Publications by authors named "Jingyi Hu"

44 Publications

Theaflavin 3, 3'-Digallate Delays Ovarian Aging by Improving Oocyte Quality and Regulating Granulosa Cell Function.

Oxid Med Cell Longev 2021 8;2021:7064179. Epub 2021 Dec 8.

Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Ovarian aging refers to the gradual decline of ovarian function with increasing physiological age, manifested as decreased ovarian reserve, elevated aging-related markers, and reduced oocyte quality. With a declining female fertility and a growing aging population, it is urgent to delay ovarian aging to maintain fertility and improve the life quality of women. Theaflavin 3, 3'-digallate (TF3) is a naturally bioactive polyphenol compound extracted from black tea, and its antioxidant properties play an important role in maintaining human health and delaying aging; however, the effects of TF3 on female reproduction and ovarian function are not yet clear. Here, we show that TF3 can preserve primordial follicle pool, partially restore the estrous cycle, and increase the offspring number of aged mice. Meanwhile, TF3 gavage increased the number of oocytes retrieved, decreased the level of reactive oxygen species, increased the level of glutathione, and decreased the abnormal rate of oocyte spindle after ovulation induction. Moreover, TF3 inhibited human granulosa cell apoptosis and improved their antioxidative stress ability. High-throughput sequencing and small-molecule-targeted pharmacological prediction show that TF3 affects multiple pathways and gene expression levels, mainly involved in reproductive and developmental processes. It may also affect cellular function by targeting mTOR to regulate the autophagic pathway, thereby delaying the process of ovarian aging. This study shows that TF3 can be used as a potential dietary supplement to protect ovary function from aging and thereby improving the life quality of advanced-age women.
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http://dx.doi.org/10.1155/2021/7064179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674650PMC
December 2021

A Facile Low-Dose Photosensitizer-Incorporated Dissolving Microneedles-Based Composite System for Eliciting Antitumor Immunity and the Abscopal Effect.

ACS Nano 2021 12 3;15(12):19468-19479. Epub 2021 Dec 3.

Institute of Pharmaceutics, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Nanomedicine-based photodynamic therapy (PDT) for melanoma treatment has attracted great attention. However, the complex design of polymer nanoparticles and high doses of photosensitizers used in intravenous injections (for sufficient accumulation of drugs in tumor lesions) pose a huge challenge to the commercialization and further clinical application. Herein, we fabricated the carrier-free nanoassemblies of a chlorin e6 (L-Ce6 NAs)-integrated fast-dissolving microneedles patch (L-Ce6 MNs) enriching only about 3 μg of Ce6 in the needle tips a facile fabrication method. The L-Ce6 MNs had sufficient mechanical strength to penetrate the skin and facilitated the transportation of L-Ce6 NAs to a depth of 200-500 μm under the skin, thereby achieving efficient and accurate drug delivery to tumor lesions. In a xenograft mouse melanoma model, the L-Ce6 MNs-based PDT with low dose of Ce6 (0.12 mg/kg) exerted efficient ablation of the primary lesions through reactive oxygen species (ROS) generation. More importantly, a significant abscopal effect was also elicited by activating immunogenic cell death (ICD) and releasing danger-associated molecular patterns (DAMPs), which in turn promoted dendritic cells (DCs) maturation and the subsequent antigen presentation, thereby facilitating the T-cell-mediated immune response without synergetic immunotherapies. Collectively, our findings indicate the facile, controllable, and fast-dissolving microneedles patch with a low dose of photosensitizers presented great therapeutic potential for enhanced photoimmunotherapy.
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http://dx.doi.org/10.1021/acsnano.1c06225DOI Listing
December 2021

Combination of Nanomaterials in Cell-Based Drug Delivery Systems for Cancer Treatment.

Pharmaceutics 2021 Nov 8;13(11). Epub 2021 Nov 8.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

Cell-based drug delivery systems have shown tremendous advantages in cancer treatment due to their distinctive properties. For instance, delivery of therapeutics using tumor-tropic cells like neutrophils, lymphocytes and mesenchymal stem cells can achieve specific tumor targeting due to the "Trojan Horse" effect. Other circulatory cells like erythrocytes and platelets can greatly improve the circulation time of nanoparticles due to their innate long circulation property. Adipocytes, especially cancer-associated adipocytes, play key roles in tumor development and metabolism, therefore, adipocytes are regarded as promising bio-derived nanoplatforms for anticancer targeted drug delivery. Nanomaterials are important participants in cell-based drug delivery because of their unique physicochemical characteristics. Therefore, the integration of various nanomaterials with different cell types will endow the constructed delivery systems with many attractive properties due to the merits of both. In this review, a number of strategies based on nanomaterial-involved cell-mediated drug delivery systems for cancer treatment will be summarized. This review discusses how nanomaterials can be a benefit to cell-based therapies and how cell-derived carriers overcome the limitations of nanomaterials, which highlights recent advancements and specific biomedical applications based on nanomaterial-mediated, cell-based drug delivery systems.
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http://dx.doi.org/10.3390/pharmaceutics13111888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621332PMC
November 2021

Relationship between Acute Mastitis and Constitution of Traditional Chinese Medicine in Chinese Breastfeeding Mothers.

Evid Based Complement Alternat Med 2021 13;2021:2255511. Epub 2021 Oct 13.

Integrated Chinese and Western Medicine Department of Breast Surgery, Longhua Hospital, Affiliated Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Objective: The purpose of this study was to explore the relationship between acute mastitis and the constitution of traditional Chinese medicine (TCM) and the potential risk factors of acute mastitis in Chinese breastfeeding mothers.

Method: A retrospective study on infant feeding practices was conducted in the Breast Surgery Department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between February 2017 and March 2018. A total of 184 women with acute mastitis and 201 women without mastitis of childbearing age were included in this study. All participants filled a baseline questionnaire on demographic characteristics, previous deliveries, and mastitis history and other possible risk factors; data were collected by face-to-face interview. Logistic regression analysis was conducted to ascertain pertinent risk factors affecting the incidence of acute mastitis. The biased constitution of TCM of participants was identified through questionnaires surveyed with the TCM constitution table (ZYYXH/T157-2009). The relationship between acute mastitis and the constitution of TCM was assessed.

Results: The protective factors included regular nipple cleansing and cesarean section. The risk factors were nipple infection, Primipara, improper diet, emotional stimuli, postpartum colostrum overdue for more than 72 h, breastfeeding more than 7 times each day, and late primiparity age. Forty-five percent of acute mastitis occurred within 8 weeks after postpartum, and the most common biased constitution of TCM at this period was Qi-Deficiency Constitution (QDC) and Qi-Stagnation Constitution (QSC). Another peak was 25-48 weeks after delivery, accounting for 18%, and the most common biased constitution of TCM was QSC and QDC. More participants were or were prone to be classified as Balanced Constitution (BC) in the control group than the case group (88.5% vs 29.6%), while QDC was the most common constitution of TCM in the case group. The logistic regression analysis further proved that BC was the protective factor of acute mastitis while QDC was a risk factor.

