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Mesenchymal stem cells (MSCs) are a prevalent source for stem cell therapy and play a crucial role in modulating both innate and adaptive immune responses. Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in liver cells and involves immune system activation, leading to histological changes, tissue damage, and clinical symptoms. A recent publication by Jiang et al , highlighted the potential of MSCs to mitigate in NAFLD progression by targeting various molecular pathways, including glycolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. In this editorial, we comment on their research and discuss the efficacy of MSC therapy in treating NAFLD., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in premenopausal women, often linked to abdominal obesity, insulin resistance, and metabolic issues. With its heterogeneous nature, PCOS treatment should be tailored to individual symptoms and patient preferences. This study examines collaboration networks among countries, institutions, authors, references, and journals related to PCOS treatment., Methods: Web of Science data was analyzed using VOSviewer and CiteSpace for bibliometric visualization. Chinese and Western medicine treatments for PCOS were reviewed, emphasizing symptom-targeted solutions., Results: Data from 4682 records authored by 400 individuals from 515 institutes in 62 countries revealed China as the leading contributor. Notable authors include Monash University and Richard S. Legro. Common research themes include adipocytes, inflammation, insulin sensitivity, oxidative stress, and the gut microbiome. Tailoring treatment to individual needs is essential, focusing on hyperandrogenism, ovulation, and insulin resistance, with lifestyle counseling to address obesity., Conclusion: This bibliometric analysis provides valuable insights into the research status of PCOS treatment. China has made significant contributions, and complementary and alternative therapies, such as traditional Chinese medicine and acupuncture, have also shown beneficial effects recently. The research on inflammation, oxidative stress, and the gut microbiome may provide new targets and strategies for the treatment of PCOS. The recognition of the metabolic problems in PCOS patients facilitates the formulation of more personalized treatment plans to improve the prognosis of patients.

Bushen Tiaoxue Granules (BTG) is an empirical Chinese herbal formula that has been used for the treatment of subfertility. The protective effect of BTG on controlled ovarian hyperstimulation (COH)-induced impaired endometrial receptivity has been reported in our previous study. This study aims to explore the mechanisms of BTG on ameliorating abnormal morphology of endometrium based on network pharmacology. Active compounds of BTG were identified via the traditional Chinese medicine systems pharmacology and UPLC-MS technology. The SwissTargetPrediction platform and HERB database were used to screen out the putative targets of BTG. Potential targets of endometrial dysfunction caused by COH were obtained from three GEO databases. Through the STRING database, the protein-protein interaction was carried out according to the cross-common targets of diseases and drugs. GO terms and KEGG pathways enrichment analyses were conducted via the Metascape database. AutoDock Vina was used for docking validation of the affinity between active compounds and potential targets. Finally, in vivo experiments were used to verify the potential mechanisms derived from network pharmacology study. A total of 141 effective ingredients were obtained from TCMSP and nine of which were verified in UPLC-MS. Six genes were selected through the intersection of 534 disease related genes and 165 drug potential targets. Enrichment analyses showed that BTG might reverse endometrial dysfunction by regulating adherens junction and arachidonic acid metabolism. Hematoxylin-eosin staining revealed that BTG ameliorated the loose and edematous status of endometrial epithelium caused by COH. The protein expression of FOXO1A, β-Catenin and COX-2 was decreased in the COH group, and was up-regulated by BTG. BTG significantly alleviates the edema of endometrial epithelium caused by COH. The mechanisms may be related to adheren junctions and activation of arachidonic acid metabolism. The potential active compounds quercetin, taxifolin, kaempferol, eriodictyol, and isorhamnetin identified from the BTG exhibit marginal cytotoxicity. Both high and low concentrations of kaempferol, eriodictyol, and taxifolin are capable of effectively ameliorating impaired hESC cellular activity., (© 2024. The Author(s).)

It is difficult and challenging to design and construct high-nuclearity Ln(III)-based clusters due to the high coordination numbers and versatile coordination geometries of Ln(III) ions. Herein, two novel octanuclear Ln(III)-based clusters [Ln 8 (H 2 L - ) 4 (HL 2- ) 4 (NO 3 ) 6 (CO 3 ) 2 ](NO 3 ) 2 ·2CH 3 CN (Ln = Nd (1) and Sm (2)) have been synthesized under solvothermal conditions. The X-ray single analysis reveals that both 1 and 2 are octanuclear structures and the eight central Ln(III) ions are bridged by two CO 3 2- anions. Catalytic study revealed that 1 and 2 can effectively catalyze the cycloaddition reaction of CO 2 and aziridines or epoxides simultaneously under mild conditions. What is more, cluster 1, as a heterogeneous catalyst, can be reused at least three times without obvious loss in catalytic activity for coupling of CO 2 and epoxides. To our knowledge, cluster 1 is the first Ln(III)-based cluster catalyst used for the conversion of CO 2 with aziridines or epoxides simultaneously. This work provides a successful strategy to integrate high-nuclear Ln(III)-based clusters for CO 2 conversion, which may open a new space for the construction of multifunctional high-nuclear Ln(III)-based clusters as efficient catalysts for CO 2 conversion.

Background: The epidemiologic characteristics and attributable risk factors of ischemic stroke in China have changed over the past three decades. An up-to-date analysis on deaths, disability-adjusted life-years (DALYs), prevalence, incidence, and attributable risk factors of ischemic stroke for China is needed. This study aims to provide a comprehensive analysis of burden and attributable risk factors of ischemic stroke at national level in China by sex from 1990 to 2019., Methods: This is a secondary analysis of the Global Burden of Disease (GBD) study 2019. All data used in this study was derived from the 2019 GBD study. Deaths, DALYs, prevalence, incidence, and attributable risk factors of ischemic stroke in China by sex from 1990 to 2019 were analyzed., Results: From 1990 to 2019, the age-standardized deaths rate decreased by 3.3%, age-standardized DALYs rate decreased by 4%, age-standardized prevalence rate increased by 33.5%, and age-standardized incidence rate of ischemic stroke in China increased by 34.7%. In 2019, ambient particulate matter pollution became an important risk factor, whereas household air pollution from solid fuels was no longer a major risk factor for ischemic stroke in China. Burden of ischemic stroke was higher in China compared to other regions. Ambient particulate matter pollution among men, and diet high in sodium, smoking, household air pollution from solid fuels among women account for the increased deaths/DALYs due to ischemic stroke in China., Conclusion: Our study revealed that great changes have occurred in burden and attributable risk factors of ischemic stroke in China in the past three decades. Distinct sex-specific differences are observed in burden and attributable risk factors., 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 Ye, Zhu, Zhang, Zhang, Fan, Jin, Hu, Xin and Li.)

Pachymic acid (Pac), a major bioactive constituent of Poria cocos , is an antioxidant that inhibits triglyceride (TG) accumulation. To the best of our knowledge, the present study investigated for the first time whether Pac activated sirtuin 6 (SIRT6) signaling to alleviate oleic acid (OA)-palmitic acid (PA)-induced lipid metabolism disorders in mouse primary hepatocytes (MPHs). In the present study, MPHs challenged with Pac were used to test the effects of Pac on intracellular lipid metabolism. Molecular docking studies were performed to explore the potential targets of Pac in defending against lipid deposition. MPHs isolated from liver-specific SIRT6-deficient mice were subjected to OA + PA incubation and treated with Pac to determine the function and detailed mechanism. It was revealed that Pac activated SIRT6 by increasing its expression and deacetylase activity. Pa prevented OA + PA-induced lipid deposition in MPHs in a dose-dependent manner. Pac (50 µM) administration significantly reduced TG accumulation and increased fatty acid oxidation rate in OA + PA-incubated MPHs. Meanwhile, as per the results of molecular docking and relative mRNA levels, Pac activated SIRT6 and increased SIRT6 deacetylation levels. Furthermore, SIRT6 deletions in MPHs abolished the protective effects of Pac against OA + PA-induced hepatocyte lipid metabolism disorders. The present study demonstrated that Pac alleviates OA + PA-induced hepatocyte lipid metabolism disorders by activating SIRT6 signaling. Overall, SIRT6 signaling increases oxidative stress burden and promotes hepatocyte lipolysis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Pan et al.)

