Publications by authors named "Xueping Yu"

58 Publications

Evaluation of prognostic value of neutrophil-to-lymphocyte ratio in patients with acute-on-chronic liver failure or severe liver injury from chronic HBV infection.

Eur J Gastroenterol Hepatol 2021 May 31. Epub 2021 May 31.

Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai Department of Infectious Diseases, the First Affiliated Hospital of Wannan Medical College, Wuhu Department of Severe Hepatopathy, Shanghai Public Health Clinical Center, Fudan University, Shanghai Department of Infectious Diseases, the First hospital of Quanzhou affiliated to Fujian Medical University, Quanzhou Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Background And Aims: Acute-on-chronic liver failure (ACLF) is associated with bacterial infection and poor outcome. Neutrophil-to-lymphocyte ratio (NLR) is used to assess bacterial infection and immune dysfunction in numerous diseases. We aimed to evaluate NLR as a prognostic biomarker and to explore its combination with accepted prognostic models in ACLF patients.

Methods: This retrospective study included patients with ACLF or severe liver injury from chronic HBV infection admitted to three tertiary academic hospitals in China from 2013 to 2019. Baseline NLR was correlated with ACLF grade, bacterial infection, survival and accepted ACLF scores.

Results: NLR values were significantly increased in nonsurvivors and patients with bacterial infection at or after admission and were unaffected by cirrhotic status in 412 transplant-free patients included in three cohorts. Compared with accepted scores, NLR showed moderate accuracy in predicting 28-day mortality and high accuracy in predicting 90-day mortality. Three levels of mortality risk were graded on the basis of NLR values (<3.10, 3.10-4.79 and >4.79), and NLR >4.79 was associated with 53.2-60.0% 28-day and 75.0-80.0% 90-day mortality in these cohorts. Multivariate analyses indicated that NLR retained statistical significance independently of CLIF consortium organ failure score (CLIF-C OFs). NLR-based CLIF-C ACLF score was primarily developed and showed excellent performance in predicting 28/90-day mortality.

Conclusions: NLR is a dependable biomarker for bacterial infection assessment and short-term mortality prediction in ACLF patients and can be used jointly with CLIF-C OFs to improve the accuracy of mortality prediction in patients with the disease. NLR-based CLIF-C ACLF model needs further validation.
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http://dx.doi.org/10.1097/MEG.0000000000002207DOI Listing
May 2021

Crystal-Plane Controlled Spontaneous Polarization of Inorganic Perovskite toward Boosting Triboelectric Surface Charge Density.

ACS Appl Mater Interfaces 2021 Jun 28;13(22):26196-26203. Epub 2021 May 28.

College of Information Science and Technology, Jinan University, Guangzhou 510632, PR China.

Triboelectric generators (TENGs) have been extensively studied as a new energy for low cost and the universally applicable prospect. Meanwhile, perovskites have been applied in TENG and show a good performance in view of high carrier mobility, long life and dielectric properties. The asymmetry structure of the orthogonal phase CsPbBr perovskite endows it with ferroelectric property and induces the misalignment of the positive and negative charge centers. Herein, the surface energy of halogen doped inorganic CsPbX (X = Cl, Br) perovskites are theoretically investigated by density functional theory (DFT) calculation, the crystal polarizability of pristine CsPbBr is improved from 0.47 Ry a.u. to 0.52 Ry a.u. (CsPbCl), indicating the polarizability of CsPbCl is higher than CsPbBr. In addition, the build-in electric field () of perovskite materials can be enhanced by the spontaneous polarization and the aligned dipoles in the could further improve the tribo-electrostatic electric field by retaining more triboelectric surface charges. In the end, CsPbCl achieved a power of 3.06 W m compared to the power of 1.34 W m of CsPbBr. This work focuses on the regulation of crystal planes using spontaneous polarization of perovskite toward achieving a high built-in electric field for enhancing triboelectric surface charge density.
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http://dx.doi.org/10.1021/acsami.1c05796DOI Listing
June 2021

Downregulation of SUMO2 inhibits hepatocellular carcinoma cell proliferation, migration and invasion.

FEBS Open Bio 2021 Jun 14;11(6):1771-1784. Epub 2021 May 14.

Department of Immunology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.

This study aimed to evaluate the prognostic value and biological function of small ubiquitin-like modifier 2 (SUMO2) in hepatocellular carcinoma (HCC). SUMO2 expression in HCC tissues was markedly higher than that in normal liver tissues, and patients with high SUMO2 expression had significantly shorter median overall survival than those with low SUMO2 expression. Furthermore, SUMO2 expression was closely correlated with lymph node metastasis and vascular invasion and was a predictor of poor prognosis. The knockdown of SUMO2 in two HCC cell lines (SMMC-7721 and Bel-7404) dramatically suppressed their proliferation, migration and invasion. Western blot analysis showed that the downregulation of SUMO2 significantly reduced the expression of Ki-67, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in SMMC-7721 and Bel-7404 cells. Similarly, quantitative reverse transcription-PCR revealed consistently decreased expression of MMP-9 and VEGF. Our data suggest that SUMO2 promotes proliferation, migration and invasion of HCC cells via mechanisms involving MMP-9 and VEGF. Therefore, SUMO2 may be a prognostic factor and a promising therapeutic target for patients with HCC.
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http://dx.doi.org/10.1002/2211-5463.13173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167860PMC
June 2021

Complete Genome Sequence of Bacillus coagulans BC01, a Promising Human Probiotic Strain Isolated from Thick Broad Bean Sauce.

Microbiol Resour Announc 2021 May 13;10(19). Epub 2021 May 13.

