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Two yeast strains, NYNU 236122 and NYNU 236180, were isolated from plant leaves collected in Tianchi Mountain, Henan Province, central China. Molecular phylogenetic analyses revealed the closest relatives of the strains are three described Kondoa species, Kondoa chamaenerii , Kondoa miscanthi , and Kondoa subrosea . Genetically, the isolated strains differed from the type strains of their three related species by 2-11(0.2-1.8%) base substitutions in the D1/D2 domain, 16-40 (2.6-5.6%) base mismatches in the internal transcribed spacer region, and more than 10.1% base substitutions in the partial RPB2 gene. Furthermore, the two strains differ physiologically from their closest related species, K. chamaenerii , in their ability to assimilate dl-lactate, nitrite, and l-lysine and their inability to assimilate nitrate. Additionally, they differ from K. miscanthi and K. subrosea in their ability to assimilate inulin, d-gluconate, and l-lysine. The species name of Kondoa tianchiensis f.a., sp. nov. is proposed with holotype CICC 33616 T (Mycobank MB 853544).

Two yeast strains were isolated from rotting wood samples collected on Qingyuan Mountain, Fujian Province, PR China. Phylogenetic analysis, based on the concatenated sequences of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit rRNA gene, revealed that these two strains represent a novel species of the genus Cyberlindnera . The proposed name for this new species is Cyberlindnera qingyuanensis f.a., sp. nov. (holotype: GDMCC 2.300; ex-type: PYCC 9925) although the formation of ascospores was not observed. The novel species differs from its close relative Cyberlindnera galapagoensis by 7.7% sequence divergence (37 substitutions and seven indels) in the D1/D2 domain and 9.7% sequence divergence (42 substitutions and 34 indels) in the ITS region, respectively. Additionally, Cyb. qingyuanensis differs from its close relative Cyb. galapagoensis by its ability to grow in cellobiose, l-rhamnose, ribitol, galactitol, and dl-lactate, its growth at 37 °C, and its inability to ferment raffinose. The Mycobank number is MB 854693.

To investigate the effect and safety of percutaneous endovascular angioplasty (PEA) with optional stenting for the treatment of severe stenosis or occlusion of subclavian artery, patients with severe stenosis ≥ 70% or occlusion of subclavian artery treated with PEA were retrospectively enrolled. The clinical data were analyzed. A total of 222 patients were retrospectively enrolled, including 151 males (68.0%) and 71 females (32.0%) aged 48-86 (mean 63.9 ± 9.0) years. Forty-seven (21.2%) patients had comorbidities. Subclavian artery stenosis ≥ 70% was present in 201 (90.5%) patients and complete subclavian occlusion in 21 (9.5%) cases. Angioplasty was successfully performed in all (100%) patients. Balloon-expandable stents were used in 190 (85.6%) cases, and self-expandable stents in 20 (9.0%) cases. Only 12 (5.4%) cases were treated with balloon dilation only. Among 210 patients treated with stent angioplasty, 71 (33.8% or 71/210) cases underwent balloon pre-dilation, 139 (66.2% or 139/210) had direct deployment of balloon-expandable stents, and 2 (1.0% or 2/210) experienced balloon post-dilation. Distal embolization protection devices were used in 5 (2.3% or 5/222) cases. Periprocedural complications occurred in 3 (1.4%) patients, including aortic dissection in 2 (0.9%) cases and right middle cerebral artery embolism in 1 (0.5%). No hemorrhage occurred. Among 182 (82.0%) patients with 6-month follow-up, restenosis > 70% occurred in 1 (0.5%) patient, and among 68 (30.6%) patients with 12-month follow-up, restenosis > 70% took place in 11 (16.2%) patients. Percutaneous endovascular angioplasty can be safely and efficiently performed for the treatment of severe stenosis ≥ 70% or occlusion of subclavian artery., (© 2024. The Author(s).)

To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion., (© 2024. The Author(s).)

Objective: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients., Methods: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation., Results: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group., Conclusions: Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299)., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to examine the role played by the physical literacy and mindfulness in the health-related quality of life (QoL) of college students. In early 2022, 24,236 college students from three universities in southern China were recruited in the study. R software and the lavvan package was utilized to build the structural equation model. The measurement model was composed of three latent factors (physical literacy, mindfulness, and quality of life) and 16 observed variables in total. The results of the measurement model indicated goodness fit with p > .05 in Chi-square result, and GFI = .92. In addition, the comparative fit index (.92), Tucker-Lewis index (.91), root-mean-square error of approximation (.07), and root of mean square residual (.11) were in accord with the cutoff model-fit criteria. The results confirm that physical literacy and mindfulness can play a significant and positive role in the structural equation model of quality of life. In addition, this study provides initial evidence that mindfulness and physical literacy could potentially buffer declines in student QoL during the COVID-19 pandemic. Moreover, this study is the first to develop a structural equation model of QoL with multiple indicators, making it a strong addition to existing research on QoL during a pandemic., (© 2024. The Author(s).)

Purpose: This study aims to investigate the effect and feasibility of intra-aortic catheter looping via transradial access in angioplasty for symptomatic intracranial severe (>70%) atherosclerotic stenosis or occlusion of large arteries (SISOLAs)., Materials and Methods: Patients with SISOLAs who underwent transradial endovascular angioplasty using the catheter looping technique in the ascending aorta were retrospectively enrolled. The clinical data and treatment outcomes were analyzed., Results: Fifteen patients aged 48-71 years were enrolled in this study. Left vertebrobasilar artery occlusion was present in 1 (6.7%) patient, severe left middle cerebral artery stenosis in 7 (46.7%) patients, severe left internal carotid artery (ICA) stenosis of the ophthalmic segment in 4 (26.7%) patients, severe left ICA stenosis of the cavernous segment in 2 (13.3%) patients, and severe right middle cerebral artery stenosis in 2 (13.3%) patients. The arterial stenosis ranged from 70 to 92% (mean 86%) before stenting. The looping of a guiding catheter in the ascending aorta via transradial access for angioplasty was successful in all patients (100%). The vertebral artery intracranial segment occlusion was successfully recanalized, while severe stenosis in the remaining 14 patients was successfully eliminated. After endovascular recanalization, the residual stenosis was reduced by 12-26% (median 18%). No puncture-related complications or surgical-related neurological complications occurred in these patients. In the follow-up angiography conducted on 10 (66.7%) patients after 6-25 months, no in-stent restenosis was detected., Conclusion: Intra-aortic guiding catheter looping via transradial access for endovascular angioplasty of SISOLAs is technically safe, feasible, and effective, especially when the transfemoral artery approach is difficult or impossible to undertake., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Xia, Cai, Yang, Zhao, Xue, Wang, Li and Gao.)

Asthma is a common chronic respiratory disease, which causes inflammation and airway stenosis, leading to dyspnea, wheezing and chest tightness. Using transgelin-2 as a target, we virtually screened the lead compound glycyrrhizin from the self-built database of anti-asthma compounds by molecular docking technology, and found that it had anti-inflammatory, anti-oxidative and anti-asthma pharmacological effects. Then, molecular dynamics simulations were used to confirm the stability of the glycyrrhizin-transgelin-2 complex from a dynamic perspective, and the hydrophilic domains of glycyrrhizin was found to have the effect of targeting transgelin-2. Due to the self-assembly properties of glycyrrhizin, we explored the formation process and mechanism of the self-assembly system using self-assembly simulations, and found that hydrogen bonding and hydrophobic interactions were the main driving forces. Because of the synergistic effect of glycyrrhizin and salbutamol in improving asthma, we revealed the mechanism through simulation, and believed that salbutamol adhered to the surface of the glycyrrhizin nano-drug delivery system through hydrogen bonding and hydrophobic interactions, using the targeting effect of the hydrophilic domains of glycyrrhizin to reach the pathological parts and play a synergistic anti-asthmatic role. Finally, we used network pharmacology to predict the molecular mechanisms of glycyrrhizin against asthma, which indicated the direction for its clinical transformation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qi, Xu, Wang, Cai, Wang and Zhou.)

Purpose: The study aimed to investigate the feasibility and effect of transradial access with intra-aortic catheter looping for the treatment of intracranial aneurysms., Materials and Methods: This retrospective one-center study was performed on patients with intracranial aneurysms which were embolized through transradial access with intra-aortic catheter looping because of the difficulty of transfemoral access or transradial access without intra-aortic catheter looping. The imaging and clinical data were analyzed., Results: A total of 11 patients were enrolled, including seven (63.6%) male patients. Most patients were associated with one or two risk factors of atherosclerosis. There were nine aneurysms in the left internal carotid artery system and two aneurysms in the right internal carotid artery system. All 11 patients had complications with different anatomic variations or vascular diseases, which made endovascular operation via the transfemoral artery difficult or a failure. The right transradial artery approach was adopted in all patients, and the success rate of intra-aortic catheter looping was 100%. Embolization of intracranial aneurysms was successfully completed in all patients. No instability of the guide catheter was encountered. No puncture site complications or surgical-related neurological complications occurred., Conclusion: Transradial access with intra-aortic catheter looping for embolization of intracranial aneurysms is technically feasible, safe, and efficient as an important supplementary approach to the routine transfemoral access or transradial access without intra-aortic catheter looping., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Ba, Cai, Yang, Zhao, Xue, Li and Gao.)