Objective: To establish a new mouse model of haemorrhagic transformation associated with delayed tissue-type plasminogen activator (tPA) treatment to provide a novel tool to study therapeutic strategies for haemorrhagic transformation., Methods: Male C57BL/6 mice were subjected to carotid artery thrombosis stimulated with ferric chloride. The thrombus was then mechanically detached to induce migration toward the intracranial circulation. To induce haemorrhagic transformation, mice were intravenously injected with 10 mg/kg tPA 4.5 h after the onset of ischaemia and were sacrificed 24 h after tPA treatment., Results: In this new model, administration of tPA 4.5 h after stroke exacerbated the risk of intracerebral haemorrhage. Thrombolysis with tPA also exacerbated cerebral infarction, brain oedema, blood-brain barrier breakdown, and neurological deficits. However, cerebral blood flow was not significantly affected., Conclusion: The present model is reproducible, easy to perform, and mimics the clinical situation of haemorrhagic transformation after tPA treatment in humans. This modified model can be used as a new tool to test experimental drugs for haemorrhagic transformation associated with delayed tPA administration after an ischaemic stroke., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

A series of heterometallic tetranuclear clusters, Ln 2 Ni 2 (NO 3 ) 4 L 4 (μ 3 -OCH 3 ) 2 ·2(CH 3 CN) (Ln = Gd( 1 ), Tb( 2 ), Dy( 3 ), Ho( 4 ), Er( 5 ); HL = methyl 3-methoxysalicylate), were synthesized solvothermally. The intramolecular synergistic effect of two metal centers of Ln(III) and Ni(II) and the exposed multimetallic sites serving as Lewis acid activators greatly increase the efficiency of the CO 2 conversion, and the yield for cluster 3 can be achieved at 96% at atmospheric pressure and low temperature. In particular, the self-assembly multimetal center with polydentate ligand shows good generality and enhanced recyclability. The design of such 3d-4f heterometallic clusters provides an effective strategy for the conversion of CO 2 under greener conditions. Meanwhile, magnetic investigations indicate that cluster 1 is a good candidate for magnetic refrigerant materials with a relatively large magnetocaloric effect (MCE) (-Δ S m = 28.5 J kg -1 K -1 at 3.0 K and 7.0 T), and cluster 3 shows single-molecular magnet behavior under zero dc field. Heterometallic clusters with special magnetic properties and good catalytic behavior for the conversion of CO 2 are rare. Thus, they are potential bifunctional materials applied in practice.

The design and construction of high-nuclear lanthanide clusters with fascinating topology and functional properties have been an active area of research, however, the development of an effective approach for obtaining high-nuclear lanthanide clusters with multifunctional properties is still extremely difficult. Up to now, a systematic approach for guiding the further expansion of Ln(III)-based clusters showing good functional properties is lacking. Herein, we design and synthesize a polydentate Schiff base ligand (HL), which reacts with β-diketonate salts Ln(acac) 3 ·2H 2 O, and a series of Ln 8 clusters [Ln 8 (acac) 6 (L) 2 (μ 3 -O) 6 (μ 2 -C 2 H 5 O) 4 (μ 2 -Hacac) 2 ]·2CH 3 CN (Ln(III) = Gd (1), Dy (2), and Ho (3); HL = pyridine-2-carboxylic acid (5-hydroxymethyl-furan-2-ylmethylene)-hydrazide, Hacac = acetylacetone) have been successfully synthesized. Single-crystal X-ray diffraction studies reveal that clusters 1-3 are isostructural and can be viewed as a Ln 8 core bridged by eighteen μ 2 -O atoms, six μ 3 -O atoms and two μ 4 -O atoms. Magnetic studies show that cluster 1-Gd8 displays a large magnetocaloric effect with -Δ S m = 46.14 J kg -1 K -1 ( T = 2.0 K and Δ H = 7.0 T); cluster 2-Dy8 exhibits single-molecule magnet behavior under zero-field conditions. It is worth mentioning that the -Δ S m of cluster 1-Gd8 is larger than that of most reported polynuclear Gd(III)-based clusters; the 2-Dy8 cluster is one of the rare polynuclear Ln n SMMs ( n ≥ 8) under zero dc field. Importantly, these Ln(III)-based clusters (1-3) can catalyze the cycloaddition of CO 2 with epoxides with high efficiency under mild conditions; and cluster 1-Gd8 as a catalyst could be reused at least three times without obvious loss of catalytic performance.

Micro ribonucleic acids (miRNAs), as a category of post-transcriptional gene inhibitors, have a wide range of biological functions, are involved in many pathological processes, and are attractive therapeutic targets. Considerable evidence in ophthalmology indicates that miRNAs play an important role in diabetic retinopathy (DR), especially in inflammation, oxidative stress, and neurodegeneration. Targeting specific miRNAs for the treatment of DR has attracted much attention. This is a review focusing on the pathophysiological roles of miRNAs in DR, diabetic macular edema, and proliferative DR complex multifactorial retinal diseases, with particular emphasis on how miRNAs regulate complex molecular pathways and underlying pathomechanisms. Moreover, the future development potential and application limitations of therapy that targets specific miRNAs for DR are discussed., 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 Zhao, Ling, Zhang, Yu, Yang and Xin.)