Thankcome Biological Science and Technology Co., Ltd., Suzhou, China

We report the whole-genome sequence of a promising human probiotic, BC01, isolated from thick broad bean sauce. BC01 is widely used in China, where it is considered a treatment for diarrhea, constipation, and allergies and an immunity booster. The complete genome sequence of BC01 will help future research to provide more molecular information about its features and safety.
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http://dx.doi.org/10.1128/MRA.00392-21DOI Listing
May 2021

Electroacupuncture at GV20‑GB7 regulates mitophagy to protect against neurological deficits following intracerebral hemorrhage via inhibition of apoptosis.

Mol Med Rep 2021 Jul 6;24(1). Epub 2021 May 6.

Department of Clinical Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China.

The acupuncture penetrating line of Baihui (GV20) to Qubin (GB7) spans the parietal, frontal and temporal lobes. The present study aimed to elucidate the mechanism by which electroacupuncture (EA) at GV20‑GB7 regulates mitophagy in intracerebral hemorrhage (ICH) and whether it serves a neuroprotective role. A whole blood‑induced ICH model was used. Mitophagy‑regulating proteins, including BCL/adenovirus E1B 19 kDa‑interacting protein 3 (BNIP3), PTEN‑induced putative kinase 1 (PINK1), Parkin and apoptosis‑associated proteins were detected by western blotting; autophagy following ICH was evaluated by immunofluorescent techniques; morphological characteristics of mitophagy were observed using transmission electron microscopy; and TUNEL assay was performed to determine the number of apoptotic cells. Immunohistochemistry was used to detect p53 expression. The protective role of EA (GV20‑GB7) via enhanced mitophagy and suppressed apoptosis in ICH was further confirmed by decreased modified neurological severity score. The results showed that EA (GV20‑GB7) treatment upregulated mitochondrial autophagy following ICH and inhibited apoptotic cell death. The mechanism underlying EA (GV20‑GB7) treatment may involve inhibition of p53, an overlapping protein of autophagy and apoptosis. EA (GV20‑GB7) treatment decreased neurobehavioral deficits following ICH but pretreatment with 3‑methyladenine counteracted the beneficial effects of EA (GV20‑GB7) treatment. In conclusion, EA (GV20‑GB7) improved recovery from ICH by regulating the balance between mitophagy and apoptosis.
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http://dx.doi.org/10.3892/mmr.2021.12131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127033PMC
July 2021

Whole exome sequencing improves mutation detection in Hailey-Hailey disease.

J Dermatol 2021 Apr 20. Epub 2021 Apr 20.

Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.

Hailey-Hailey disease (HHD) is an autosomal dominant monogenic disease that is defective in the ATP2C1 gene. In previous studies, Sanger sequencing was the main method applied to detect mutations in HHD patients, and no mutations in the ATP2C1 gene were found in 12-55% of those reported. The aim of our study was to carry out whole exome sequencing (WES) for the HHD patients in whom efforts to identify mutations by Sanger sequencing had failed, and to find a new pathogenic gene. WES was performed using genomic DNA from 13 HHD patients and 364 in-house healthy controls. Potential pathogenic mutations were subsequently validated by Sanger sequencing. As a result, eight mutations in the ATP2C1 gene were identified using WES. In the remaining five patients, we found one mutation in the ATP2A2 gene which was the causal gene of Darier's disease. Four patients had no detectable mutations in ATP2C1 and the other ATPase genes. Together with our previous study in 2019, the total mutation rate was calculated to be 47/52 (90.4%). These findings demonstrate that WES is capable of improving the mutation detection sensitivity in HHD compared with Sanger sequencing.
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http://dx.doi.org/10.1111/1346-8138.15828DOI Listing
April 2021

Delayed discharge is associated with higher complement C3 levels and a longer nucleic acid-negative conversion time in patients with COVID-19.

Sci Rep 2021 01 13;11(1):1233. Epub 2021 Jan 13.

Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, No. 250 East Street, Licheng District, Quanzhou, 362000, Fujian, China.

To determine factors associated with delayed discharge of hospitalized patients with coronavirus disease (COVID-19). This retrospective cohort study included 47 patients with COVID-19 admitted to three hospitals in Quanzhou City, Fujian Province, China, between January 21, 2020 and March 6, 2020. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with delayed discharge. The median length of hospital stay was 22 days. Patients in the delayed discharge group (length of hospital stay ≥ 21 days, n = 27) were more likely to have diarrhea, anorexia, decreased white blood cell counts, increased complement C3 and C-reactive protein levels, air bronchograms, undergo thymalfasin treatment, and take significantly longer to convert to a severe acute respiratory syndrome coronavirus (SARS-CoV-2) RNA-negative status than those in the control group (length of hospital stay, < 21 days; n = 20). In multivariate logistic regression analysis, the time to SARS-CoV-2 RNA-negative conversion (odds ratio [OR]: 1.48, 95% confidence interval [CI] 1.09-2.04, P = 0.01) and complement C3 levels (OR 1.14 95% CI 1.02-1.27, P = 0.03) were the only risk factors independently associated with delayed discharge from the hospital. Dynamic monitoring of complement C3 and SARS-CoV-2 RNA levels is useful for predicting delayed discharge of patients.
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http://dx.doi.org/10.1038/s41598-021-81010-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806718PMC
January 2021

Bifunctional Electrocatalyst with 0D/2D Heterostructure for Highly Efficient Hydrogen and Oxygen Generation.

Chem Asian J 2020 Sep 8;15(18):2892-2899. Epub 2020 Sep 8.

School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798, Singapore.