Background: Diabetes has become a serious global public health problem. With the increasing prevalence of type 2 diabetes mellitus (T2DM), the incidence of complications of T2DM is also on the rise. Sitagliptin, as a targeted drug of DPP4, has good therapeutic effect for T2DM. It is well known that sitagliptin can specifically inhibit the activity of DPP4 to promote insulin secretion, inhibit islet β cell apoptosis and reduce blood glucose levels, while other pharmacological mechanisms are still unclear, such as improving insulin resistance, anti-inflammatory, anti-oxidative stress, and anti-fibrosis. The aim of this study was to explore novel targets and potential signaling pathways of sitagliptin for T2DM., Methods: Firstly, network pharmacology was applied to find the novel target most closely related to DPP4. Semi-flexible molecular docking was performed to confirm the binding ability between sitagliptin and the novel target, and molecular dynamics simulation (MD) was carried to verify the stability of the complex formed by sitagliptin and the novel target. Furthermore, surface-plasmon resonance (SPR) was used to explored the affinity and kinetic characteristics of sitagliptin with the novel target. Finally, the molecular mechanism of sitagliptin for T2DM was predicted by the enrichment analysis of GO function and KEGG pathway., Results: In this study, we found the cell surface receptor-angiotensin-converting enzyme 2 (ACE2) most closely related to DPP4. Then, we confirmed that sitagliptin had strong binding ability with ACE2 from a static perspective, and the stability of sitagliptin-ACE2 complex had better stability and longer binding time than BAR708-ACE2 in simulated aqueous solution within 50 ns. Significantly, we have demonstrated a strong affinity between sitagliptin and ACE2 on SPR biosensor, and their kinetic characteristics were "fast binding/fast dissociation". The guiding significance of clinical administration: low dose can reach saturation, but repeated administration was needed. Finally, there was certain relationship between COVID-19 and T2DM, and ACE2/Ang-(1-7)/Mas receptor (MasR) axis may be the important pathway of sitagliptin targeting ACE2 for T2DM., Conclusion: This study used different methods to prove that ACE2 may be another novel target of sitagliptin for T2DM, which extended the application of ACE2 in improving diabetes mellitus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qi, Chen, Cai, Wang, Wei, He and Zhou.)

Periderm protects enlarged organs of most dicots and gymnosperms as a barrier to water loss and disease invasion during their secondary growth. Its development undergoes a complex process with genetically controlled and environmental stress-induced characters. Different development of periderm makes the full and partial russet of fruit skin, which diverges in inheritance with qualitative and quantitative characters, respectively, in pear pome. In addition to its specific genetics, fruit periderm has similar development and structure as that of stem and other organs, making it an appropriate material for periderm research. Recently, progress in histochemical as well as transcriptome and proteome analyses, and quantitative trait locus (QTL) mapping have revealed the regulatory molecular mechanism in the periderm based on the identification of switch genes. In this review, we concentrate on the periderm development, propose the conservation of periderm regulation between fruit and other plant organs based on their morphological and molecular characteristics, and summarize a regulatory network with the elicitors and repressors for the tissue development. Spontaneous programmed-cell death (PCD) or environmental stress produces the original signal that triggers the development of periderm. Spatio-temporal specific PCD produced by PyPPCD1 gene and its homologs can play a key role in the coordinated regulation of cell death related tissue development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Dai, Cai and Shi.)

Mesenchymal stem cells play an important role in tissue damage and repair. This role is mainly due to a paracrine mechanism, and extracellular vesicles (EVs) are an important part of the paracrine function. EVs play a vital role in many aspects of cell homeostasis, physiology, and pathology, and EVs can be used as clinical biomarkers, vaccines, or drug delivery vehicles. A large number of studies have shown that EVs derived from mesenchymal stem cells (MSC-EVs) play an important role in the treatment of various diseases. However, the problems of low production, low retention rate, and poor targeting of MSC-EVs are obstacles to current clinical applications. The engineering transformation of MSC-EVs can make up for those shortcomings, thereby improving treatment efficiency. This review summarizes the latest research progress of MSC-EV direct and indirect engineering transformation from the aspects of improving MSC-EV retention rate, yield, targeting, and MSC-EV visualization research, and proposes some feasible MSC-EV engineering methods of transformation.

Chronic cough is very common in respiratory clinics, and no effective drugs are available. Schisandra chinensis (Turcz.) Baill. ( S. chinensis ), an important traditional Chinese medicine, has been extensively prescribed for patients with a persistent cough. Preliminary research indicated that 95% ethanol extracts (EE) of S. chinensis showed remarkable antitussive activity in guinea pigs exposed to cigarette smoke (CS). To find out the antitussive ingredients of S. chinensis , EE was divided into four fractions according to the polarity: petroleum ether extract (PEE), ethyl acetate extract (ECE), n -butyl alcohol extract, and residue extract. The antitussive, antioxidant, and anti-inflammatory effects of the four fractions were evaluated in a guinea pig model of cough hypersensitivity induced by CS exposure. Eighteen main constituents of the two effective fractions, PEE and ECE, were identified using ultra-high-pressure liquid chromatography electronic spray ion time-of-flight mass spectrometry. The cough inhibition activities of compound 1 , 3 , 9 , 10 , 17 were evaluated on citric acid induced acute cough guinea pigs. The results showed that the antitussive activity of EE was almost all contained in PEE and ECE. The 16 major peaks in PEE were identified as 15 lignans (1-12 and 14-16) and 1 triterpene (compound 13 ), and 3 major peaks (1, 17, and 18) in ECE were also identified as lignans. Three doses of five compounds brought about a significant decrease in number of cough efforts ( P  < .01), and the cough inhibition rates were between 40.9% and 85.1%. Therefore, lignans are the antitussive ingredients of S. chinensis .

Objective: To research the mitochondrial cytochrome c oxidase subunit I (MT-COI) gene methylation levels in patients with occupational chronic benzene poisoning, and to explore effective molec μlar biomarkers in patients with occupational chronic benzene poisoning. Methods: 38 confirmed cases of occupational chronic benzene poisoning were selected in the case group. 46 healthy people who underwent physical in our hospital were selected in the control group. Pyrosequencing was used to detect the methylation sites of methylation sites, flow cytometry was used to detect peripheral blood cell count levels, and non-parametric statistical methods were used to analyze the differences in detection results between the two groups. Results: The methylation level of mitochondrial MT-COI site 1 (2.21±0.81) % in the case group was less than that in the control group, and the difference was statistically significant ( P <0.05) . The methylation level of mitochondrial MT-COI site 2 (2.31±0.96%) in the case group was less than that in the control group, and the difference was statistically significant ( P <0.05) . The methylation average level of mitochondrial MT-COI (2.26±0.75) % in the case group was less than that in the control group, and the difference was statistically significant ( P <0.05) . Analysis of the average level of methylation found that the methylation level of mitochondrial MT-COI was correlated with WBC ( P <0.05) . Analysis of the average level of methylation found that the methylation level of mitochondrial MT-COI was correlated with platelets ( r =0.254、0.280, P <0.05) . Conclusion: The level of mitochondrial MT-COI gene methylation in patients with occupational chronic benzene poisoning may be related to the sensitivity to benzene exposure. Mitochondrial MT-COI gene methylation may serve as a potential predictive biomarker for benzene poisoning.

Objective: To observe the clinical effect of priligy (dapoxetine hydrochloride) combined with behavioral therapy and psychological counseling in the treatment of primary premature ejaculation (PPE)., Methods: A total of 202 PPE patients diagnosed from 2017 to 2018 were randomized into a control (n = 100) and an experimental group (n = 102), the former treated with oral priligy at 30 mg 1－3 hours before anticipated sexual activity, and the latter by the same medication combined with 30-minute behavioral therapy and psychological counseling once a month for two times. The therapeutic effects were evaluated according to the Premature Ejaculation Profile (PEP) scores of the patients at 1 and 2 months of treatment., Results: After 1 month of treatment, both groups of the patients showed significant improvement, as compared with the baseline, in the PEP scores on personal distress related to ejaculation (P < 0 05), interpersonal difficulty related to ejaculation (P < 0.05) and satisfaction with sexual intercourse (P < 0.05) but not on perceived control over ejaculation (P > 0.05). At 2 months, however, the patients' scores on all the four PEP items were dramatically improved, even more significantly in the experimental than in the control group, as on perceived control over ejaculation (2.73 ± 0.95 vs 2.22 ± 0.68, P < 0.05), personal distress related to ejaculation (2.97 ± 1.07 vs 2.57 ± 0.69, P < 0.05), interpersonal difficulty related to ejaculation (3.19 ± 1.03 vs 2.77 ± 0.69, P < 0 05) and satisfaction with sexual intercourse (2.85 ± 0.99 vs 2.35 ± 0.63, P < 0.05). There was no statistically significant difference in the incidence rate of adverse events between the experimental and control groups (21.6% vs 20.0%, P > 0.05), and all the symptoms were relieved within 24 hours., Conclusions: Priligy combined with behavioral therapy and psychological counseling is more effective than priligy alone in improving the sexual function of PPE patients, raise their interest in sexual life and increase the intimacy between the partners, and can even achieve clinical cure in some patients.