Conclusions: The protective factors of acute mastitis were regular nipple cleansing and cesarean section. The risk factor was nipple infection. Among all the constitutions of TCM, BC was a protective factor, while QDC was a risk factor. For all breastfeeding mothers with various constitutions of TCM, regular nipple cleansing and breast vacuuming, a healthy lifestyle, and a positive mental state can keep mastitis away.
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http://dx.doi.org/10.1155/2021/2255511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528590PMC
October 2021

Exploring the Molecular Mechanism of Astragali Radix-Curcumae Rhizoma against Gastric Intraepithelial Neoplasia by Network Pharmacology and Molecular Docking.

Evid Based Complement Alternat Med 2021 4;2021:8578615. Epub 2021 Oct 4.

Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.

Background: Astragali Radix-Curcumae Rhizoma (ARCR), a classic drug pair, has been widely used for the treatment of gastric intraepithelial neoplasia (GIN) in China. However, the underlying mechanisms of this drug pair are still unknown. Thus, elucidating the molecular mechanism of ARCR for treating GIN is imperative.

Methods: The active components and targets of ARCR were determined from the TCMSP database, and the differentially expressed genes related to GIN were identified from the GSE130823 dataset. The protein-protein interaction (PPI) network and ARCR-active component-target-pathway network were constructed by STRING 11.0 and Cytoscape 3.7.2, respectively. In addition, a receiver operating characteristic curve (ROC) was conducted to verify the key targets, and enrichment analyses were performed using R software. Molecular docking was carried out to test the binding capacity between core active components and key targets.

Results: 31 active components were obtained from ARCR, among which 22 were hit by the 51 targets associated with GIN. Gene Ontology (GO) functional enrichment analysis showed that biological process (BP), molecular function (MF), and cellular component (CC) were most significantly enriched in response to a drug, catecholamine binding, and apical part of the cell, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated ARCR against GIN through regulation of neuroactive ligand-receptor interaction, nitrogen metabolism, calcium signaling pathway, chemical carcinogenesis-receptor activation, drug metabolism, gap junction, and cancers. In the PPI network, 15 potential targets were identified, of which nine key targets were proven to have higher diagnostic values in ROC. Molecular docking revealed a good binding affinity of active components (quercetin, bisdemethoxycurcumin, and kaempferol) with the corresponding targets (CYP3A4, CYP1A1, HMOX1, DRD2, DPP4, ADRA2A, ADRA2C, NR1I2, and LGALS4).

Conclusion: This study revealed the active components and molecular mechanism by which ARCR treatment is effective against GIN through regulating multipathway, such as neuroactive ligand-receptor interaction, nitrogen metabolism, and calcium signaling pathway.
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http://dx.doi.org/10.1155/2021/8578615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505068PMC
October 2021

Correlation of early cognitive dysfunction with inflammatory factors and metabolic indicators in patients with Alzheimer's disease.

Am J Transl Res 2021 15;13(8):9208-9215. Epub 2021 Aug 15.

Department of Clinical Laboratory, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin Neurosurgery Institute, Tianjin Huanhu Hospital Tianjin 300350, China.

Objective: The aim of this investigation was to clarify the correlation of early cognitive dysfunction (CD) with inflammatory factors and metabolic indicators in patients with Alzheimer's disease (AD).

Methods: Eighty patients with AD who were referred to our hospital from May 2019 to May 2020 were selected as the research group (RG) and 71 non-AD patients served as the control group (CG). The two groups were compared regarding the changes in their mini-mental state examination (MMSE) scores and inflammatory factors as well as metabolic indicators. The correlation of MMSE with inflammatory factors and metabolic indicators was analyzed by Pearson correlation analysis.

Results: The RG presented with lower MMSE scores than the CG. Interleukin (IL-6), C-reactive protein (CRP), IL-1β levels, low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), fasting plasma glucose (FPG), and systolic blood pressure (SBP) were all higher in the RG as compared to the CG, while high density lipoprotein cholesterol (HDL-C), ApoE and ApoAI were lower (all P<0.05). The MMSE score was negatively associated with IL-6, CRP, IL-1β, LDL-C, TC, TG, FPG and SBP levels, and was positively correlated with HDL-C, ApoE and ApoAI levels.

Conclusions: Inflammatory factors and metabolic indicators are highly correlated with early CD in patients with AD, and thus may be excellent potential indicators for the future diagnosis and treatment of AD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430204PMC
August 2021

Designing New-Generation Piezoelectric Transducers by Embedding Superior Graphene-Based Thermal Regulators.

Adv Mater 2021 Oct 27;33(41):e2103141. Epub 2021 Aug 27.

Center for Nanochemistry (CNC), Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, P. R. China.

Cascaded-piezoelectric-transducers (CPETs) is a key component in modern energy-conversion fields, possessing versatile applications in ultrasonic scalpels, acoustic levitation, and sonar. However, serious self-heating inevitably occurs inside high-power CPETs, severely limiting their practical applications in broader fields. To tackle this, multidirectional heat-escape channels of multidimensional (multi-D, 3D/2D) graphene films are introduced in designing new-type thermal regulators. A porous AlN-ceramic thermal-sink is creatively selected as a template for directly synthesizing graphene via a two-step chemical vapor deposition strategy. This perfect combination of 3D/2D-graphene and the AlN ceramic can integrate their complementary advantages in uniformizing, transmitting, and releasing heat. Amazingly, in the new-generation CPETs embedded with these graphene-based thermal regulators, the self-heating-induced temperature rise can be substantially reduced by ≈60% (far exceeding actual demand standard). As another kernel parameter, electroacoustic-energy-conversion efficiency is dramatically improved in the new-generation CPETs. Briefly, this research realizes the first synthesis of a novel multi-D-graphene/AlN-ceramic hybrid, and propels its brand-new application directions in new-generation energy-conversion- and thermal-management-related territories.
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http://dx.doi.org/10.1002/adma.202103141DOI Listing
October 2021

Research progress on proteasome subunits in regulating occurrence and development of hepatocellular carcinoma.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Jun;50(3):396-402

Institute of Immunology.

