Efficacy of Getong Tongluo Capsule () for Convalescent-Phase of Ischemic Stroke and Primary Hypertension: A Multicenter, Randomized, Double-Blind, Controlled Trial.

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION: GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

Fasting Plasma Glucose and Coronary Heart Disease in a Rural Population of North Henan, China.

Even in individuals without diabetes, the incidence of coronary heart disease (CHD) increases with the rise in fasting plasma glucose (FPG); however, the threshold of FPG for CHD in rural areas of China is unclear. We retrospectively examined 2,987 people. Coronary angiography records were used to determine the presence of CHD as well as its severity. Risk factors for CHD and the relationship between different levels of FPG and CHD were analyzed. After adjusting for age, hypertension, dyslipidemia, smoking, drinking, chronic kidney disease, and previous ischemic stroke, the incidence of CHD in nondiabetic women began to increase when FPG exceeded 5.2 mmol/L (odds ratio (OR) = 1.438, 95% confidence interval (CI) = 1.099-1.880, p=0.008), and the degree of coronary artery lesions also became more severe (OR = 1.406, 95% CI = 1.107-1.788, p=0.005). However, no such correlations were found in nondiabetic men. In conclusion, among the nondiabetic women in rural areas of northern Henan, both the incidence of CHD and the severity of lesions increased when FPG levels were greater than 5.2 mmol/L, while no significant correlation between FPG and CHD was observed in diabetes-free men.

Two-dimensional nanocoating-enabled orthopedic implants for bimodal therapeutic applications.

As one of the promising orthopedic materials, polyetheretherketone (PEEK) has high chemical durability and similar mechanical properties to the cortical bone; nevertheless, the inherent bioinert nature of PEEK dramatically impedes its broader clinical applications in the management of bone infection. To address this challenge, herein, we developed a multifunctional two-dimensional (2D) nanocoating to assemble graphene oxide (GO) nanosheets, a polydopamine (pDA) nanofilm, and an oligopeptide onto the surface of porous sulfonated PEEK (SPEEK). The resulting multifunctional PEEK implants exhibited enhanced cytocompatibility, alkaline phosphatase activity, and calcium matrix deposition as well as osteogenesis-associated gene expression. Moreover, the animal experiments based on a rabbit femur defect model confirmed that the 2D nanocoating prominently boosted the in vivo osseointegration and bone remodeling. Besides, the GO/pDA hybrid complex anchoring on the SPEEK surface through π-π stacking can generate robust antibacterial phototherapy resulting from the synergetic photothermal/photodynamic therapeutic effects. Accordingly, this work provides a paradigm to empower inert PEEK implants with bi-/multi-modal therapeutic applications, such as against bone infection treatment.

The Chinese herb Fructus Broussonetiae aids learning and memory in chronic cerebral hypoperfusion by reducing proinflammatory microglia activation in rats.

The neuroprotective role of Fructus Broussonetiae in a model of chronic cerebral hypoperfusion with cognitive decline was focused on neural plasticity and microglia/macrophage polarization. Chronic cerebral hypoperfusion was induced by bilateral common carotid artery ligation. Fructus Broussonetiae shortened escape latency and added the number of platform crossings of rats, up-regulated the expression of synaptophysin in the gray matter and increased myelin basic protein expression in the white matter. Further mechanistic experiments were conducted to examine microglia activation and M1/M2 polarization. It was shown that Fructus Broussonetiae reduced the activation of microglia revealed by decreased expression of ionized calcium-binding adapter molecule-1, inhibited M1 polarization of microglia and improved microglial M2 polarization shown by down-regulated the expression of inducible nitric oxide synthase and Fc fragment of IgG receptor IIIa and up-regulated the expression of arginase-1. In conclusion, the Chinese herb Fructus Broussonetiae can improve cognitive function following chronic cerebral hypoperfusion by down-regulating the activation of microglia, inhibiting microglial M1 polarization, and improving neural plasticity.

[Analysis of outcomes of randomized controlled trial on compound Chinese herbal medicine formulas in treatment of vascular cognitive impairment caused by cerebral small vessel].

The purpose of the study is to analyze the outcomes of randomized controlled trial(RCT) of Chinese herbal medicine formula(CHMF) in the treatment of vascular cognitive impairment caused by cerebral small vessel disease(CSVD-VCI), and provide suggestions for future studies in this field. Three English databases, four Chinese databases, and two online registration websites of clinical trials were searched with use of the search strategy established in advance. Relevant RCTs published in recent ten years were screened, and necessary information was extracted to assess the risk of bias and analyze the outcomes of these RCTs. As a result, a total of 10 461 articles were retrieved, of which 8 681 were kept after de-duplication, and 41 RCTs were included after screening, with a generally higher risk of bias. The outcomes of included RCTs were classified into 9 categories, namely, clinical symptom outcomes, neuroimaging outcomes, neuroelectrophysiological outcomes, blood biochemical outcomes, hemorheology outcomes, physical signs, syndrome scores of traditional Chinese medicine(TCM), clinical effective rate, and safety outcomes. Among them, the most frequently reported outcomes of included RCTs were blood biochemical outcomes, and clinical symptom outcomes showed the highest reporting rate. Besides, 9 RCTs reported syndrome scores of TCM as the outcomes and illustrated corresponding evaluation criteria. The analysis showed that the application of RCT outcomes in this field had clinical rationality and limitations, and there were also some deficiencies in the trial design level, namely, no distinction between primary and secondary outcomes, insufficient blind methods, not detailed description of outcomes, disunity of evaluation tools, and despised endpoint outcomes. These limitations and deficiencies were negatively affecting the quality of RCTs of CHMF in the treatment of CSVD-VCI. Therefore, we suggest that future researchers should be well prepared in the top-level design stage, and actively construct the core outcome set of this field, so as to improve the quality of clinical trials.