Objective: This study aims to explore the role of GNAS in accelerating the progression of osteoporosis by inhibiting osteogenesis of BMSCs by the Wnt pathway., Patients and Methods: GNAS levels in OP tissues and BMSCs undergoing osteogenesis for different time points were detected. Regulatory effects of GNAS on osteogenesis-related gene expressions, ALP activity, capability of mineralization, and activation of the Wnt pathway in BMSCs were assessed through a series of functional experiments. At last, rescue experiments were performed to further verify the significance of the Wnt pathway during GNAS-mediated osteogenesis development., Results: GNAS was downregulated in OP tissues relative to normal bone tissues. With the prolongation of osteogenesis, GNAS level gradually increased in BMSCs. Knockdown of GNAS downregulated expression levels of ALP and RUNX2, and attenuated ALP activity and capability of mineralization in BMSCs. GNAS was able to activate the Wnt pathway in BMSCs. Notably, overexpression of Wnt3a could reverse the regulatory effects of GNAS on osteogenesis-related gene expressions, ALP activity, and capability of mineralization in BMSCs., Conclusions: Downregulation of GNAS suppresses osteogenesis of BMSCs through the Wnt pathway, thus aggravating the progression of osteoporosis.

The dual expression of CD5 and MYC protein (DECM) on B-lymphocytes may arise at a specific stage of de novo diffuse large B-cell lymphoma (DLBCL). This study retrospectively reviewed 210 patients with de novo DLBCL at the Affiliated Hospital of Jiangnan University between 2006 and 2017. DECM was significantly correlated with a worse prognosis than that in either the CD5 + or MYC + or CD5 - MYC - patients. Furthermore, patients with DECM showed a similar outcome to MYC + BCL2 + lymphoma patients who have extremely poor survival rates. Multivariate analysis demonstrated that DECM was a significant independent predictor for overall survival (P < .0001) and progression-free survival (P < .0001) in DLBCL. DLBCL patients with DECM showed significantly inferior clinical outcomes compared to the CD5 + , MYC + or CD5 - MYC - patients. Combinational therapeutic modalities might be a candidate approach to improve the prognosis of these patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

To establish and validate the design space of the Digeda-4 flavored decoction( DGD-4D) extraction process by using the quality by design( Qb D) concept. With DGD-4D decoction pieces as a model drug,with the transfer rate of aesculin,picroside I,picroside Ⅱ,geniposide and the yield of extract as critical quality attributes( CQAs),the single factor experiment design was used to determine the level of each factor; the Plackett-Burman experiment design was used to select the critical process parameters( CPPs);and the Box-Behnken experiment design was used to optimize the extraction process. The design space of the DGD-4D extraction process was established,and finally,four experimental points were selected to verify the established model. The single factor experiment determined the levels of each factor,including soaking time 60 min and 30 min,water adding volume 12 times and 8 times,extraction time 90 min and 30 min,number of extraction times 3 times and 1 time,as well as extraction temperature 100 ℃ and 90 ℃.By Plackett-Burman experimental design,the DGD-4D water addition,extraction time and number of extraction times were determined to be CPPs. The Box-Behnken experimental variance analysis showed that P of the regression model was less than 0. 01 and the misstated value was more than 0. 01,indicating that the model had good predictive ability,and the operation space of CPPs in the DGD-4D extraction process was determined as follows: the amount of water addition was 10-12 times; extraction time 50-80 min; and number of extraction times was 3 times. The design space of DGD-4D extraction process based on the concept of Qb D is conducive to improving the stability of product quality and laying a foundation for the future development of DGD-4D.

Objective: To investigate effects of using a large-sized coil first on embolizing cerebral aneurysms compared with conventional coils., Materials and Methods: Forty-six patients with 51 saccular intracranial aneurysms who underwent embolization with a large-sized coil first were enrolled as the large-sized coil group. There were 33 female and 13 male patients with a mean age of 56.9 ± 8.8 years. The treatment modality was coiling alone in 30 aneurysms and stent-assisted coiling in 21. Meanwhile, 50 patients with 53 intracranial aneurysms who were treated with conventional-sized coils were selected as the control conventional-sized coil group, including 36 female and 14 male patients with a mean age of 54.6 ± 5.8 years. The treatment modality was coiling alone in 29 aneurysms and stent-assisted coiling in 24 aneurysms. The occlusion rate, percent packing volume, total coil number and length, and follow-up occlusion rate were compared between the 2 groups., Results: Significantly (P < 0.001) decreased percent packing volume (19.54% ± 6.44% vs. 27.39% ± 5.68%), decreased coil number (2.98 ± 1.09 vs. 6.38 ± 1.65), and length (26.20 ± 26.57 vs. 44.35 ± 35.88 cm) were achieved in the large versus the conventional coil group. At angiographic follow-up of 8 months, only 1 aneurysm (2.2%) recurred in the large coil group compared with 5 aneurysms recurrent (11.1%) in the conventional coil group., Conclusions: The use of a large-sized coil as the first one for embolizing cerebral aneurysms may be a better embolization strategy because it achieves similar initial occlusion rates, decreased packing density, decreased coil numbers and lengths, and reduced recurrence prevalence at follow-up., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Liver function is routinely assessed in clinical practice as liver function tests provide sensitive indicators of hepatocellular injury. However, the prognostic value of enzymes that indicate hepatic injury has never been systematically investigated in lymphoma, including diffuse large B-cell lymphoma (DLBCL)., Methods: This study examined the prognostic value of baseline aspartic transaminase (AST) in DLBCL patients. The association between AST and clinical features was analyzed in 179 DLBCL patients treated from 2006 to 2016. All enrolled patients were treated with R-CHOP or R-CHOP-like chemotherapy. Log-rank test, univariable analysis, and subgroup analysis were performed to evaluate the impact of AST on survival., Results: AST 33.3 U/L was considered to be the optimal threshold value for predicting prognosis. A higher AST level was associated with advanced stage (P = 0.001), poorer performance status (P = 0.014), elevated lactate dehydrogenase level (P <  0.0001), presence of B symptoms (P = 0.001), high-risk International Prognostic Index (IPI, IPI 3-5) (P = 0.002), non-germinal center B-cell subtypes (P = 0.038), hepatitis B virus surface antigen positivity (P = 0.045) and more extra nodal involvement (ENI, ENI ≥ 2) (P = 0.027). Patients with a higher AST level had a shorter overall survival (OS) (2-year OS rate, 53.6% vs. 83.6%, P <  0.001). Subgroup analysis indicated that higher AST levels have poorer prognostic values in patients without B symptoms and LDH positive groups., Conclusion: A pretreatment AST level is associated with OS in DLBCL patients treated with R-CHOP or similar chemotherapy regimens. A high pretreatment AST level might be a reliable prognostic factor for predicting a dismal outcome in DLBCL patients. Serum AST levels may be investigated for use as an easily determinable, inexpensive biomarker for risk assessment in patients with DLBCL.

Purpose: The effects and complications of hybrid procedure (combined carotid endarterectomy and carotid stenting) to revascularize chronic long-segment occlusion of internal carotid artery (ICA) are currently unknown and the purpose of this study., Methods: Sixty-five patients with long-segment occlusion of ICA were prospectively enrolled and divided into two groups of revascularization with hybrid operation (n = 30) and medication group (n = 35), and clinical and angiographic data were analyzed., Results: The duration from symptom onset to revascularization ranged 17-120 days (mean 40.5 ± 5.0) in the hybrid operation, with a success revascularization rate of 100%. All patients had thrombi extracted with the clot length ranging 5-8 cm (mean 6.3 ± 0.9). The thrombolysis in cerebral infarction grade (TICI) was significantly (P < 0.0001) greater immediately after (median 2,) than before recanalization (0). Periprocedural complications included recurrent laryngeal nerve injury in one patient and intracranial hemorrhage in another (6.7%), but no severe neurological deficits occurred. The symptoms were significantly (P < 0.0001) improved after compared with before operation, with the modified Rankin score of 2.5 ± 0.6 at 3 months postoperation which was significantly (P < 0.0001) improved compared with before revascularization (3.4 ± 0.6). Follow-up angiography revealed patent ICA in all patients with hybrid operation. In the medication alone group, no significant (P > 0.05) improvement was observed with the mRS score of 3.5 ± 0.8 at admission and 3.4 ± 0.7 at 3 months, which was significantly (P < 0.001) greater than in the hybrid operation., Conclusion: Hybrid operation may be safe and effective in revascularizing long-segment occlusion of internal carotid artery for prevention of further ischemic events.