Proteasome is the eukaryotic organelle responsible for degradation of short-lived proteins and involved in maintaining cellular protein homeostasis. It has been reported that during the occurrence and development of hepatocellular carcinoma (HCC), the regulatory particle subunits of proteasome regulate a series of tumor-related proteins, and proliferation, survival-associated signaling molecules, including PTEN gene, P53, Bcl-2, Bcl-2 interacting mediator of cell death (Bim), cyclin-dependent kinase 4(CDK4), transforming growth factor β receptor (TGFBR), E2F1, growth factor receptor-bound protein 2 (GRB2) . Meanwhile, these subunits regulate some tumor-associated pathway protein, such as signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT), inducing their malfunction to promote the occurrence, proliferation, invasion and metastasis of HCC. The core particle subunits are more to perform the degradation of HCC-related proteins, so inhibitors targeting the core particle show a good anti-tumor effect. This review summarizes the current research progress on the regulation and mechanism of proteasome subunits in promoting the occurrence and development .
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http://dx.doi.org/10.3724/zdxbyxb-2021-0146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710273PMC
June 2021

L-Theanine Alleviates IMQ-Induced Psoriasis Like Skin Inflammation by Downregulating the Production of IL-23 and Chemokines.

Front Pharmacol 2021 26;12:719842. Epub 2021 Jul 26.

Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Psoriasis, the most common skin inflammatory disease, is characterized by massive keratinocyte proliferation and immune cell infiltration into epidermis. L-Theanine (L-THE), a nonproteinogenic amino acid derived from green tea (Camellia sinensis), has been proved to possess the properties of anti-inflammatory, antidepressants and neuroprotective. However, whether L-THE has a therapeutic effect on psoriasis is still unknown. In this study, we found that the epidermal thickness and inflammatory response were significantly reduced in Imiquimod (IMQ)-induced psoriasis mice by applying with L-THE on mice skin. The expression of proliferation and inflammation associated genes such as , and was also downregulated by L-THE. Furthermore, L-THE inhibited the production of IL-23 in dendritic cells (DCs) after IMQ treatment, and decreased the levels of chemokines in keratinocytes treated with IL-17A by downregulating the expression of IL-17RA. RNA-seq and KEGG analysis revealed that L-THE significantly regulated the expression of IL-17A and NF-κB signaling pathway-associated genes. Metabolomics analysis displayed that L-THE promoted propanoate metabolism which has been reported to inhibit the activity of TH17 cells. Therefore, our results demonstrated that L-THE significantly decreases the levels of IL-23 and chemokines, and attenuates IMQ-induced psoriasis like skin inflammation by inhibiting the activation of NF-κB and IL-17A signaling pathways, and promoting the propanoate metabolism. Our findings suggest that topical applied L-THE can be used as a topical drug candidate for the treatment of psoriasis or as an adjuvant treatment of ustekinumab or secukinumab to prevent the relapse of psoriasis.
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http://dx.doi.org/10.3389/fphar.2021.719842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350042PMC
July 2021

Associations Between Diabetes and Idiopathic Pulmonary Fibrosis: a Study-level Pooled Analysis of 26 Million People.

J Clin Endocrinol Metab 2021 10;106(11):3367-3380

Department of Anorectal Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Context: Diabetes mellitus (DM) is a systemic disease characterized by chronic hyperglycemia associated with inflammation and oxidative stress, and the lung may be a target organ of diabetic microvascular damage. Several studies have indicated a positive association between idiopathic pulmonary fibrosis (IPF) and diabetes with controversial findings.

Objective: Primary outcomes were to compare the prevalence of DM among individuals with IPF to non-IPF controls, and the prevalence of IPF among individuals with DM to non-DM controls.

Methods: Data sources include PubMed, EMBASE, and the Cochrane Library. Studies contained sufficient data to calculate the prevalence of DM among individuals with and without IPF, or the prevalence of IPF among individuals with and without DM. Two investigators independently identified eligible studies and extracted data. Pooled odds ratio (OR) with 95% CI was the summary effect measure.

Results: Eighteen studies including 26 410 623 individuals met the eligibility criteria, of whom 16 recruited people with IPF and 2 recruited people with DM. The OR of DM in IPF patients was 1.54 (95% CI, 1.30-1.84; P < .001) compared to that in non-IPF controls. However, compared with that in non-DM patients, the risk of IPF in DM patients was not found to be significantly reduced (OR: 0.89; 95% CI, 0.64-1.25; P = .497).

Conclusion: This meta-analysis suggests that people with IPF have 1.54 times increased odds of diabetes compared to non-IPF controls, while whether patients with DM have an increased risk of IPF is still controversial. Further large, prospective cohort studies investigating the prevalence of IPF in diabetic patients are warranted.
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http://dx.doi.org/10.1210/clinem/dgab553DOI Listing
October 2021

F-florbetapir PET/MRI for quantitatively monitoring myelin loss and recovery in patients with multiple sclerosis: A longitudinal study.

EClinicalMedicine 2021 Jul 23;37:100982. Epub 2021 Jun 23.

Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.

Background: Amyloid positron emission tomography (PET) can measure in-vivo demyelination in patients with multiple sclerosis (MS). However, the value of F-labeled amyloid PET tracer, F-florbetapir in the longitudinal study for monitoring myelin loss and recovery has not been confirmed.

Methods: From March 2019 to September 2020, twenty-three patients with MS and nine healthy controls (HCs) underwent a hybrid PET/MRI at baseline and expanded disability status scale (EDSS) assessment, and eight of 23 patients further underwent follow-up PET/MRI. The distribution volume ratio (DVR) and standard uptake value ratio (SUVR) of F-florbetapir in damaged white matter (DWM) and normal-appearance white matter (NAWM) were obtained from dynamic and static PET acquisition. Diffusion tensor imaging-derived parameters were also calculated. Data were expressed as mean ± standard deviation with 99% confidence interval (99%CI).

Finding: The mean DVR (1.08 ± 0.12, 99%CI [1.02 ~ 1.14]) but not the mean SUVR of DWM lesions was lower than that of NAWM in patients with MS (1.25 ± 0.10, 99%CI [1.20 ~ 1.31]) and HCs (1.29 ± 0.08, 99%CI [1.23 ~ 1.36]). A trend toward lower mean fractional anisotropy (374.95 ± 45.30 vs. 419.07 ± 4.83) and higher mean radial diffusivity (0.45 ± 0.05 vs. 0.40 ± 0.01) of NAWM in patients with MS than those in HCs was found. DVR decreased in DWM lesions with higher MD (rho = -0.261, 99%CI [-0.362 ~ -0.144]), higher AD (rho = -0.200, 99%CI [-0.318 ~ -0.070]) and higher RD (rho = -0.198, 99%CI [-0.313 ~ -0.075]). Patients' EDSS scores were reduced ( = 0.04, 99%CI [-0.005 ~ 0.084]) with decreased index of global demyelination in the longitudinal study.