Huoluo Yinao decoction mitigates cognitive impairments after chronic cerebral hypoperfusion in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Huoluo Yinao decoction (HLYND) has been used to ameliorate cognitive impairment induced by chronic cerebral hypoperfusion in clinical for years. However, the exact mechanisms remain unknown. AIM OF THE STUDY: To investigate the effects and mechanisms underlying HLYND-mediated improvement in cognitive deficits associated with chronic cerebral hypoperfusion. MATERIALS AND METHODS: Thirty-six Sprague-Dawley rats were randomly allocated to three groups: sham, model, and HLYND. Daily administration of HLYND or volume-matched vehicle by gavage was initiated 1 day after bilateral carotid artery stenosis (BCAS) and continued for 42 days. The Morris water maze (MWM) test was used to assess cognitive functions from days 36-42. Via western blot and immunofluorescent staining, restoration of neuronal plasticity and remyelination of white matter were evaluated by analyzing the expression profiles of MAP-2, synaptophysin and MBP. In addition, macrophage/microglial activation was assessed by quantifying changes in Iba1, and macrophage/microglial polarization was assessed by changes in iNOS and CD16 (M1 markers), as well as Arg1 and CD206 (M2 markers). RESULTS: In the MWM test, BCAS rats showed significantly extended escape latency and reduced platform crossing times, while those in the HLYND group had shortened escape latency and increased frequency of platform crossing. In addition, rats in the model group showed decreased levels and abnormal morphological changes of MAP-2, synaptophysin and MBP, whereas HLYND administration reversed these effects. As expected, Iba1 levels were elevated in both the model and HLYND groups but rats in the model group showed increased levels of the M1 markers, iNOS and CD16, and a correspondent decrease in the M2 marker, Arg1. In contrast, in the HLYND group, iNOS and CD16 levels were suppressed, while Arg1 levels were elevated. CONCLUSIONS: Our findings demonstrate that HLYND mitigates cognitive impairment after chronic cerebral hypoperfusion in rats through mechanisms involving increased neuronal plasticity and white matter remyelination, with a subtile modulation of macrophage/microglial polarization toward the M2 phenotype.

Identification and classification of traditional Chinese medicine syndrome types among senior patients with vascular mild cognitive impairment using latent tree analysis.

OBJECTIVE: To treat patients with vascular mild cognitive impairment (VMCI) using traditional Chinese medicine (TCM), it is necessary to classify the patients into TCM syndrome types and to apply different treatments to different types. In this paper, we investigate how to properly carry out the classification for patients with VMCI aged 50 or above using a novel data-driven method known as latent tree analysis (LTA). METHOD: A cross-sectional survey on VMCI was carried out in several regions in Northern China between February 2008 and February 2012 which resulted in a data set that involves 803 patients and 93 symptoms. LTA was performed on the data to reveal symptom co-occurrence patterns, and the patients were partitioned into clusters in multiple ways based on the patterns. The patient clusters were matched up with syndrome types, and population statistics of the clusters are used to quantify the syndrome types and to establish classification rules. RESULTS: Eight syndrome types are identified: Qi deficiency, Qi stagnation, Blood deficiency, Blood stasis, Phlegm-dampness, Fire-heat, Yang deficiency, and Yin deficiency. The prevalence and symptom occurrence characteristics of each syndrome type are determined. Quantitative classification rules are established for determining whether a patient belongs to each of the syndrome types. CONCLUSION: A solution for the TCM syndrome classification problem for patients with VMCI and aged 50 or above is established based on the LTA of unlabeled symptom survey data. The results can be used as a reference in clinic practice to improve the quality of syndrome differentiation and to reduce diagnosis variances across physicians. They can also be used for patient selection in research projects aimed at finding biomarkers for the syndrome types and in randomized control trials aimed at determining the efficacy of TCM treatments of VMCI.

Green and efficient extraction of rutin from tartary buckwheat hull by using natural deep eutectic solvents.