Objective: To investigate the safety and long-term effect of using the Wingspan stent for severe symptomatic atherosclerotic basilar artery stenosis (≥70%)., Materials and Methods: Between July 2007 and April 2013, we had 91 consecutive patients (age range 41-82 years old) with symptomatic severe basilar stenosis (70-99%) who underwent Wingspan stenting at our center. All patients had stenosis-related temporary ischemic attack or strokes. We analyzed the demographic data, pre- and post-procedural cerebral angiography, technical success rate, peri-procedural complications, and clinical and imaging follow-ups., Results: The Wingspan stenting procedure was successful in all patients: The stenosis was reduced from 82.2% ± 5.8% pre-stenting to 15.9% ± 5.7% post-stenting. The 30-day peri-operative rate for stroke or death was 14.3%, which included ischemic stroke in 12 cases (12/91 = 13.2%) and subarachnoid hemorrhage in one case (1/91 = 1.1%), with a fatal or disabling stroke rate of 2.2%. Among the 77 patients with clinical follow-up assessment within 7-60 months (mean 31.3 ± 15.1 months) after stenting, four patients (5.2%) had posterior ischemia, including one patient with disabling ischemic stroke (1.3%) and three patients (3.9%) with temporary ischemic attack. The 2-year cumulative stroke rate was 16% (95% CI: 8.2-23.8%). Among 46 patients with imaging assessments at 3-45 months (mean, 9.5 ± 8.3) post-stenting, six (13.0%) patients had restenosis, including two (2/46 = 4.3%) with symptomatic restenosis., Conclusions: The benefit of stenting for patients with severe basilar artery stenosis (> 70%) may lie in lowering the long-term fatal and disabling stroke rate; and as long as the peri-operative stroke rate can be kept at a relatively lower level, patients with severe basilar stenosis can benefit from basilar artery stenting., (© The Author(s) 2016.)

Objective: To develop a new model of vascular dementia for evaluating Chinese medicine prescriptions., Methods: Eighty-eight male Wistar rats were randomly divided into 4 groups. At d 00 , d 42 , d 70 , d 98 (n i =20, 20, 24, 24) during fatty-feeding, rats in each group were further divided into 10 or 12 subgroups (n i =2), respectively. Lacunar stroke were replicated with the injection of thrombi which coagulated artificially from itself blood. The median lethal doses (LD 50 ) were regressed from accumulative mortality in each geometric thrombus doses (k=0.75, 0.5, 0.85, 0.85), respectively. The degree of vascular dementia was evaluated as exploratory, learning and memorizing abilities. The median effective dose of thrombus for replicating rat model was regressed from dementia scores which were derived from the abilities. The linear correlation was regressed between the values of LD 50 or effective dose (ED 50 ) and the durations (days) of hypercholesterolemia. This model of vascular dementia was pathologically confirmed as the neural injuries from lacunar stroke in rats., Results: The hypercholesterolemia was indicated as elevated total cholesterol, triglyeerides low-density lipoprotein cholesterol, and decreased high-density lipoprotein cholesterol. The values of LD5 0 with its 95% confidence intervals (CI) were 1525.0 (1361.0-1709.0), 584.3 (490.1-696.6), 168.7 (163.7-173.8), or 62.4 (59.5-65.4) mg/mL, at d 00 , d 42 , d 70 , and d 98 , respectively. There is a linear regression between the values of LD 50 and the durations of hypercholesterolemia (y=-15.33x+1390.0, r=0.963, P<0.05). The values of ED 50 with its 95% CI were 528.8 (340.5-821.4), 217.0 (20.84-2259.0), 96.3 (23.4-402.6), or 47.0 (43.7-50.6) mg/mL from dementia score, at d 00 , d 42 , d 70 , and d 98 , respectively. There is a linear regression between the values of ED 50 and the durations of hypercholesterolemia (y=-4.992x+484.2, r=0.965, P<0.05). The neural injuries were demonstrated as neural degeneration and necrosis., Conclusions: For evaluating Chinese medicine, a model of vascular dementia in rats is set up with the lacunar stroke from self-thrombosis during hypercholesterolemia. This model from lacunar stroke is useful to investigate the pathogenesis and treatment of vascular dementia.

Purpose: We aimed to investigate the safety and effectiveness of intracranial stenting in a population with severe (≥ 70%) symptomatic intracranial internal carotid artery (ICA) atherosclerotic stenosis., Methods: Fifty-eight patients with severe intracranial ICA atherosclerotic stenosis were prospectively enrolled. The baseline data, cerebral angiography, success rate, perioperative complications, clinical and imaging follow-up were prospectively analyzed., Results: All patients had successful intracranial stenting (100%), and the mean degree of stenosis was improved from 84.3% ± 7.5% to 23.5% ± 5.1% after the stent procedure. During the 30-day perioperative period, only one patient (1.7%) had ischemic stroke. Seven patients (12.1%) had headache and dysphoria. Thirty-six patients (62.1%) had clinical follow-up for 6-68 months after stenting. Five female patients (13.9%) had ipsilateral stroke including one death, but no disabling stroke, while three other patients (8.3%) had ipsilateral temporary ischemic attack (TIA). The recurrent stroke rate was higher in patients presenting with stroke (4/17, 23.5%) than in patients presenting with TIA (1/19, 5.3%), with no statistical significance (P = 0.33). Thirteen patients (22.4%) had imaging follow-up of 5-12 months following stenting, five of whom (38.5%) had in-stent restenosis., Conclusion: Intracranial stenting for patients with intracranial ICA atherosclerotic stenosis has a low perioperative stroke rate and decent outcome on long-term follow-up, despite a relatively high in-stent restenosis rate.

Introduction: This study was to investigate the periprocedural stroke rates, safety, and long-term effect of Wingspan stenting for symptomatic severe stenosis of the middle cerebral artery (MCA) at a high-volume center., Methods: Between July 2007 and April 2013, 196 consecutive patients with severe MCA atherosclerotic stenosis (≥70%) who were treated with Wingspan stenting were retrospectively studied. All patients had arterial stenosis-related temporary ischemic attack or strokes. The demographic data, cerebral angiography, technical success rate, periprocedural complications, and clinical and imaging follow-up were analyzed., Results: The successful stenting rate was 98.0%, and the stenosis rate was improved from pre-stenting (80.6 ± 8.3 %) to post-stenting (15.5 ± 6.8%). The 30-day periprocedural stroke or death rate was 7.1%, with a disabling or fatal rate of 2.6%. The perioprocedural stroke rate was significantly (P < 0.01) greater in the early learning stage (16.0%) than in the later technical maturation stage (4.1%). The total periprocedural ischemic and perforator stroke rates were greater in patients with the most stenosis in the distal MCA 1/3 segment (6.8 and 5.7%, respectively) than in the proximal and middle 2/3 segments (0.9 and 0%, respectively). The ipsilateral stroke or death rate beyond 30 days (6-69 months, mean 30 ± 16) was 4.8%, with the 1- and 2-year cumulative stroke rates of 9.6 and 12.1%, respectively. Imaging follow-up 6-69 months (mean 10.9 ± 8.5) revealed restenosis in 21 cases (20.4 %)., Conclusion: Intracranial stenting of MCA stenoses may have the potential of better clinical outcomes if patients are properly selected and treated by an experienced operator at a high-volume center.

Purpose: To investigate the safety and outcome of intracranial stenting for intracranial atherosclerotic stenosis (IAS)., Materials and Methods: Between July 2007 and April 2013, 433 consecutive patients with IAS > 70% underwent intracranial Wingspan stenting, and the data were prospectively analyzed., Results: Intracranial stenting was successful in 429 patients (99.1%), and the mean stenosis rate was improved from prestenting (82.3 ± 7.6)% to poststenting (16.6 ± 6.6)%. During the 30-day perioperative period, 29 patients (6.7%) developed stroke. The total perioperative stroke rate was significantly (P < 0.01) higher in the basilar artery area than in others, whereas the hemorrhagic stroke rate was significantly (P < 0.05) greater in the middle cerebral artery area than in others. The experience accumulation stage (13%) had a significantly (P < 0.05) higher stroke rate than the technical maturation stage (4.8%). Clinical follow-up 6-69 months poststenting revealed ipsilateral stroke in 20 patients (5.5%). The one- and two-year cumulative stroke rates were 9.5% and 11.5%, respectively; the two-year cumulative stroke rate was significantly (P < 0.05) greater in the experience accumulation stage (18.8%) than in the technical maturation stage (9.1%)., Conclusion: Wingspan stenting for intracranial atherosclerotic stenosis is safe and the long-term stroke rate after stenting is low in a Chinese subpopulation.

