Exploring the boost of steaming with wine on Ligustri Lucidi Fructus in treating postmenopausal osteoporosis based on superior "multi-component structure" and iron/bone metabolism coregulation.

BACKGROUND: Clinical studies indicated that postmenopausal osteoporosis (PMOP) often accompanied by iron overload risk factor, which exacerbated bone metabolism disorders and accelerated PMOP. Previous research found that multicomponent in Ligustri Lucidi Fructus (FLL) or wine-steamed FLL (WFLL) acted on the common targets of iron overload and PMOP simultaneously, which indicated that FLL and WFLL probably regulated iron/bone metabolism dually. Additionally, WFLL had more superior effect according to the theory of Chinese medicine for thousands of years. PURPOSE: To reveal the "superior multi-component structure (SMCS)" and its molecular mechanisms in parallelly down-regulating iron overload and rescuing bone metabolism by WFLL. DESIGNS AND METHODS: HPLC fingerprinting was established to compare the chemical profiles of FLL and WFLL; Then, the chemical compositions and quality markers of FLL and WFLL were analyzed by UPLC-Orbitrap-MS/MS coupled with OPLS-DA; the dynamic contents of quality markers and the multi-component structure at different wine steaming times (WST) were simultaneously determined by HPLC-DAD. Meanwhile, the dynamic efficacy of FLL at different WST were hunt by systematic zebrafish model. Subsequently, potential mechanism of WFLL in treating PMOP accompanied with iron overload was obtained from network pharmacology (NP) and molecular docking (MD). Finally, zebrafish and ovariectomy rat model were carried out to validate this potential mechanism. RESULTS: HPLC fingerprints similarity of 15 batches in FLL and WFLL were among 0.9-1.0. 126 compositions were identified, including 58 iridoids, 25 terpenes, 30 phenylethanoids, 7 flavonoids and 6 others. 20 quality markers associated with WFLL was revealed, and the ratio of phenylethanols: Iridoids: Triterpenes (P/I/T) was converted from 1: 15: 4.5 to 1: 0.8: 0.9 during steaming (0 - 24 h) calculated by the quantification of 11 quality markers; the bone mineralization and motor performance of zebrafish larvae indicated that the optimum efficacy of WFLL at 12 h (p < 0.05) in which the SMCS of P/I/T was converted to 1: 4: 1.8. NP discovered that BMP-Smad pathway is one of the potential mechanisms of FLL in anti PMOP and then regulated bone formation and iron overload simultaneously. MD revealed that 17 active ingredients and 10 core targets genes could spontaneously bind with appropriate affinity. Rats model verified that FLL and WFLL significantly reversed PMOP, based on the improvement in bone formation indexes (ALP, OPG, OGN), iron metabolism indicators (hepcidin, ferritin), bone microstructure (BMD, BV/TV, Tb. Th, Tb. N); Moreover, WFLL significant enhanced reversal effect in anti-PMOP compared to FLL (p < 0.05). FLL and WFLL increased genes and proteins expression (Hep, BMP-6, p-Smad1/5, Smad4) related to BMP-Smad pathway compared with model group, and WFLL was more superior than FLL (p< 0.05). CONCLUSION: The SMCS of FLL was optimized by wine-steam, WFLL represented a dual effect in downregulating iron overload and promoting bone formation, and the BMP-Smad pathway is one of the potential molecular mechanisms.

Psychological Status and Influencing Factors Among Pregnant Women Undergoing In Vitro Fertilization.