A novel MoS quantum dots/CoSe nanosheet (MoS QDs/CoSe ) hybrid with 0D/2D heterostructure has been developed. The CoSe nanosheets (NSs) enable an excellent oxygen evolution reaction (OER) activity with increasing vacancy configuration on one hand, while the MoS QDs serve as an eminent hydrogen evolution reaction (HER) catalyst on the other. By integrating MoS QDs and CoSe NSs, the hybrid exhibits excellent electrocatalytic performances in HER and OER. The unique 0D/2D hetero-interface increases the exposed active sites and facilitates electron transfer, thereby boosting the electrocatalytic activity. Relatively low overpotentials of 82 mV and 280 mV are required to drive the current density of 10 mA/cm for HER and OER, with corresponding Tafel slopes of 69 and 75 mV/dec, respectively. As such, this work provides an efficient yet simple approach to construct bifunctional electrocatalysts with enhanced activity and stability.
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http://dx.doi.org/10.1002/asia.202000419DOI Listing
September 2020

Oxygen doped MoS quantum dots for efficient electrocatalytic hydrogen generation.

J Chem Phys 2020 Apr;152(13):134704

Center for Programmable Materials, School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.

In this study, we report an oxygen-doped MoS quantum dot (O-MoS QD) hybrid electrocatalyst for the hydrogen evolution reaction (HER). The O-MoS QDs were prepared with a one-pot microwave method by hydrazine-mediated oxygen-doping. The synthetic method is straightforward, time-saving, and can be applied in large scale preparation. Ultra-small O-MoS QDs with the average size of 5.83 nm and 1-4 layers can be uniformly distributed on the surface of reduced graphene oxide (RGO). Benefited from the unique structure and the doping effect of oxygen in the MoS QDs and the great number of active sites, the O-MoS QD hybrid displayed outstanding electrocatalytic performance toward HER. A low overpotential of 76 mV at 10 mA/cm and a Tafel slope of 58 mV/dec were obtained in an acidic solution toward HER. Additionally, the resultant O-MoS QD hybrid also exhibited excellent stability and durability toward HER, displaying negligible current density loss after 1000 cycles of cyclic voltammetry. The design and synthesis of the electrocatalyst in this work open up a prospective route to prepare active and stable electrocatalysts toward substituting precious metals for hydrogen generation.
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http://dx.doi.org/10.1063/1.5142204DOI Listing
April 2020

High efficiency solar cells tailored using biomass-converted graded carbon quantum dots.

Nanoscale 2019 Aug;11(32):15083-15090

Zhongshan Branch of State Key Laboratory of Electronic Thin Films and Integrated Devices, University of Electronic Science and Technology of China, Zhongshan Institute, Zhongshan 528402, PR China.

The solar-to-electric conversion efficiency of mesoscopic solar cells is highly dependent on electron extraction under solar irradiation and determines the charge recombination processes within devices. Boosting charge transfer via building energy level alignment has been proved to be a promising method to enhance the output power of solar cells. In the current work, we present the successful fabrication of functional biomass-converted carbon quantum dots with graded energy levels by doping nitrogen or sulphur atoms from lotus root powder. When employed as light absorbers for mesoscopic solar cells, light harvesting and electron extraction can be markedly increased arising from the band alignment of graded carbon quantum dots, yielding maximal power conversion efficiencies of 0.158% and 0.208% for bi- and tri-cascaded photovoltaics, respectively. The primary results demonstrate that the employment of an energy-graded architecture is a promising strategy to optimize the device output. Following this line of thought, we further fabricate a co-sensitized device by integrating graded carbon quantum dots with N719 dyes to enhance the electron extraction capability. The final device yields an efficiency as high as 9.04%, showing the potential application of carbon quantum dots in high-performance solar cells.
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http://dx.doi.org/10.1039/c9nr05957aDOI Listing
August 2019

Hepatitis B e antigen induces the expansion of monocytic myeloid-derived suppressor cells to dampen T-cell function in chronic hepatitis B virus infection.

PLoS Pathog 2019 04 18;15(4):e1007690. Epub 2019 Apr 18.

Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.

Chronic hepatitis B virus (HBV) infection is associated with functionally impaired virus-specific T cell responses. Although the myeloid-derived suppressor cells (MDSCs) are known to play a critical role in impairing antiviral T cell responses, viral factors responsible for the expansion of MDSCs in chronic hepatitis B (CHB) remain obscure. In order to elucidate the mechanism of monocytic MDSCs (mMDSCs) expansion and T cell function suppression during persistent HBV infection, we analyzed the circulation frequency of mMDSCs in 164 CHB patients and 70 healthy donors, and found that the proportion of mMDSCs in HBeAg (+) CHB patients was significantly increased compared to that in HBeAg (-) patients, which positively correlated with the level of HBeAg. Furthermore, exposure of peripheral blood mononuclear cells (PBMCs) isolated from healthy donors to HBeAg led to mMDSCs expansion and significant upregulation of IL-1β, IL-6 and indoleamine-2, 3-dioxygenase (IDO), and depletion of the cytokines abrogated HBeAg-induced mMDSCs expansion. Moreover, HBeAg-induced mMDSCs suppressed the autologous T-cell proliferation in vitro, and the purified mMDSCs from HBeAg (+) subjects markedly reduced the proliferation of CD4+ and CD8+ T cells and IFN-γ production, which could be efficiently restored by inhibiting IDO. In summary, HBeAg-induced mMDSCs expansion impairs T cell function through IDO pathway and favors the establishment of a persistent HBV infection, suggesting a mechanism behind the development of HBeAg-induced immune tolerance.
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http://dx.doi.org/10.1371/journal.ppat.1007690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472891PMC
April 2019

BTLA/HVEM Signaling: Milestones in Research and Role in Chronic Hepatitis B Virus Infection.

Front Immunol 2019 29;10:617. Epub 2019 Mar 29.

Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.

B- and T-lymphocyte attenuator (BTLA) is an immune-regulatory receptor, similar to CTLA-4 and PD-1, and is mainly expressed on B-, T-, and all mature lymphocyte cells. Herpes virus entry mediator (HVEM)-BTLA plays a critical role in immune tolerance and immune responses which are areas of intense research. However, the mechanisms of the BTLA and the BTLA/HVEM signaling pathway in human diseases remain unclear. This review describes the research milestones of BTLA and HVEM in chronological order and their role in chronic HBV infection.
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http://dx.doi.org/10.3389/fimmu.2019.00617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449624PMC
August 2020

Development and Validation of a Novel Model to Predict Liver Histopathology in Patients with Chronic Hepatitis B.