Background: Tissue-type plasminogen activator (tPA) remains the sole FDA approved thrombolytic drug for ischemic stroke. But delayed thrombolytic therapy with tPA may increase the risk of hemorrhagic transformation. Many Chinese herbal medicines have been used as tPA helpers to enhance the capacity of tPA and minimize the risk of hemorrhagic transformation. The efficacy of Chinese herbal medicines on tPA thrombolysis is not systematically analyzed., Methods: We searched the following three databases up to January 2022: Web of Science, PubMed, and Scopus. Studies that reported the efficacy and safety of Chinese herbal medicines on tPA thrombolysis in experimental stroke were included. The efficacy outcomes were neurological score and infarct volume, the safety outcomes were cerebral hemorrhage and blood brain barrier (BBB) damage. We used the checklist of CAMARADES to assess the quality of included studies. Standardized mean difference (SMD) with 95% confidence intervals were used to assess all the outcomes. Subgroup analyses were performed to explore the sources of heterogeneity. Trim and fill method and Egger's test were used to assess the potential publication bias. Sensitivity analyses were used to identify the stability of the results., Results: A total of nine studies including 11 Chinese herbal medicines fulfilled the inclusion criteria and were subsequently analyzed. The pooled data demonstrated that Chinese herbal medicines improved neurological score (2.23 SMD, 1.42-3.04), infarct volume (1.08 SMD, 0.62-1.54), attenuated cerebral hemorrhage (1.87 SMD, 1.34-2.4), and BBB dysfunction (1.9 SMD, 1.35-2.45) following tPA thrombolysis in experimental stroke. Subgroup analysis indicated that the route of drug delivery, dosage of tPA, and stroke model used may be factors inducing heterogeneity and influencing the efficacy., Conclusion: Treatment with Chinese herbal medicines significantly improved neurological score and infarct volume, reduced cerebral hemorrhage and BBB damage after tPA thrombolysis. This study supports Chinese herbal medicine as an adjuvant therapy in reducing the side effects of tPA thrombolysis after acute ischemic stroke. The results should be interpreted with more caution since this article was based on animal studies., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: Many studies among different ethnic populations suggested that angiotensin converting enzyme (ACE) gene polymorphisms were associated with susceptibility to Alzheimer's disease (AD). However, the results remained inconclusive. In the present meta-analysis, we aimed to clarify the effect of ACE polymorphisms on AD risk using all available relevant data., Methods: Systemic literature searches were performed using PubMed, Embase, Alzgene and China National Knowledge Infrastructure (CNKI). Relevant data were abstracted according to predefined criteria., Results: Totally, 82 independent cohorts from 65 studies were included, focusing on five candidate polymorphisms. For rs1799752 polymorphism, in overall analyses, the insertion (I) allele conferred increased risk to AD compared to the deletion (D) allele (I vs. D: OR = 1.091, 95% CI = 1.007-1.181, p = 0.032); while the I carriers showed increased AD susceptibility compared with the D homozygotes (II + ID vs. DD: OR = 1.131, 95% CI = 1.008-1.270, p = 0.036). However, none of the positive results passed FDR adjustment. In subgroup analysis restricted to late-onset individuals, the associations between rs1799752 polymorphism and AD risk were identified using allelic comparison (OR = 1.154, 95% CI = 1.028-1.295, p = 0.015, FDR = 0.020), homozygotes comparison, dominant model and recessive model (II vs. ID + DD: OR = 1.272, 95% CI = 1.120-1.444, p < 0.001, FDR < 0.001). Nevertheless, no significant association could be revealed after excluding studies not in accordance with Hardy-Weinberg equilibrium (HWE). In North Europeans, but not in East Asians, the I allele demonstrated increased AD susceptibility compared to the D allele (OR = 1.096, 95% CI = 1.021-1.178, p = 0.012, FDR = 0.039). After excluding HWE-deviated cohorts, significant associations were also revealed under homozygotes comparison, additive model (ID vs. DD: OR = 1.266, 95% CI = 1.045-1.534, p = 0.016, FDR = 0.024) and dominant model (II + ID vs. DD: OR = 1.197, 95% CI = 1.062-1.350, p = 0.003, FDR = 0.018) in North Europeans. With regard to rs1800764 polymorphism, significant associations were identified particularly in subgroup of European descent under allelic comparison (T vs. C: OR = 1.063, 95% CI = 1.008-1.120, p = 0.023, FDR = 0.046), additive model and dominant model (TT + TC vs. CC: OR = 1.116, 95% CI = 1.018-1.222, p = 0.019, FDR = 0.046). But after excluding studies not satisfying HWE, all these associations disappeared. No significant associations were detected for rs4343, rs4291 and rs4309 polymorphisms in any genetic model., Conclusions: Our results suggested the significant but modest associations between rs1799752 polymorphism and risk to AD in North Europeans. While rs4343, rs4291 and rs4309 polymorphisms are unlikely to be major factors in AD development in our research., Competing Interests: No authors have competing interests.

Influenza is an acute respiratory infection caused by the influenza virus, and vaccination against influenza is considered the best way to prevent the onset and spread. MDCK (Madin-Darby canine kidney) cells are typically used to isolate the influenza virus, however, their high tumorigenicity is the main controversy in the production of influenza vaccines. Here, MDCK-C09 and MDCK-C35 monoclonal cell lines were established, which were proven to be low in tumorigenicity. RNA-seq of MDCK-C09, MDCK-C35, and MDCK-W73 cells was performed to investigate the putative tumorigenicity mechanisms. Tumor-related molecular interaction analysis of the differentially expressed genes indicates that hub genes, such as CUL3 and EGFR, may play essential roles in tumorigenicity differences between MDCK-C (MDCK-C09 and MDCK-C35) and MDCK-W (MDCK-W73) cells. Moreover, the analysis of cell proliferation regulation-associated molecular interaction shows that downregulated JUN and MYC, for instance, mediate increased proliferation of these cells. The present study provides a new low-tumorigenic MDCK cell line and describes the potential molecular mechanism for the low tumorigenicity and high proliferation rate., (Copyright © 2020. Published by Elsevier Ltd.)

Endothelial progenitor cells (EPCs) are multipotential stem cells considered to have immense clinical value for revascularization. However, the clinical application of EPCs has been hampered by their clinical potency in ischemic anoxic environments. This study aimed to explore the effect of microRNA-210 (miR-210) on EPCs under oxygen-glucose deprivation (OGD) conditions. We generated a model of EPCs cultured under OGD conditions to simulate ischemia and explore the expression of miR-210 in vitro . With longer exposure to hypoxia, we found that miR-210-3p expression was highly upregulated in OGD groups compared to that in controls from 4 to 24 h, but not miR-210-5p. We then transfected a miR-210-3p mimic and inhibitor into EPCs, and after 24 h, we exposed them to OGD conditions for 4 h to simulate ischemia. We detected miR-210 by real-time polymerase chain reaction (RT-PCR) and tested the proliferation, migration, and tube formation of normal EPCs and OGD-treated EPCs by CCK-8, transwell chamber, and Matrigel assays, respectively. The direct targets of miR-210-3p were predicted using miRWalk. Compared to that in normal EPCs, higher miR-210-3p expression was found in OGD-treated EPCs ( p < 0.05). Moreover, upregulation of miR-210-3p was found to promote proliferation, migration, and tube formation in EPCs under normal and OGD conditions ( p < 0.05), whereas down-regulation inhibited these abilities in OGD-treated EPCs ( p < 0.05). Repulsive guidance molecule A (RGMA), a negative regulator of angiogenesis, was predicted to be a target of miR-210-3p. Accordingly, upregulation of miR-210-3p was found to inhibit its expression at the protein level in OGD-treated EPCs, whereas downregulation of miR-210-3p inhibited its expression ( p < 0.05). A dual-luciferase reporter system confirmed that RGMA is a direct target of miR-210-3p. MicroRNA-210-3p overexpression enhances the angiogenic properties of OGD-treated EPCs by inhibiting RGMA.

Background: Precise subtype classification based on underlying pathophysiology is important to prevent recurrent attack in minor stroke patients. A newly developed Atherosclerosis, Small vessel disease, Cardiac source, Others (ASCO) phenotypic classification system aims to characterize patients using different grades of evidence for stroke subtypes. However, this system has not been specifically applied to minor stroke population. In our study, the impact of using the newer ASCO criteria on minor stroke etiologies was investigated, and compared with that of Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification., Methods: Consecutive patients with minor ischemic stroke (NIHSS ≤3) were assessed and subtyped by the ASCO and TOAST systems. Stroke etiologies were presented and compared. The McNemar test and k statistic were used to analyze the difference and concordance between the 2 algorithms, respectively., Results: A total of 604 first-ever minor stroke patients were analyzed in the present study. Using TOAST classification, large artery atherosclerosis was the most frequent subtype (281, 46.5%), followed by small artery occlusion category (165, 27.3%). When ASCO was applied, 37 different profiles of stroke etiologies were identified. Using grade 1 of evidence, atherosclerosis (A1) was the most frequent subtype (308, 51.0%), followed by small vessel disease (S1, 178, 29.5%). Under consideration of grades 1 and 2, 239 (39.6%) patients were classified into more than 1 category. The ASCO system revealed determined etiologies in 104 of the 137 patients classified to cause undetermined subtype by TOAST classification. Good to very good accordance was observed between ASCO grade 1 and TOAST schemes across etiologic subtypes (κ = 0.719-0.832) except cause undetermined category (κ = 0.470)., Conclusion: Application of ASCO decreased the proportion of patients assigned to cause undermined category compared to TOAST system. Comprehensive characteristics of ASCO system might be helpful in the personalized therapy or secondary prevention for individual patients in the future., (© 2019 S. Karger AG, Basel.)