Interpretation: Our exploratory study suggests that dynamic F-florbetapir PET/MRI may be a very promising tool for quantitatively monitoring myelin loss and recovery in patients with MS.

Funding: Shanghai Pujiang Program, Shanghai Municipal Key Clinical Specialty, Shanghai Shuguang Plan Project, Shanghai Health and Family Planning Commission Research Project, Clinical Research Plan of SHDC, French-Chinese program "Xu Guangqi".
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http://dx.doi.org/10.1016/j.eclinm.2021.100982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234356PMC
July 2021

Adhesion-Enhanced Vertically Oriented Graphene on Titanium-Covered Quartz Glass toward High-Stability Light-Dimming-Related Applications.

ACS Nano 2021 Jun 26;15(6):10514-10524. Epub 2021 May 26.

School of Materials Science and Engineering, Peking University, Beijing 100871, P.R. China.

Improving the adhesion property of graphene directly grown on an insulating substrate is essential for promoting the reliability and durability of the related applications. However, effective approaches have rarely been reported, especially for vertically oriented graphene (VG) films grown on insulating templates. To tackle this, we have developed a facile synthetic strategy by introducing an ultrathin (10 nm-thick) titanium (Ti) film on a quartz glass substrate as the adhesion layer, for plasma-enhanced chemical vapor deposition (PECVD) growth of VG films. This synthetic process induces the formation of Ti, oxygen (O), carbon (C)-containing adhesion layer (Ti (O, C)), offering improved interfacial adhesion due to the formation of chemical bonds among Ti and C atoms. Dramatically improved surface and interface stabilities have been achieved, with regard to its counterpart without a Ti adhesion layer. Moreover, we have also realized precise controls of the transparent/conductive property, surface roughness, and hydrophobicity, , by varying the VG film growth time. We have also demonstrated the very intriguing application potentials of the hybrids in light-dimming related fields, that is, electro-heating defogging lenses and neutral density filters toward medical endoscope defogging and camera photography.
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http://dx.doi.org/10.1021/acsnano.1c03063DOI Listing
June 2021

Randomised clinical trial: Efficacy and safety of Qing-Chang-Hua-Shi granules in a multicenter, randomized, and double-blind clinical trial of patients with moderately active ulcerative colitis.

Biomed Pharmacother 2021 Jul 13;139:111580. Epub 2021 Apr 13.

Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China. Electronic address:

Qing-Chang-Hua-Shi (QCHS) is a Chinese herbal formula, which is composed of 11 herbs. Studies have also shown that QCHS granules can alleviate colitis in animal models by preventing inflammatory responses and suppressing apoptosis through the MEK/ERK signaling pathway. To determine the efficacy and safety of QCHS granules in patients with moderately active UC. We performed a multicenter, randomized, placebo-controlled, double-blind study of patients with moderately active UC who did not respond to 4 weeks of mesalazine therapy at the maximum dose. Patients were randomly assigned to groups and administered QCHS granules (125 g/day, n = 59) or an identical placebo, which was similar to the QCHS granules in color and taste (125 g/day, n = 60), with continued 5-ASA 4 g/d therapy for 12 weeks. The primary outcome was the rate of clinical response and clinical remission at week 12. The secondary outcomes were health-related quality of life, endoscopic response rate, and mucosal healing rate. Any changes in mucus/bloody stool and diarrhea were recorded. Out of the 119 enrolled patients at 10 different centers in China, 102 patients completed the trial. Clinical remission and clinical response were seen in 31.48% and 92.59% of QCHS-treated patients, and 12.50% and 72.92% of placebo-treated patients, respectively. There was a significant difference between the two treatment groups. More patients receiving QCHS granules vs. placebo achieved remission of mucus/bloody stool (70.37% vs. 47.92%, P = 0.0361). Adverse event rates were similar (QCHS granules 38.33%; placebo 25.42%). In conclusion, QCHS granules were superior to the placebo in introducing clinical remission and mucosal healing, as well as in relieving mucus/blood stool in patients with moderately active and 5-ASA-refractory UC.
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http://dx.doi.org/10.1016/j.biopha.2021.111580DOI Listing
July 2021

Decreased serum fibroblast growth factor 19 level is a risk factor for type 1 diabetes.

Ann Transl Med 2021 Mar;9(5):376

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: Increasing evidence suggests that fibroblast growth factor 19 (FGF19) is a regulator of glucose metabolism and may provide a new therapeutic target for type 1 diabetes (T1D). However, the clinical relevance of FGF19 in T1D remains unclear. In this study, we examined the relationship between the serum FGF19 concentration and T1D.

Methods: This study included 81 newly diagnosed T1D patients and 80 sex- and age-matched healthy controls. The correlation between the FGF19 concentration and clinical characteristics of T1D patients and healthy controls was investigated. Logistic regression analysis was performed to determine whether levels of FGF19 were independently associated with T1D.

Results: The fasting serum FGF19 levels in the T1D group were significantly lower than those in the control group [159.9 (100.0-272.7) 205.0 (126.9-307.9) pg/mL, P=0.008]. In all subjects, serum FGF19 levels were negatively correlated with fasting blood glucose (FBG) (r=-0.192, P=0.015). In the control group, serum FGF19 levels were positively correlated with total cholesterol (TC) (r=0.338, P=0.002) and low-density lipoprotein cholesterol (LDL-c) (r=0.300, P=0.007). In addition to sex and body mass index (BMI), FGF19 was an independent impact factor for T1D [odds ratio (OR) =0.541, P=0.023; adjusted for sex, age, BMI, presence of hypertension, and presence of dyslipidemia].

Conclusions: Low serum FGF19 level is associated with T1D, which could serve as a risk factor for T1D.
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http://dx.doi.org/10.21037/atm-20-5203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033349PMC
March 2021

Interleukin-22 From Type 3 Innate Lymphoid Cells Aggravates Lupus Nephritis by Promoting Macrophage Infiltration in Lupus-Prone Mice.

Front Immunol 2021 26;12:584414. Epub 2021 Feb 26.