Objective: To confirm the anticancer effect of total annonaceous acetogenins (TAAs) abstracted from Annona squamosa Linn. on human hepatocarcinoma., Methods: The inhibitory effect of TAAs was demonstrated in H22-bearing mice. The potency of TAAs was confirmed as its 50% inhibiting concentration (IC50) on Bel-7402 cell under Sulfur Rhodamine B staining. Both underlying mechanisms were explored as cellular apoptosis and cell cycle under flow cytometry. Mitochondrial and recipient apoptotic pathways were differentiated as mitochondrial membrane potential under flow cytometry and caspases activities under fluorescence analysis., Results: The inhibitory rate of TAAs in mice was 50.98% at 4 mg/kg dose. The IC50 of TAAs on Bel-7402 was 20.06 µg/mL (15.13-26.61µg/mL). Effective mechanisms of TAAs were confirmed as both of arresting cell cycle at G1 phase and inducing apoptosis dose- and time-dependently. Mitochondrial and recipient pathways involved in apoptotic actions of TAAs., Conclusion: TAAs is effective for hepatocarcinoma, via inhibiting proliferation and inducing apoptosis.

Purpose: To investigate the safety, effect and instent restenosis rate of Wingspan stenting in treating patients with intracranial vertebral artery atherosclerotic stenosis (70-99%) concurrent with contralateral vertebral artery atherosclerotic diseases., Materials and Methods: Eighty-eight patients with severe symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) combined with contralateral vertebral artery atherosclerotic diseases were treated with the Wingpsan stent. All the baseline, cerebral angiography, success rate, perioperative complications, clinical and imaging follow-up data were prospectively analyzed., Results: The success rate of stenting was 100%, and the mean stenotic rate was reduced from prestenting (84.9±6.8)% to poststenting (17.2±5.9)%. The perioperative stroke rate was 1.1%. Among eighty patients (90.9%) with clinical follow-up 8-62 months (mean 29.3±17.2) poststenting, five (6.3%) had posterior circulation TIA only, three (3.8%) had mild stroke in the posterior circulation but recovered completely, and another five patients greater than 70 years old died of non-ischemic stroke. Imaging follow-up in 46 patients (52.3%) 5-54 months (mean 9.9±9.9) following stenting revealed instent restenosis in 12 patients (26.1%) including 7 (58.3%) symptomatic restenosis. Age and residual stenosis were the two factors to significantly (P<0.05) affect instent restenosis., Conclusion: Wingspan stenting in the intracranial vertebral artery atherosclerotic stenosis combined with contralateral vertebral artery atherosclerotic diseases has a low perioperative stroke rate and a good preventive effect on long-term ischemic stroke, but the instent restenosis rate is a little high., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: In Chinese folk medicine, the leaves of Ligustrum robustum Blume (LR) were commonly used in the treatment of obesity and hyperlipidemia. This study aimed to evaluate the anti-obesity effect and mechanisms of total phenylpropanoid glycosides from Ligustrum robustum Blume (LRTPG) in fatty diet-fed C57BL/6J mice., Materials and Methods: C57BL/6J mice were divided randomly into 6 groups, i.e., control, model, positive (Orlistat 0.12g/kg), and LRTPG at three dosages (0.3, 0.6 or 1.2g/kg), respectively. Control mice were fed with standard diet; the others were fed with fatty diet. After 4 weeks׳ modeling, therapy mice were intragastrically administrated with positive drug or LRTPG for 5 weeks, respectively. Pharmacodynamic effects including body weight, fat weight, Lee׳s index, serum lipid levels, morphological changes and adipocyte area ratio were evaluated. The mechanisms were explored as the factors related to lipids metabolism in gene expressions by real-time PCR, and assured as the protein level of differential gene by Western blotting., Results: The anti-obesity effects of LRTPG in all treated mice were shown as decreased body weight, fat mass, Lee׳s index, total cholesterol (TC) level, and adipocyte area. The mechanisms were demonstrated as elevated mRNA and protein levels of adipose leptin, and consequently decreasing mRNA of adipose acyl coenzyme A: diacylglycerol acyltransferase (DGAT) with increasing mRNA of hepatic cholesterol 7α-hydroxylase (CYP7A1), which led to inhibition of triglyceride (TG) synthesis and promotion of cholesterol catabolism., Conclusions: The anti-obesity effect of LRTPG in fatty diet-fed mice was related to the up-regulation of leptin, which may provide scientific evidence supporting the traditional usage of LR on obesity in China., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To study the growth inhibition effect of Brucea javanica Fruit Oil Emulsion (BJFOE) on human ovarian caner SKOV3 cells and the transplanted tumor of SKOV3 nude mice., Methods: Growth inhibition effects of different concentrations BJFOE alone or its combination with cisplatin on human ovarian cancer cell SKOV3 were measured using MTT method. The orthotopic transplantation tumor model of human ovarian cancer SKOV3 cell lines was established in nude mice. Totally 32 ovarian cancer nude mice were randomly divided into 4 groups, i.e., the blank control group (Group A), the BJFOE group (Group B), the BJFOE combined Cisplatin group (Group C), and the Cisplatin control group (Group D), 8 in each group. Mice in Group A were intraperitoneally injected with normal saline (0.2 mL/ 20 g), once per two days. Mice in Group B were intraperitoneally injected with BJFOE (0.2 mL/20 g), once per two days. Mice in Group C were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL on the first day, and intraperitoneally injected with BJFOE on the second day. Mice in Group D were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL, once per two days. All mice were injected for six times, and sacrificed 48 h after the last injection. The lesion formation of the abdominal tumor tissue was observed. Tumor specimens were obtained to perform HE staining. Expression levels of MRP-1/CD9 and integrinα-5 were detected using Western blot., Results: The inhibition of BJFOE was time-dose depend- ently correlated with its inhibition effect of SKOV3 cells. The inhibition effect of BJFOE in combination of cisplatin was significantly superior to that of using any of the two drugs alone. Western blot results showed expression levels of MRP-1/CD9 and integrinα-5 were up-regulated in Group B and Group D with statistical difference (P < 0.05). But they were down-regulated in Group C with statistical difference (P < 0.05)., Conclusions: Intraperitoneal injecting BJFOE was feasible and effective for treating ovarian cancer. BJFOE also could inhibit the invasion and migration of tumor cells targeting at MRP-1/CD9 and integrinα-5. But its specific anti-tumor mechanism was not clearly probed.

Xin-Ke-Shu (XKS), a patent traditional Chinese medicine (TCM) preparation, has been commonly used for the treatment of coronary heart disease in China. In order to understand its mechanism of action, a metabonomic approach based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) was utilized to profile the plasma metabolic fingerprints of atherosclerosis (AS) rabbits with and without XKS treatment. The metabolic profile of model group clearly separated from normal, and that of XKS group was closer to the control group. Metabolites with significant changes during atherosclerosis were characterized as potential biomarkers related to the development of atherosclerosis by using orthogonal partial least-squares-discriminate analysis (OPLS-DA). Twenty potential biomarkers, including l-acetylcarnitine (1), propionylcarnitine (2), unknown (3), phytosphingosine (4), glycoursodeoxycholic acid (5), LPC(14:0) (6), sphinganine (7), LPC(20:5) (8), LPC(16:1) (9), LPC(18:2) (10), LPC(18:3) (11), LPC(22:5) (12), LPC(16:0) (13), LPC(18:1) (14), LPC(22:4) (15), LPC(17:0) (16), LPC(20:2) (17), elaidic carnitine (18), LPC(18:0) (19) and LPC(20:1) (20), were identified by their accurate mass and MS(E) spectra. The derivations of those biomarkers can be regulated by administration of XKS, which suggested that the intervention effect of XKS against AS may involve in regulating the lipid perturbation including fatty acid β-oxidation pathway, sphingolipid metabolism, glycerophospholipid metabolism and bile acid biosynthesis. This study indicated that the UPLC-Q/TOF MS-based metabonomics not only gave a systematic view of the pathomechanism of AS, but also provided a powerful tool to study the efficacy and mechanism of complex TCM prescriptions., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Objective: To study the anti-inflammatory and antibacterial effects of different processed products of Rosa laevigata root and stem., Methods: Different processed products were obtained from Rosa laevigata root and stem by frying with vinegar,salt,honey and black bean juice. Their antibacterial effect was observed on bacteria such as Bacillus subtilis, Staphylococcus aureus and Escherichia coli; The mice auricle swelling method was used in anti-inflammatory experiment by using xylene. The mice cotton granuloma method was used to observe the chronic inflammatory effect., Results: The antibacterial effects of processed products of Rosa laevigata root were better than that of the stem, especially the honey processed root. All processed products had no obvious effect on mouse auricular swelling. The raw root,salt processed stem, honey processed stem and honey processed root of Rosa laevigata had an inhibitory effect on cotton-pellet inducing mouse granuloma., Conclusion: The honey processed root of Rosa laevigata have significant antibacteral effect and anti-inflammatory effect on chronic infammation.

