ObjectiveTo investigate the effect of Niuhuang Qingxinwan （NHQXW） in improving intracerebral hemorrhage （ICH） with Tanre Fushi （phlegm-heat and fu-organ excess） syndrome by maintaining blood-brain barrier （BBB） integrity， and to explore its potential mechanism. MethodsMale mice were administered with 15% autologous feces for 3 consecutive days to simulate spontaneous Tanre Fushi syndrome， followed by surgical induction of collagenase-induced ICH on the fourth day. Mice were randomly assigned to seven groups： Sham， Sham+NHQXW-H， collagenase， collagenase+feces， and NHQXW intervention groups at low （NHQXW-L， 0.225 g·kg^-1）， medium （NHQXW-M， 0.45 g·kg^-1）， and high （NHQXW-H， 0.9 g·kg^-1） doses. Treatments were administered for 3 days after surgery. NHQXW effects on Tanre Fushi syndrome were assessed via fecal water content and small intestinal carbon propulsion rate. Protective effects of NHQXW against ICH with Tanre Fushi syndrome were evaluated by measuring hematoma volume， neurological deficits， and brain water content. BBB integrity was further assessed using Evans blue staining， hematoxylin-eosin （HE） staining， immunofluorescence， and Western blot for Claudin-5， plasmalemma vesicle-associated protein （PLVAP）， matrix metalloproteinase （MMP）-2， and MMP-9. The potential mechanism of NHQXW was investigated by detecting protein expression of protein kinase B （Akt）， extracellular signal-regulated kinase 1/2 （ERK1/2）， signal transducer and activator of transcription 3 （STAT3）， Yes-associated protein （YAP）， and their phosphorylated forms. ResultsCompared with the collagenase+feces group， NHQXW-M and NHQXW-H significantly reduced fecal water content （P<0.05， P<0.01） and intestinal propulsion rate （P<0.01）， alleviated neurological deficits （P<0.01）， decreased hematoma volume （P<0.01） and Evans blue extravasation （P<0.01）， increased Claudin-5 protein expression （P<0.05， P<0.01） and fluorescence intensity （P<0.01）， and decreased PLVAP protein expression （P<0.01） and fluorescence intensity （P<0.05， P<0.01）， as well as MMP-2 （P<0.05， P<0.01） and MMP-9 （P<0.01） expression. NHQXW-H downregulated p-Akt （P<0.05）， p-ERK1/2 （P<0.05）， p-STAT3 （P<0.01）， and p-YAP （P<0.05）， with the most significant effect observed on STAT3 phosphorylation. ConclusionNHQXW effectively alleviates neurological deficits and BBB injury in ICH mice with Tanre Fushi syndrome， primarily by inhibiting STAT3 activation.

Stroke is a neurological disease characterized by cerebral ischemia or hemorrhagic injury， leading to death and disability worldwide. At present， there is still a lack of neuroprotective drugs for the treatment of stroke. Niuhuang Qingxin pills are Chinese patent medicine recommended by guidelines and expert consensus for preventing and treating stroke. Studies have shown that Niuhuang Qingxin pills have sedative， anticonvulsant， antipyretic， and other pharmacological effects. Moreover， the main components， such as flavonoids， phenolic acids， and saponins， also exhibit strong pharmacological activities which can improve stroke-induced nerve damage. Studies have confirmed that representative ingredients such as baicalin and ginsenosides can interfere with multiple pathological events， including blood-brain barrier destruction， oxidative stress， inflammatory response， apoptosis， and autophagy， and the mechanisms of the essential ingredients are related to the action on important targets such as Kelch-like ECH-associated protein 1 （Keap1）， matrix metalloproteinase-9 （MMP-9）， and high-mobility group box 1 （HMGB1）， and involvement in the regulation of Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB）， nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathways. This article summarized the research status of Niuhuang Qingxin pills and the experimental pharmacological progress of common ingredients in the prevention and treatment of stroke to provide clues for further research into Niuhuang Qingxin pills and the development of active ingredients of traditional Chinese medicines.