Endometrial receptivity refers to the ability of endometrium to accept and accommodate endometrial implantation in the process of embryo implantation in implantation window period. It is an important factor affecting the rate of blastocyst implantation in assisted reproduction. It is worth mentioning that ovulation-promoting drugs in current assisted reproduction technology could reduce endometrial receptivity and inhibit blastocyst implantation, greatly affecting the success rate of assisted reproduction. By searching Chinese Scientific Citation Database, it was found that 121 studies from 2006 to 2017 showed that Chinese Bushen Huoxue prescriptions could significantly improve the development of pinopodes in the implantation window, promote the expression of endometrial receptors ER, PR, integrinβ3, LIF, LPA3 and other molecules, and thus enhancing endometrial receptivity and improving embryo implantation. In the theory of traditional Chinese medicine, kidney deficiency is an important factor causing infertility. Chinese Bushen Huoxue prescriptions could nourish the kidney-essence, and promote blood circulation, playing an important role in treating infertility with combined application of western medicine and traditional Chinese medicine. These studies suggest that Chinese Bushen Huoxue prescriptions could improve endometrial receptivity, and their mechanisms are worth further investigation. This article has summarized the research progress of Chinese Bushen Huoxue prescriptions in the field of assisted reproduction, summarized the deficiency of current researches, and preliminarily discussed the potential application prospect of Chinese Bushen Huoxue prescriptions in the treatment of infertility., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Background/aims: This study is aimed at identification of miR-195-5p/MMP14 expression in cervical cancer (CC) and their roles on cell proliferation and invasion profile of CC cells through TNF signaling pathway in CC., Methods: Microarray analysis, gene set enrichment analysis (GSEA) and DAVID were used to analyze differentially expressed miRNAs, mRNAs and signaling pathways. MiR-195-5p and MMP14 expression levels in CC cell were determined by qRT-PCR. Western blot was employed to measure MMP14 and TNF signaling pathway-relating protein level. Luciferase reporter system was used to confirm the targeting relationship between MMP14 and miR-195-5p. Cell proliferation and invasion was respectively deeded by CCK8, transwell. In vivo experiment was carried out to study the impact of MMP14 and miR-195-5p on CC development in mice., Results: The microarray analysis and the results of qRT-PCR determined that miR-195-5p was under-expressed and MMP14 was over-expressed in CC cells. GSEA and DAVID analysis showed that TNF signaling pathway was regulated by miR-195-5p/MMP14 and activated in cervical carcinoma cells. The miR-195-5p and MMP14 have a negative regulation relation. In vivo experiment found that down-regulated MMP14 and up-regulated miR-195-5p suppressed the tumor development., Conclusion: Our results suggest that MMP14 is a direct target of miR-195-5p, and down-regulated MMP14 and up-regulated miR-195-5p suppressed proliferation and invasion of CC cells by inhibiting TNF signaling pathway., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Tumor microenvironment plays a critical role in cancer pathogenesis. In this study, we performed transcriptomic analysis of stromal cells from patients diagnosed with endometrial carcinoma. Endometrial stromal cells from patients and healthy donors were cultured and total RNA was extracted for RNA integrity examination and gene profiling analysis. Gene ontology (GO) and KEGG analysis were also performed. In this study, we found that, in endometrial stromal cells from endometrial cancer patients, a total of 605 genes were changed (fold change ≥2, p -value <0.05). From these, 275 were up-regulated and 330 were down-regulated genes. In addition, GO analysis showed that the differentially expressed genes (DEGs) were involved in various biological processes including cell adhesion, biological adhesion, bone development and extracellular matrix organization. Furthermore, KEGG analysis of the DEGs identified four pathways including Wnt signaling pathway, cadherin signaling pathway, ECM-receptor interaction, and focal adhesion. Our study identified 605 DEGs in stromal cells from endometrial carcinoma which mapped to a variety of biological processes. These results may contribute to understanding the molecular mechanisms o of endometrial carcinoma pathogenesis., Competing Interests: None., (IJCEP Copyright © 2017.)

The purpose of this study was to determine the expression of growth differentiation factor 15 (GDF15) and explore its clinical significance in epithelial ovarian cancer (EOC) patients. The expression of GDF15 in EOC tissues and serum samples was evaluated using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. The association of GDF15 expression with clinicopathologic parameters was analyzed. Survival time was assessed using the Kaplan-Meier technique and Cox regression model. Both in EOC tissues and serum, high GDF15 levels were obviously related with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, ascites, and chemoresistance. Kaplan-Meier analysis indicated that EOC patients with high GDF15 expression showed poorer progression-free survival (PFS) and overall survival (OS). Multivariate analysis demonstrated that GDF15 expression was an independent predictor of PFS in EOC patients. Our study shows that elevated GDF15 expression was associated with poor prognosis in EOC patients. We suggest that GDF15 is a novel biomarker for the early detection of EOC, prediction of the response to chemotherapy, and screening for recurrence in EOC patients.

Background: Ischemic stroke (IS) is a common disease, often resulting in death or disability. Previous studies on prognosis of stroke mainly focused on the baseline condition or modern expensive tests. However, the change of clinical symptoms during acute stage is considerably neglected. In our study, we aim to develop a new prognostic scale to predict the 90-day outcome of IS patients., Methods: In this retrospective cohort study, a secondary data analysis was performed on 489 patients extracted from 1046 patients of 4 hospitals. A new prognostic scale was constructed to predict the recovery of IS mainly based on the National Institutes of Health Stroke Scale (NIHSS) score, traditional Chinese Medicine (TCM) symptoms & signs and the changes during the first 3 days of patients in the 3 TCM hospitals. Receiver Operating Characteristic (ROC) curve was used to determine the cutoff point for prediction. In the end, the scale was used to test the outcome of IS patients in Xuanwu hospital., Results: The new prognostic scale was composed of 8 items including age degree (OR = 3.32; 95 % CI: 1.72-6.42), history of diabetes mellitus (DM) (OR = 2.20; 95 % CI: 1.19-4.08), NIHSS score (OR = 3.08; 95 % CI: 2.16-4.40), anxiety (OR = 3.17; 95 % CI: 1.90-5.29) and irritability (OR = 4.61; 95 % CI: 1.36-15.63) on the 1st day of illness onset, change in NIHSS score (OR = 2.49; 95 % CI: 1.31-4.73), and circumrotating (OR = 7.80; 95 % CI: 1.98-30.64) and tinnitus (OR = 13.25; 95 % CI: 1.55-113.34) during the first 3 days of stroke onset. The total score of the scale was 16.5 and the cutoff point was 9.5, which means patients would have poor outcome at 90 days of stroke onset if the score was higher than 9.5. The new scale was validated on the data of Xuanwu hospital, and the value of its sensitivity, specificity and overall accuracy were 69.6 %, 83.3 % and 75.0 % respectively., Conclusions: The 8-item scale, mainly based on TCM symptoms, NIHSS score and their changes during the first 3 days, can predict the 90-day outcome for IS patients while it still needs to be further validated and optimized clinically.

The aim of this study was to explore the immune protective mechanism of rMOMP protein vaccine in intraocular hypertension and retinal optic nerve injury in rats. The rMOMP protein ophthalmic vaccine was prepared and quality-controlled. Sixty normal adult SD rats were randomly divided into two groups to establish a chronic ocular hypertension model and an optic nerve injury model. The model rats were vaccinated with rMOMP-CS ophthalmic vaccine. Fluorogold retrograde tracing was used to observe retinal ganglion cells, and an immunofluorescence method to determine the expression of retinal GAP43, CD3, BDNF, and GDNF. rMOMP protein ophthalmic vaccine met the requirements for medicinal use. The number of retinal ganglion cells (RGCs) of the rMOMP-CS group in the chronic ocular hypertension model was significantly higher than that of the CS group (P < 0.05). The count of RGCs of the rMOMP-CS group in the optic nerve clamping injury model was significantly higher than that of the CS group (P < 0.01). Thus, rMOMP protein ophthalmic vaccine can induce an increase in the expression of retinal neurotrophic factors, thereby exerting a protective effect on damaged retinal optic nerve.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the corresponding author and the editorial office of Microbes and Infection. An independent reviewer of the retraction request was also appointed given that one of the authors is the Editor-in- Chief. For figure 1C, Lanes 1 and 2 appear to share some unexpected similarities, except for the bottom band, which also appear to be the band of interest. Sections of Figure 2C appear similar to sections of Figure 5D of a paper that had already appeared in Molecular Microbiology, volume 83, issue 5 (2012) 1006-1023. https://doi.org/10.1111/j.1365-2958.2012.07985.x. In figure 3A, Flow cytograms share identical/similar patterns highlighted in various colours. Peculiarly, some of these patterns can be seen as horizontal rotations of others along the axis that separates different quadrants. (ie red green & purple). Moreover, some quadrants appear to have very high densities of events that are suprisingly limited by quadrant gates (most noticeably quadrants B2 from the second column of panels. Figure 5A-B it was found that there were duplicated bands were produced. Figures 5C and 5D, it was found that bands across each individual gel appear identical. One of the conditions of submission of a paper for publication is that authors declare explicitly that the paper has not been previously published and is not under consideration for publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a misuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process”., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: To characterize prognostic and risk factors of central nervous system (CNS) metastases in patients with epithelial ovarian cancer (EOC)., Methods: A retrospective analysis of Xijing Hospital electronic medical records was conducted to identify patients with pathologically confirmed EOC and CNS metastases. In addition to patient demographics, tumor pathology, treatment regimens, and clinical outcomes, we compared putative cancer stem cell marker CD133 expression patterns in primary and metastatic lesions as well as in recurrent EOC with and without CNS metastases., Results: Among 1366 patients with EOC, metastatic CNS lesions were present in 29 (2.1%) cases. CD133 expression in primary tumor was the only independent risk factor for CNS metastases; whilst the extent of surgical resection of primary EOC and platinum resistance were two independent factors significantly associated with time to CNS metastases. Absence of CD133 expression in primary tumors was significantly associated with high platinum sensitivity in both patient groups with and without CNS metastases. Platinum resistance and CD133 cluster formation in CNS metastases were associated with decreased survival, while multimodal therapy including stereotactic radiosurgery (SRS) for CNS metastases was associated with increased survival following the diagnosis of CNS metastases., Conclusions: These data suggest that there exist a positive association between CD133 expression in primary EOC, platinum resistance and the increased risk of CNS metastases, as well as a less favorable prognosis of EOC. The absence of CD133 clusters and use of multimodal therapy including SRS could improve the outcome of metastatic lesions. Further investigation is warranted to elucidate the true nature of the association between platinum sensitivity, CD133 expression, and the risk and prognosis of CNS metastases from EOC.

In addition to the typical size, Cryptococcus neoformans can enlarge its size to form titan cells during infection, and its diameter can reach up to 100 μm. Clinical reports about cryptococcal titan cells are rare. Most studies focus on aspects of animal models of infection with titan cells. Herein, we report the clinical and imaging characteristics and histopathologic features of 3 patients with titan cells and 27 patients with pathogens of typical size, and describe the morphological characteristics of titan cells in details. Histologically, 3 patients with titan cells show necrosis, fibrosis and macrophage accumulation. The titan cells appear in necrotic tissue and between macrophages, and have thick wall with unstained halo around them and diameters range from 20 to 80 μm with characteristic of narrow-necked single budding. There are also organisms with typical size. All 27 patients with normal pathogens show epithelioid granulomatous lesions. There is no significantly difference in clinical and imaging feature between the two groups. Cryptococcus neoformans exhibits a striking morphological change for the formation of titan cells during pulmonary infection, which will result in misdiagnosis and under diagnosis. The histopathological changes may be new manifestation, which need to be further confirmed by the study with animal models of infection and the observation of more clinical cases. Careful observation of the tissue sections is necessary.

Objective: To analyze effects of high mobility group AT-hook 2 (HMGA2) on malignant degree, invasion, metastasis, proliferation and cellular morphology of ovarian cancer cells., Methods: Three methods were applied to observe the effect on HMGA2 expression in ovarian cancer cells and ovarian epithelial cells., Results: After the application of siRNA-HMGA2, number of T29A2-cell clones was decreased, there was significant difference compared with the negative control Block-iT. After application of let-7c, number of T29A2+ cell clones was decreased significantly, however, after the application of Anti-let-7, the number of clones restored, and there was no significant difference compared with the negative control group. After interference, the number of T29A2- cells which passed through Matrigel polycarbonate membrane were significantly lower than the negative control group. After the treatment of siRNA-HMGA2, let-7c and sh-HMGA2 respectively, growth and proliferation of T29A2-, T29A2+ and SKOV3 were slower, and the phenomenon was most obvious in SKOV3. Stable interference of HMGA2 induced mesenchymal-epithelial changes in the morphology of SKOV3-sh-HMGA2., Conclusions: HMGA2 can promote malignant transformation of ovarian cancer cells, enhance cell invasion and metastasis, and promote cell growth and proliferation of ovarian cancer cells, which can cause ovarian cancer to progress rapidly and affect the quality of life., (Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)

Cytochrome P450 1A1 (CYP1A1) A4889G polymorphism was supposed to be associated with endometrial cancer risk, but previous studies reported conflicting results. We therefore performed a meta-analysis of all relevant studies to get a comprehensive assessment of the association between CYP1A1 A4889G polymorphism and endometrial cancer risk. The pooled odds ratios (OR) with the corresponding 95% confidence interval (95% CI) was calculated to assess the association. Finally, ten studies with a total of 1,682 endometrial cancer cases and 2,510 controls were finally included into the meta-analysis. Meta-analysis of the total ten studies showed that CYP1A1 A4889G polymorphism was not associated with endometrial cancer risk (ORG versus A = 1.14, 95% CI 0.83-1.57, P OR = 0.417; ORGG versus AA = 1.23, 95% CI 0.70-2.18, P OR = 0.470; ORGG versus AA/AG = 1.03, 95% CI 0.59-1.81, P OR = 0.919; ORGG/AG versus AA = 1.22, 95% CI 0.82-1.81, P OR = 0.336). Subgroup analyses by ethnicity further showed that there was also no obvious association between CYP1A1 A4889G polymorphism and endometrial cancer risk in both Caucasians and Asians. Sensitivity analysis by excluding single study in turns showed that the pooled estimations were not stable. Therefore, evidence for currently available data suggests that CYP1A1 A4889G polymorphism is not associated with endometrial cancer risk. However, more studies with large number of participants are needed to further assess the association precisely.

The combination of fenretinide and selenite on ovarian cancer cells was investigated to assess its effects on proliferation and ability to induce apoptosis. Our results showed that fenretinide and selenite in combination significantly suppress the proliferation of ovarian cancer cells and induced apoptosis (including reactive oxygen species generation, and the loss of mitochondrial membrane potential) compared with either drug used alone. The caspase3/9-dependent pathway was triggered significantly in combination treatment, and moreover, the AMPK pathway also mediated the apoptosis induction in fenretinide and selenite combination. Fenretinide and selenite combination treatment was demonstrated to suppress tumor growth in vivo, this drug combination has been thus found to have an enhanced anti-tumor effect on ovarian cancers cells.

Objective: To explore the effect of phlegm-heat syndrome on the degree of neurological deficit and provide some data support for the correct recognition of the relationship between phlegm-heat syndrome and neurological deficits in stroke patients., Methods: Clinical information were collected on 294 patients with acute ischemic stroke (AIS) whose syndrome and National Institute of Health stroke scale (NIHSS) score were checked at baseline (within the first 3-day admission) and at 7, 14, 28, and 90 days after admission to our clinical research centre. We explored the effect of phlegm-heat syndrome on the degree of neurological deficit following stroke by applying a repeated measures analysis of variance., Results: Stroke patients with phlegm-heat syndrome had higher NIHSS score than patients without the syndrome (P <0.01), and there appeared to be a decrease in NIHSS score over time in all patients (P <0.01)., Conclusions: Phlegm-heat syndrome in patients who have suffered stroke has an effect on the degree of neurological deficiency. Disappearance of phlegm-heat syndrome may improve the degree of neurological deficit observed in stroke patients.

Objective: To investigate the operative treatment for first-treated patients with malignant ovarian germ cell tumors who need preservation of fertility., Methods: The clinical data of 105 patients who were treated with fertility-sparing surgery in 11 hospitals from 1992 to 2010 were collected to evaluate the outcomes of different primary surgical operative procedures. All 105 cases were performed the surgeries that preserved fertility and divided into three groups according to the surgical approaches, comprehensive staging surgery group: 47 cases (44.8%) received comprehensive staging surgeries that including the ipsilateral oophorectomy + omentectomy + retropertoneal lymph node dissection ± appendectomy + multiple biopsies;oophorectomy group:45 cases (42.9%)received ipsilateral oophorectomy ± biopsy of contralateral ovary ± omentectomy;tumor resection group:13 cases (12.4%) received enucleation of the mass with preservation of the ovary. Differences were compared among the three groups of patients in the surgery-related indicators, complications, fertility and prognosis., Results: (1) Surgery-related indicators:the average blood loss of the comprehensive staging surgery group, the oophorectomy group and the tumor resection group were 496, 104 and 253 ml, the mean operation time were 176, 114 and 122 minutes, respectively, and there were significant differences among three groups (P = 0.011, P = 0.000). (2) Complication:the surgical complication rates of the three groups were 17% (8/47), 0 and 1/13, with significant differences (P = 0.015). (3) Reproductive function status: the pregnancy rate and birth rate of the three groups were no significant differences (9/19 vs. 7/19 vs. 2/3, P = 0.515; 8/19 vs. 5/19 vs. 2/3, P = 0.636). (4) PROGNOSIS: the recurrence rate of the three groups were significant differences [13% (6/47) vs. 0 vs. 2/13, P = 0.013], but the death rate with no significant differences [6% (3/47) vs. 0 vs. 0, P = 0.129]; The five-year survival rate of three different groups were 89%, 100% and 100% (P > 0.05), while disease free survival rate were 85%, 100% and 83% (P < 0.05), respectively., Conclusions: Compared with comprehensive staging surgery, oophorectomy group have higher surgical security and satisfactory prognosis, considerable pregnancy rates and birth rate. The tumor resection security may be reliable, but the prognosis is poor.

Heterosis is widely used in genetic crop improvement; however, the genetic basis of heterosis is incompletely understood. The use of whole-genome segregating populations poses a problem for establishing the genetic basis of heterosis, in that interactions often mask the effects of individual loci. However, introgression line (IL) populations permit the partitioning of heterosis into defined genomic regions, eliminating a major part of the genome-wide epistasis. In our previous study, based on mid-parental heterosis (HMP) value with single-point analysis, 42 heterotic loci (HLs) associated with six yield-related traits were detected in wild and cultivated rice using a set of 265 ILs of Dongxiang common wild rice (Oryza rufipogon Griff.). In this study, the genetic effects of HLs were determined as the combined effects of both additive and dominant gene actions, estimated from the performance values of testcross F1s and the dominance effects estimated from the HMP values of testcross F1s. We characterized the gene action type at each HL. Thirty-eight of the 42 HLs were over-dominant, and in the absence of epistasis, four HLs were dominant. Therefore, we favour that over-dominance is a major genetic basis of 'wild-cultivar' crosses at the single functional Mendelian locus level.

Objective: To explore the correlation between stroke of qi deficiency syndrome (QDS) and the neurological impairment degree, and to study its correlation between QDS and its long-term prognosis., Methods: Recruited were 706 stroke patients with complete clinical information including diagnostic scale scoring of elements such as wind, fire, phlegm, blood stasis, qi deficiency, and yin deficiency, scoring of The National Institutes of Health Stroke Scale (NIHSS) within 72 h from attack, on the 7th, 14th, 28th, and 90th day after attack, and Barthel index (BI) scoring on the 90th day. They were assigned to the QDS group (330 cases) and the non-QDS group (376 cases). The NIHSS scores at different time points were compared between the two groups using analysis of variance of repeated measure data. The correlation between each syndrome element and the long-term prognosis of stroke was studied using Logistic regression analysis., Results: Higher NIHSS score was found in patients of QDS than those of non-QDS at each time point (P < 0.01). Statistical difference existed in NIHSS score between the two groups at each time point (P < 0.01, P < 0.05). Besides, NIHSS score decreased gradually as time went by. The occurrence frequencies of blood stasis syndrome and phlegm syndrome were higher at each time point. On the 90th day after attack, 427 patients with BI > or = 95 (accounting for 60%) had favorable prognosis, while 279 with BI < 95 (accounting for 40%) had unfavorable prognosis. QDS at each time point was negatively correlated with the 90th-day BI, with the B value being -0.496, -0.714, -0.867, -0.567, and -0.764, respectively., Conclusions: Stroke patients of QDS had more severe neurological impairment than those of non-QDS. Stroke patients of acute-stage QDS was closely correlated with unfavorable prognosis on the 90th day after attack. Early actively invigorating healthy qi plays an important role in improving the long-term prognosis of stroke patients.

The study on the genetic basis of heterosis has received significant attention in recent years. In this study, using a set of introgression lines (ILs) and corresponding testcross F(1) populations, we investigated heterotic loci (HL) associated with six yield-related traits in both Oryza sativa L. subsp. indica and japonica. A total of 41 HL were detected on the basis of mid-parent heterosis values with single-point analysis. The F(1) test-cross population showed superiority in most yield-related traits and was characterized by a high frequency of overdominant HL. Thirty-eight of the 41 HL were overdominant, and in the absence of epistasis, three HL were dominant, suggesting that heterotic effects at the single-locus level mainly appeared to be overdominant in rice. Twenty-four HL had a real positive effect, suggesting that they are viable candidates for the improvement of rice yield potential. Compared with the quantitative trait loci (QTLs) detected in the ILs, only six out of the 41 (14.6%) HL were detected in QTL analysis under the same statistical threshold, indicating that heterosis and trait performance may be conditioned by different sets of loci.

Background: Hypoxia inducible factor 1 (HIF-1) is a key transcriptional factor activated during cerebral ischemia, which regulates a great number of downstream genes, including those associated with cell death. In the present study, we aimed to test the hypothesis that post-ischemic HIF-1α up-regulation might promote autophagy activation; thereby, HIF-1α inhibitor 2ME2 might prevent neurons from ischemic injury through inhibiting autophagy., Methods: Global ischemia was induced using the four-vessel occlusion model (4-VO) in Sprague-Dawley rats (male, 250-280g). 2-Methoxyestradiol (2ME2, 5mg/kg, i.p.) was administrated to down-regulate HIF-1α expression. Post-ischemic beclin-1 and LC3 protein expression was determined at different time points through Western blot assay. Neuronal injury was determined by cresyl violet staining and TUNEL staining in coronal histological sections., Results: The expression of beclin-1 and the ratio of LC3-II/LC3-I increased significantly at 12 and 24 h after ischemia. 2ME2 could remarkably inhibit the up-regulation of beclin-1 and the increase of LC3-II/LC3-I ratio during reperfusion. Moreover, 2ME2 and 3-MA exhibited powerful protective effects against ischemic/reperfusion induced neuronal injury., Conclusions: This study confirmed that autophagy participated in post-ischemic neuronal injury. 2ME2, a HIF-1α inhibitor, might significantly decrease autophagy activation after cerebral ischemia and relieve post-ischemic neuronal injury. Our findings demonstrate that autophagy could be a potential target for neuronal protection after cerebral ischemia.

