Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Objective To explore the efficacy and action mechanism of a novel phenothiazine derivative,DA414,in rats with intracerebral hemorrhage(ICH).Methods Male Sprague-Dawley(SD)rats(aged 8～10 weeks,weighing 250～300 g)were randomly divided into sham operation,model,and low and high dose DA414 groups[5 and 10 mg/(kg·d)],with 20 animals per group.The size and extent of injury in the ICH area were measured by magnetic resonance imaging(MRI)and histopathological slices.Neurological function was evaluated with a behavioral grading system.Western blotting was used to detect the expression of ferroptosis-related factor,glutathione peroxidase 4(GPX4).Multiplex immunohistochemistry was employed to quantitatively evaluate microglial activation in perihematomal tissue.RT-qPCR was applied to measure the mRNA expression levels of NLRP3 inflammasome components(NLRP3,Caspase-1,IL-1β),pro-inflammatory(IL-18,TLR4,IL-6,TNF-α)and anti-inflammatory cytokines(IL-4,IL-10).The integrity of the blood-brain barrier(BBB)was assessed by Evans blue staining,and the biosafety of DA414 for the liver,kidneys and heart was assessed by HE staining and clinical biochemical tests.Results DA414 significantly promoted the absorption of hematoma,reduced neuronal injury,and improved neurological function scores.DA414 significantly up-regulated the ferroptosis regulatory factor GPX4(P<0.01),and also significantly inhibited the activation of microglia after ICH(P<0.001).RT-qPCR indicated that DA414 treatment resulted in down-regulation of mRNA expression in the inflammasome pathway(NLRP3,Caspase-1,IL-1β,all P<0.01)and pro-inflammatory cytokines(TLR4,IL-6,both P<0.05;IL-18,TNF-α,both P<0.01)and up-regulation of anti-inflammatory cytokines(IL-4,IL-10,both P<0.05),suggesting that DA414 exerts its neuroprotective effect probably by regulating ferroptosis and inflammation.Safety assessment revealed that DA414 had no significant effect on BBB integrity or damage to the liver,kidneys,and heart in rats.Conclusion DA414 exerts significant neuroprotective effects in ICH model by targeted inhibition for ferroptosis and modulating inflammatory response.Our study provides an experimental foundation for ICH treatment.

Background::Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo. This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients. Methods::Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment.Results::Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t= 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001). Conclusions::Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

Objective To investigate the potential pathogenesis of depression and the improving effect of glutathione (GSH)in the process.Methods Sixty male C57BL/6J mice (6-8 weeks old)were randomly divided into sham operation group (SHAM),post-stroke depression (PSD)group and chronic social defeat depression (CSDS)group,with 20 animals in each group.Open field test,elevated plus maze test,tail suspension test,and sucrose preference test were performed to identify whether they exhibited depressive-like behaviors.After the tissue samples of medial prefrontal cortex (mPFC)were harvested from the 2 models and control mice,neurotransmitter-targeted metabolomics sequencing was carried out.Principal component analysis (PCA)and correlation analysis were performed to explore the expression of metabolites in each group of mice to screen differential metabolites.Kyoto Encyclopedia of Genes and Genomes (KEGG)enrichment analysis was used to predict the metabolic pathways related to the depression models.The expression of key differential metabolites related to ferroptosis,including glutathione (GSH),malondialdehyde (MDA)and glutathione peroxidase 4 (GPX4).The effect of exogenous supplementation of GSH was observed by whether the depressive-like behavior of the model mice was improved.Results The results of neurotransmitter-targeted metabolomics analysis showed significant differences in the metabolic levels of the 3 groups of mice. Among the 38 metabolites detected in the mPFC,6 were specifically decreased in PSD and 4 were specifically decreased in CSDS.GSH,L-tryptophan,and L-lysine were significantly decreased in both PSD and CSDS groups (P<0.05 ).KEGG analysis indicated that the main pathways involved in the differential metabolites included GSH metabolism,beta-amino acid metabolism,and alanine,aspartate and glutamate metabolism. GSH/GSSG assay kit indicated that the ratio of reduced GSH/oxidized GSH (GSH/GSSG)in the mPFC of the 2 depression models was significantlly decreased (P<0.05 ),and the ferroptosis-related index test found that the 2 depression model mice had increased MDA level and significantly reduced GPX4-positive cells compared with the control group (P<0.05).Exogenous supplementation of GSH in the depression models extended the open arm time in the elevated plus maze test,increased the central zone time in the open field test (P<0.05),and reduced the immobility time in the tail suspension test (P<0.05),significantly improving the depressive-like behaviors.Conclusion There are 13 metabolite imbalances in the brain tissues of PSD and CSDS mice,and ferroptosis triggered by abnormal GSH metabolism may play an important role in the occurrence of depression.Exogenous supplementation of GSH improves depressive-like behaviors in mice.