Objective: This retrospective study aimed to observe the psychological status and analyze the influencing factors among pregnant women undergoing in vitro fertilization (IVF). Methods: A total of 456 pregnant women who underwent IVF and were admitted to the Second Hospital of Hebei Medical University from June 2021 to January 2022 were included as research subjects. General data of all subjects, including previous miscarriage history, infertility duration, number of IVF treatments, factors contributing to infertility, endometrial thickness, and embryo quality, were collected. Univariate/multivariate logistic regression analysis was performed to identify the risk factors associated with the psychological status of pregnant women undergoing IVF. Results: In this study, 191 (41.89%) patients were diagnosed with anxiety disorder, and 131 (28.73%) patients were diagnosed with depression. Significant differences were observed between the anxiety group and the non-anxiety group in terms of previous miscarriage history, infertility duration, number of IVF treatments, ovarian factors of infertility, oviduct factors of infertility, uterus factors of infertility, endometrial thickness, and embryo quality (all P < .05). Similarly, significant differences were found between the depression group and the non-depression group in terms of previous miscarriage history, infertility duration, number of IVF treatments, ovarian factors of infertility, oviduct factors of infertility, uterus factors of infertility, endometrial thickness, and embryo quality (all P < .05). Multivariate logistic regression analysis indicated that the number of IVF treatments was an independent risk factor for both anxiety and depression status (all P < .05). Conclusions: Among pregnant women undergoing IVF, psychological states such as anxiety and depression may be associated with the number of IVF treatments, endometrial thickness, and embryo quality.

Pharmacodynamic Material Basis and Potential Mechanism Study of Spatholobi Caulis in Reversing Osteoporosis.

Objective: To elucidate the mechanism of Spatholobi Caulis (SC) in treating osteoporosis (OP) integrated zebrafish model and bioinformatics. Methods: Skeleton staining coupled with image quantification was performed to evaluate the effects of SC on skeleton mineralization area (SSA) and total optical density (TOD). Zebrafish locomotor activity was monitored using the EthoVision XT. Bioactive compounds of SC and their corresponding protein targets were acquired from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Potential therapeutic targets for OP were summarized through retrieving 5 databases, and then, the overlapping genes between SC and OP were acquired. The core genes were selected by CytoHubba. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional analysis of the intersection target genes were carried out by R software. Finally, the molecular docking simulation was manipulated between the ingredients and the hub genes. Results: Compared with the model group, SC significantly increased the SSA and TOD at 10 mg/mL and improved the locomotor activity in a dose-dependent manner (p < 0.001). 33 components of SC were associated with 72 OP-related genes including 10 core genes (MAPK1, VEGFA, MMP9, AKT1, AR, IL6, CALM3, TP53, EGFR, and CAT). Advanced Glycation End Product (AGE) Receptor for AGE (RAGE) signaling pathway was screened out as the principal pathway of SC in anti-OP. The bioactive components (Aloe-emodin, Emodin, Formononetin, Licochalcone A, Luteolin, and Lopac-I-3766) have excellent affinity to core genes (MAPK1, VEGFA, MMP9, AKT1, and IL6). Conclusion: SC had the hierarchical network characteristics of "multicomponents/multitargets/multifunctions/multipathways" in reversing OP, but AGE-RAGE signaling pathway may be the main regulatory mechanism.

Morroniside Protects Human Granulosa Cells against H2O2-Induced Oxidative Damage by Regulating the Nrf2 and MAPK Signaling Pathways.

Morroniside is the main ingredient of Cornus officinalis and has a variety of biological activities including antioxidative effects. Ovarian granulosa cells (GCs) are responsible for regulating the development and atresia of follicles, which are susceptible to oxidative stress. In this study, we determined whether morroniside can inhibit the oxidative stress of GCs induced by hydrogen peroxide (H2O2), leading to improved oocyte quality. The oxidative damage and apoptosis of ovarian GCs cultured in vitro were induced by the addition of H2O2. After pretreatment with morroniside, the levels of ROS, MDA, and 8-OHdG in ovarian GCs were significantly decreased. Morroniside significantly upregulated p-Nrf2 and promoted the nuclear translocation of Nrf2, which transcriptionally activated antioxidant SOD and NQO1. In addition, morroniside significantly regulated the levels of apoptosis-related proteins Bax, Bcl-2, cleaved caspase-9, and cleaved caspase-3 via the p38 and JNK pathways. These results suggest that morroniside can reduce the oxidative damage and apoptosis of ovarian GCs induced by H2O2.

Ethyl Extract of Blaps rynchopetera Fairmaire Ameliorates Experimental Aerobic Vaginitis by Inhibiting Autophagy Activation.

To investigate the therapeutic effects of Blaps rynchopetera Fairmaire (BRF) extracts on the autophagy activation in a rat model of aerobic vaginitis (AV), forty-eight adult female SD rats of the AV model were divided into five groups according to different treatments with the cream matrix, antibiotics (clindamycin phosphate, 20 mg/g), low-concentration extracts (100 mg/g), medium-concentration extracts (200 mg/g), or high-concentration extracts (300 mg/g). Two weeks after treatment, we conducted a series of assays, including measuring the improved Donders score and pH value of vaginal secretions, H&E staining, immunohistochemical (IHC) staining, western blotting, and ELISA, for evaluating the protein expression of autophagy biomarkers Beclin1 and LC3B. In vitro, BRF ethyl extracts had the lowest minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). After administration in AV rats, the improved Donders score, pH value, and vaginal histopathology score of vaginal secretions in the model and low-concentration groups were not statistically different from those in the normal group. In contrast, these indicators improved significantly in other treatment groups, especially in the high-concentration group. Additionally, when compared to the normal group, IHC, western blot, and ELISA revealed no statistically significant difference in the expressions of Beclin1 and LC3B in the model and low-concentration groups, but decreased to varying degrees in the clindamycin, medium-concentration, and high-concentration groups, with no correlation between Beclin1 and LC3B. Medium- and high-concentration BRF ethyl extracts effectively treated AV in rats by inhibiting excessive autophagy activation and could be applied in the clinic future.

Effects of Bushen-Tiaojing-Fang on the pregnancy outcomes of infertile patients with repeated controlled ovarian stimulation.

Bushen-Tiaojing-Fang (BSTJF) is commonly used to treat infertility. This study investigated the effects of BSTJF on the pregnancy outcomes of patients with repeated controlled ovarian stimulation (COS), on mitochondrial function, and on oxidative stress in ovarian granulosa cells (GCs) and follicular fluid (FF). The samples and clinical data of 97 patients, including 35 in the control group, 29 in the placebo group and 33 in the BSTJF group, were collected for this study. The mitochondrial ultrastructure, ATP content, mitochondrial DNA (mtDNA) number, 8-hydroxy-2-deoxyguanosine (8-OHdG), Mn-superoxide dismutase (Mn-SOD), glutathione peroxidase (GSH-Px) activity levels, and mRNA expression levels of Mn-SOD, GSH-Px, and nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) were analyzed. The high-grade embryo (P < 0.001), implantation (P = 0.033), and clinical pregnancy (P = 0.031) rates, as well as the ATP content (P = 0.014), mtDNA number (P = 0.035), GSH-Px activity (P = 0.004 in GCs and P = 0.008 in FF) and mRNA expression levels (P = 0.019), were significantly lower in the placebo group than in the control group, whereas the 8-OHdG content was significantly (P = 0.006 in FF) higher in the placebo group than in the control group. Compared with those in the placebo group, the high-grade embryo rate (P = 0.007), antioxidant enzyme activity (P = 0.037 and 0.036 in Mn-SOD; P = 0.047 and 0.030 in GSH-Px) and mRNA level (P < 0.001 in Nrf2, P = 0.039 in Mn-SOD and P = 0.002 in GSH-Px) were significantly higher in the BSTJF group, as were changes in mitochondrial ultrastructure, ATP (P = 0.040) and mtDNA number (P = 0.013). In conclusion, BSTJF can improve oxidative stress in patients with repeated COS and pregnancy outcomes.

[Acupuncture Treatment Reduces Body Weight Possibly by Down-regulating Insulin and Leptin Resistance, and Up-regulating Soluble Leptin Receptor Level in Prediabetic Patients].

OBJECTIVE: To observe the effect of acupuncture of Feishu (BL 13), Pishu (BL 20), etc. on body weight, blood lipid, leptin (LP) and soluble leptin receptor (sOB-R) levels in prediabetic patients, so as to explore its mechanisms underlying treatment and prevention of prediabetes. METHODS: A total of 100 prediabetic patients were randomly assigned to medication (Metformin) group (n＝35), acupuncture group (n＝35) and simple lifestyle intervention group (n＝30) with random number table method. All the patients of the 3 groups were treated with lifestyle intervention (reasonable diet and moderate physical exercise) and ordered to stop administration of any hypoglycemic drugs during the treatment period. Bilateral Feishu (BL 13), Pishu (BL 20), Weishu (BL 21), Shenshu (BL 23), Zusanli (ST 36) and Sanyinjiao (SP 6) were punctured with filiform needles which were manipulated by lifting, thrusting and twirling repeatedly for about 2 min every 5 min during 30 minutes' needle retaining. The acupuncture treatment was conducted once every other day for 12 weeks. Patients of the medication group were ordered to orally take Metformin tablets (0.5 g/time, twice a day) for continuous 12 weeks. Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), 2 h-postprandial blood glucose (2 h-PBG), fasting blood glucose (FBG), glycosyla-ted hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), fasting insulin (FINS), serum LP and sOB-R levels were measured before and after the treatment. RESULTS: After the treatment, the BMI in the acupuncture group, and BMI, WC and WHR in the medication group were significantly decreased relevant to their own pre-treatment in each group (P<0.05, P<0.01). Following the treatment, the levels of FBG, 2 h-PBG, HbA1C, TC, TG, FINS, HOMA-IR and LP in both acupuncture and medication groups, and FBG in the simple lifestyle intervention group were significantly decreased in comparison with their own pre-treatment in each group (P<0.01, P<0.05), and the levels of FBG, 2 h-PBG, HbA1C, TC and TG, HOMA-IR and LP in both acupuncture and medication groups were all considerably lower than those of the simple lifestyle intervention group (P<0.01，P<0.05). The level of FINS in the medication group was significantly lower than that of the simple lifestyle intervention group (P<0.05). Additionally, following the treatment, serum sOB-R contents in both acupuncture and medication groups were obviously increased compared with their own pre-treatment in each group and also relevant to the simple lifestyle intervention group (P<0.01). No significant changes were found in the simple lifestyle intervention group in all the above-mentioned blood indexes except FBG (P>0.05). CONCLUSION: Acupuncture can induce body weight loss, down-regulate FINS, insulin resistance and LP resistance, and up-regulate sOB-R content in prediabetic patients, displaying a positive role in the treatment of prediabetes.

Cycloastragenol ameliorates experimental heart damage in rats by promoting myocardial autophagy via inhibition of AKT1-RPS6KB1 signaling.

Cycloastragenol, a naturally occurring compound in Astragali Radix, has been demonstrated to possess various pharmacological actions including anti-aging, anti-inflammation, anti-fibrosis, antibacterial, liver and endothelium protection. However, whether cycloastragenol ameliorates heart failure remains unclear. Isoproterenol administration to rats triggered classic cardiac damage, as demonstrated by objective parameters of cardiac dysfunction. The treatment of cycloastragenol improved deranged cardiac parameters in the isoproterenol-induced heart damage model in a dose-dependent manner. At the same time, cycloastragenol markedly ameliorated cardiac histological changes and down-regulated serum levels of various neuroendocrine factors including norepinephrine, aldosterone, brain natriuretic peptide, endothelin 1, angiotensin II and so on. Moreover, the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in rat heart were also inhibited by cycloastragenol. Mechanistically, augmenting autophagy of myocardial cells via the inhibition of AKT1-RPS6KB1 signaling contributed to the improvement of isoproterenol-induced rat heart failure by cycloastragenol. These results suggest that cycloastragenol ameliorates cardiac dysfunction and remodeling through promoting autophagy in myocardial cells and suppressing MMP-2 and MMP-9 expressions, indicating that it could be a drug candidate for patients with congestive heart failure.

Serum proteomic analysis of the anti­arthritic effects of sinomenine on rats with collagen­induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized by inflammatory synovitis, and the subsequent destruction of articular cartilage and bone. Sinomenine is a traditional Chinese medicine, which has been employed as a clinical treatment for RA for several years in China. The present study investigated the anti­arthritic effects of sinomenine on Sprague­Dawley rats with collagen­induced arthritis (CIA). The differentially expressed proteins in serum were measured by proteomic analysis in order to generate a differentially expressed protein network. A total of 320 differentially expressed proteins were detected in the drug­treated group compared with in the control group. In the sinomenine­treated group, 79 differentially expressed proteins were detected compared with in the model group, and among these, 46 proteins were upregulated. Gene ontology analysis revealed that five functions were affected by sinomenine treatment of CIA rats compared with in the model group. In addition, Ingenuity® Pathway Analysis was used to measure enriched signaling pathways, which revealed nuclear factor­κB, histones, heat shock proteins and protein kinase B as core proteins, generating ~60 pair associations in the network. To the best of our knowledge, the present study is the first to perform proteomic analysis in sinomenine­treated CIA rats, and the results revealed that numerous targets were involved in the process. In addition, the present study provided a novel approach and evidence for exploring the biological effects of sinomenine. Therefore, the findings of the present study may provide a novel insight into the anti­RA mechanisms of sinomenine, and may justify further exploration into its function in other relevant diseases.

Sinomenine inhibits the inflammatory responses of human fibroblast-like synoviocytes via the TLR4/MyD88/NF-κB signaling pathway in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder mainly characterized by inflammation of the synovial tissue that can lead to destruction of bone and cartilage. Sinomenine is an alkaloid extracted from the stem of the Chinese medicinal plant Sinomenium acutum. It has been reported that sinomenine has immunosuppressive and anti-inflammatory properties. However, the molecular mechanism underlying the effect of sinominine on IL-1ß-induced human RA fibroblast-like synoviocytes (RAFLS) is poorly understood. Therefore, in this study, we investigated the effect of sinomenine on the expression of inflammatory cytokines in IL-1ß-treated human RAFLS in vitro and the underlying mechanism. RAFLS viability was evaluated using the MTS assay after sinomenine treatment. The levels of inflammatory cytokines were measured with ELISA, RT-PCR and western blot, respectively. The levels of TLR4 and its downstream signaling targets were determined by western blot analysis. We found that sinomenine suppressed not only NO and PGE2 production but also iNOS and COX-2 expression in IL-1ß-induced RAFLS. It also inhibited the expression of TNF-α and IL-6 in IL-1ß-stimulated RAFLS. Furthermore, sinomenine prevented IL-1ß-induced TLR4, MyD88 and p-NF-κB p65 expression. Taken together, these results demonstrated that sinomenine prevented IL-1ß-induced inflammation in human RAFLS at least in part by inhibiting the TLR4/MyD88/NF-κB signaling pathway, suggesting that sinomenine could be a potential agent in the treatment of RA.

Sinomenine decreases MyD88 expression and improves inflammation-induced joint damage progression and symptoms in rat adjuvant-induced arthritis.

Sinomenine (SIN) is the active principle of the Chinese medical plant Sinomenium acutum which is widely used for the treatment of rheumatoid arthritis (RA) in China. Recently, several groups indicated that myeloid differentiation primary response protein 88 (MyD88) might be associated with disease progression of RA. Here, we observed the effect of SIN on MyD88 expression and showed its therapeutic role in RA. First, immunohistochemical staining in clinical specimens showed that MyD88 was mainly located in characteristic pathological structures of RA synovial tissues. Second, we found that MyD88 was overexpressed in the synovial tissues of the rats with adjuvant-induced arthritis (AIA). Treatment with SIN markedly decreased the expression of MyD88 in AIA rats. Finally, we provided evidences that SIN suppressed inflammation response and inflammation-induced joint destructive progression and arthritis symptoms in AIA rats. Therefore, SIN is an effective therapeutic agent for RA. Targeting MyD88 signaling may provide new methods for the treatment of RA.

Safety and efficacy of ethylenediaminetetraacetic acid for removing microcapsules.

BACKGROUND: Microencapsulated islets are used to prevent immune rejection associated with pancreatic islet transplantation, but cellular overgrowth affects transplantation success, necessitating removal of microcapsules prior to retransplantation. This study aimed to investigate the safety and efficacy of ethylendiaminetetraacetic acid (EDTA) for the removal of microcapsules surrounding islet cells. METHODS: Microcapsule dissolution was investigated after in vitro exposure to EDTA for 72 h. Dissolution, blood biochemical markers, and pathologic changes in abdominal organs were observed after intraperitoneal administration of different concentrations of EDTA to rats with abdominally transplanted empty microcapsules. The extent of overgrowth and time to adhesion development were recorded after implantation of microencapsulated islets into the abdominal cavity of diabetic rats. EDTA (0-240 mmol/L) was injected to observe the transplantation effect and ability to dissolve microcapsules. RESULTS: There was a positive correlation between the rate of microcapsule dissolution and EDTA concentration in vitro. Following administration of 60 mmol/L EDTA, the majority of microcapsules within the abdominal cavity were dissolved and the retrieval rate was 2.6%. No adverse effects, abnormal blood biochemical markers, or organ damage were observed in rats 1 mo following intraperitoneal injection with EDTA at doses up to 60 mmol/L. Microcapsule retrieval and blood glucose were significantly higher in cases of grade II cellular overgrowth than in cases of grade 0-I overgrowth. CONCLUSIONS: EDTA (60 mmol/L) dissolved microcapsules in vivo without affecting islet cell viability or secretion capacity, and without affecting blood biochemical markers. Optimal dissolution was achieved with grade 0-I overgrowth after implantation of microencapsulated islets.

[Effect of acupuncture on serum leptin level in patients with type II diabetes mellitus].

OBJECTIVE: To study the relationship between serum leptin and insulin resistance, and to analyze the effect of acupuncture on serum leptin level in patients with type-II diabetes mellitus (DM). METHODS: A total of 80 type-II DM patients were randomized into acupuncture and medication groups. Acupuncture was applied to Yishu (EX), Feishu (BL13), Pishu (BL 20), etc. according to syndrome identification. The treatment was given once every other day for 12 weeks. For patients in the medication group, Glibenclamide (2.5-7.5 mg/time, 1-2 times/d according to blood sugar level) was given for 12 weeks. Fasting blood glucose (FBG), fasting insulin (FINS) and fasting leptin (FLP) were detected by using glucose oxidase method, radioimmunoassay and ELISA, respectively. Insulin sensitivity index (ISI) and homeostasis model assessment-insulin resistance (HOMA-IR) were calculated. RESULTS: In comparison with pre-treatment, FBG levels and HOMA-IR in both acupuncture and medication groups, and FINS and FLP levels in the acupuncture group were decreased significantly (P < 0.01), while ISI in both acupuncture and medication groups, and FINS level in the medication group were increased remarkably after the treatment (P < 0.01). Comparison between two groups showed that after the treatment, FINS and FLP levels, and HOMA-IR of the acupuncture group were considerably lower than those of the medication group (P < 0.01), while ISI of the acupuncture group was significantly higher than that of the medication group (P < 0.01). CONCLUSION: Acupuncture therapy is effective in lowering FLP level, which may contribute to its clinical effect in improving type-II DM.

Meta-analysis of scalp acupuncture for acute hypertensive intracerebral hemorrhage.

OBJECTIVES: Scalp acupuncture (SA) is a commonly used therapeutic approach for primary intracerebral hemorrhage (ICH) in Traditional Chinese Medicine (TCM), but the efficacy and safety of SA therapy are still undetermined. The aim of this study is to systematically evaluate the efficacy and safety of SA therapy for the treatment of acute hypertensive ICH. METHODS: Literature reports with randomized controlled clinical trials and controlled clinical trials on SA therapy for acute hypertensive ICH were searched, and the efficacy and safety of SA therapy were evaluated by using the Cochrane systematic review methods. The primary outcome measures were death or dependency at the end of long-term follow-up (at least 3 months) and adverse events. The secondary outcome measure was neurological deficit improvement at the end of the treatment course. RESULTS: Seven (7) independent trials (230 patients) were included in this study. All trials described the methods of randomization in which four trials had adequate concealment of randomization at the level of grade A, but no trial included sham acupuncture as a control group. None of the trials included "death or dependency" as a primary outcome measure. Four (4) trials contained safety assessments and stated that no adverse event was found, whereas the other three trials did not provide the information about adverse events. By using random effects statistical model, it was found that patients with acute hypertensive ICH who received SA therapy had significantly improved neurological deficit scores (Z = 4.97, p < 0.01). CONCLUSIONS: Although SA therapy is widely used to treat acute hypertensive ICH in TCM, the efficacy and safety of SA therapy remain to be further determined. No evidence is available on whether SA therapy can be used to treat acute ICH according to the primary outcome measure. However, SA therapy appears to be able to improve neurological deficit in patients with acute hypertensive ICH.