Biomed Res Int 2019 27;2019:1621627. Epub 2019 Feb 27.

Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.

It is still vague for chronic hepatitis B (CHB) patients with normal or mildly increasing alanine aminotransferase (ALT) level to undergo antiviral treatment or not. The purpose of our study was to establish a noninvasive model based on routine blood test to predict liver histopathology for antiviral therapy. This retrospective study enrolled 258 CHB patients with liver biopsy from the First Hospital of Quanzhou (training cohort, n=126) and Huashan Hospital (validation cohort, n=132). Histologic grading of necroinflammation (G) and liver fibrosis (S) was performed according to the Scheuer scoring system. A novel model, ATPI, including aspartate aminotransferase (AST), total bilirubin (TBil), and platelets (PLT), was developed in training cohort. The area under ROC curves (AUC) of ATPI for predicting antiviral therapy indication was 0.83 in training cohort and was 0.88 in the validation cohort, respectively. Similarly, ATPI also displayed the highest AUC in predicting antiviral therapy indication in CHB patients with normal or mildly increasing ALT level. In conclusion, ATPI is a novel independent model to predict liver histopathology for antiviral therapy in CHB patients with normal and mildly increased ALT levels.
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http://dx.doi.org/10.1155/2019/1621627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415284PMC
July 2019

[Clinical observation on the muscle tension staged acupuncture for stroke hemiplegia].

Zhongguo Zhen Jiu 2018 Oct;38(10):1035-8

the First Affiliated Hospital of Heilongjiang University of CM, Harbin 150040, China.

Objective: To compare the clinical curative effect of muscle tension staged acupuncture and conventional acupuncture in the treatment of stroke hemiplegia.

Methods: Sixty-two patients with stroke hemiplegia were randomly divided into an observation group and a control group, 31 cases in each one. In the observation group, the muscle tension staged acupuncture was given, the six stages of Brunnstrom were classified as relaxation period and spasmodic period. The (consciousness-restoring resuscitation) combined with the hand and foot meridian acupuncture were applied at Shuigou (GV 26), Jianyu (LI 15), Quchi (LI 11), Shousanli (LI 10), Hegu (LI 4), Liangqiu (ST 34), Zusanli (ST 36), Shangjuxu (ST 37), Jiexi (ST 41) during relaxation period; mainly by hand and foot meridian and meridian, the acupoints were Jianliao (TE 14), Tianjing (TE 10), Waiguan (TE 5), Yangchi (TE 4), Houxi (SI 3), Huantiao (GB 30), Yanglingquan (GB 34), Chengshan (BL 57), Xuanzhong (GB 39), Shenmai (BL 62), Qiuxu (GB 40) during spasmodic period. In the control group, referring to 's , mainly by hand meridian, the governor vessel and foot meridian, phasing was not considered in the acupuncture treatment plan. Both groups were treated one time a day for 4 weeks. The neurological deficit scores were observed before and after treatment of the two groups and the efficacy was evaluated.

Results: There was one case dropped in each group. After treatment, the neurological deficit scores of the two groups was lower than those before treatment (both <0.05), and the observation group was lower than the control group (<0.05). The cured and markedly effective rate was 66.7% (20/30) in the observation group, which was higher than 36.7% (11/30) in the control group, the difference between the two groups was statistically significant (<0.05).

Conclusion: The muscle tension staged acupuncture is better than the conventional acupuncture for the treatment of stroke hemiplegia.
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http://dx.doi.org/10.13703/j.0255-2930.2018.10.002DOI Listing
October 2018

[Effects of acupoint specificity on claustrophobia].

Zhongguo Zhen Jiu 2018 Sep;38(9):948-52

the Third Branch of Department of Acupuncture and Moxibustion, the First Affiliated Hospital of Heilongjiang University of CM, Harbin 150040.

Objective: To observe the effectiveness of acupuncture on claustrophobia, and to explore the effects of acupoint specificity on claustrophobia.

Methods: This was an evaluator-blinded randomized controlled trial. One hundred and sixty patients who presented with claustrophobia during magnetic resonance imaging examination were randomized into an acupoint group, a non-acupoint group, a sham-acupoint group and a blank group, 40 cases in each one. The patients in the acupoint group were treated with acupuncture at Zhaohai (KI 6), Taichong (LR 3), Lingdao (HT 4), Neiguan (PC 6), Shenmen (HT 7), Danzhong (CV 17), Baihui (GV 20) and Fengchi (GB 20). The patients in the non-acupoint group were treated with acupuncture at points 0.5 next to the acupoints above. The patients in the sham-acupoint group were treated with acupuncture at acupoints not closely correlated to claustrophobia in corresponding segment. All the acupuncture was given once. No treatment was used in the blank group. The state anxiety questionnaire (S-AI) was observed in all the patients at the end of MRI examination before and after treatment. The clinical therapeutic effects were compared among four groups.

Results: Compared before treatment, the S-AI score was reduced in the acupoint group, non-acupoint group and sham-acupoint group after treatment (<0.05, <0.01); the differences of S-AI score before and after treatment in the blank group were not statistically significant (>0.05). After treatment, the S-AI scores in the acupoint group, non-acupoint group and sham-acupoint group was lower than that in the blank group (<0.05, <0.01), and the differences of S-AI score were higher than that in the blank group (<0.01). The S-AI score in the acupoint group was lower than that in the non-acupoint group and sham-acupoint group (<0.05), and the difference of S-AI score was higher than those in the non-acupoint group and sham-acupoint group (<0.05). The difference of S-AI score in the non-acupoint group was higher than that in sham-acupoint group (<0.05). The total effective rate was 92.5% (37/40) in the acupoint group, which was significantly superior to 25.0% (10/40) in the non- acupoint group, 17.5% (7/40) in the sham-acupoint group and 5.0% (2/40) in the blank group (<0.05, <0.01).