In this study, an efficient extraction technique using a combination of ultrasound and natural deep eutectic solvents (NADESs) was developed. Some basic physical properties, including viscosity, polarity, and solubility, of thirteen NADESs prepared from natural components were investigated systematically. Results show that the solubility of rutin increased in choline chloride- and glycerol-based NADESs by 660-1577times compared to water. NADESs with high rutin extractability can be designed by combining NADESs components. A maximum of 9.5mg/g rutin was extracted from tartary buckwheat hull with extraction efficiencies of 95%. NADESs can be recovered and recycled. In addition, the biocompatibility and biodegradability of the tested NADESs were also evaluated. The results demonstrated that these NADESs were excellent solvents with extremely low toxicities and favorable biodegradabilities. Our findings suggest that NADESs can be used as green solvents for the extraction of bioactive ingredients.

Apoptosis of human pancreatic carcinoma cell-1 cells induced by Yin Chen Hao Decoction.

AIM: To evaluate human pancreatic carcinoma cell line (PANC-1) cells apoptosis and Bcl-2 and Bax expression induced by Yin Chen Hao Decoction (YCHD). METHODS: The cell growth inhibitory rate was determined by MTT assay. Apoptosis of PANC-1 cells before and after treatment with YCHD was determined by TUNEL staining. Expression of the apoptosis-associated genes, Bcl-2 and Bax, was detected by immunohistochemical staining and reverse transcription -PCR. RESULTS: YCHD inhibited the growth of PANC-1 cells. Following treatment with YCHD for 24-96 h, the apoptotic rate of PANC-1 cells increased with time. In addition, the positive rate of Bcl-2 protein expression decreased in a time-dependent manner, whereas the positive rate of Bax protein expression increased in a time-dependent manner. Following treatment of with YCHD for 24-96h, expression of BAX mRNA increased gradually and BCL-2 mRNA reduced gradually with time. CONCLUSION: YCHD induces apoptosis of PANC-1 cells mediated in part via up-regulation of BAX and down-regulation of BCL-2.

Purification, preliminary characterization and in vitro immunomodulatory activity of tiger lily polysaccharide.

A water-soluble polysaccharide (LLPS) from tiger lily was extracted by ultrasonic wave-assisted extraction. The LLPS, which was isolated by alcohol precipitation, was further purified by DEAE Sepharose Fast Flow and Sephadex G-100 chromatography, which resulted in LLPS fractions in LLPS-1, LLPS-2 and LLPS-3, with molecular weights of 350.5, 403.3 and 146.2kDa, respectively. LLPS-1 and LLPS-2 primarily consisted of glucose and mannose in a molar ratio of nearly 1:2 and 1:1, respectively. In contrast, LLPS-3 was primarily composed of arabinose, galactose, glucose and mannose in a molar ratio of nearly 2:2:2:1. LLPS fractions could stimulate the proliferation of macrophages. The in vitro immunomodulatory activity of the fractions was evaluated. The results showed that treatment with 25-400 µg/mL of LLPS fractions could increase phagocytic activity and nitric oxide production of macrophages in a dose-dependent manner.

[Effect of acupuncture on the speech and acoustics level in patients with dysarthria].

OBJECTIVE: To observe the effect of acupuncture combined with speech therapy for dysarthria after stroke or cerebral trauma. METHODS: Sixty-one cases were randomly divided into two groups. The observation group (30 cases) was treated with speech therapy and acupuncture at Lianquan (CV 23), Jinjin (EX-HN 12), Yuye (EX-HN 13), Fengchi (GB 20), Yifeng (TE 17) and Wangu (GB 12) as major acupoints, while the control group (31 cases) was treated with speech therapy only. The changes of speech and acoustics indices were evaluated after 9 weeks treatment. RESULTS: The word articulation and correct rate of text of patients in two groups were both obviously improved after treatment (both P < 0.01). The total effective rate of 96.7% (29/30) in observation group was superior to that of 67.7% (21/31) in control group (P < 0.01). The maximum phonation time (MPT) of patients tested by aeromechanics analyzer were obviously prolonged in observation group (12 cases) and control group (11 cases) (both P < 0.01), and the improvement in observation group was more obvious (P < 0.01). CONCLUSION: Acupuncture combined with speech therapy can improve the effect on language and acoustics level for dysarthria.

Synthesis, characterization, and in vivo targeted imaging of amine-functionalized rare-earth up-converting nanophosphors.

Rare-earth up-converting nanophosphors (UCNPs) have great potential to become a new generation of biological luminescent labels, but their use has been limited by difficulties in obtaining water-soluble UCNPs bearing appropriate functional groups. To address this problem, we report herein a simple and efficient procedure for the preparation of amine-functionalized UCNPs by a modified hydrothermal microemulsion route assisted with 6-aminohexanoic acid. The amine content of the resultant UCNPs has been determined to be (9.5+/-0.8) x 10(-5) mol/g, which not only confers excellent dispersibility in aqueous solution, but also allows further conjugation with targeted molecules such as folic acid (FA) as a ligand. By means of the laser scanning up-conversion luminescence microscopy (LSUCLM) and the in vivo up-conversion luminescence (UCL) imaging under excitation at the CW infrared laser at 980 nm, FA-coupled UCNPs have been demonstrated to be effective in targeting folate-receptor overexpressing HeLa cells in vitro and HeLa tumor in vivo and ex vivo. These results indicated that our UCNPs could be used as whole-body targeted UCL imaging agents.