents, EZ group) were selected from Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from January 2017 to January 2022. Stent apposition was evaluated based on reconstructive images of high-resolution flat detector CT. The complications 30 d after surgery and during 6-24 months of follow-up were recorded. Based on DSA or CTA 6 months after surgery, the patency of the two stents was evaluated. Univariate analysis and multivariate Logistic regression analysis were used to determine the independent risk factors for in-stent restenosis.Results:(1) Forty-nine patients had incomplete stent apposition (ISA) after stent release: 24 patients with ISA in E2 group (16.8%, 24/143; 15 of type I and 9 of type II) and 25 with ISA in the EZ group (12.4%, 25/202, 11 of type I and 14 of type II) were found, without statistical difference ( χ 2=1.334, P=0.248); however, ISA incidence in the EZ group (19.0% and 10.3%) was significantly lower than that in the E2 group (41.4% and 25.6%) when the diameter ratio of anterior and posterior vessels of the stenosis lesions≥1.30 or the angle of stent≥75° ( χ 2=4.228, P=0.040; χ 2=4.531, P=0.033). (2) Within 30 d of stenting, 17 patients developed neurological dysfunction-related complications: 8 patients in EZ group and 9 in E2 group were noted, without significant difference ( P=0.324). Clinical follow-up was obtained in 317 patients, and 20 patients developed long-term stroke associated with responsible lesion vessels: 12 patients in EZ group and 8 in E2 group were noted, without significant difference ( P=0.995). (3) Totally, 298 patients received imaging follow-up 6 months after surgery, and 65 patients developed in-stent restenosis: 36 patients in EZ group and 29 in E2 group were noted, without significant difference ( χ 2=0.309, P=0.578). Multivariate Logistic regression analysis showed that diabetes ( OR=2.714, 95% CI: 1.437-5.126, P=0.002), stent apposition ( OR=3.435, 95% CI: 1.223-9.652, P=0.019), lesion stenosis length ( OR=1.176, 95% CI: 1.065-1.300, P=0.001) and immediate postoperative residual stenosis ( OR=1.038, 95% CI: 1.004-1.074, P=0.029) were independent influencing factors for in-stent restenosis. Conclusions:Enterprise 2 and Neuroform EZ stents have high stent apposition and safety in sICAS treatment, but in cases with large diameter ratio of the anterior and posterior vessels of the stenosis lesions (diameter ratio≥1.30) or large angle of the stent (≥75°), Neuroform EZ stent has better stent apposition. Patients with diabetes, ISA, long lesion stenosis or high residual stenosis may trend to have in-stent restenosis.

Objective:To establish the carotid artery in-stent restenosis (ISR) models in Bama pigs after Neuroform EZ stent implantation, and observe and summarize their imaging and pathological characteristics.Methods:Thirteen healthy Bama pigs from Guangxi Province were chosen; carotid artery intima was injuried by balloon over-dilation; Neuroform EZ stents were implanted at the vascular injury sites to establish ISR models. Blood flow at areas accepted carotid artery stent implantation in Bama pigs was monitored by bedside color ultrasound every 2 weeks after surgery; once hemodynamic changes (acceleration or deceleration of the blood flow) in stents were detected, DSA, intravascular ultrasound (IVUS), optical coherence tomography (OCT) and high-resolution MRI (HR-MRI) were performed immediately. Bama pigs were then sacrificed and tissues at the stents were taken; HE staining was used to observe the pathological changes.Results:Thirteen Neuroform EZ stents were implanted into 13 Bama pigs after balloon over-dilation of the unilateral carotid arteries with a technical success rate of 100%. Hemodynamic changes in stents were detected in these 13 pigs (10 with acceleration and 3 with deceleration) at (12.46±3.57) weeks after stenting (ranged from 6-18 weeks); ISR of different degrees was found in all these 13 pigs by DSA with an average stenosis rate of (44.23±9.39)%. IVUS and OCT found that the main body of stents was covered by hyperplastic intima, and thickened intima resulted in local lumen stenosis; and obvious vascular wall enhancement in these lumens was shown on HR-MRI. HE staining showed rupture of intravascular internal elastic lamina and severely arterial intimal hyperplasia;and the hyperplastic intima was mainly composed of smooth muscle cells.Conclusion:Carotid artery ISR models in Bama pigs can be accurately and reliably established at approximately 12 weeks by tearing endovascular intima with balloon over-dilation and implanting Neuroform EZ stents, and multiple imaging and pathology methods confirm that ISR is caused by hyperplastic intima.

Objective:To compare the efficacies of Enterprise 1 stent and Enterprise 2 stent in treating symptomatic intracranial atherosclerotic stenosis (ICAS).Methods:From January 2018 to April 2021, 76 patients with symptomatic ICAS treated by Enterprise 2 stent (implanting Enterprise 2 stents, EP2 group) and 52 patients with symptomatic ICAS treated with Enterprise 1 stent (implanting Enterprise 1 stents, EP1 group) were chosen from Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University. DSA was performed immediately after stent implantation and residual vascular stenosis rate was analyzed and compared between the 2 groups. Stent apposition of the 2 groups were evaluated according to reconstruction images of high-resolution flat detector CT; patients were divided into incomplete stent apposition (ISA) group and complete stent apposition group, accordingly; their clinical data were compared. Multivariate Logistic regression was used to analyze the independent influencing factors for ISA. Incidences of perioperative complications and short-term in-stent restenosis (6 months after implantation) in the EP2 group and EP1 group were observed.Results:Intracranial stent was successfully implanted in all patients, with technical success rate of 100%. Significant difference was noted in EP1 group between pre-implanted vascular stenosis rate (80.85±12.14)% and post-implanted residual vascular stenosis rate ([21.44±8.11]%, P<0.05); significant difference was noted in EP2 group between pre-implanted vascular stenosis rate (81.83±12.85)% and post-implanted residual vascular stenosis rate ([21.53±7.76]%, P<0.05); no significant difference was noted in pre-implanted vascular stenosis rate, post-implanted residual stenosis rate, or angles of stent between EP1 group and EP2 group ( P>0.05). According to high-resolution flat detector CT scan, the ISA incidence in EP2 group (10.5%) was significantly lower than that in EP1 group (25.0%, P<0.05); compared with the complete stent apposition group, the ISA group had significantly higher post-implanted residual stenosis rate, higher proportions of patients with calcification at the stenosis, larger angles of stent, higher diameter ratio of anterior and posterior vessels of the stenosis lesions, and lower proportion of patients with Enterprise 2 stent implantation ( P<0.05). Multivariate Logistic regression analysis showed that the angle of stents, diameter ratio of anterior and posterior vessels of the stenosis lesions and Enterprise 2 stent implantation were independent influencing factors for stent apposition; and Enterprise 2 stent implantation was an proactive factor for complete stent apposition. Perioperative complication rate showed significant difference between EP1 group and EP2 group (1.3% vs. 7.7%, P<0.05). Short-term in-stent restenosis between EP2 group and EP1 group was significantly different (26.1% vs. 7.0%, P<0.05). Conclusion:Compared with Enterprise 1 stent, Enterprise 2 stent has better apposition, higher safety, and lower incidence of short-term in-stent restenosis, enjoying clinical application value in treating symptomatic ICAS.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled