Publications by authors named "Wei-Wei Sun"

52 Publications

Retraction notice to "Role of hepatic neuropeptide Y-Y1 receptors in a methionine- cholinedeficient model of non-alcoholic steatohepatitis" [Life Sci. 245 (2020) 117356].

Life Sci 2021 Sep 7;281:119210. Epub 2021 Jul 7.

Department of Cardiology, Southwest Hospital, Third Military Medical University, China. Electronic address:

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Concern has been raised by a reader about both the inappropriateness of certain methods used to prepare Figures 1A and 3A; as well as the lack of important information including the exact age of the mice and details of the ELISA used. These issues could undermine the scientific grounds of the article. Apologies are offered to readers of the journal that this was not detected during the submission process.
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http://dx.doi.org/10.1016/j.lfs.2021.119210DOI Listing
September 2021

Observation and measurement of applied anatomical features for thoracic intervertebral foramen puncture on computed tomography images.

World J Clin Cases 2021 Jun;9(18):4607-4616

Department of Pain Management, Nanjing Drum Tower Hospital, Clinical College of Xuzhou Medical University, Nanjing 210008, Jiangsu Province, China.

Background: Thoracic intervertebral foramen puncture is the key step for interventional therapy on the thoracic nerve roots or dorsal root ganglia. The anatomical features of the thoracic spine are complex, and puncture injury to the pleura, blood vessels, spinal cord, and other tissues may cause serious complications. The spatial anatomical characteristics and related parameters for thoracic intervertebral foramen puncture remain poorly understood.

Aim: To observe and summarize the spatially applied anatomical characteristics for intervertebral foramen puncture on different vertebral segments.

Methods: A total of 88 patients (41 males and 47 females) who underwent thoracic minimally invasive interventional treatment at Nanjing Drum Tower Hospital from January 2019 to June 2020 were included. Computed tomography images of 167 thoracic vertebral segments scanned in the prone position were collected. The width of the intertransverse space (D), the height of the rib neck/head above the lower transverse process (D), the width of the lateral border of the articular process/lamina (W), and the width of the posterior border of the vertebral body (W) were measured. At the upper 1/3 of the intervertebral foramina, the horizontal inclination angle (α) from the lateral border of the articular process/lamina to the posterolateral border of the vertebral body was measured. The ratios D/D and W/W were calculated. The intervertebral foramen parameters were compared between segments.

Results: No rib head/neck occlusion (D/D > 0) was found in the intertransverse spaces of T1-2 and T12-L1. The incidence of occlusion for the upper thoracic segments (T1-5, = 138), middle thoracic segments (T5-9, = 116), and lower thoracic segments (T9-L1, = 80) were 76.81%, 100%, and 82.50%, respectively. The incidence of occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments ( < 0.05). The incidence of > 1/2 occlusion (D/D > 1/2) for the upper, middle, and lower thoracic segments was 7.97%, 74.14%, and 32.50%, respectively. The incidence of > 1/2 occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments ( < 0.05). W was longer than W on T1-2 to T9-10 and shorter than W on T10-11 to T12-L1. The horizontal puncture angle (α) into the external opening of the intervertebral foramina was positively correlated with the segments of the thoracic vertebrae from the cephalic to caudal portion (left: = 0.772, < 0.01; right: = 0.771, < 0.01), and the horizontal inclination angle for T11-12 and T12-L1 was 90°.

Conclusion: It is necessary to identify the spatial impact of the rib head/neck on the puncture path of the intervertebral foramina and design appropriate puncture angles for different segments.
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http://dx.doi.org/10.12998/wjcc.v9.i18.4607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223838PMC
June 2021

Downregulated RPS-30 in Angiostrongylus cantonensis L5 plays a defensive role against damage due to oxidative stress.

Parasit Vectors 2020 Dec 9;13(1):617. Epub 2020 Dec 9.

Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, PR China.

Background: Eosinophilic meningitis, caused by fifth-stage larvae of the nematode (roundworm) Angiostrongylus cantonensis, is mainly attributed to the contribution of eosinophils to tissue inflammatory responses in helminthic infections. Eosinophils are associated with the killing of helminths via peroxidative oxidation and hydrogen peroxide generated by the dismutation of superoxide produced during respiratory bursts. In contrast, when residing in the host with high level of eosinophils, helminthic worms have evolved to attenuate eosinophil-mediated tissue inflammatory responses for their survival in the hosts. In a previous study we demonstrated that the expression of the A. cantonensis RPS 30 gene (Acan-rps-30) was significantly downregulated in A. cantonensis L5 roundworms residing in cerebrospinal fluid with a high level of eosinophils. Acan-RPS-30 is a protein homologous to the human Fau protein that plays a pro-apoptotic regulatory role and may function in protecting worms from oxidative stress.

Methods: The isolation and structural characterization of Acan-RPS-30 were performed using rapid amplification of cDNA ends (RACE), genome walking and bioinformatics. Quantitative real-time-PCR and microinjection were used to detect the expression patterns of Acan-rps-30. Feeding RNA interference (RNAi) was used to knockdown the apoptosis gene ced-3. Microinjection was performed to construct transgenic worms. An oxidative stress assay was used to determine the functions of Acan-RPS-30.

Results: Our results showed that Acan-RPS-30 consisted of 130 amino acids. It was grouped into clade V with C. elegans in the phylogenetic analysis. It was expressed ubiquitously in worms and was downregulated in both L5 larvae and adult A. cantonensis. Worms expressing pCe-rps30::Acan-rps-30::rfp, with the refractile "button-like" apoptotic corpses, were susceptible to oxidative stress. Apoptosis genes ced-3 and ced-4 were both upregulated in the transgenic worms. The phenotype susceptible to oxidative stress could be converted with a ced-3 defective mutation and RNAi. rps-30 mutant worms were resistant to oxidative stress, with ced-3 and ced-4 both downregulated. The oxidative stress-resistant phenotype could be rescued and inhibited by through the expression of pCe-rps30::Acan-rps-30::rfp in rps-3 mutant worms.

Conclusion: In C. elegans worms, downregulated RPS-30 plays a defensive role against damage due to oxidative stress, facilitating worm survival by regulating downregulated ced-3. This observation may indicate the mechanism by which A. cantonensis L5 worms, with downregulated Acan-RPS-30, survive in the central nervous system of humans from the immune response of eosinophils.
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http://dx.doi.org/10.1186/s13071-020-04495-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724845PMC
December 2020

Accuracy study of a binocular-stereo-vision-based navigation robot for minimally invasive interventional procedures.

World J Clin Cases 2020 Aug;8(16):3440-3449

Department of Pain Management, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.

Background: Medical robot is a promising surgical tool, but no specific one has been designed for interventional treatment of chronic pain. We developed a computed tomography-image based navigation robot using a new registration method with binocular vision. This kind of robot is appropriate for minimal invasive interventional procedures and easy to operate. The feasibility, accuracy and stability of this new robot need to be tested.

Aim: To assess quantitatively the feasibility, accuracy and stability of the binocular-stereo-vision-based navigation robot for minimally invasive interventional procedures.

Methods: A box model was designed for assessing the accuracy for targets at different distances. Nine (three sets) lead spheres were embedded in the model as puncture goals. The entry-to-target distances were set 50 mm (short-distance), 100 mm (medium-distance) and 150 mm (long-distance). Puncture procedure was repeated three times for each goal. The Euclidian error of each puncture was calculated and statistically analyzed. Three head phantoms were used to explore the clinical feasibility and stability. Three independent operators conducted foramen ovale placement on head phantoms (both sides) by freehand or under the guidance of robot (18 punctures with each method). The operation time, adjustment time and one-time success rate were recorded, and the two guidance methods were compared.

Results: On the box model, the mean puncture errors of navigation robot were 1.7 ± 0.9 mm for the short-distance target, 2.4 ± 1.0 mm for the moderate target and 4.4 ± 1.4 mm for the long-distance target. On the head phantom, no obvious differences in operation time and adjustment time were found among the three performers ( > 0.05). The median adjustment time was significantly less under the guidance of the robot than under free hand. The one-time success rate was significantly higher with the robot ( < 0.05). There was no obvious difference in operation time between the two methods ( > 0.05).

Conclusion: In the laboratory environment, accuracy of binocular-stereo-vision-based navigation robot is acceptable for target at 100 mm depth or less. Compared with freehand, foramen ovale placement accuracy can be improved with robot guidance.
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http://dx.doi.org/10.12998/wjcc.v8.i16.3440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457116PMC
August 2020

Chinese Medicine Sequential Therapy Improves Pregnancy Outcomes after Surgery for Endometriosis-Associated Infertility: A Multicenter Randomized Double-blind Placebo Parallel Controlled Clinical Trial.

Chin J Integr Med 2020 Feb 29;26(2):92-99. Epub 2020 Jan 29.

Department of Gynecology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.

Objective: To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility.

Methods: A multicenter, randomized, double-blind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017, 101 patients in each group. The two groups received continuous intervention at 1-5 days after surgery, for 6 menstrual cycles. Before ovulation, the CM group was treated Huoxue Xiaoyi Granule (); after ovulation, Bushen Zhuyun Granule ( was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment, and female hormone levels in the follicular and luteal phases were measured during the 1st, 3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome, and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment.

Results: (1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101), 34.7% (35/101) vs. 20.8% (21/101), both P<0.05]. (2) Follicle development: the incidence of dominant follicles, rate of cumulative cycle ovulation, and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group [93.8% (350/373) vs. 89.5% (341/381), 80.4% (275/342) vs. 69.1% (253/366), 65.8% (181/275) vs 56.1% (142/253), P<0.05 or P<0.01]). The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group [11.7% (40/342) vs. 17.8% (65/366), P<0.05). (3) Endometrial receptivity: after treatment, both endometrial types and endometrial blood flow types in the CM group were mainly types A and B, while those in the placebo group were mainly types B and C, with a significant difference between the two groups (both P<0.05). (4) Adverse events: the incidence of adverse events between the two groups was not significantly different (P>0.05).

Conclusion: Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy, improve follicular development, promote ovulation, improve endometrial receptivity, while being a safe treatment option. (Trial registration No. NCT02676713).
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http://dx.doi.org/10.1007/s11655-019-3208-2DOI Listing
February 2020

Role of hepatic neuropeptide Y-Y1 receptors in a methionine-choline-deficient model of non-alcoholic steatohepatitis.

Life Sci 2020 Mar 25;245:117356. Epub 2020 Jan 25.

Department of Cardiology, Southwest Hospital, Third Military Medical University, China. Electronic address:

Aims: NPY-Y1R plays an important role in dietary regulation. Although germline knockdown of NPY-Y1R in mice alleviates high-fat-diet-induced obesity and increases CPT1α levels in the liver, the role of the Y1 receptor in specific tissues has not been studied.

Main Methods: MCD diet is the most widely used method to establish a model of lean NASH in a short time. We therefore evaluated the role of liver NPY-Y1R in NASH progression.

Key Findings: In mice with liver-specific knockout of NPY-Y1R (LivKO) and wild-type control littermates fed MCD diet for 4 weeks, NPY-Y1R deficiency significantly decreased body and liver weight. Moreover, NPY-Y1R deletion protected mice against hepatic steatosis and injury. LivKO decreased TG, TC, and FFA levels in the liver and alanine aminotransferase activity in plasma. To clarify the mechanism, we evaluated the key enzymes involved in triglyceride hydrolase and fatty-acid oxidase. Expression of ATGL, CPT1α, and ACO was significantly increased in LivKO mice, whereas expression of fatty-acid synthase was significantly decreased. mRNA expression analysis revealed a marked reduction of genes involved in de-novo lipogenesis and monosaturated fatty-acid synthesis, including sterol-regulatory element-binding protein 1c and fatty-acid synthase. Moreover, liver injury-related factors were significantly decreased in LivKO mice, such as TNF-α, inducible nitric oxide synthase, and MCP-1. Thus, NPY-Y1R deficiency in the liver alleviates lipid deposition and injury. However, NPY-Y1R did not affect inflammation and fibrosis.

Significance: NPY-Y1R deficiency in the liver directly suppresses not only hepatic steatosis, but also liver injury, and thus provides a treatment option for NASH.
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http://dx.doi.org/10.1016/j.lfs.2020.117356DOI Listing
March 2020

The Establishment of an In Vivo HIV-1 Infection Model in Humanized B-NSG Mice.

Virol Sin 2020 Aug 21;35(4):417-425. Epub 2019 Dec 21.

CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China.

Suitable animal models for human immunodeficiency virus type 1 (HIV-1) infection are important for elucidating viral pathogenesis and evaluating antiviral strategies in vivo. The B-NSG (NOD-PrkdcscidIl2rgtm1/Bcge) mice that have severe immune defect phenotype are examined for the suitability of such a model in this study. Human peripheral blood mononuclear cells (PBMCs) were engrafted into B-NSG mice via mouse tail vein injection, and the repopulated human T-lymphocytes were observed at as early as 3-weeks post-transplantation in mouse peripheral blood and several tissues. The humanized mice could be infected by HIV-1, and the infection recapitulated features of T-lymphocyte dynamic observed in HIV-1 infected humans, meanwhile the administration of combination antiretroviral therapy (cART) suppressed viral replication and restored T lymphocyte abnormalities. The establishment of HIV-1 infected humanized B-NSG mice not only provides a model to study virus and T cell interplays, but also can be a useful tool to evaluate antiviral strategies.
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http://dx.doi.org/10.1007/s12250-019-00181-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462958PMC
August 2020

Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation.

mBio 2019 12 17;10(6). Epub 2019 Dec 17.

CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China

Multiple cellular metabolic pathways are altered by HIV-1 infection, with an impact on immune activation, inflammation, and acquisition of non-AIDS comorbid diseases. The dysfunction of tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenesis, but the underlying mechanism remains unknown. In this study, we demonstrated that the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, is activated by Trp metabolites to promote HIV-1 infection and reactivation. AHR directly binds to the HIV-1 5' long terminal repeat (5'-LTR) at the molecular level to activate viral transcription and infection, and AHR activation by Trp metabolites increases its nuclear translocation and association with the HIV 5'-LTR; moreover, the binding of AHR with HIV-1 Tat facilitates the recruitment of positive transcription factors to viral promoters. These findings not only elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis but also suggest that a downstream target AHR may be a potential target for modulating HIV-1 infection. Cellular metabolic pathways that are altered by HIV-1 infection may accelerate disease progression. Dysfunction in tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenesis, but the mechanism responsible was not known. This study demonstrates that Trp metabolites augment the activation of aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, to promote HIV-1 infection and transcription. These findings not only elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis but also suggest that a downstream target AHR may be a potential target for modulating HIV-1 infection.
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http://dx.doi.org/10.1128/mBio.02591-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918076PMC
December 2019

Long noncoding RNA MALAT1 releases epigenetic silencing of HIV-1 replication by displacing the polycomb repressive complex 2 from binding to the LTR promoter.

Nucleic Acids Res 2019 04;47(6):3013-3027

CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.

Long noncoding RNAs (lncRNAs) may either repress or activate HIV-1 replication and latency; however, specific mechanisms for their action are not always clear. In HIV-1 infected CD4+ T cells, we performed RNA-Sequencing (RNA-Seq) analysis and discovered an up-regulation of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), an lncRNA previously described in cancer cells that associate with cancer pathogenesis. Moreover, we found that MALAT1 promoted HIV-1 transcription and infection, as its knockdown by CRISPR/Cas9 markedly reduced the HIV-1 long terminal repeat (LTR)-driven gene transcription and viral replication. Mechanistically, through an association with chromatin modulator polycomb repressive complex 2 (PRC2), MALAT1 detached the core component enhancer of zeste homolog 2 (EZH2) from binding with HIV-1 LTR promoter, and thus removed PRC2 complex-mediated methylation of histone H3 on lysine 27 (H3K27me3) and relieved epigenetic silencing of HIV-1 transcription. Moreover, the reactivation of HIV-1 stimulated with latency reversal agents (LRAs) induced MALAT1 expression in latently infected cells. Successful combination antiretroviral therapy (cART) was accompanied by significantly diminished MALAT1 expression in patients, suggesting a positive correlation of MALAT1 expression with HIV-1 replication. Our data have identified MALAT1 as a promoter of HIV-1 transcription, and suggested that MALAT1 may be targeted for the development of new therapeutics.
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http://dx.doi.org/10.1093/nar/gkz117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451131PMC
April 2019

Wogonin affects proliferation and the energy metabolism of SGC-7901 and A549 cells.

Exp Ther Med 2019 Jan 28;17(1):911-918. Epub 2018 Nov 28.

College of Pharmacy, Harbin University of Commerce, Harbin, Heilongjiang 150076, P.R. China.

Many studies have focused on the identification of therapeutic targets for the treatment of certain types of cancer. Wogonin is a natural flavonoid compound that exhibits a potent anti-cancer effect. The underlying mechanism of wogonin may therefore reveal an effective way to identify novel therapeutic targets. In the current study, growth curves and MTT assays were performed to determine the effects of wogonin in human gastric cancer cells (SGC-7901) and human lung adenocarcinoma cells (A549), respectively. Changes in morphology were observed using hematoxylin and eosin (H&E) staining. The activities of key enzymes in the glycolysis and tricarboxylic acid cycle were measured using spectrophotometry. Western blot analysis was performed to determine the expression levels of hypoxia inducible factor-1α (HIF-1α) and monocarboxylate transporter-4 (MCT-4). Wogonin inhibited cell proliferation in a time- and dose-dependent manner in SGC-7901 and A549 cells. H&E staining suggested that wogonin induced cell morphology changes. In SGC-7901 cells, lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) activities and adenosine triphosphate (ATP) generation were decreased significantly by wogonin treatment compared with the untreated control. In A549 cells, wogonin significantly reduced LDH activity, but exhibited no significant effects on kinase activities or ATP generation. Furthermore, wogonin significantly decreased HIF-1α and MCT-4 protein expression in SGC-7901 cells, but not in A549 cells. The results demonstrated that wogonin inhibited the energy metabolism, cell proliferation and angiogenesis in SGC-7901 and A549 cells by negatively regulating HIF-1α and MCT-4 expression. The differential regulatory roles of wogonin in metabolism-associated enzymes in human gastric cancer and lung adenocarcinoma cells indicated its various antitumor mechanisms. The different metabolic regulatory mechanisms exhibited by wogonin in different tumor tissues should therefore be considered for antitumor therapy.
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http://dx.doi.org/10.3892/etm.2018.7023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307470PMC
January 2019

SUN2 Modulates HIV-1 Infection and Latency through Association with Lamin A/C To Maintain the Repressive Chromatin.

mBio 2018 05 1;9(3). Epub 2018 May 1.

CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China

The postintegrational latency of HIV-1 is characterized by reversible silencing of long terminal repeat (LTR)-driven transcription of the HIV genome. It is known that the formation of repressive chromatin at the 5'-LTR of HIV-1 proviral DNA impedes viral transcription by blocking the recruitment of positive transcription factors. How the repressive chromatin is formed and modulated during HIV-1 infection remains elusive. Elucidation of which chromatin reassembly factor mediates the reorganization of chromatin is likely to facilitate the understanding of the host's modulation of HIV-1 transcription and latency. Here we revealed that "Sad1 and UNC84 domain containing 2" (SUN2), an inner nuclear membrane protein, maintained the repressive chromatin and inhibited HIV LTR-driven transcription of proviral DNA through an association with lamin A/C. Specifically, lamin A/C tethered SUN2 to the nucleosomes 1 and 2 of the HIV-1 5'-LTR to block the initiation and elongation of HIV-1 transcription. SUN2 knockdown converted chromatin to an active form and thus enhanced the phosphorylation of RNA polymerase II and its recruitment to the 5'-LTR HIV-1 proviral DNA, leading to reactivation of HIV-1 from latency. Conversely, the exogenous factors such as tumor necrosis factor alpha (TNF-α) induced reactivation, and the replication of HIV-1 led to the disassociation between SUN2 and lamin A/C, suggesting that disruption of the association between SUN2 and lamin A/C to convert the repressive chromatin to the active form might be a prerequisite for the initiation of HIV-1 transcription and replication. Together, our findings indicate that SUN2 is a novel chromatin reassembly factor that helps to maintain chromatin in a repressive state and consequently inhibits HIV-1 transcription. Despite the successful use of scores of antiretroviral drugs, HIV latency poses a major impediment to virus eradication. Elucidation of the mechanism of latency facilitates the discovery of new therapeutic strategies. It has been known that the formation of repressive chromatin at the 5'-LTR of HIV-1 proviral DNA impedes viral transcription and maintains viral latency, but how the repressive chromatin is formed and modulated during HIV-1 infection remains elusive. In this study, we performed in-depth virological and cell biological studies and discovered that an inner nuclear membrane protein, SUN2, is a novel chromatin reassembly factor that maintains repressive chromatin and thus modulates HIV-1 transcription and latency: therefore, targeting SUN2 may lead to new strategies for HIV cure.
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http://dx.doi.org/10.1128/mBio.02408-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930302PMC
May 2018

Chinese Medicine in Management of Chronic Disease Endometriosis.

Chin J Integr Med 2020 Feb 17;26(2):88-91. Epub 2019 Jan 17.

Department of Gynecology, Guang'anmen Hospital, China Academy of Traditional Chinese Medicine, Beijing, 100053, China.

Endometriosis (EM), a refractory, highly recurrent and life-threatening chronic disease, requires long-term management and long-term drug treatment. Our previous studies showed that Chinese medicine (CM) can inhibit the postoperative recurrence of EM, improve quality of life, shorten the time to conception and increase pregnancy rates. CM produces few adverse reactions with high safety. These characteristics might be associated with the mechanism of CM's inhibition of recurrence. Therefore, we believe that CM may represent a good choice for long-term drug treatment and is worthy of clinical application.
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http://dx.doi.org/10.1007/s11655-018-2937-3DOI Listing
February 2020

Dendritic cells maturated by co-culturing with HIV-1 latently infected Jurkat T cells or stimulating with AIDS-associated pathogens secrete TNF-α to reactivate HIV-1 from latency.

Virulence 2017 11 16;8(8):1732-1743. Epub 2017 Aug 16.

b Key Laboratory of Molecular Virology and Immunology , Institut Pasteur of Shanghai, Chinese Academy of Sciences , Shanghai , China.

Elucidation of mechanisms underlying the establishment, maintenance of and reactivation from HIV-1 latency is essential for the development of therapeutic strategies aimed at eliminating HIV-1 reservoirs. Microbial translocation, as a consequence of HIV-1-induced deterioration of host immune system, is known to result in a systemic immune activation and transient outbursts of HIV-1 viremia in chronic HIV-1 infection. How these microbes cause the robust HIV-1 reactivation remains elusive. Dendritic cells (DCs) have previously been shown to reactivate HIV-1 from latency; however, the precise role of DCs in reactivating HIV-1 from latently infected T-cell remains obscure. In this study, by using HIV-1 latently infected Jurkat T cells, we demonstrated that AIDS-associated pathogens as represented by Mycobacterium bovis (M. bovis) Bacillus Calmette-Guérin (BCG) and bacterial component lipopolysaccharide (LPS) were unable to directly reactivate HIV-1 from Jurkat T cells; instead, they mature DCs to secrete TNF-α to accomplish this goal. Moreover, we found that HIV-1 latently infected Jurkat T cells could also mature DCs and enhance their TNF-α production during co-culture in a CD40-CD40L-signaling-dependent manner. This in turn led to viral reactivation from Jurkat T cells. Our results reveal how DCs help AIDS-associated pathogens to trigger HIV-1 reactivation from latency.
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http://dx.doi.org/10.1080/21505594.2017.1356535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810491PMC
November 2017

New arylpyrazoline-coumarins: Synthesis and anti-inflammatory activity.

Eur J Med Chem 2017 Sep 26;138:170-181. Epub 2017 Jun 26.

Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, PR China; School of Material Science Chemical Engineering, ChuZhou University, ChuZhou 239000, PR China. Electronic address:

To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of new phenyl-pyrazoline-coumarin derivatives (4a∼4m) were designed and synthesized. Compounds 4a and 4b were determined by X-ray crystallography. All of the compounds have been screened for their anti-inflammatory activity characterized by evaluating their inhibition against LPS-induced IL-6 release. Among them, compound 4m showed the highest anti-inflammatory activity with inhibiting IL-6, TNF-α and nitric oxide (NO) production lipopolysaccharide (LPS)-stimulated. The further study showed that title compound 4m could significantly suppress expressions of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and the productions of IL-6, TNF-α, NO through NF-κB/MAPK signaling pathway. The anti-inflammatory activity of compound 4m was determined by carrageenan induced paw edema. Furthermore in vivo evaluation results indicated that compound 4m could inhibit AA-induced rat ankle joints.
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http://dx.doi.org/10.1016/j.ejmech.2017.06.044DOI Listing
September 2017

Current views on neuropeptide Y and diabetes-related atherosclerosis.

Diab Vasc Dis Res 2017 07 20;14(4):277-284. Epub 2017 Apr 20.

1 Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China.

Diabetes-induced atherosclerotic cardiovascular disease is the leading cause of death of diabetic patients. Neuronal regulation plays a critical role in glucose metabolism and cardiovascular function under physiological and pathological conditions, among which, neurotransmitter neuropeptide Y has been shown to be closely involved in these two processes. Elevated central neuropeptide Y level promotes food intake and reduces energy expenditure, thereby increasing adiposity. Neuropeptide Y is co-localized with noradrenaline in central and sympathetic nervous systems. As a major peripheral vascular contractive neurotransmitter, through interactions with its receptors, neuropeptide Y has been implicated in the pathology and progression of diabetes, by promoting the proliferation of endothelial cells and vascular fibrosis, which may contribute to diabetes-induced cardiovascular disease. Neuropeptide Y also participates in the pathogenesis of atherosclerosis, the major form of cardiovascular disease, via aggravating endothelial dysfunction, growth of vascular smooth muscle cells, formation of foam cells and platelets aggregation. This review highlights the causal role of neuropeptide Y and its receptor system in the development of diabetes mellitus and one of its complications: atherosclerotic cardiovascular disease. The information from this review provides both critical insights onto the mechanisms underlying the pathogenesis of atherosclerosis and evidence for the development of therapeutic strategies.
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http://dx.doi.org/10.1177/1479164117704380DOI Listing
July 2017

The central mechanism of risperidone-induced hyperprolactinemia.

Prog Neuropsychopharmacol Biol Psychiatry 2017 06 20;76:134-139. Epub 2017 Mar 20.

Department of Cardiology, Southwest Hospital, Third Military Medical University, PR China; School of Medicine, Illawarra Health and Medical Research Institute, University of Wollongong, NSW 2522, Australia. Electronic address:

Risperidone is known to increase prolactin secretion in treating mental illness patients. This side-effect is thought to be mediated via central signaling pathway. However, the exact pathway involved between risperidone and hyperprolactinemia are still unknown. Therefore, we have treated mice with risperidone and investigated the central mechanisms. The present study showed that in risperidone treated group, the level of the serum prolactin significantly increased, which was consistent with increased positive prolactin staining in pituitary gland. Elevated c-fos expression was observed in the arcuate hypothalamic nucleus (Arc) where we found 65% c-fos positive neurons co-localised with neuropeptide Y (NPY) in mice treated with risperidone. In addition, the results from in situ hybridization showed that the NPY mRNA in the Arc was significantly increased, whereas the tyrosine hydroxylase (TH) mRNA dramatically decreased compared with control group in the paraventricular hypothalamic nucleus (PVN). These findings revealed that risperidone may mediate the transcriptional regulation of Arc NPY and TH in the PVN. Furthermore, risperidone induced a decreased dopamine synthesis in the PVN and thus reduced the dopamine-induced inhibition of prolactin release, ultimately lead to hyperprolactinemia. Therefore, insights into these neuronal mechanisms open up potential new ways to treat schizophrenia patients in order to ameliorate hyperprolactinemia.
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http://dx.doi.org/10.1016/j.pnpbp.2017.03.009DOI Listing
June 2017

Elevated Type II Secretory Phospholipase A2 Increases the Risk of Early Atherosclerosis in Patients with Newly Diagnosed Metabolic Syndrome.

Sci Rep 2016 12 12;6:34929. Epub 2016 Dec 12.

Department of Cardiology, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, China.

A critical association between type II secretory phospholipase A2 (sPLA2-IIa) and established atherosclerotic cardiovascular disease has been demonstrated. However, the contribution of sPLA2-IIa to early atherosclerosis remains unknown. This study investigated the association between early-stage atherosclerosis and sPLA2-IIa in metabolic syndrome (MetS) patients. One hundred and thirty-six MetS patients and 120 age- and gender-matched subjects without MetS were included. Serum sPLA2-IIa protein levels and activity were measured using commercial kits. Circulating endothelial activation molecules (vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and P-selectin), and carotid intima-media thickness (cIMT), were measured as parameters of vascular endothelial dysfunction and early atherosclerosis. MetS patients exhibited significantly higher sPLA2-IIa protein and activity levels than the controls. Both correlated positively with fasting blood glucose and waist circumference in MetS patients. Additionally, MetS patients exhibited strikingly higher levels of endothelial activation molecules and increased cIMT than controls. These levels correlated positively with serum sPLA2-IIa protein levels and activity. Moreover, multivariate analysis showed that high sPLA2-IIa protein and activity levels were independent risk factors of early atherosclerosis in MetS patients. This study demonstrates an independent association between early-stage atherosclerosis and increased levels of sPLA2-IIa, implying that increased sPLA2-IIa may predict early-stage atherosclerosis in MetS patients.
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http://dx.doi.org/10.1038/srep34929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5150250PMC
December 2016

[The effect of nuclear factor erythroid-2-related factor2 on the changes of cardiac function and electrocardiogram in rats after exhausted exercise].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2016 Feb;32(2):146-151

Department of Cardiology, No. 252 Hospital of PLA, Baoding 071000.

Objective: In order to provide the experimental basis for the prevention of exercise-induced cardiac injury, we evaluated the effects of nuclear factor erythroid-2-related factor2(Nrf2) on the changes of cardiac function and electrocardiogram in rats after exhaustive exercise.

Methods: SD rats were randomly divided into 5 groups (=6):control group (Con), exhaustied exercise group (EE), 6h, 12 h, 24 h recovery from exhaustied exercise group(EER6 EER12 EER24). The animal models of exercise-induced myocardial injury were established according to Thomas' method.Rats were forced to swim until they were exhausted.The electrocardiograms were recorded in conscious rats. Cardiac function of rats was recorded and analyzed by Millar pressure-volume system. The changes of catalase(CAT), glutathione peroxidase(GPX), Nrf2 and reactive oxygen speies(ROS) were detected by ELISA, respectively.

Results: ①Compared with the control group and recovery groups(EER6, EER12, and EER24), the heart rate (HR), left ventricular end systolic pressure (Pes), arterial elasticity (Ea), the maximum rate of left ventricular pressure rise (dP/dt), peak rate of left ventricular pressure decline (-dP/dt) and left ventricular end diastolic pressure volume relationship curve slope (ESPVR) in the EE group decreased significantly, while left ventricular end diastolic volume (Ved), Pes, left ventricular end systolic volume (Ves), stroke volume, and Tau value increased significantly. Besides, HR, Pes, dP/dt, -dP/dt in recovery groups were significantly different with those in EE group, but there had no difference with those in the Con group. ②Compared with the control group, heart rate was increased, QT intervals were prolonged P wave, R wave and ST segments were increased in EE and recovery groups, but the changes of above-mentioned indexes in recovery groups had no statistical significant difference with those in EE group.③ Compared with the control group,the contents of ROS, Nrf2 were increased in EE group, while the content of GPX was decreased. Moreover, the content of CAT in EER6 group was the lowest in all groups. ④ The level of Nrf2 in serum was positively correlated with ROS and -dP/dt, and negatively correlated with HR, Ea. The level of ROS in Serum was positively correlated with EF, -dP/dt, and was negatively correlated with HR, Ea, dP/dt.

Conclusions: Exhausted exercise caused changes of cardiac bioelectricity, impaired both the cardiac systolic and diastolic function, especially the diastolic disfunction. However, with recovery time after exhausted exercise prolonged, cardiac systolic and diastolic function recovered gradually, which was related to the reduced oxidative stress levels modulated by the increased Nrf2-induced changes of GPX and CAT.
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http://dx.doi.org/10.13459/j.cnki.cjap.2016.02.013DOI Listing
February 2016

Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice.

Sci Rep 2015 May 27;5:10512. Epub 2015 May 27.

Department of Cardiology, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, China.

We have previously observed that knockout of Niemann-Pick C1-Like 1 (NPC1L1), a cholesterol transporter essential for intestinal cholesterol absorption, reduces the output of dry stool in mice. As the food intake remains unaltered in NPC1L1-knockout (L1-KO) mice, we hypothesized that NPC1L1 deficiency may alter the gut microbiome to reduce stool output. Consistently, here we demonstrate that the phyla of fecal microbiota differ substantially between L1-KO mice and their wild-type controls. Germ-free (GF) mice have reduced stool output. Inhibition of NPC1L1 by its inhibitor ezetimibe reduces stool output in specific pathogen-free (SPF), but not GF mice. In addition, we show that GF versus SPF mice have reduced intestinal absorption and increased fecal excretion of cholesterol, particularly after treatment with ezetimibe. This negative balance of cholesterol in GF mice is associated with reduced plasma and hepatic cholesterol, and likely caused by reduced expression of NPC1L1 and increased expression of ABCG5 and ABCG8 in small intestine. Expression levels of other genes in intestine and liver largely reflect a state of cholesterol depletion and a decrease in intestinal sensing of bile acids. Altogether, our findings reveal a broad role of microbiota in regulating whole-body cholesterol homeostasis and its response to a cholesterol-lowering drug, ezetimibe.
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http://dx.doi.org/10.1038/srep10512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444975PMC
May 2015

Toll-Interacting Protein Suppresses HIV-1 Long-Terminal-Repeat-Driven Gene Expression and Silences the Post-Integrational Transcription of Viral Proviral DNA.

PLoS One 2015 27;10(4):e0125563. Epub 2015 Apr 27.

Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.

Toll-interacting protein (Tollip) is a host adaptor protein for negatively regulating Toll-like receptor 2-, 4-, and IL-1R (interleukin-1 receptor)-mediated signaling. We found that Tollip expression could be induced in MDDCs (monocyte-derived dendritic cells) by HIV-1 particles and recombinant gp120 glycoprotein. Hence, we investigated the role of Tollip in modulating HIV-1 infection. We found that Tollip expression suppressed NF-κB-dependent HIV-1 long terminal repeat (LTR)-driven transcription and thus inhibited HIV-1 infection. Our protein truncation experiments proved that the intact C-terminus of Tollip was required for inhibition of both NF-κB activity and HIV-1 LTR-driven gene expression. Intriguingly, Tollip silenced the post-integrational transcription of HIV-1 proviral DNA, indicating the potential role of Tollip in maintaining viral persistence. Our results reveal the novel role of host factor Tollip in modulating HIV-1 infection, and may suggest the hijacking of Tollip as the negative regulator of the TLR pathway and even the downstream signaling, by HIV-1 for maintaining persistent infection. Further elucidation of the mechanisms by which HIV-1 induces Tollip expression and identification of the role of Tollip in modulating HIV-1 latency will facilitate the understanding of host regulation in viral replication and benefit the exploration of novel strategies for combating HIV-1 infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0125563PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411168PMC
January 2016

[Relationship between multi-gene proteins in colorectal carcinoma complicated with chronic schistosomiasis: an immunohistochemical study by using tissue microarray techniques].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2014 Aug;26(4):405-9

Objective: To investigate the relationship between p53, COX-2, Bax, c-myc genes and colorectal carcinoma complicated with chronic schistosomiasis.

Methods: One hundred and sixty patients with colorectal carcinoma were selected and divided into two groups; a schistosomiasis group (colorectal carcinoma complicated with chronic schistosomiasis, n = 80) and a non-schistosomiasis group (colorectal carcinoma uncomplicated with chronic schistosomiasis, n = 80). The tissue microarray techniques and immunohistochemistry method were used in all the patients to detect the expressions of p53, COX-2, Bax and c-myc proteins.

Results: The positive rate and level of p53 protein expression in the schistosomiasis group were lower than those in the non-schistosomiasis group, but there were no significant differences between the two groups (both P > 0.05). The COX-2 protein in both groups was positive, but the positive expression level of COX-2 in the schistosomiasis group was higher than that in the nonschistosomiasis group, and there was a significant difference between the two groups (P < 0.01). The positive rate and level of Bax protein expression were not significantly different between the two groups (both P > 0.05). The positive rate of c-myc expression in the schistosomiasis group was higher than that in the non-schistosomiasis group, with a significant difference (P < 0.01), but the positive expression level was lower than that in the non-schistosomiasis group, and there was a significant difference between the two groups (P < 0.01).

Conclusions: Schistosome infection may impact on the deficiency of p53 of human colorectal cancer cells. It may promote the excessive expression of COX-2 protein, which is an indirect carcinogenic factor. The expression of Bax gene has no correlation with schistosome infection. The schistosome chronic infection may cause a persistent low level expression of c-myc gene.
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August 2014

Panax notoginseng saponins inhibits atherosclerotic plaque angiogenesis by down-regulating vascular endothelial growth factor and nicotinamide adenine dinucleotide phosphate oxidase subunit 4 expression.

Chin J Integr Med 2015 Apr 6;21(4):259-65. Epub 2014 Mar 6.

Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, 250012, China.

Objective: To investigate the mechanism of Panax notoginseng saponins (PNS), an effective component extracted from Panax notoginseng, on atherosclerotic plaque angiogenesis in atherosclerosis-prone apolipoprotein E-knockout (ApoE-KO) mice fed with high-fat, high-cholesterol diet.

Methods: Twenty ApoE-KO mice were divided into two groups, the model group and the PNS group. Ten normal C57BL/6J mice were used as a control group. PNS (60 mg/kg) was orally administered daily for 12 weeks in the PNS group. The ratio of plaque area to vessel area was examined by histological staining. The tissue sample of aortic root was used to detect the CD34 and vascular endothelial growth factor (VEGF) expression areas by immunohistochemistry. The expression of VEGF and nicotinamide adenine dinucleotide phosphate oxidase subunit 4 (NOX4) were measured by reverse transcription polymerase chain reaction and Western blotting respectively.

Results: After treatment with PNS, the plaque areas were decreased (P<0.05). CD34 expressing areas and VEGF expression areas in plaques were significantly decreased (P<0.05). Meanwhile, VEGF and NOX4 mRNA expression were decreased after treatment with PNS. VEGF and NOX4 protein expression were also decreased by about 72% and 63%, respectively (P<0.01).

Conclusion: PNS, which decreases VEGF and NOX4 expression, could alleviate plaque angiogenesis and attenuate atherosclerosis.
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http://dx.doi.org/10.1007/s11655-014-1832-4DOI Listing
April 2015

Flavonoids from Podocarpus macrophyllus and their cardioprotective activities.

J Asian Nat Prod Res 2014 9;16(2):222-9. Epub 2013 Dec 9.

a Department of Traditional Chinese Medicine , Qilu Hospital, Shandong University , Jinan , 250012 , China.

One new 8-aryl flavone, podocarflavone A (1), together with 15 previously reported flavonoids were isolated from the twigs and leaves of Podocarpus macrophyllus. Their structures were established on the basis of extensive spectroscopic analysis and by the comparison with spectroscopic data reported in the literature. Antioxidant capacities of the isolated substances were determined using the 1,1-diphenyl-2-picrylhydrazyl, ferrous ions, and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical in vitro assays, and their cytoprotective activities were also tested on H2O2-induced apoptosis in H9c2 cardiomyocytes. The results showed that those flavonoids exhibited significant cardioprotective effects by decreasing the H2O2-induced death of H9c2 cell, and the levels of lactate dehydrogenase and creatine kinase, and by inhibiting the elevated intracellular concentration of reactive oxygen species.
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http://dx.doi.org/10.1080/10286020.2013.861821DOI Listing
March 2014

Controlling the recurrence of pelvic endometriosis after a conservative operation: comparison between Chinese herbal medicine and western medicine.

Chin J Integr Med 2013 Nov 22;19(11):820-5. Epub 2012 Dec 22.

Department of Gynecology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China,

Objective: To compare the clinical effect of Chinese medicine (CM) and Western medicine (WM) for controlling the recurrence of pelvic endometriosis after a conservative operation.

Methods: The study was a multi-center, randomized, parallel controlled and prospective clinical trial. Patients were randomly divided into two groups: CM group (106 cases) and WM group (102 cases). Drugs were given to patients during 1-5 days of the first menstruation after a conservative operation in both groups. Patients with stages I and II (revised American Fertility Society) were treated for 3 months, while the patients with stages III and IV were treated for 6 months. The patients in the CM group were treated using three types of Chinese herbal medicine based on syndrome differentiation. Patients in the WM group were treated using gonadotropin releasing hormone agonist (GnRH-a) or gestrinone. Patients treated with GnRH-a received add-back therapy of Tibolone Tablets once a day after 4 months of treatment. Any cases of dysmenorrheal chronic pelvic pain, menstruation and any adverse reactions of patients were recorded once a month during the preoperative and postoperative periods and once every 3 months during the follow-up period. During the preoperative, postoperative and the follow-up periods, patients underwent type B ultrasonography of the pelvis and measurements of serum CA125 levels, gynecologic examination, routine evaluations of blood, urine, hepatic function (glutamate pyruvate transaminase), renal function (blood urea nitrogen) and electrocardiograms. During the follow-up period they underwent type B pelvic ultrasonography, measurement of serum CA125 levels and further gynecologic examinations. The two treatments were compared for clinical recurrence rates, pregnancy rates and the incidence of adverse reactions.

Results: The incidence and timing of recurrence of endometriosis were not significantly different between the two groups. The first pregnancy achieved by the patient in the CM group was significantly earlier than that in the WM group (P <0.05). Moreover, the incidence of adverse reactions in the WM group was significantly higher than in the CM group (P <0.01).

Conclusions: Treatment with Chinese herbal medicines prevented the recurrence of endometriosis after a conservative operation, improved the conception rate and showed fewer and lighter adverse reactions than did treatment with WM therapy. Treatment with Chinese herbal medicine meets the need of patients wishing to have a child following endometriosis and is an appropriate form of clinical treatment.
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http://dx.doi.org/10.1007/s11655-012-1247-zDOI Listing
November 2013

N-myc downstream-regulated gene 1/Cap43 may function as tumor suppressor in endometrial cancer.

J Cancer Res Clin Oncol 2012 Oct 8;138(10):1703-15. Epub 2012 Jun 8.

Department of Pathology, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital, NO.85, Wujin Road, Shanghai 200080, People's Republic of China.

Purpose: N-myc downstream-regulated gene 1 (NDRG1) reportedly regulates tumor progression in various cancers. Our previous studies showed that NDRG1 was aberrantly overexpressed in human endometrial cancer tissues. The purpose of the present study was to investigate the role of NDRG1 in endometrial carcinogenesis.

Methods: A short hairpin RNA (shRNA)-mediated gene silencing strategy was employed to stably suppress the expression of NDRG1 in endometrial cancer Ishikawa cells. The influence of NDRG1 silencing on cancer cell biological behaviors was examined through observing in vitro tumor cell proliferation, colony formation, cell migration and invasion. Moreover, the mammalian NDRG1 expression vector pcDNA3.1(+)/NDRG1 was constructed to determine the effects of NDRG1 overexpression on cell proliferation and migration. Additionally, gene expression microarray analysis was conducted to identify NDRG1 downstream target genes after NDRG1 knockdown.

Results: It was demonstrated that NDRG1 knockdown significantly enhanced Ishikawa cell proliferation and dramatically promoted cell migration and invasion. Furthermore, overexpression of NDRG1 in Ishikawa cells greatly inhibited cell proliferation and migration. Through microarray analysis and data mining, a large cohort of NDRG1-repressed target genes were identified. Additionally, through comparing the current microarray results with those obtained previously in studies of cervical and ovarian cancer cells conducted by us, 19 more specific common downstream target genes were identified.

Conclusions: It was demonstrated that NDRG1 might carry out a tumor suppressor function during endometrial carcinogenesis. The identification of downstream target genes should afford meaningful hints for prospective investigations. The tumor suppressor function of NDRG1 may open a new window for the target therapy of endometrial cancer.
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http://dx.doi.org/10.1007/s00432-012-1249-4DOI Listing
October 2012

[Fluorescence spectra analysis of whey protein isolate-dextran conjugate].

Guang Pu Xue Yu Guang Pu Fen Xi 2011 Dec;31(12):3307-10

College of Light Industry and Food Sciences, South China University of Technology, Guangzhou 510640, China.