Department of Rheumatology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). Our previous studies demonstrated increased serum and renal Interleukin (IL)-22 in LN patients and MRL/lpr mice. This study investigated the role of IL-22 and its mechanism in LN. Here, we found that IL-22 was mainly produced by type 3 innate lymphoid cells (ILC3) in kidney of MRL/lpr mice. The systemic illness and local renal lesion were significantly alleviated in IL-22 or IL-22R gene knockout (KO) mice (IL-22 KO or IL-22R KO MRL/lpr mice) than control mice (MRL/lpr mice). IL-22 KO or IL-22R KO MRL/lpr mice had significantly slighter infiltration of macrophage in kidney than MRL/lpr mice. Consistently, by RNA-Seq, the expression of (CC motif) ligand 2 (CCL2) and (CXC motif) ligand 10 (CXCL10) was decreased in kidney of KO mice compared with control mice. By immunoblotting, significantly increased levels of STAT3 phosphorylation were found in the kidney of control mice compared to KO mice. , primary kidney epithelial cells from control mouse stimulated with recombinant IL-22 (rIL-22) expressed higher levels of CCL2, CXCL10, and phosphorylated STAT3. At the same time, when primary kidney epithelial cells were treated with rIL-22, transwell assay demonstrated their supernatant recruited more macrophages. In human kidney epithelial cell line (HK2) cells, when treated with rIL-22, we observed similar results with primary mouse kidney epithelial cells. Moreover, when cells were stimulated with rIL-22 following pre-treatment with STAT3 pathway inhibitor, the expression of CCL2 and CXCL10 were significantly reversed. Our findings demonstrate that IL-22 binding to IL-22R in kidney epithelial cells activated the STAT3 signaling pathway, enhanced the chemokine secretion and then promoted macrophage infiltration to the kidney of MRL/lpr mice, thus aggravated LN in lupus-prone mice. These findings indicate that IL-22 may play a pathogenic role in LN and may provide a promising novel therapeutic target for LN.
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http://dx.doi.org/10.3389/fimmu.2021.584414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953152PMC
July 2021

Efficacy and safety of early ultrafiltration in patients with acute decompensated heart failure with volume overload: a prospective, randomized, controlled clinical trial.

BMC Cardiovasc Disord 2020 10 14;20(1):447. Epub 2020 Oct 14.

Department of Critical Care Medicine (Specialty of Heart Failure), Tongren Hospital, Shanghai Jiaotong University School of Medicine, No. 1111 Xianxia Road, Shanghai, 200336, China.

Background: Ultrafiltration decreases total body water and improves the alveolar to arterial oxygen gradient. The aims of the study were to investigate the efficacy and safety of early ultrafiltration in acute decompensated heart failure (ADHF) patients.

Methods: 100 patients with ADHF within 24 h of admission were randomly assigned into early ultrafiltration (n = 40) or torasemide plus tolvaptan (n = 60) groups. The primary outcomes were weight loss and an increase in urine output on days 4 and 8 of treatment.

Results: Patients who received early ultrafiltration for 3 days achieved a greater weight loss (kg) (- 2.94 ± 3.76 vs - 0.64 ± 0.91, P < 0.001) and urine increase (mL) (198.00 ± 170.70 vs 61.77 ± 4.67, P < 0.001) than the torasemide plus tolvaptan group on day 4. From days 4 to 7, patients in the early ultrafiltration group received sequential therapy of torasemide and tolvaptan. Better control of volume was reflected in a greater weight loss (- 3.72 ± 3.81 vs - 1.34 ± 1.32, P < 0.001) and urine increase (373.80 ± 120.90 vs 79.5 ± 52.35, P < 0.001), greater reduction of B-type natriuretic peptide (BNP) (pg/mL) (- 1144 ± 1435 vs - 654.02 ± 889.65, P = 0.037), NYHA (New York Heart Association) functional class (- 1.45 ± 0.50 vs - 1.17 ± 0.62, P = 0.018), jugular venous pulse (JVP) score (points) (- 1.9 ± 1.13 vs - 0.78 ± 0.69, P < 0.001), inferior vena cava (IVC) diameter (mm) (- 15.35 ± 11.03 vs - 4.98 ± 6.00, P < 0.001) and an increase in the dyspnea score (points) (4.08 ± 3.44 vs 2.77 ± 2.03, P = 0.035) in the early ultrafiltration group on day 8. No significant differences were found in the readmission and mortality rates in the 2 patient groups at the 1-month and 3-month follow-ups. Both groups had a similar stable renal profile.

Conclusion: Early ultrafiltration is superior to diuretics for volume overload treatment initiation of ADHF patients. Trial registration Chinese Clinical Trial Registry, ChiCTR2000030696, Registered 10 March 2020-Retrospectively registered, https://www.chictr.org.cn/showproj.aspx?proj=29099 .
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http://dx.doi.org/10.1186/s12872-020-01733-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556949PMC
October 2020

Relationship of miRNA-146a to systemic lupus erythematosus: A PRISMA-compliant meta-analysis.

Medicine (Baltimore) 2020 Oct;99(40):e22444

Department of Rheumatism and Immunity, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine.

Background And Objective: miRNA-146a is a microRNA that plays an important role in systemic lupus erythematosus (SLE). Several studies have examined the role of miRNA-146a in SLE, but have demonstrated equivocal or even contradictory conclusions. Therefore, this meta-analysis aimed to assess the role of miRNA-146a in SLE by examining data from previous studies.

Methods: A meta-analysis of relevant papers published before August 31, 2019, in the WanFang, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), PubMed, EMBASE, and Web of Science databases was performed to verify the relationship of miRNA-146a expression level to SLE. Two investigators independently extracted the data and conducted a quality assessment of the studies. All statistical analyses were performed using Stata 14.0. Trial sequence analysis (TSA) was conducted to assess the quality and strength of the studies using the TSA software.

Results: Six publications, involving 151 SEL patients and 132 healthy individuals as controls were included in this meta-analysis. The results showed that the expression of miRNA-146a was associated with SLE risk [standard mean difference (SMD) = -1.21, 95% confidence interval (95% CI) (-2.18, -0.23), P = .015]. The stratified analysis revealed that the expression of miRNA-146a was highly related to higher SLE risk among Asian (SMD = -1.30, 95% CI (-2.52, -0.07), P = .038) and Caucasian (SMD = -0.72, 95% CI (-1.20, -0.24), P = .003) populations. Besides, the serum levels of miRNA146a were significantly different (SMD = -1.73, 95% CI (-3.11, -0.36), P = .014). The TSA revealed that the cumulative Z-curve crossed the typical boundary value, and reached the TSA monitoring boundary, but did not reach the required information size. This indicates that even if the cumulative sample size did not meet required information size, no more trials were needed and a reliable conclusion was reached in advance. Sensitivity analyses indicated the instability of the meta-analysis.

Conclusions: Overall, the expression of miRNA-146a is associated with SLE risk. Therefore, miRNA-146a is a promising candidate for the effective diagnosis of SLE. But, due to the limitations of this study, it is necessary to cautiously explain the results of this study.

Systematic Review Registration: PROSPERO CRD42019151381.
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http://dx.doi.org/10.1097/MD.0000000000022444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535641PMC
October 2020

Qingchang Huashi Formula attenuates DSS-induced colitis in mice by restoring gut microbiota-metabolism homeostasis and goblet cell function.

J Ethnopharmacol 2021 Feb 15;266:113394. Epub 2020 Sep 15.

State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China. Electronic address:

Ethnopharmacological Relevance: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disease of the gastrointestinal tract, consisting of ulcerative colitis (UC) and Crohn's disease (CD). Gut microbiota and their metabolites may play a role in the pathogen of IBD, especially of the UC. Qingchang Huashi Formula (QHF), a traditional Chinese medicine formula, has shown therapeutic effect on treating UC based on the clinical practice without clear pharmacological mechanism.

Aim Of The Study: The aim of this study was to clearly define the effect of QHF and its components, Baitouweng (PBR) and Baizhi (ADR) on treating UC.

Materials And Methods: Pharmacodynamic effects of QHF and single herb were evaluated in dextran sulfate sodium (DSS) induced acute or chronic colitis mice. Body weight loss, disease activity index (DAI) and colon length were estimated. Histological changes were observed by H&E staining. The number and abundance of gut microbiota were measured with 16S rRNA sequencing. LC-MS and GC-MS were used to detect the concentration of metabolites (e.g., bile acids (BAs) and short chain fatty acids (SCFAs)). The goblet cell was observed by Alcian blue/periodic acid-Schiff (AB/PAS) straining and the crypt stem cell was estimated by immunohistochemical analyses. The colorectal tissues were used to detect levels of IL-1β, IL-6 and TNF-α by ELISA or qRT-PCR. The expression of NLRP3, Caspase 1 and IL-1β were examined by western blotting.

Results: QHF significantly inhibited colitis, protected mice from the loss of body weight and colon shorten. Comparatively, ADR and PBR showed strong efficacy in inhibiting DSS-induced colitis. We verified that while ADR was responsible for QHF's effect on maintaining gut microbiota homeostasis and metabolism, PBR was more prominent in keeping crypt stem cells proliferation and colonic goblet cells function. Moreover, we demonstrated that the alleviation of colitis by QHF was associated with the restoration of gut microbiota-metabolism homeostasis, protection of intestinal epithelial barrier and regulation of NLRP3/IL-1β pathway.

Conclusions: The finding of the present study suggested that QHF is curative in DSS-induced colitis by restoring gut microbiota-metabolism homeostasis and goblet cells function. An optimized QHF was constituted by ADR and PBR, which showed comparable efficacy on colitis to that of QHF. Our work probed out the active constitutes as well as the relevant pharmacological mechanisms of QHF, shedding light on potential new drug combination for the treatment of IBD.
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http://dx.doi.org/10.1016/j.jep.2020.113394DOI Listing
February 2021

Fibroblast Growth Factor 19 Levels Predict Subclinical Atherosclerosis in Men With Type 2 Diabetes.

Front Endocrinol (Lausanne) 2020 22;11:282. Epub 2020 May 22.

National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China.

Fibroblast growth factor 19 (FGF19) plays an indispensable role in regulating bile acid, glucose, and lipid metabolism, and alterations of its circulating concentration is associated with the development of type 2 diabetes (T2D). Atherosclerosis is directly related to the death-deriving diabetic macroangiopathy in T2D, yet relationships between FGF19 and atherosclerosis in T2D remain unclear. The aim of this study was to investigate the association of circulating FGF19 levels with the development of subclinical atherosclerosis (subAS) in patients with T2D in a 3-year prospective study. In the present study, 153 newly diagnosed T2D patients without subAS were recruited at baseline, and 137 of them completed a 3-year follow-up. FGF19 levels were measured in fasting serum samples collected at baseline and the third-year visits. Carotid, femoral, and iliac intima-media thickness (IMT) were detected by high-resolution B-mode ultrasound to determine the presence of subAS. Logistic regression analysis was applied to assess the relationship between serum FGF19 and subAS in patients with T2D. At baseline, serum FGF19 levels were positively correlated with carotid IMT and iliac IMT in men ( = 0.239, = 0.036; = 0.309, = 0.006). At the 3-year follow-up, 25 out of 153 patients developed subAS, and FGF19 levels in men were higher in the subAS group than in the non-subAS group [202.7 (177.9-373.6) vs. 133.4 (85.6-171.3) pg/ml, = 0.028]. Furthermore, in men, higher baseline levels of FGF19 were independently associated with a greater risk of subAS at year 3 in patients with T2D with an odds ratio (OR) of 4.798 per 1 standard deviation (SD) of the FGF19 concentration [OR = 4.798 (95% CI, 1.680-13.706), = 0.003]. Baseline FGF19 levels yielded an area under the receiver operating characteristic curve of 0.769 to predict the development of subAS at year 3 in men with T2D. Serum FGF19 levels could help in predicting the development of atherosclerosis in men with T2D.
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http://dx.doi.org/10.3389/fendo.2020.00282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258879PMC
May 2021

Remote sensing and modeling fusion for investigating the ecosystem water-carbon coupling processes.

Sci Total Environ 2019 Dec 23;697:134064. Epub 2019 Aug 23.

National Engineering Laboratory for Applied Technology of Forestry & Ecology in South China, Central South University of Forestry and Technology, Changsha, Hunan Province 410004, China.

The water and carbon cycles are tightly linked and play a key role in the material and energy flows between terrestrial ecosystems and the atmosphere, but the interactions of water and carbon cycles are not quite clear. The global climate change and intensive human activities could also complicate the water and carbon coupling processes. Better understanding the coupled water-carbon cycles and their spatiotemporal evolution can inform management and decision-making efforts regarding carbon uptake, food production, water resources, and climate change. The integration of remote sensing and numeric modeling is an attractive approach to address the challenge. Remote sensing can provide extensive data for a number of variables at regional scale and support models, whereas process-based modeling can facilitate investigating the processes that remote sensing cannot well handle (e.g., below-ground and lateral material movement) and backcast/forecast the impacts of environmental change. Over the past twenty years, an increasing number of studies using a variety of remote sensing products together with numeric models have examined the water-carbon interactions. This article reviewed the methodologies for integrating remote sensing data into these models and the modeling of water-carbon coupling processes. We first summarized the major remote sensing datasets and models used for studying the coupled water-carbon cycles. We then provided an overview of the methods for integrating remote sensing data into water-carbon models, and discussed their strengths and challenges. We also prospected the development of potential new remote sensing datasets, modeling methods, and their potential applications in the field of eco-hydrology.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134064DOI Listing
December 2019

Modulating the Electronic Properties of Graphene by Self-Organized Sulfur Identical Nanoclusters and Atomic Superlattices Confined at an Interface.

ACS Nano 2018 Nov 27;12(11):10984-10991. Epub 2018 Sep 27.

Center for Advanced Quantum Studies, Department of Physics , Beijing Normal University , Beijing , 100875 , People's Republic of China.

Ordered atomic-scale superlattices on a surface hold great interest both for basic science and for potential applications in advanced technology. However, controlled fabrication of superlattices down to the atomic scale has proven exceptionally challenging. Here we develop a segregation method to realize self-organization of S superlattices at the interface of graphene and S-rich Cu substrates. Via scanning tunneling microscope measurements, we directly image well-ordered identical nanocluster superlattices and atomic superlattices under the cover of graphene. Scanning tunneling spectra show that the superlattices in turn could modulate the electronic structure of top-layer graphene. Importantly, a special-ordered S monatomic superlattice commensurate with a graphene lattice is found to drive semimetal graphene into a symmetry-broken phase-the electronic Kekulé distortion phase-which opens a bandgap of ∼245 meV.
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http://dx.doi.org/10.1021/acsnano.8b04874DOI Listing
November 2018

Selective serotonin reuptake inhibitor and selective serotonin and norepinephrine reuptake inhibitor use and risk of fractures in adults: A systematic review and meta-analysis.

Int J Geriatr Psychiatry 2018 12 24;33(12):1688-1708. Epub 2018 Sep 24.

University of Manchester, Manchester, UK.

Objective: To evaluate the association between selective serotonin reuptake inhibitor (SSRI) and selective serotonin and norepinephrine reuptake inhibitor (SNRI) use and risk of fractures in older adults.

Methods: We systematically identified and analyzed observational studies comparing SSRI/SNRI use for depression with non-SSRI/SNRI use with a primary outcome of risk of fractures in older adults. We searched for studies in MEDLINE, PsycINFO, Embase, DARE (Database of Abstracts or Reviews of Effects), the Cochrane Library, and Web of Science clinical trial research registers from 2011 for SSRIs and 1990 for SNRIs to November 29, 2016.

Results: Thirty-three studies met our inclusion criteria; 23 studies were included in meta-analysis: 9 case-control studies and 14 cohort studies. A 1.67-fold increase in the risk of fracture for SSRI users compared with nonusers was observed (relative risk 1.67, 95% CI 1.56-1.79, P = .000). The risk of fracture increases with their long-term use: within 1 year, the risk is 2.9% or 1 additional fracture in every 85 users; within 5 years, the risk is 13.4% or 1 additional fracture in every 19 users. In meta-regression, we found that the increase in risk did not differ across age groups (odds ratio = 1.006; P = .173). A limited number of studies on SNRI use and the risk of fractures prevented us from conducting a meta-analysis.

Conclusions: Our systematic review showed an association between risk of fracture and the use of SSRIs, especially with increasing use. Age does not increase this risk. No such conclusions can be drawn about the effect of SNRIs on the risk of fracture because of a lack of studies.
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http://dx.doi.org/10.1002/gps.4974DOI Listing
December 2018

Using Model-Based Recursive Partitioning for Treatment-Subgroup Interactions Detection in Real-World Data: A Myocardial Infarction Case Study.

Stud Health Technol Inform 2018 ;247:576-580

Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, China.

The effects of treatment often vary over subpopulations characterized by baseline patient features. Detection of such treatment-subgroup interaction is of central importance to precision medicine and personalized care. In this paper, we propose an analytical framework for treatment-subgroup interactions detection and treatment effectiveness heterogeneity evaluation in a real-world data setting. Model-based recursive partitioning analysis (MOB) is used for subgroup identification, filter-based confounder selection and multivariate logistic regression are used for confounding reduction and treatment effectiveness assessment. We illustrate this approach by a real-world case study that analyzes the effects of 15 drugs among patients with myocardial infarction (MI) using China Acute Myocardial Infarction (CAMI) registry data. The results show that our approach effectively identifies meaningful patient subgroups involved in treatment-subgroup interactions and thus can potentially aid decision making in personalized medicine.
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June 2018

Precision Cohort Finding with Outcome-Driven Similarity Analytics: A Case Study of Patients with Atrial Fibrillation.

Stud Health Technol Inform 2017 ;245:491-495

Pfizer China, Beijing, China.

Dividing patients into similar groups plays a significant role in implementing personalized care. Clinicians and researchers have been applying patient grouping techniques in disease phenotyping, risk stratification, and personalized medicine. However, the current approaches are either based on pure domain knowledge where the underlying patient similarity cannot be precisely quantified, or based on unsupervised clustering techniques which completely ignore the clinical context of measuring patient similarity. In the study, we propose an outcome-driven approach to identify clinically similar patients which are grouped together as a precision cohort. The approach quantitatively measures the similarity between patients in terms of a particular clinical outcome of interest, thus patients who have a similar clinical outcome tend to be grouped into the same group. We demonstrate the effectiveness of the approach in a real-world case study: from an atrial fibrillation patient cohort that is usually considered to be at high risk for ischemic stroke (IS), according to current clinical guidelines. Our approach successfully identified a precision cohort of patients with truly low risk of IS.
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June 2018

Synthesis and biological evaluation of curcumin analogs as β-amyloid imaging agents.

Future Med Chem 2017 09 25;9(14):1587-1596. Epub 2017 Aug 25.

Engineering Research Center of Bio-process of Ministry of Education, School of Food Science & Engineering, Hefei University of Technology, Hefei, Anhui, 230009, PR China.

Aim: Detection of β-amyloid (Aβ) plaques in the brain is a very promising biomarker approach for early diagnosis of Alzheimer's disease (AD).

Materials & Methods: A series of curcumin analogs (1,5-diphenyl-1,4-pentadien-3-one derivatives) were synthesized and evaluated. Specific binding to Aβ plaques was demonstrated in vitro using postmortem AD homogenates, and the fluorescent staining and autoradiography in vitro of postmortem AD brain sections were performed.

Results: Some compounds showed high binding affinities with Aβ plaques. Fluorescent staining indicated that compound 4e clearly stained Aβ plaques within AD brain sections. In biodistribution, radioiodinated ligand [I]4e exhibited high brain uptake and favorable clearance from the brain. Autoradiography in vitro further confirmed the high affinities of [I]4e.

Conclusion: The results strongly suggested that [I]4e might be developed into potential amyloid imaging agent for the detection of senile plaques in AD. [Formula: see text].
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http://dx.doi.org/10.4155/fmc-2017-0079DOI Listing
September 2017

An Automatic Approach for Analyzing Treatment Effectiveness Based on Medication Hierarchy - The Myocardial Infarction Case Study.

Stud Health Technol Inform 2017 ;235:106-110

Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, China.

Treatment effectiveness plays a fundamental role in patient therapies. In most observational studies, researchers often design an analysis pipeline for a specific treatment based on the study cohort. To evaluate other treatments in the data set, much repeated and multifarious work including cohort construction, statistical analysis need to be done. In addition, as treatments are often with an intrinsic hierarchical relationship, many rational comparable treatment pairs can be derived as new treatment variables besides the original single treatment one from the original cohort data set. In this paper, we propose an automatic treatment effectiveness analysis approach to solve this problem. With our approach, clinicians can assess the effect of treatments not only more conveniently but also more thoroughly and comprehensively. We applied this method to a real world case of estimating the drug effectiveness on Chinese Acute Myocardial Infarction (CAMI) data set and some meaningful results are obtained for potential improvement of patient treatments.
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April 2018

Predictive model for inflammation grades of chronic hepatitis B: Large-scale analysis of clinical parameters and gene expressions.

Liver Int 2017 11 19;37(11):1632-1641. Epub 2017 Apr 19.

Department of Digestive Diseases of Huashan Hospital, Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, China.

Background: Liver biopsy is the gold standard to assess pathological features (eg inflammation grades) for hepatitis B virus-infected patients although it is invasive and traumatic; meanwhile, several gene profiles of chronic hepatitis B (CHB) have been separately described in relatively small hepatitis B virus (HBV)-infected samples. We aimed to analyse correlations among inflammation grades, gene expressions and clinical parameters (serum alanine amino transaminase, aspartate amino transaminase and HBV-DNA) in large-scale CHB samples and to predict inflammation grades by using clinical parameters and/or gene expressions.

Methods: We analysed gene expressions with three clinical parameters in 122 CHB samples by an improved regression model. Principal component analysis and machine-learning methods including Random Forest, K-nearest neighbour and support vector machine were used for analysis and further diagnosis models. Six normal samples were conducted to validate the predictive model.

Results: Significant genes related to clinical parameters were found enriching in the immune system, interferon-stimulated, regulation of cytokine production, anti-apoptosis, and etc. A panel of these genes with clinical parameters can effectively predict binary classifications of inflammation grade (area under the ROC curve [AUC]: 0.88, 95% confidence interval [CI]: 0.77-0.93), validated by normal samples. A panel with only clinical parameters was also valuable (AUC: 0.78, 95% CI: 0.65-0.86), indicating that liquid biopsy method for detecting the pathology of CHB is possible.

Conclusions: This is the first study to systematically elucidate the relationships among gene expressions, clinical parameters and pathological inflammation grades in CHB, and to build models predicting inflammation grades by gene expressions and/or clinical parameters as well.
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http://dx.doi.org/10.1111/liv.13427DOI Listing
November 2017

[Association between microRNA single nucleotide polymorphisms and the risk of hepatocellular carcinoma].

Rev Med Chil 2016 Apr;144(4):508-15

Background: Hepatocellular carcinoma (HCC) has a high morbidity and mortality. Single nucleotide polymorphisms (SNPs) of microRNA (miRNA) may be associated with the susceptibility to develop certain malignant tumors.

Aim: To study the association between SNPs of miRNA and hepatocellular carcinoma in peripheral blood samples.

Material And Methods: Three SNPs in miRNA were studied in peripheral blood samples of 498 patients with HCC and 520 controls.

Results: A significant association was observed between rs13299349 in miRNA3152 and HCC. AA genotype or A allele were significantly associated with increased risk of HCC. A allele was associated with the size and number of tumor foci. There was also a relationship between rs10061133 in miRNA449b and HCC. The G allele was significantly associated with increased risk of HCC compared with A allele.

Conclusions: This study links rs13299349 in miRNA3152 and rs10061133 in miRNA449b with the risk of developing HCC.
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http://dx.doi.org/10.4067/S0034-98872016000400013DOI Listing
April 2016

Integrating powdered activated carbon into wastewater tertiary filter for micro-pollutant removal.

J Environ Manage 2016 Jul 12;177:45-52. Epub 2016 Apr 12.

Department of Water Management, Faculty of Civil Engineering and Geoscience, Delft University of Technology, P.O. Box 5048, 2600, GA, Delft, The Netherlands.

Integrating powdered activated carbon (PAC) into wastewater tertiary treatment is a promising technology to reduce organic micro-pollutant (OMP) discharge into the receiving waters. To take advantage of the existing tertiary filter, PAC was pre-embedded inside the filter bed acting as a fixed-bed adsorber. The pre-embedding (i.e. immobilization) of PAC was realized by direct dosing a PAC solution on the filter top, which was then promoted to penetrate into the filter media by a down-flow of tap water. In order to examine the effectiveness of this PAC pre-embedded filter towards OMP removal, batch adsorption tests, representing PAC contact reactor (with the same PAC mass-to-treated water volume ratio as in the PAC pre-embedded filter) were performed as references. Moreover, as a conventional dosing option, PAC was dosed continuously with the filter influent (i.e. the wastewater secondary effluent with the investigated OMPs). Comparative results confirmed a higher OMP removal efficiency associated with the PAC pre-embedded filter, as compared to the batch system with a practical PAC residence time. Furthermore, over a filtration period of 10 h (approximating a realistic filtration cycle for tertiary filters), the continuous dosing approach resulted in less OMP removal. Therefore, it was concluded that the pre-embedding approach can be preferentially considered when integrating PAC into the wastewater tertiary treatment for OMP elimination.
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http://dx.doi.org/10.1016/j.jenvman.2016.04.003DOI Listing
July 2016

Influence of activated carbon preloading by EfOM fractions from treated wastewater on adsorption of pharmaceutically active compounds.

Chemosphere 2016 May 15;150:49-56. Epub 2016 Feb 15.

Faculty of Civil Engineering and Geoscience, Delft University of Technology, P.O. Box 5048, 2600GA Delft, The Netherlands.

In this study, the preloading effects of different fractions of wastewater effluent organic matter (EfOM) on the adsorption of trace-level pharmaceutically active compounds (PhACs) onto granular activated carbon (GAC) were investigated. A nanofiltration (NF) membrane was employed to separate the EfOM by size, and two GACs with distinct pore structures were chosen for comparison. The results showed that preloading with EfOM substantially decreased PhAC uptake of the GACs; however, comparable PhAC adsorption capacities were achieved on GACs preloaded by feed EfOM and the NF-permeating EfOM. This indicates that: (1) the NF-rejected, larger EfOM molecules with an expectation to block the PhAC adsorption pores exerted little impact on the adsorbability of PhACs; (2) the smaller EfOM molecules present in the NF permeate contributed mainly to the decrease in PhAC uptake, mostly due to site competition. Of the two examined GACs, the wide pore-size-distributed GAC was found to be more susceptible to EfOM preloading than the microporous GAC. Furthermore, among the fourteen investigated PhACs, the negatively charged hydrophilic PhACs were generally subjected to a greater EfOM preloading impact.
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http://dx.doi.org/10.1016/j.chemosphere.2016.01.121DOI Listing
May 2016
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