Objective This study aimed to investigate the therapeutic efficacy of Sanjie Quban recipe in a keloid nude mice model and its impact on transforming growth factor-β 1(TGF-β1).Methods Keloid tissue after surgical resection was subcutaneously transplanted into the backs of healthy SPF BALB/C female nude mice,aged 6～8 weeks,and a keloid nude mice model was thus established.The mice were randomly divided into three groups,the Sanjie Quban recipe group,the Asiaticoside tablet group and the control gnup,with five in each group.They were respectively treated with Sanjie Quban recipe,Asiaticoside tablets,or sterile pure water.After 28 days of continuous gavage,the keloid tissue was exfoliated and weighed,and HE staining,Masson staining,and immunohistochemical staining for TGF-β1 were conducted.Differences in keloid weight between the three groups before and after treatment were compared,as were the differences in collagen fiber,fibroblast numbers,and TGF-β1 expression between the three groups after treatment.Results The difference in keloid weight before and after treatment in the Asiaticoside tablet group was greater than that of the control group,and the weight difference before and after treatment keloid treatment was the largest in the Sanjie Quban recipe group(P＜0.01).Compared with the control group,collagen fibers in the Sanjie Quban recipe group were looser and less numerous,and fibroblasts were decreased in number.The expression of TGF-β1 in the Sanjie Quban recipe group was decreased compared with that of the control group(P＜0.01).Conclusions Sanjie Quban recipe has certain therapeutic effects on keloids.The mechanism may involve reducing the expression of TGF-βl in keloid tissue and thereby reducing the proliferation of fibroblasts and the synthesis of extracellular matrix.This study provides experimental and theoretical bases for the clinical treatment of keloids with Chinese medicine.

At present， major depressive disorder （MDD） is highly prevalent with advanced neurological disorders as the main pathological manifestations. As the physiological function bearer of higher neural activity， gray matter has become the focus of MDD treatment. However， recent research has shown that white matter and gray matter are independent of each other in the central nervous system （CNS）， and their functions are integrated and linked. In addition to gray matter damage， white matter damage is also the core driving event of disease progression and determines the outcome of MDD. At the treatment level， the current drug treatment of MDD mainly focuses on gray matter repair， while ignoring the importance of white matter integrity for the treatment of the disease， which has become the weakness of the current treatment of MDD. Traditional Chinese medicine （TCM） has good application potential in white matter repair. This paper elaborated on the following three aspects. ① The roles of white matter damage in the occurrence and development of MDD were summarized. ② The key link of white matter repair in MDD was elaborated with microglia microenvironment regulation as the entry point. ③ The application value of TCM in white matter repair in MDD was analyzed. This review aims to highlight the importance of white matter integrity in the treatment of MDD and is expected to expand the understanding dimension of the activity of related Chinese medicines in MDD from the perspective of white matter repair and analyze its potential application value.

Acute ischemic stroke is a cerebrovascular disease with high incidence， high mortality and disability， and high recurrence rate， which seriously endangers patients’ health. Thrombolytic drugs play a key role in the treatment of acute ischemic stroke by activating plasminogen， rapidly dissolving thrombi， reducing platelet aggregation， and achieving successful recanalization. In this study， we reviewed the principle of action of thrombolytic drugs， their classification and use on the basis of current research progress at home and abroad. The results show that the safety and efficacy of thrombolytic drugs have improved significantly from the first generation of thrombolytic drugs， streptokinase， which is not fibrin-specific， to the third generation of thrombolytic drugs， tenecteplase， which not only retain the characteristics of directly activating plasminogen， but also enhance the specificity of fibrin and prolong the half-life. With the development of research， small-molecular compounds with the inhibition of plasminogen activator， or the modification of thrombolytic drugs with strong anti-plasminogen activator inhibition activity in vivo， or the search for new small-molecular substances with thrombolytic effect from microorganisms and natural plants， have become the focus of research on new thrombolytic drugs. The new thrombolytic drugs are likely to replace the current thrombolytic drugs because of greater thrombolytic efficacy and fewer side effects.

ObjectiveTo explore the distribution of traditional Chinese medicine （TCM） syndromes of alopecia areata （AA）， and to provide reference for TCM clinical syndrome differentiation and classification of AA. MethodsAA patients who visited the specialized hairiness clinic of Beijing China-Japan Friendship Hospital were included. A questionnaire was developed including general information of the patients， history of hair loss （onset time， triggers and exacerbating factors， disease progression）， current symptoms （symptoms and signs）， medical history， personal history， family history， and hair microscopy examination results. The factor analysis and cluster analysis were used to determine the syndrome elements and to summarize the syndrome types. ResultsA total of 600 patients with AA were included， including 218 males （36.33%） and 382 females （63.67%）. Totally， 128 patients （21.33%） had a family history of hair loss， and 326 patients （54.33%） had a previous related underlying disease. The leading triggering and exacerbating factors of AA were tension and anxiety， accounting for 335 cases （55.83%） and 285 cases （47.50%）， respectively. The top 10 symptoms involved among patients were scalp oil， anxiety， irritability， dreaminess， fatigue， itching， tension， weakness and dandruff. The factor analysis showed that the factor rotation converged after 9 iterations， and finally obtained 12 common factors and 34 variables， with a cumulative contribution rate of 58.59%. In terms of disease location of AA， the main syndrome elements were liver， spleen and kidney， and the disease nature syndrome elements were mainly dampness-heat， qi stagnation， yin deficiency， qi deficiency， and blood deficiency. The clustering analysis of the 12 common factors showed that TCM syndromes could be summarized into four categories： internal retention of damp-heat， liver-kidney deficiency， qi and blood deficiency， and liver constraint and spleen deficiency. There were significant differences in the distribution of TCM syndromes in patients of different ages and genders （P＜0.001）. ConclusionThe main disease location of AA is in the liver， spleen， and kidney， with the liver being the key. The disease mechanism of AA is a deficiency-excess complex， initially manifested as excess and later becoming deficiency. The TCM syndromes mainly include four types which are internal retention of damp-heat， liver-kidney deficiency， qi and blood deficiency， and liver constraint and spleen deficiency.