A total of 8375 genic simple sequence repeat (SSR) loci were discovered from a unigene set assembled from 116282 transcriptomic unigenes in this study. Dinucleotide repeat motifs were the most common with a frequency of 65.11%, followed by trinucleotide (32.81%). A total of 4100 primer pairs were designed from the SSR loci. Of these, 343 primer pairs (repeat length ≥15 bp) were synthesized with an M13 tail and tested for stable amplification and polymorphism in four Pyrus accessions. After the preliminary test, 104 polymorphic genic SSR markers were developed; dinucleotide and trinucleotide repeats represented 97.11% (101) of these. Twenty-eight polymorphic genic SSR markers were selected randomly to further validate genetic diversity among 28 Pyrus accessions. These markers displayed a high level of polymorphism. The number of alleles at these SSR loci ranged from 2 to 17, with a mean of 9.43 alleles per locus, and the polymorphism information content (PIC) values ranged from 0.26 to 0.91. The UPGMA (unweighted pair-group method with arithmetic average) cluster analysis grouped the 28 Pyrus accessions into two groups: Oriental pears and Occidental pears, which are congruent to the traditional taxonomy, demonstrating their effectiveness in analyzing Pyrus phylogenetic relationships, enriching rare Pyrus EST-SSR resources, and confirming the potential value of a pear transcriptome database for the development of new SSR markers.

Xin-Ke-Shu (XKS) is a patent drug used for coronary heart diseases in China. This study evaluated the protective effect of XKS against isoproterenol (ISO)-induced myocardial infarction (MI). For its underlying mechanism in rats with MI, a metabonomic approach was developed using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/QTOF-MS). Plasma metabolites were profiled in MI rats, pretreated orally with or without XKS. Two genres of metabolic biomarkers were used to elucidate the pharmacological action of XKS: pathological biomarkers and pharmaco biomarkers. Fifteen metabolites significantly varying between MI rats and normal rats were characterized as potential pathological biomarkers related to MI, including L-acetylcarnitine (1), L-isoleucyl-L-proline (2), tyramine (3), isobutyryl-L-carnitine (4), phytosphingosine (5), sphinganine (6), L-palmitoylcarnitine (7), lysoPC(18:0) (8), uric acid (9), L-tryptophan (10), lysoPC(18:2) (11), lysoPC(16:0) (12), docosahexaenoic acid (13), arachidonic acid (14) and linoleic acid (15). Among them, eight (1-6, 9 and 10) were first reported as pathological biomarkers related to ISO-induced MI, which mainly involved into fatty acid β-oxidation pathway, sphingolipid metabolism, proteolysis, tryptophan metabolism and purine metabolism. The metabolites significantly varying between MI rats with and without XKS pretreatment were considered as pharmaco biomarkers. A total of 17 pharmaco biomarkers were recognized, including 15 pathological biomarkers (1-15), hexanoylcarnitine (16) and tetradecanoylcarnitine (17). The results suggested that pretreatment of XKS protected metabolic perturbations in rats with MI, major via lipid pathways, amino acid metabolism and purine metabolism, which also provided a promising approach for evaluating the pharmacodynamics and mechanism of traditional Chinese medicines (TCM) formulas., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Aim: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon tetrachloride (CCl₄)-induced chronic hepatitis., Methods: PHT model was replicated with CCl₄ in rats for 84 d. Model was identified by measuring the ascetic amounts, hepatic function, portal pressure in vivo, splenic index, and pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was assessed by immunohistochemistry. IPPRLs were performed at d₀, d₂₈, d₅₆, and d₈₄. After phenylephrine-induced constriction, Gly was geometrically used to reduce PHT. Gly action was expressed as median effective concentration (EC₅₀) and area under the curve (AUC). Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads., Results: PHT model was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and elevated portal pressure. Pathological findings had shown normal hepatic structure at d₀, degenerations at d₂₈, fibrosis at d₅₆, cirrhosis at d₈₄ in PHT rats. Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with CCl₄-induced chronic hepatitis. Gly potencies were increased gradually along with PHT development, characterized with its EC₅₀ at 2.80 × 10⁻¹⁰, 3.03 × 10⁻¹¹, 3.77 × 10⁻¹¹ and 4.65×10⁻¹¹ mol/L at d₀, d₂₈, d₅₆ and d₈₄, respectively. Existed iNOS was located at hepatocyte at d₀, stellate cells at d₂₈, stellate cells and macrophages at d₅₆, and macrophages in portal triads at d₈₄. Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development. AUC values of Gly were positively correlated with existed iNOS levels in portal triads., Conclusion: Gly reduces indirectly PHT in IPPRL with CCl₄-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.

Objective: To investigate the influence of pleiotrophin (PTN) on the growth of rat hepatocytes., Methods: Primary rat hepatocytes were isolated from male Sprague-Dawley rats and divided into three groups: group A (negative control), cultivated in normal culture medium; group B (positive control), cultivated with culture medium supplemented with supernatant from the embryonic fibroblast 3T3 cell line; group C (experimental), cultivated with culture medium supplemented with human recombinant (hr) PTN (100 ng/ml). The hepatocytes' growth rate and level of secreted albumin (ALB) were evaluated by microscopy and biochemical assay, respectively. Significance of between-group differences were assessed by one-way ANOVA, and pairwise comparisons were performed by the least significant difference test., Results: The growth rates of hepatocytes in groups A, B and C were 2.800+/-0.084%, 4.300+/-0.132% and 3.800+/-0.053%, respectively. The growth rate of group B was significantly higher than the other two groups (F = 333.735, P less than 0.05). For all groups, the highest levels of secreted ALB were detected between the second and sixth day of culture, with g/L concentrations at day 2, 4 and 6 of: group A, 0.550+/-0.010, 0.900+/-0.030 and 0.300+/-0.040; group B, 0.900+/-0.030, 1.300+/-0.020 and 1.400+/-0.030; group C, 0.900+/-0.010, 1.160+/-0.010 and 0.700+/-0.050. The secreted ALB of group B was significantly higher than that of the other two groups (F = 651.355, 338.831 and 863.205, P less than 0.05 )., Conclusion: PTN can benefit in vitro culturing of rat hepatocytes by stimulating growth and enhancing their ability to secrete albumin.

Objective: To observe the synergistic effect of beta-elemene Injection (betaI) combined Paclitaxel Injection (PI) on breast cancer MB-468 cells and to study possible mechanisms., Methods: Breast cancer MB-468 cells were treated with betaI (2.5, 5.0, 10.0, 20.0, 40.0, 80.0, 160.0, 320.0, and 640.0 microg/mL), PI (0.00100, 0.00200, 0.00400, 0.00800, 0.01600, 0.03125, 0.06250, 0.12500, and 0.25000 microg/mL), and betaI combined PI for 24 h and 48 h respectively. Cell proliferation was determined using SRB assay. Cell apoptosis and cell cycle phase distribution were detected using flow cytometry. The post-intervention expressions of cell cycle proteins [cyclin-dependent kinase (CDK1), cyclin-B1, P21(cip1), and P27(kip1)] were detected by Western blot., Results: Beta-elemene or paclitaxel inhibited the growth of MB-468 cell line. The IC50 and IC20 values treated with beta-elemene for 24 h were 34.20 and 52.59 microg/mL and for 48 h were 10.15 and 17.81 microg/mL respectively, while the IC50 values treated with paclitaxel for 24 h and 48 h were 2.449 and 1.698 microg/mL respectively. Beta-elemene (20 and 40 microg/mL respectively) and Paclitaxel (0.016 and 0.008 microg/mL respectively) synergistically inhibited cell proliferation of MB-468 cells, with Q value > 1.15. Beta-elemene alone (52.59 microg/mL) apparently decreased the expression of cyclin-B1 protein. The expression of cyclin-B1 protein in the combined group was also lower than that in the PI group (1.698 microg/mL). The expression of P27(kip1) was up-regulated when compared with that in the betaI group or the PI group., Conclusion: Beta-elemene had synergistic effect with Paclitaxel, and its possible mechanism might be correlated with down-regulating the cell cycle protein cyclin-B1 expression and up-regulating the P27(kip1) expression.

Objective: To compare the efficacy and safety of docetaxol, pemetrexed and EGFR-TKIs in the second-line treatment for patients with advanced non-small cell lung cancer., Methods: The clinical data of 170 patients with advanced non-small cell lung cancer who failed standard first-line chemotherapy were reviewed. Those who received docetaxol as second-line therapy were designated as group A (n = 60), those who received pemetrexed as second-line therapy were designated as group B (n = 49), and those who received EGFR-TKIs as second-line therapy were designated as group C (n = 61). PFS and MST were estimated by Kaplan-Meier method and the differences between groups were compared by log-rank test., Results: The response rate in the groups A, B and C group was 15.0% (9/60), 24.5% (12/49) and 36.1% (22/61), respectively. The PFS after second-line therapy in the groups A, B and C was 5.49 months (95%CI: 4.03 - 6.95 months), 5.42 months (95%CI: 4.23 - 6.60 months) and 9.31 months (95%CI: 6.88 - 11.73 months), respectively (P = 0.045). The MST after second-line therapy in the groups A, B and C was 14.89 months (95%CI: 11.23 - 18.55 months), 15.81 months (95%CI: 12.11 - 19.52 months) and 17.47 months (95%CI: 13.38 - 21.56 months), respectively (P = 0.574). Regression analysis showed that the performance status score (PS) and response for second-line treatment are independent prognostic factors in each sub-group, and pathological type is an independent prognostic factor in the group C (P = 0.003)., Conclusions: The safety of the three drugs used as second-line treatment for patients with advanced non-small-cell lung cancer, who failed standard first-line chemotherapy, is comparable, but the EGFR-TKIs group has the highest response rate, and the EGFR-TKIs group has the longest PFS with a statistically significant difference, while there is no significant difference in MST among the three groups. When patients receive second-line treatment, the performance status < 2 and the response rate for second-line treatment are independent prognostic factors. Furthermore, pathological type (adenocarcinoma) is also an independent prognostic factor for EGFR-TKIs as second-line treatment.