Conclusion: Acupuncture showes superior effect on claustrophobia, and its tranquilizing effect may be related with acupoint specificity.
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http://dx.doi.org/10.13703/j.0255-2930.2018.09.011DOI Listing
September 2018

Mitophagy, a potential therapeutic target for stroke.

J Biomed Sci 2018 Nov 30;25(1):87. Epub 2018 Nov 30.

Heilongjiang University Of Chinese Medicine, Harbin, 150040, Heilongjiang province, China.

Mitochondria autophagy, termed as mitophagy, is a mechanism of specific autophagic elimination of mitochondria. Mitophagy controls the quality and the number of mitochondria, eliminating dysfunctional or excessive mitochondria that can generate reactive oxygen species (ROS) and cause cell death. Mitochondria are centrally implicated in neuron and tissue injury after stroke, due to the function of supplying adenosine triphosphate (ATP) to the tissue, regulating oxidative metabolism during the pathologic process, and contribution to apoptotic cell death after stroke. As a catabolic mechanism, mitophagy links numbers of a complex network of mitochondria, and affects mitochondrial dynamic process, fusion and fission, reducing mitochondrial production of ROS, mediated by the mitochondrial permeability transition pore (MPTP). The precise nature of mitophagy's involvement in stroke, and its underlying molecular mechanisms, have yet to be fully clarified. This review aims to provide a comprehensive overview of the integration of mitochondria with mitophagy, also to introduce and discuss recent advances in the understanding of the potential role, and possible signaling pathway, of mitophagy in the pathological processes of both hemorrhagic and ischemic stroke. The author also provides evidence to explain the dual role of mitophagy in stroke.
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http://dx.doi.org/10.1186/s12929-018-0487-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271612PMC
November 2018

Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant.

Oncotarget 2018 Sep 13;9(76):34213-34228. Epub 2018 Jul 13.

Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Chronic hepatitis B virus (CHB) infection is a significant public threat. Current interferon-α (IFN-α) based therapies and anti-viral drugs have failed to clear the infection in the majority of CHB patients and animal models. In our previous study, we established a combined protocol that employed a 3-day pretreatment with granulocyte-macrophage colony stimulating factor (GM-CSF) prior to a standard HBV vaccine. It achieved a 90% reduction of HBsAg level in the HBsAg transgenic mouse model. This protocol, while effective, remains too complex for clinical use. In this study, we formulated a new regimen by combining GM-CSF, IFN-α and a recombinant HBV vaccine (GM-CSF/IFN-α/VACCINE) into a single preparation and tested its efficacy in a HBV infection model. After four vaccinations, both serum HBeAg and HBsAg were cleared, accompanied by a 95% reduction of HBV hepatocytes and the presence of a large number of infiltrating CD8 T cells in the liver. Mechanistically these robust responses were initiated by a vaccine-induced conversion of CCR2-dependent CD11bLy6C monocytes into CD11bCD11c DCs. This finding sheds light on the potential mechanism of action of the GM-CSF-based vaccine adjuvant and provides definable markers for clinical assessment during future testing of such highly potent vaccine protocols in HBV patients.
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http://dx.doi.org/10.18632/oncotarget.25789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188151PMC
September 2018

Effects of konjac glucomannan and acetylated distarch phosphate on the gel properties of pork meat myofibrillar proteins.

J Food Sci Technol 2018 Aug 10;55(8):2899-2909. Epub 2018 Jul 10.

1Jiangnan University, Wuxi, China.

The effects of konjac glucomannan (KGM) and acetylated distarch phosphate (ADSP) on properties of pork meat myofibrillar protein (MP) were investigated using rotary rheometer, colorimeter, texture analyzer, Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and confocal laser scanning microscope (CLSM). The addition of KGM and ADSP resulted in increase in both storage modulus (G') and water holding capacity. Whiteness of MP gels was not influenced by the addition of KGM or ADSP, but the texture of MP gels changed apparently with the incorporation of KGM or ADSP. The temperature sweep showed that the increase in G' was associated with the gelatinization of ADSP and its synergistic effect with KGM. The FTIR indicated that the addition of KGM and ADSP enhanced the hydrogen bond in the gel system. The addition of KGM and ADSP changed the microstructures of MP gels, indicating the possible interactions among KGM, ADSP and MP. The images of CLSM showed that starch granules filled in the gap in the protein network, meanwhile the KGM evenly dispersed in the protein network structure.
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http://dx.doi.org/10.1007/s13197-018-3208-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046029PMC
August 2018

CDCA5 regulates proliferation in hepatocellular carcinoma and has potential as a negative prognostic marker.

Onco Targets Ther 2018 20;11:891-901. Epub 2018 Feb 20.

Department of Infectious Diseases, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, China.

Background: CDCA5 plays an important role in the development of various human cancers, but the associated mechanisms have not been investigated in hepatocellular carcinoma (HCC).

Materials And Methods: We evaluated expression levels and functions of CDCA5 in HCC and showed that CDCA5 is upregulated in HCC tissues compared with paired or unpaired normal liver tissues.

Results: Increased CDCA5 expression in HCCs was significantly associated with shorter survival of patients. Knockdown of CDCA5 using lentivirus-mediated shRNA significantly inhibited cell proliferation and suppressed cell survival, as well as induced cell cycle arrest at the G2/M phase and cell apoptosis of HCC cells. The tumor suppression effects of CDCA5 knockdown were mediated by decreased expression of cyclin-dependent kinase 1 (CDK1) and CyclinB1, which were increased in HCC tissues comparing with adjacent normal liver tissues. Moreover, upregulation of CDCA5 was positively associated with increased CDK1 and CyclinB1 expression in HCC tissues.