PTEN (phosphatase and tensin homologue deleted on chromosome ten)/PI3K (phosphatidylinositol 3-kinase)/Akt/mTOR (mammalian target of rapamycin) signaling pathway, which is commonly dysregulated in a broad array of human malignancies, controls the assembly of eukaryotic translation initiation factor 4F (eIF4F) complex through regulation of eIF4E binding proteins (4E-BPs) phosphorylation. And accumulated data over the past two decades implicated eIF4F complex as one of the promising targets for anticancer therapy. It has been confirmed that the translation initiation of mRNA coding for hypoxia-inducible factor-1α (HIF-1α) and survivin, which had been considered as the two major determinants of tumor radiosensitivity, are both controlled by eIF4F complex. Also, eIF4F complex controls the expression of VEGF and bFGF, the two well-known pro-angiogenic factors involved in developing radioresistance. Therefore eIF4F complex plays a pivotal role in regulation of radiosensitivity. In this article, we postulate that cell-permeable, phosphorylation-defective 4E-BP fusion proteins, which could be prepared by substituting the mTOR recognition motif located in N-terminal of 4E-BPs with protein transduction domain from HIV-1 TAT, HSV-1 VP22 or PTD4, could not only inhibit tumor growth but also enhance tumor response to radiation therapy through disruption of eIF4F complex assembly. In our opinion, the recombinant fusion proteins are superior to mTOR inhibitors for they do not cause immunosuppression, do not lead to Akt activation, and could be easily prepared by prokaryotic expression. If the hypothesis was proved to be practical, the cell-permeable, phosphorylation-defective 4E-BP fusion proteins would be widely used in clinical settings to improve tumor response to radiotherapy in the near future., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Bacterial vaginosis (BV) is one of the most common infectious diseases among sexually active women and is associated with the increased acquisition of a variety of sexually transmitted diseases. This study aimed to compare the efficacy of a non-antibiotic sucrose gel against an antibiotic metronidazole gel for the treatment of BV., Methods: A randomized, double-blinded, multi-center, parallel-group, placebo-controlled phase III clinical trial was conducted at eight hospitals in China. A total of 560 subjects with clinically diagnosed BV were randomly assigned into three groups for vaginally receiving sucrose, metronidazole, and placebo gels, respectively, twice daily for five consecutive days. The efficacy of therapeutic cure, defined as an achievement of both microbiologic cure (a Nugent score of 3 or less) and clinical cure (a resolution of the clinical findings from the baseline visit), was evaluated at the 1st and 2nd test-of-cure (TOC) visits at 7-10 and 21-35 days after the start of treatment, respectively., Results: Therapeutic cure rates for sucrose, metronidazole, and placebo gel groups were 83.13%, 71.30% and 0.92%, at the 1st TOC, and 61.04%, 66.67% and 7.34%, at the 2nd TOC, respectively. While there was no significant difference between the sucrose and metronidazole gel groups at the 2nd TOC (P = 0.305), and sucrose gel was more effective than metronidazole gel at the 1st TOC (P = 0.009)., Conclusion: These findings suggest that sucrose gel restores normal vaginal flora more rapidly than metronidazole gel and can be used as a novel treatment for BV.

Cerebral amyloid angiopathy is a common feature in Alzheimer's disease (AD), which is characterized by amyloid deposit around brain vessels including capillaries. The origin of the amyloid protein of CAA remains controversial. In our work, we provide data to show that primary umbilical vein endothelial cells (HUVEC) harbor APP processing secretases and can produce Abeta(42) under starvation. Starvation can increase the secretion of Abeta(42) by altering the expression of beta-secretases (BACE1) and gamma-secretases (APH and PEN2). This process is regulated by macroautophagy. Suppression of macroautophagy induction by 3MA further increased the level of Abeta(42) produced under starvation in HUVECs. These results suggest that starvation-induced Abeta(42) secretion might contribute to the formation of CAA and hence vascular degeneration in AD., (Copyright 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Objective: Exposure to chemotherapy causes various adverse effects on the ovaries including premature ovarian failure and infertility. GnRH antagonist cetrorelix could reverse the ovarian damage during chemotherapy, but the mechanism remains unclear. The objectives of this study were to examine the role of the cetrorelix for prevention of mitochondria-dependent apoptosis in granulosa cells of rats during the treatment with cyclophosphamide(Cy), if the mitochondria-dependent apoptotic process was involved., Methods: Female SD rats were injected with cetrorelix before and after administration of saline, or Cy. Main outcome measures were the apoptotic indexes, serum hormones, ultrastructure of granulosa cells, mitochondrial membrane potential, the kinetics of cytochrome c (Cyt-c) processing in cells, and apoptotic markers., Results: The ovarian apoptotic indexes as shown by TUNEL assay were reduced by cetrorelix pretreatment and the rats regained normal hormonal profile. The ultrastructure and JC-1 fluorescence intensity assessments showed cetrorelix pretreatment inhibited mitochondrial dysfunction in granulosa cells induced by chemotherapy. Western blot analysis showed that cetrorelix suppressed the release of Cyt-c from mitochondria to cytoplasm. Meanwhile, cetrorelix pretreatment expressed less Bax, caspase-3 and Cyt-c in granulosa cells compared with chemotherapy alone., Conclusion: Cetrorelix could reduce the apoptosis in granulosa cells through inhibiting mitochondria-dependent apoptosis triggered by chemotherapy., (Copyright 2010 Elsevier Inc. All rights reserved.)

Apolipoprotein E (APOE) promoter polymorphisms have long been linked to Alzheimer disease (AD) susceptibility, although the established data remains controversial. Using meta-analysis, our study aimed to clarify the nature of the genetic risks contributed by the three polymorphisms for developing AD. Medline, Embase, and Alzgene search identified 40 studies with 9,662 cases and 9.696 controls. Both -491A/T polymorphism (AA vs AT + TT: OR = 1.49, 95% CI=1.29-1.72) and -219T/G polymorphism (TT vs TG + GG: OR=1.30, 95% CI=1.10-1.55) showed a significant association with AD susceptibility; however, significant association was not identified in the analysis for -427T/C polymorphism (TT vs TC + CC: OR =1.03, 95% CI= 0.82-1.30). Among the APOE epsilon 4} carriers, the -491A homozygotes were at higher risk to develop AD compared with the -491T carriers (OR=1.42, 95% CI =1.15-1.76). For subjects carrying the -491AA genotype, the presence of the APOE epsilon4 allele increased the risk of AD 4.37-fold (95% CI=3.43-5.56). Subgroup analysis restricted to the late-onset or the Caucasian individuals revealed a similar association as that identified without restriction regarding -491A/T polymorphism. Our results confirm a significant but modest association between APOE promoter -491A/T and -219T/G polymorphisms and AD susceptibility.

Introduction: Genetic studies restricted to young adult ischemic stroke patients may help in excluding the potentially confounding variables encountered with advanced age; thus, allowing a more precise risk evaluation derived from the inherited mutations alone. Through meta-analysis, this study was conducted to determine the genetic risk contributed by each susceptibility gene polymorphism, particularly in adult early-onset ischemic stroke patients., Materials and Methods: Electronic databases were searched for all the case-control studies relating to any candidate genes for ischemic stroke. The range of age was 18-50 years for cases. Fixed or random effects model was used depending on the heterogeneity between studies., Results: Twenty-six studies were finally included in this meta-analysis; these studies focused on 7 candidate genes. A significant but modest association was identified for 2 polymorphisms, namely, methylenetetrahydrofolate reductase (MTHFR) C677T (OR = 1.44, 95% CI = 1.14-1.80) and apolipoprotein E (ApoE) epsilon2-4 (OR = 2.53, 95% CI = 1.71-3.73). Although the pooled analysis for platelet glycoprotein Ia (GPIa) C807T showed a positive association (OR = 1.50, 95% CI=1.10-2.05), the Egger's test indicated the existence of publication bias (t=5.27, P>|t|=0.034)., Conclusions: Genetic abnormalities specific to homocysteine and lipid metabolism increase the risk for ischemic stroke at an early age. These data may offer important implications for future genetic association studies for stroke.