Aim: To develop a pharmacodynamic model of portal hypertension from chronic hepatitis., Methods: Pathological changes and collagen depositions were analyzed using morphometry to confirm CCl₄-induced chronic hepatitis. At d₀, d₂₈, d₅₆ and d₈₄ of the process, the portal perfused velocities (μL/min) in isolated rat livers were exactly controlled with a quantified pump. The pressure (mmHg) was monitored with a Physiological System. The geometric concentrations of phenylephrine or acetylcholine were added to a fixed volume (300 mL) of the circulating perfusate. The equation, the median effective concentration and its 95% confidence intervals of phenylephrine or acetylcholine were regressed with Prism-4 software in non-linear fit and various slopes. In the isolated perfused rat livers with chronic hepatitis, both median effective concentrations were defined as the pharmacodynamic model of portal hypertension., Results: At d₀, d₂₈, d₅₆ and d₈₄, the equations of portal pressure potency from the concentrations of phenylephrine used to constrict the portal vein in isolated perfused rat livers were Y = 0.1732 + 0.3970/[1 + 10((-4.3061-0.4407 X))], Y = -0.004934 + 0.12113/[1 + 10((-3.1247-0.3262 X))], Y = 0.0104 + 0.2643/[1 + 10((-8.8462-0.9579 X))], and Y = 0.01603 + 0.12107/[1 + 10((-5.1134-0.563 X))]; the median effective concentrations were 1.69 × 10⁻¹⁰ mol/L, 2.64 × 10⁻¹⁰ mol/L, 5.82 × 10⁻¹⁰ mol/L, and 8.24 × 10⁻¹⁰ mol/L, respectively. The equations from the concentrations of acetylcholine used to relax the portal vein were Y = -0.4548 + 0.3274/[1 + 10((6.1538 + 0.5554 X))], Y = -0.05391 + 0.06424/[1 + 10((3.8541 + 0.3469 X))], Y = -0.2733 + 0.22978/[1 + 10((3.0472 + 0.3008 X))], and Y = -0.0559 + 0.053178/[1 + 10((5.6336 + 0.5883 X))]; the median effective concentrations were 8.40 × 10⁻¹⁰ mol/L, 7.73 × 10⁻¹² mol/L, 5.98 × 10⁻¹¹ mol/L, and 2.66 × 10⁻¹⁰ mol/L, respectively., Conclusion: A pharmacodynamic model of portal hypertension in isolated perfused rat livers with chronic hepatitis was defined as the median effective concentrations of phenylephrine and acetylcholine.

Objective: To compare the efficacy of second-line EGFR-TKIs followed by third-line pemetrexed with second-line pemetrexed followed by third-line EGFR-TKIs in patients with advanced lung adenocarcinoma., Methods: From March 2007 to August 2008, 83 patients with advanced lung adenocarcinoma who failed standard first-line chemotherapy were included in this study. The patients who received EGFR-TKIs as second-line therapy followed by third-line pemetrexed were designated as group A (n = 45). The patients who received pemetrexed as second-line therapy followed by third-line EGFR-TKIs were designated as group B (n = 38). PFS and MST were estimated with Kaplan-Meier analysis and the difference between groups were compared with Log-rank test., Results: The progression-free survival (PFS) after second-line therapy in the groups A and B was 8.05 months (95% CI, 5.90 to 10.20) and 4.20 months (95% CI, 3.33 to 5.06), respectively (P = 0.001). The PFS after second-line therapy in smokers and non-smokers was 3.69 months (95% CI, 5.00 to 7.59) and 7.12 months (95% CI, 5.51 to 8.38), respectively (P = 0.007). The PFS of male and female patients was 5.56 months (95% CI, 4.02 to 7.10) and 6.85 months (95% CI, 4.98 to 7.58), respectively (P = 0.279). The PFS after third-line therapy in groups A and B was 6.88 months (95% CI, 5.07 to 8.69) and 7.60 months (95% CI, 5.59 to 9.12) respectively, (P = 0.899). The PFS after third-line therapy in smokers and non-smokers was 4.95 months (95% CI, 2.83 to 7.05) and 8.49 months (95% CI, 6.27 to 10.76), respectively (P = 0.050). The PFS after third-line therapy in male and female patients was 5. 96 months (95% CI, 4.02 to 7.91) amd 8.38 months (95% CI, 5.68 to 11.07), respectively (P = 0.176). The MST in groups A and B was 23.60 months (95% CI, 19.23 to 28.00) and 15.58 months (95% CI, 11.85 to 19.32), respectively (P = 0.021). The MST in smokers and non-smokers was 11.99 months (95% CI, 8.55 to 15.49) and 23.18 months (95% CI, 19.33 to 27.02), respectively (P = 0.001). The MST in male and female patients was 17.40 months (95% CI, 13. 19 to 21.61) and 22.74 months (95% CI, 18.29 to 27.19), respectively (P = 0.111)., Conclusions: Second line EGFR TKIs followed by third line pemetrexed regimen improves the PFS and MST compared with the regimen second line pemetrexed followed by third line EGFR TKIs in patients with advanced lung adenocarcinoma. Smoking status is an independent prognostic factor. Survival is not influenced by gender. Prospective clinical trials are needed to confirm these findings.

Background: Sterile larvae--maggots of the green bottle blowfly Lucilia sericata are employed as a treatment tool for various types of chronic wounds. Previous studies reported that excretions/secretions (ES) of the sterile larvae could prevent and remove the biofilms of various species of bacteria. In the present study we assessed the effect of ES from the larvae pretreated with Pseudomonas aeruginosa on the bacteria biofilms., Methods and Findings: We investigated the effects of ES from the maggot pretreated with P. aeruginosa on the biofilms using microtitre plate assays and on bactericidal effect using the colony-forming unit (CFU) assay. The results showed that only 30 µg of the ES from the pretreated maggots could prevent and degrade the biofilm of P. aeruginosa. However, the CFU count of P. aeruginosa was not decrease when compared to the ES from non pretreated maggots in this study condition. It is suggested that the ES from the pretreated maggot was more effective against biofilm of P. aeruginosa than sterile maggot ES., Conclusions: Our results showed that the maggot ES, especially the bacteria-pretreated larva ES may provide a new insight into the treatment tool of the bacterial biofilms.

We evaluated cancer risk with three VEGF polymorphisms (-460C>T, -2578C>A, 1612G>A) based on current available studies. -460C>T did not appear to influence cancer risks. -2578C carriers had a 30% reduction of colorectal cancer (CRC) risk in comparison with AA homozygote (OR: 0.70, CI: 0.56-0.88). 1612G carriers had a striking 84% reduction of gastric cancer risk in comparison with AA homozygote. Multiple pair-wise comparisons suggested a recessive role for both -2578A and 1612A risk allele. Further studies with larger samples, well-matched controls and homogenous ethnic background are warranted to confirm these findings. We recommend more efforts into the investigation of 1612G>A with cancer risks.

Purpose: Bibliometric evaluation provides a method for evaluating trends in publications related to a specific topic. This search focused on pressure ulcer (PU) care; journals and authors with the greatest contribution and impact were emphasized., Design: Bibliometric evaluation., Methods: Data encompassing the period from 1990 to 2009 were extracted from the Science Citation Index online version. We analyzed selected documents with "pressure ulcer" as a part of the title, abstract, or key words and reported the following parameters: trends of publication output, document types, subject category, journal pattern, authorship, and research in nursing disciplines., Results: The annual number of articles on PUs grew at a rapid rate, from approximately 39 in 1991 to 259 in 2009. The main subject categories in which research on PUs was conducted were surgery and nursing, each of which accounted for more than 10% of total articles. The United States was the dominant country in terms of volume of articles. The relationship between nurse staffing and PU-related outcomes is currently the major focus of PU nursing research, followed by risk assessment scale evaluations., Conclusion: We found that the number of PU-related publications has grown at a rapid rate over the past 20 years, reflecting an increasing awareness of the importance of PU prevention and management.