The mixed whey protein isolate (WPI)-dextran was treated by dry-heating to prepare Maillard reaction products (MRPs), which was characterized by the browning. The free amino groups content significantly decreased by 35.77% and 30.53% in glycated protein samples, as the molecular weight of dextran increased from 67 to 150 kD, respectively. This suggested that it was more difficult to be linked with WPI molecule when the chain length of dextran was increased. The characteristic of WPI-dextran conjugate was studied by fluorescence spectra in the paper. The maximum fluorescence intensity at 405 nm was obviously enhanced and G67 showed high fluorescence intensity than G150 over the wavelength range form 350 to 500 nm. This result revealed that the flourescent substance, a feature in Maillard reaction model system, was generated. As showed in the fluorescence spectra, the maximum fluorescence intensity at 470 nm was significantly decreased and the fluorescence intensity in each solution was in the order as follows: WPI>G150>G67. Moreover, the measurement of surface hydrophobicity index further showed that the hydrophobicity of WPI could be suppressed due to these two kinds of different molecular weight dextran.
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December 2011

[Transport and release of Cd, Pb and Cr from the Yangtze Estuarine sediments during sediment resuspension event].

Huan Jing Ke Xue 2011 Sep;32(9):2512-21

Key Laboratory of Geographic Information Science, Ministry of Education, College of Resources and Environmental Science, East China Normal University, Shanghai 200062, China.

The effects of resuspension energy and duration on release and transport of sediment bound Cd, Pb and Cr in the southern coastal areas of Yangtze Estuary were analyzed experimentally using a particle entrainment simulator (PES). In the sediment resuspension experiment, concentrations of dissolved Cd, Pb and Cr in the overlying water were 0.015-0.157, 0.013-0.890 and 0.066-1.468 microg x L(-1) respectively, and concentrations of particulate Cd, Pb and Cr varied between 0.37-5.40, 8.3-137.1 and 31.6-557.7 microg x g(-1) respectively. Before the biofilm in column surface was not damaged by disturbance, a large number of Cd adsorption to biofilm was released to the overlying water during the resuspension, but after part of the biofilm was damaged with the enhanced disturbance energy, Pb and Cr were released from the sediments to overlying water in short-term. Intensity of physical disturbance was the main factor that influenced the variation of particulate heavy metal concentrations. Results of resuspension fluxes showed that Cd, Pb and Cr released to the water by resuspension were then re-adsorption to suspended particles, and gradually deposited in the bottom sediments when the hydrodynamic conditions weakened, which had less harm to the aquatic ecosystems of Yangtze Estuary. The resuspension process of Cd, Pb and Cr mainly includes the following migration and transformation process: adsorptions of heavy metals in biofilm, direct release and diffusion of dissolved heavy metals from pore water, oxidative release of sulfide associated metals in sediments, re-adsorption of heavy metals to suspended particles in overlying water and deposition of particulate heavy metals.
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September 2011

The expression of protein inhibitor of activated signal transducers and activators of transcription 3 in the evolutionary process of gastric cancer.

Eur J Intern Med 2011 Oct 28;22(5):e31-5. Epub 2011 May 28.

Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai 201600, China.

Objective: To study the expression of PIAS3 (protein inhibitor of activated signal transducers and activators of transcription 3) in the evolutionary process of gastric cancer.

Methods: Samples were taken from the endoscopic biopsy specimens of 125 patients. Gastric mucosal lesions were diagnosed in HE staining, and chronic atrophic gastritis (CAG) with intestinal metaplasia (IM) were distinguished in AB-PAS and HID-AB staining. The expressions of PIAS3 gene in different types of gastric mucosal lesions were detected by immunocytochemistry and in situ hybridization. The results were analyzed using IPP 6.0 image analysis system, from which the average optical density was obtained of positive cells.

Results: There were 25 patients with chronic superficial gastritis (CSG), 87 CAG (30 with complete intestinal IM, 27 with incomplete intestinal IM, 21 with complete colonic IM, 9 with incomplete colonic IM), 8 dysplasia (DYS) and 5 gastric cancer (GC). In the expressions of PIAS3 mRNA and protein, a difference was not found between the patients with CSG and those with CAG with complete or incomplete intestinal IM; however, a significant difference was statistically found among patients with CSG (or intestinal IM), complete colonic IM, incomplete colonic IM, DYS and GC, expression levels of which stepped down one by one.

Conclusions: There are differences in the PIAS3 expression from different stages of gastric precancerous conditions/lesions to GC, which may reveal a close relationship between expression reduction or loss of PIAS3 and gastric tumorigenesis.
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http://dx.doi.org/10.1016/j.ejim.2011.04.002DOI Listing
October 2011

A genome-wide association study identifies two new risk loci for Graves' disease.

Nat Genet 2011 Aug 14;43(9):897-901. Epub 2011 Aug 14.

State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.

Graves' disease is a common autoimmune disorder characterized by thyroid stimulating hormone receptor autoantibodies (TRAb) and hyperthyroidism. To investigate the genetic architecture of Graves' disease, we conducted a genome-wide association study in 1,536 individuals with Graves' disease (cases) and 1,516 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,510 controls. We confirmed four previously reported loci (in the major histocompatibility complex, TSHR, CTLA4 and FCRL3) and identified two new susceptibility loci (the RNASET2-FGFR1OP-CCR6 region at 6q27 (P(combined) = 6.85 × 10(-10) for rs9355610) and an intergenic region at 4p14 (P(combined) = 1.08 × 10(-13) for rs6832151)). These newly associated SNPs were correlated with the expression levels of RNASET2 at 6q27, of CHRNA9 and of a previously uncharacterized gene at 4p14, respectively. Moreover, we identified strong associations of TSHR and major histocompatibility complex class II variants with persistently TRAb-positive Graves' disease.
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http://dx.doi.org/10.1038/ng.898DOI Listing
August 2011

Effects of pressure on the glucose-ammonium sulphite caramel solutions.

Food Chem 2011 Jul 18;127(2):596-601. Epub 2011 Jan 18.

College of Light Industry and Food Sciences, South China University of Technology, Guangzhou 510640, China.

Effects of pressure on glucose-ammonium sulphite solutions were investigated. The reactant (i.e. glucose), intermediate products content, and browning intensity of advanced stages were tested using an UV-Vis spectrophotometer and a high performance liquid chromatograph to gain a better understanding of the influence of pressure on the glucose-ammonium model Maillard reaction system. This study indicates that pressure could promote the first step of the reaction, i.e. condensation reaction between SO(3)(2-)/ammonium and glucose, but inhibit the increase of A(294), A(420) and 5-hydroxymethyl-2-furaldehyde content. The mechanism of inhibiting the glucose-ammonium model Maillard reaction might be that pressure increases dissociative SO(3)(2-) content in solutions and inhibits the degradation of the Amadori rearrangement product.
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http://dx.doi.org/10.1016/j.foodchem.2011.01.049DOI Listing
July 2011
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