Conclusion: The present data warrant consideration of CDCA5 as a prognostic biomarker and therapeutic target for HCC.
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http://dx.doi.org/10.2147/OTT.S154754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824752PMC
February 2018

Validation and comparison of seventeen noninvasive models for evaluating liver fibrosis in Chinese hepatitis B patients.

Liver Int 2018 09 24;38(9):1562-1570. Epub 2018 Jan 24.

Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.

Background & Aims: To avoid liver biopsy, many noninvasive models comprised of serum markers for liver fibrosis assessment have been developed. Given that most of them were developed in hepatitis C cohorts and few of them have been validated in Chinese hepatitis B patients, we aim to conduct this validation and compare their diagnostic accuracies in such a population.

Methods: A total of 937 HBV-infected patients who underwent liver biopsy were included in this single-centre retrospective study. The diagnostic accuracies of the 17 noninvasive models were assessed by areas under the receiver-operating characteristic curves (AUROCs), using histologically evaluated fibrotic stages of the biopsy specimens as standards. To compare efficiencies of the models, a grading system based on AUROC levels was developed.

Results: For discriminating significant fibrosis in all patients, the best three noninvasive models were King's score (AUROC = 0.756), Virahep-C model (AUROC = 0.756) and GPR (AUROC = 0.744); and for diagnosing cirrhosis, Lok index (AUROC = 0.832), FI (AUROC = 0.820) and FIB-4 (AUROC = 0.818) got the first three places. AUROCs in HBeAg-positive group were generally higher than those in HBeAg-negative group. In addition, based on the grading system, Virahep-C and GPR outstood others in evaluating liver fibrosis in all patients.

Conclusions: In Chinese HBV-infected patients, Virahep-C models and GPR had high accuracies in diagnosing liver fibrosis and cirrhosis, while the most discussed models like APRI and FIB-4 did not outstand. Assessment should take into account the HBeAg sero-status, since these noninvasive models were more appropriate for HBeAg-positive patients than HBeAg-negative ones.
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http://dx.doi.org/10.1111/liv.13688DOI Listing
September 2018

Differentially Expressed Intrahepatic Genes Contribute to Control of Hepatitis B Virus Replication in the Inactive Carrier Phase.

J Infect Dis 2018 03;217(7):1044-1054

Departmentof Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.

Background: The natural history of chronic hepatitis B virus (HBV) infection was divided into 4 phases. Patients in the inactive carrier (IC) status and immune tolerant (IT) phase had normal alanine aminotransferase levels but huge different viral loads. The mechanism underlying low viral replication status in IC phase is unknown.

Methods: We determined the intrahepatic transcriptomes of 83 chronic hepatitis B patients by microarray analysis of liver biopsies, and screened the effect of differentially regulated genes on HBV replication using specific small interfering RNAs in vitro.

Results: The gene profile distinguishing active chronic hepatitis from IT and IC was predominantly composed of immune-related genes. The liver transcriptomes between the IT and IC phase were largely similar, and 109 expressed genes were significantly different. By performing systematic screening, 5 candidate genes including EVA1A, which were expressed at a relative higher level in IC phase than IT, were identified to regulate HBV replication and gene expression in cellular models.

Conclusions: The immune-related pathways were up-regulated in the active chronic hepatitis phase but not in the IT and IC phase. A number of intrahepatic genes highly expressed in the IC phase may participate in the control of HBV replication and determine the inactive status of HBV infection.
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http://dx.doi.org/10.1093/infdis/jix683DOI Listing
March 2018

A strategy for evaluating pathway analysis methods.

BMC Bioinformatics 2017 Oct 13;18(1):453. Epub 2017 Oct 13.

Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, Fort Detrick, MD, 21702, USA.

Background: Researchers have previously developed a multitude of methods designed to identify biological pathways associated with specific clinical or experimental conditions of interest, with the aim of facilitating biological interpretation of high-throughput data. Before practically applying such pathway analysis (PA) methods, we must first evaluate their performance and reliability, using datasets where the pathways perturbed by the conditions of interest have been well characterized in advance. However, such 'ground truths' (or gold standards) are often unavailable. Furthermore, previous evaluation strategies that have focused on defining 'true answers' are unable to systematically and objectively assess PA methods under a wide range of conditions.

Results: In this work, we propose a novel strategy for evaluating PA methods independently of any gold standard, either established or assumed. The strategy involves the use of two mutually complementary metrics, recall and discrimination. Recall measures the consistency of the perturbed pathways identified by applying a particular analysis method to an original large dataset and those identified by the same method to a sub-dataset of the original dataset. In contrast, discrimination measures specificity-the degree to which the perturbed pathways identified by a particular method to a dataset from one experiment differ from those identifying by the same method to a dataset from a different experiment. We used these metrics and 24 datasets to evaluate six widely used PA methods. The results highlighted the common challenge in reliably identifying significant pathways from small datasets. Importantly, we confirmed the effectiveness of our proposed dual-metric strategy by showing that previous comparative studies corroborate the performance evaluations of the six methods obtained by our strategy.

Conclusions: Unlike any previously proposed strategy for evaluating the performance of PA methods, our dual-metric strategy does not rely on any ground truth, either established or assumed, of the pathways perturbed by a specific clinical or experimental condition. As such, our strategy allows researchers to systematically and objectively evaluate pathway analysis methods by employing any number of datasets for a variety of conditions.
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http://dx.doi.org/10.1186/s12859-017-1866-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640951PMC
October 2017

Autophagy, Endoplasmic Reticulum Stress and the Unfolded Protein Response in Intracerebral Hemorrhage.