Objective: XIAP is one of the most important members of the inhibitors of apoptosis family. It is upregulated in various malignancies, including human ovarian carcinomas, it promotes invasion, metastasis, growth, and survival of malignant cells, and it also confers resistance to some chemotherapeutic drugs. We observed the effect of XIAP gene RNA interference (RNAi) on the proliferation, apoptosis, tumorigenicity, and chemosensitivity of the human ovarian carcinoma cells A2780/cp70., Study Design: We used a human U6 promoter-driven DNA template approach to induce short hairpin RNA-triggered RNAi to block XIAP gene expression in the human ovarian cancer cell line A2780/cp70. A corresponding site-mutated vector was constructed as a negative control (pSilencer 2.1-NC). The expression of XIAP mRNA and protein among the stable transfected cells and the untransfected ones was detected by RT-PCR and Western blotting. The cell growth was examined and drug sensitivity was assayed using the MTT assay. Cell apoptosis was measured by flow cytometry and the tumorigenicity by using nude mice., Results: Three stable transfected cell lines: A2780/cp70-s2, A2780/cp70-NC, and A2780/cp70-neo were established. The expression levels of XIAP gene mRNA and protein in A2780/cp70-s2 were 63.3% and 60.8%, lower than in A2780/cp70-NC, A2780/cp70-neo, and untransfected A2780/cp70 cells. The cell proliferation of A2780/cp70-s2 was reduced by up to 62.2+/-1.9%. Compared with the other cell lines, the changes in apoptotic rate in A2780/cp70-s2 was 31.1+/-1.3%, obviously increasing (P<0.05). The knockdown of XIAP retards tumorigenicity in nude mice and after 21 days the average tumor weight of the A2780/cp70-s2 group was lower by 1.62+/-0.11g (P<0.05). And the survival index in A2780/cp70-s2 cells was markedly reduced with the addition of 1 microM and 10 microM cisplatinum, respectively (P<0.05)., Conclusions: XIAP gene RNAi inhibited the proliferation of ovarian carcinoma cells and caused cells to be more sensitive to cisplatin through the reduction of its mRNA and protein. These results suggest that XIAP is an ovarian cancer-related gene and that XIAP is a potential target for therapeutic anti-cancer drugs.

Purpose: Carbapenems are important agents for the therapy of Gram-negative bacillus infections, and the development of their resistance hampers effective therapeutic options. The purpose of this study was to assess the major mechanisms and risk factors leading to carbapenem resistance in clinical Pseudomonas aeruginosa isolates., Methods: Thirty-four clinical isolates with differing degrees of carbapenem susceptibility were analyzed for carbapenemase, porin, and efflux systems. Risk factor analysis was performed using a case-control study., Results: Eighteen of 24 carbapenem-resistant isolates were producers of carbapenemase. Diminished expression of oprD and overexpression of effluxes were present in five and seven carbapenem-resistant isolates, respectively. The number of days from admission to the day of positive culture and days of antibiotic apply were identified as the independent predictors of infection with carbapenem-resistant P. aeruginosa., Conclusions: Carbapenemase production is a major mechanism of P. aeruginosa isolates involved in this study. Increased length of hospital stay and days of antibiotic application were the most important risk factors identified for carbapenem resistance.

Aims: To investigate the inhibiting mechanism of multi-drug resistance (MDR) using expression vectors of short hairpin RNA (shRNA) in a MDR human ovarian cancer cell line (A2780/cp70)., Methods: Two shRNA expression vectors were constructed and introduced into A2780/cp70 cells. Expression of MRP2 mRNA was assessed by RT-PCR, and Mrp2 expression was determined by Western blot and immunocytochemistry. Apoptosis and sensitization of the cells to cisplatinum were quantified by flow cytometry and methyl-thiazol-tetrazolium (MTT) assays. Cellular cisplatinum accumulation was assayed by laser scanning confocal microscopy (LSCM)., Results: In A2780/cp70 cells transfected with MRP2-A and MRP2-B shRNA expression vectors, RT-PCR showed that MRP2 mRNA expression was reduced by 41.8% (P < 0.05), 30.9% (P < 0.01) (transient transfection) and 39.6% (P < 0.05), 29.4% (P < 0.01) (stable transfection), respectively. Western blot and immunocytochemistry showed that Mrp2 expression was significantly and specifically inhibited. Resistance against cisplatinum was decreased from 173- to 119-fold (P < 0.05), 64-fold (P < 0.01) (transient transfection) and to 117-fold (P < 0.05), 60-fold (P < 0.01) (stable transfection). Furthermore, shRNA vectors significantly enhanced the cellular cisplatinum accumulation. The combination of shRNA vectors and cisplatinum significantly induced the apoptosis of cells., Conclusions: shRNA expression vectors effectively reduce MRP2 expression and can restore the sensitivity of drug-resistant cancer cells to conventional chemotherapeutic agents.

Objective: GnRH antagonist cetrorelix could reserve the ovarian follicles during chemotherapy, but the mechanism remains unclear. The objectives of this study were to examine the overall effect of cetrorelix against ovarian failure and to define if the apoptotic process was involved., Methods: Female SD rats were injected with cetrorelix before and after administration of saline, or cyclophosphamide (Cy), or oral etoposide (VP). Main outcome measures were the number of ovarian follicles, serum hormones, ovary histology and apoptotic markers., Results: The females exposed to Cy or VP had reduced body and ovary weights, which could be restored by cetrorelix pretreatment. Single cetrorelix treatment could increase the number of primordial follicles, but reduce the number of growing and mature follicles. As a consequence, the ovaries exposed to cetrorelix prior to Cy or VP showed significantly higher numbers of follicles at all developing stages than those exposed to Cy or VP alone. Meanwhile, the ovarian apoptotic indexes as shown by TUNEL assay were reduced by cetrorelix pretreatment and the ovary expressed less caspases-3 and more Bcl-2 compared with chemotherapy alone. Moreover, the rats regained normal hormonal profile after cetrorelix pretreatment without any alterations in ovarian expression of estrogen receptor (ER)alpha, ERbeta, or progesterone receptor (PR)., Conclusion: Cetrorelix could reduce the chemotherapy-induced ovarian damage through regulating the expression of Bcl-2 and caspases-3 in the ovary, without any expressional alterations of nuclear receptors, suggesting the apoptosis pathway involved.

Objective: Aurora-A, a novel member of the serine/threonine kinase family, has been reported to be correlated with tumorigenesis. Our aim was to investigate whether Aurora-A expression correlates with clinicopathologic factors and prognosis of cervical carcinoma patients., Design/setting: Retrospective study., Population: Seventy-four cervical carcinoma patients, between 1996 and 2002., Methods: Reverse transcription-polymerase chain reaction and Western blot assays were performed to detect the expression of Aurora-A gene in cervical carcinoma cells and paired cancerous and corresponding noncancerous tissues from 74 cervical carcinoma patients. The expression of Aurora-A protein in tissues was also determined by immunohistochemistry. The relationships of Aurora-A expression with clinical factors and prognosis of patients were evaluated by statistical analysis., Results: The expression of Aurora-A mRNA and protein was significantly higher in cervical carcinoma cells than in normal cervical epithelial cell (p<0.05). The expression of Aurora-A mRNA in cancerous tissues was significantly higher than that in corresponding noncancerous tissues (p<0.001). The expression of Aurora-A protein was also increased in tumor tissues by immunochemistry. Aurora-A transcript expression was correlated with FIGO stage (p=0.018), tumor differentiation (p=0.014), parametrial invasion (p=0.024), lymphnode or hematogenous metastasis (p=0.005 or 0.019), but not other clinicopathological factors. Patients with high Aurora-A expression had a poorer disease-free survival and overall survival rates than patients with low Aurora-A expression. Multivariate analysis showed that high Aurora-A mRNA expression was an independent prognostic factor (risk ratio: 2.88; p=0.005)., Conclusions: Aurora-A might be used as a prognostic marker for cervical carcinoma patients.