Objective: To observe the effect of salvianolic acid B (SalB) on high energy phosphate and activity of ATPase of cerebral ischemia in mice, and to study the role of SalB on hydrocephalus further., Method: NIH mice were divided into four groups randomly: Sham-operated group, cerebral ischemia group, SalB-treated group and Nimodipine (Nim)-collated group. In Sal B-treated group, mice were injected with SalB (22.5 mg x kg(-1)) in vena caudalis at 30 min before the experiment. In Nim-collated group, Nim (0.03 mg x kg(-1)) was injected into tail vein at the same time, while the mice in Sham-operated group and cerebral ischemia group were injected the same volume normal saline. The acute cerebral ischemia model was established by ligating bilateral common carotid arteries for 30 min in mice, then the mice were killed and the content of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), phosphocreatine (PCr) were observed, and the cerebral energy charge (EC) was computed. At the same time, activity of Na(+) -K(+) -ATPase and Ca2(+) -ATPase, content of water in brain tissue were measured., Result: Compared with cerebral ischemia group, EC and content of ATP, ADP, PCr in SalB-treated group heightened evidently (P < 0.01). Moreover, activity of Na(+)-K+ ATPase and Ca2+ ATPase in SalB-treated group had a remarkable increase (P < 0.01). But the content of water in brain tissue decreased markedly (P < 0.05)., Conclusion: The mechanism that SalB can relieve content of water in brain tissue of cerebral ischemia in mice, may be associated with improving the content of high-energy phosphoric acid compounds and enhancing the activity of ATPase.

Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CGRP). The present study aimed to investigate the cardiovascular effects of IMDs (IMD1-47 and IMD8-47) in rats. Intravenous administration of 150 nmol IMDs continuously decreased mean arterial pressure and inhibited cardiac function. Administration with IMDs decreased left ventricular end-systolic pressure (LVESP) and maximal rate of left-ventricle pressure development (+/-LVdp/dt(max)), and elevated left ventricular end-diastolic pressure (LVEDP). Changes with IMD1-47 treatment were close to that with IMD8-47 (P>0.05). Perfusion of isolated rat hearts in vitro with IMD8-47 (10(-8) and 10(-7)mol/L) resulted in lower LVSP, by 40 and 56% (P<0.01); lower +LVdp/dt (max), by 33 and 47% (P<0.01); lower -LVdp/dt(max), by 25 and 39% (P<0.01); but higher coronary perfusion flow (CPF), by 25% (P<0.05) and 33% (P<0.01), respectively, than controls. However, both IMD8-47 and IMD1-47 (from 10(-13) to 10(-7)mol/L) relaxed preconstricted aortic rings in a dose-dependent manner. Intravenous administration of IMD1-47 and IMD8-47 (10(-7)mol/L) in vivo increased the cyclic adenosine monophosphate (cAMP) content by 68 and 150% (both P<0.01), respectively, in myocardia and 320 and 281% (both P<0.01), respectively, in aortas, compared with controls. Perfusion of isolated hearts with IMD1-47 and IMD8-47 (10(-7)mol/L) enhanced cAMP content by 24% (P<0.05) and 73% (P<0.01), respectively, compared with controls. IMDs inhibited 3H-Leucine incorporation in cardiomyocytes in a concentration-dependent manner. IMD1-47 and IMD8-47 (10(-7) and 10(-8)mol/L) decreased 3H-Leucine incorporation by 12-25% (P<0.01) and 14-18% (P<0.01), respectively. IMD mRNA was detected in cultured neonatal cardiomyocytes and isoproterenol-induced hypertrophic myocardia but not normal myocardia of adult rats. These results suggest that IMD might be a regulatory factor for cardiovascular function and myocardial hypertrophy as a cardiovascular active peptide.

Mice deficient for p66shcA represent an animal model to link oxidative stress and aging. p66shcA is implicated in oxidative stress response and mitogenic signaling. Phosphorylation of p66shcA on Ser36 is critical for its function in oxidative stress response. Here we report the identification of ERK as the kinase phosphorylating p66shcA on Ser36. Activation of ERKs was necessary and sufficient for Ser36 phosphorylation. p66shcA interacted with ERK and was demonstrated to be a substrate for ERK, with Ser36 being the major phosphorylation site. Furthermore, in response to H2O2, inhibition of ERK activation repressed p66shcA-dependent phosphorylation of FOXO3a and the down-regulation of its target gene p27kip1. Down-regulation of p27 might promote cell survival, as p27 played a proapoptotic role in oxidative stress response. As a feedback regulation, Ser36 phosphorylated p66shcA attenuated H2O2-induced ERK activation, whereas p52/46shcA facilitated ERK activation, which required tyrosine phosphorylation of CH1 domain. p66shcA formed a complex with p52/46ShcA, which may provide a platform for efficient signal propagation. Taken together, the data suggest there exists an interplay between ERK and ShcA proteins, which modulates the expression of p27 and cell response to oxidative stress.

Adrenomedullin (ADM) has the vasodilatory properties and involves in the pathogenesis of vascular calcification. ADM could be degraded into more than six fragments in the body, including ADM(27-52), and we suppose the degrading fragments from ADM do the same bioactivities as derived peptides from pro-adrenomedullin. The present study carries forward by assessing the effects on vascular calcification of the systemic administration of ADM(27-52). The rat vascular calcific model was replicated with vitamin D3 and nicotine. ADM or/and ADM(27-52) were systemically administrated with mini-osmotic pump beginning at seventh day after the model replication for 25 days. Vascular calcific nodules histomorphometry, vascular calcium content, vascular calcium uptake, alkaline phosphatase activity, and osteopontin-mRNA quantification in aorta were assessed. ADM limited 40.2% vascular calcific nodules (P<0.01), did not effect on calcium content (P>0.05), reduced 44.4% calcium uptake (P<0.01), lowered 21.1% alkaline phosphatase activity (P<0.01), and regulated 40.9% downwards osteopontin-mRNA expression (P<0.01) in the aorta of rats with vascular calcification. ADM(27-52) receded 32.0% vascular calcific nodules (P<0.01), taken from 55.5% calcium content (P<0.01), did not affect calcium uptake (P>0.05), inhibited 22.5% alkaline phosphatase activity (P<0.01), and restrained 21.9% osteopontin-mRNA expression (P<0.01) in the aorta of rats with vascular calcification. Both of ADM and ADM(27-52) did interact on vascular calcification each other. ADM could partially antagonize the effects of ADM(27-52) in taking from calcium content (17.5%, P<0.01) and in receding vascular calcific nodules (18.6%, P<0.01). ADM could obviously enhance the action of ADM(27-52) in inhibiting alkaline phosphatase activity (14.4%, P<0.01) and in reducing calcium uptake (11.4%, P<0.01). ADM(27-52) could partially antagonize the effects of ADM on regulating downwards osteopontin-mRNA expression (17.0%, P<0.01). It is concluded that ADM(27-52) derived from ADM acts as an inhibitory agent on vascular calcification, with special mechanisms different from ADM derived from ADM progenitor molecule.

Objective: To research the mechanism of Danzhi-xiaoyao San (DZXYS) for treating Alzheimer's disease model of rats dealt with D-galactose., Method: An Alzheimer's disease-like model of rats has been set up with sc. D-galactose 150.0 mg kg-1 D-1 x 49 d. Comparing with Acricept in 0.54 mg kg-1 D-1 dosage as a positive control drug, DZXYS in 12.636 g kg-1 D-1 x 49 d dosage has orally been administrated orally to treat the injury in the Alzheimer's disease-like model of rats. The energy charge in the cerebral tissues had been detested with waters liquid chromatography; the protein content and DNA content in the cerebral tissues had been detested with ultraviolet assay, the relative content of aldose reductase-mRNA is detested with RT-PCR. The difference was analyzed between the control rats without D-galactose, the model rats dealt with D-galactose, the model rats treated with Aricept and the model rats treated with DZXYS, it is significant as P<0.05., Result: 1) DZXYS can not affect the energy charge in their cerebral tissues. 2) DZXYS can increase the protein content from 0.3139 +/- 0.019468 to 0.3213 +/- 0.015528 (ni=10, P>0.05) in their cerebral tissues. 3) DZXYS can increase the total DNA content from 1.093 +/- 0.267 to 1.488 +/- 0.341 (ni=10, P<0.01) in their cerebral tissues. 4) DZXYS can increase the content of AR-mRNA in their cerebral tissue from 0.732 +/- 0.159 to 1.418 +/- 0.277 (ni=5, P<0.01)., Conclusion: It suggests that DZXYS could be effective in human Alzheimer's disease for its stabling gene expression, maintaining protein characteristics, recovering signal transduction in the Alzheimer's disease-like model rats dealt with D-galactose.

In this study, we employed rat model of acute myocardial necrosis induced by isoproterenol (ISO) to study the possible roles of corin, the protease uniquely distributing in myocardium to convert pro-brain natriuretic peptide (proBNP) to BNP, and neutral endopeptidase (NEP), the major enzyme to degrade BNP, in changing the levels of BNP. In rats with isoproterenol alone, the myocardium necrosis occurred and the cardiac function was inhibited; the BNP contents in plasma and myocardium were upregulated, so did the myocardial corin mRNA level; the NEP activity in plasma and myocardium were downregulated. Omapatrilat (OMA) treatment relieved myocardial lesions and improved cardiac function. In the plasma and myocardium, omapatrilat treatment increased BNP contents, reduced NEP activity; in myocardium, mRNA level of proBNP and corin decreased, but NEP mRNA expression increased. Our study confirmed that omapatrilat treated myocardial necrosis effectively and suggested that increased BNP in rats with myocardial necrosis could depend on increased production and conversion as well as decreased degradation.