Transl Neurosci 2017 20;8:37-48. Epub 2017 May 20.

Department of Clinical Medicine, Heilongjiang University of Chinese Medicine, 24 Heping Road, Harbin, Heilongjiang, 150040, P. R.China.

Intracerebral hemorrhage (ICH) is a subtype of stroke that is followed by primary and secondary brain injury. As a result of the injury, cell metabolism is disrupted and a series of stress responses are activated, such as endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), leading to the re-establishment of cell homeostasis or cell death. As an important mechanism of cell homeostasis, autophagy has been widely studied, and the associations between autophagy, ER stress, and the UPR have also been demonstrated. Whether these mechanisms are beneficial or detrimental remains a matter of controversy, but there is no doubt as to their vital functions. An understanding of the mechanisms of injury and recovery after ICH is crucial to develop therapeutic strategies. In this review, we summarize the related studies and highlight the roles of autophagy, ER stress, and the UPR in disease, especially in ICH. We also provide an overview of therapeutic approaches that target autophagy, and we discuss the prospects for modulating autophagy, ER stress, and UPR mechanisms in ICH therapy.
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http://dx.doi.org/10.1515/tnsci-2017-0008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444040PMC
May 2017

Enrichment of Ly6C monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model.

Hum Vaccin Immunother 2017 12 12;13(12):2872-2882. Epub 2017 Jul 12.

a Key Laboratory of Medical Molecular Virology of the Ministry of Health and Ministry of Education, School of Basic Medical Sciences , Fudan University , Shanghai , China.

Adjuvants are considered a necessary component for HBV therapeutic vaccines but few are licensed in clinical practice due to concerns about safety or efficiency. In our recent study, we established that a combination protocol of 3-day pretreatments with GM-CSF before a vaccination (3 × GM-CSF+VACCINE) into the same injection site could break immune tolerance and cause over 90% reduction of HBsAg level in the HBsAg transgenic mouse model. Herein, we further investigated the therapeutic potential of the combination in AAV8-1.3HBV-infected mice. After 4 vaccinations, both serum HBeAg and HBsAg were cleared and there was a 95% reduction of HBV-positive hepatocytes, in addition to the presence of large number of infiltrating CD8 T cells in the livers. Mechanistically, the HBV-specific T-cell responses were elicited via a 3 × GM-CSF+VACCINE-induced conversion of CCR2-dependent CD11b Ly6C monocytes into CD11bCD11c DCs. Experimental depletion of Ly6C monocytes resulted in a defective HBV-specific immune response thereby abrogating HBV eradication. This vaccination strategy could lead to development of an effective therapeutic protocol against chronic HBV in infected patients.
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http://dx.doi.org/10.1080/21645515.2017.1344797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718782PMC
December 2017

Data-driven prediction of adverse drug reactions induced by drug-drug interactions.

BMC Pharmacol Toxicol 2017 06 8;18(1):44. Epub 2017 Jun 8.

Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, MD, 21702, USA.

Background: The expanded use of multiple drugs has increased the occurrence of adverse drug reactions (ADRs) induced by drug-drug interactions (DDIs). However, such reactions are typically not observed in clinical drug-development studies because most of them focus on single-drug therapies. ADR reporting systems collect information on adverse health effects caused by both single drugs and DDIs. A major challenge is to unambiguously identify the effects caused by DDIs and to attribute them to specific drug interactions. A computational method that provides prospective predictions of potential DDI-induced ADRs will help to identify and mitigate these adverse health effects.

Method: We hypothesize that drug-protein interactions can be used as independent variables in predicting ADRs. We constructed drug pair-protein interaction profiles for ~800 drugs using drug-protein interaction information in the public domain. We then constructed statistical models to score drug pairs for their potential to induce ADRs based on drug pair-protein interaction profiles.

Results: We used extensive clinical database information to construct categorical prediction models for drug pairs that are likely to induce ADRs via synergistic DDIs and showed that model performance deteriorated only slightly, with a moderate amount of false positives and false negatives in the training samples, as evaluated by our cross-validation analysis. The cross validation calculations showed an average prediction accuracy of 89% across 1,096 ADR models that captured the deleterious effects of synergistic DDIs. Because the models rely on drug-protein interactions, we made predictions for pairwise combinations of 764 drugs that are currently on the market and for which drug-protein interaction information is available. These predictions are publicly accessible at http://avoid-db.bhsai.org . We used the predictive models to analyze broader aspects of DDI-induced ADRs, showing that ~10% of all combinations have the potential to induce ADRs via DDIs. This allowed us to identify potential DDI-induced ADRs not yet clinically reported. The ability of the models to quantify adverse effects between drug classes also suggests that we may be able to select drug combinations that minimize the risk of ADRs.

Conclusion: Almost all information on DDI-induced ADRs is generated after drug approval. This situation poses significant health risks for vulnerable patient populations with comorbidities. To help mitigate the risks, we developed a robust probabilistic approach to prospectively predict DDI-induced ADRs. Based on this approach, we developed prediction models for 1,096 ADRs and used them to predict the propensity of all pairwise combinations of nearly 800 drugs to be associated with these ADRs via DDIs. We made the predictions publicly available via internet access.
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http://dx.doi.org/10.1186/s40360-017-0153-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465578PMC
June 2017

A tracheal scaffold of gelatin-chondroitin sulfate-hyaluronan-polyvinyl alcohol with orientated porous structure.

Carbohydr Polym 2017 Mar 7;159:20-28. Epub 2016 Dec 7.

Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, PR China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, PR China; Key Laboratory of Biomedical Materials Science and Engineering, Ministry of Education, Guangzhou 510006, PR China; Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, PR China. Electronic address:

Scaffold of gelatin-chondroitin sulfate-hyaluronan-polyvinyl alcohol (GCH-PVA) with orientated microtubule structure and good hydrophilicity was fabricated by unidirectional freeze-drying method mimicking the composition and structure of tracheal cartilage extracellular matrix. PVA was incorporated to improve flexibility and viscoelasticity of GCH scaffold. All wet scaffolds showed similar compressive elastic modulus with native cartilage. GCH-PVA scaffolds showed high relative remaining stress during relaxation indicating good mechanical stability. The hysteresis ratio during cyclic compression increased gradually with PVA content and close to native cartilage. During multiple frequency compression, all scaffolds showed a low loss tangent close to native cartilage, and PVA incorporation enhanced the elasticity of scaffolds when they were stressed under high frequency. The incorporation of PVA promoted gene expression of adhesion related integrin αβ and actin by mouse bone marrow mesenchymal stem cells (mBMSCs). With the orientated microtubule structure, cells ingrowth into scaffolds was facilitated by dynamic culture method.
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http://dx.doi.org/10.1016/j.carbpol.2016.12.017DOI Listing
March 2017

Using Chemical-Induced Gene Expression in Cultured Human Cells to Predict Chemical Toxicity.

Chem Res Toxicol 2016 11 4;29(11):1883-1893. Epub 2016 Nov 4.

Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, US Army Medical Research and Materiel Command , Fort Detrick, Maryland 21702, United States.

Chemical toxicity is conventionally evaluated in animal models. However, animal models are resource intensive; moreover, they face ethical and scientific challenges because the outcomes obtained by animal testing may not correlate with human responses. To develop an alternative method for assessing chemical toxicity, we investigated the feasibility of using chemical-induced genome-wide expression changes in cultured human cells to predict the potential of a chemical to cause specific organ injuries in humans. We first created signatures of chemical-induced gene expression in a vertebral-cancer of the prostate cell line for ∼15,000 chemicals tested in the US National Institutes of Health Library of Integrated Network-Based Cellular Signatures program. We then used the signatures to create naı̈ve Bayesian prediction models for chemical-induced human liver cholestasis, interstitial nephritis, and long QT syndrome. Detailed cross-validation analyses indicated that the models were robust with respect to false positives and false negatives in the samples we used to train the models and could predict the likelihood that chemicals would cause specific organ injuries. In addition, we performed a literature search for drugs and dietary supplements, not formally categorized as causing organ injuries in humans but predicted by our models to be most likely to do so. We found a high percentage of these compounds associated with case reports of relevant organ injuries, lending support to the idea that in vitro cell-based experiments can be used to predict the toxic potential of chemicals. We believe that this approach, combined with a robust technique to model human exposure to chemicals, may serve as a promising alternative to animal-based chemical toxicity assessment.
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http://dx.doi.org/10.1021/acs.chemrestox.6b00287DOI Listing
November 2016

Serum Interleukin (IL)-9 and IL-10, but not T-Helper 9 (Th9) Cells, are Associated With Survival of Patients With Acute-on-Chronic Hepatitis B Liver Failure.

Medicine (Baltimore) 2016 Apr;95(16):e3405

From the Department of Infectious Diseases and Clinical Laboratory (XY, YZ, JL, RG, MS, DM, ZL, ZS), the First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou; Department of Infectious Diseases (YD), the Second People's Hospital of Pingxiang, Pingxiang; and Department of Infectious Diseases (XY, JZ), Huashan Hospital, Fudan University, Shanghai, China.

CD4 T helper (Th) cells are reported to be essential for initiating and maintaining an effective immune response to hepatitis B virus (HBV) infection. Th9 cells are a new subset of CD4 Th cells that produce interleukin (IL)-9 and IL-10. The present study aimed to investigate the percentage of Th9 cells relative to the number of CD4 cells in peripheral blood. We also measured serum IL-9 and IL-10 levels in different stages of HBV infection and their relationship with progress and prognosis of liver disease. Whole blood samples from 111 patients with HBV infection, including 39 chronic hepatitis B (CHB), 25 HBV-liver cirrhosis (HBV-LC), 21 acute-on-chronic liver failure (ACLF) patients, and 26 healthy controls were collected. The percentage of Th9 cells and serum IL-9 and IL-10 levels were determined. There was no significant difference in the percentage of Th9 cells and serum IL-9 and IL-10 levels among different groups, nor were these related to hepatitis B e antigen status, complications of cirrhosis, inflammation index, or prognosis indexes. There was no change in the percentage of Th9 cells before and after antiviral treatment in CHB patients. There was no correlation of Th9 cells with survival of ACLF patients. However, IL-9 and IL-10 levels were significantly higher in the nonsurvived ACLF patients compared to survived ACLF patients. Furthermore, baseline IL-9 level predicted the prognosis of ACLF patients with 87.5% sensitivity and 61.5% specificity.Thus, our data indicate that Th9 cells were unlikely involved in the pathogenesis of HBV infection, but elevation in IL-9 and IL-10 may signal poor prognosis for ACLF.
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http://dx.doi.org/10.1097/MD.0000000000003405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845832PMC
April 2016

[Case of stiff-person syndrome].

Zhongguo Zhen Jiu 2015 Dec;35(12):1257

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December 2015

[Operation and essence of Toutianliang manipulation by professor ZHANG Jin].

Zhongguo Zhen Jiu 2016 Jan;36(1):53-5

Toutianliang manipulation is the most representative compound needling technique of traditional reinforcing and reducing and has the remarkable efficacy on heat syndrome with muscle and bone involved for example. Professor ZHANG Jin is one of the famous acupuncture master in China and has contributed his lifelong to the research of acupuncture manipulation techniques. He has summarized 24 single-type manipulations and has given the comprehensive explanation of the manipulations for meridian conduction, reinforcing or reducing techniques for the excess or deficiency. In the paper, Toutianliang manipulation was introduced briefly and the key operation steps had been discussed.
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January 2016