As an active hydroxyanthraquinone ingredient, emodin is abundant in Chinese medicine herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum.Modern pharmacological studies have shown that emodin has a variety of pharmacological activities including anti-tumor, anti-inflammatory and immunoregulatory, antibacterial and anti-viral effects, myocardial protection, neuroprotection, renal protection, bone protection, antifibrosis and so on, which indicate its high medicinal value and broad application prospects.This article aims to summarize the progress in the pharmacological activity and mechanism of action of emodin published in domestic and international journals over the last 5 years and highlight the potential targets and molecular signaling pathways linked with emodin, so as to provide some clues and references for further development and clinical application of emodin.

[This corrects the article DOI: 10.1016/j.apsb.2021.09.017.].

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By in vivo and in vitro experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression in vivo and in vitro abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.

Objective To explore the clinical characteristics and correlation of adult primary nephrotic syndrome (PNS) with thyroid dysfunction,and early identify high-risk adult PNS patients with abnormal thyroid function by clinical data.Methods The clinical data of 101 adult PNS patients in Heji Hospital Affiliated to Changzhi Medical College from March 2015 to December 2017 were retrospectively analyzed.According to the thyroid function,the patients were divided into 2 groups:normal thyroid function group (67 cases) and thyroid dysfunction group (34 cases),including 9 cases with low triiodothyronine (T3) syndrome and 25 cases with subclinical hypothyroidism.The clinical data were compared,and the correlation between thyroid-stimulating hormone (TSH) and 24 h urinary protein,blood albumin and systolic blood pressure were analyzed.Results The incidence of thyroid dysfunction in adult PNS patients was 33.66％ (34/101),including 21 cases of membranous nephropathy,8 cases of minimal change disease,4 cases of IgA nephropathy and 1 case of membranoproliferative nephritis.The 24 h urinary protein in thyroid dysfunction group was significantly higher than that in normal thyroid function group:(8.76 ± 3.62) g vs.(6.96 ± 3.43) g,the albumin was significantly lower than that in normal thyroid function group:(21.82 ± 4.89) g/L vs.(24.49 ± 4.14) g/L,and there were statistical differences (P＜0.05 or ＜0.01);there was no significant difference in gender composition,age,course of disease,systolic blood pressure,diastolic blood pressure,body mass index,hemoglobin,platelet,creatinine,cystatin C,fasting blood glucose,total cholesterol,triacylglycerol,low-density lipoprotein cholesterol (LDL-C),fibrinogen,complement C3,IgG,IgM,IgA,PNS types and comorbidities between 2 groups (P＞0.05).The results of subgroup analysis results showed that the systolic blood pressure in subclinical hypothyroidism patients of thyroid dysfunction group was significantly higher than that in normal thyroid function group and the low T3 syndrome patients of thyroid dysfunction group:(148.16 ± 18.09) mmHg (1 mmHg =0.133 kPa) vs.(139.55 ± 18.77) and (127.78 ± 16.81) mmHg,the 24 h urinary protein was significantly higher than that in normal thyroid function group:(9.00 ± 3.64) g vs.(6.96 ± 3.43) g,the albumin was significantly lower than that in normal thyroid function group:(21.71 ± 5.26) g/L vs.(24.49 ± 4.14) g/L,and there were statistical differences (P＜0.05).Pearson correlation analysis result showed that TSH had no correlation with 24 h urinary protein and systolic blood pressure (r =0.193 and 0.072,P =0.053 and 0.472);however TSH was negatively correlated with albumin (r =-0.340,P =0.001).Conelusions In adult PNS patients with thyroid dysfunction,membranous nephropathy is the most common,followed by minimal change disease.The systolic blood pressure in PNS patients with subclinical hypothyroidism is significantly higher than that in patients with normal thyroid function and low T3 syndrome.In adult PNS patients,the lower the blood albumin is,the more likely they have thyroid dysfunction.