Publications by authors named "Huajun Li"

50 Publications

Red blood cell distribution width and tumor necrosis factor-α for the early prediction of coronary artery lesion in Kawasaki disease: a retrospective study.

Eur J Pediatr 2021 Sep 7. Epub 2021 Sep 7.

Department of Infectious, Xinhua Hospital Affiliated to Shanghai Jiaotong University Medical College, No. 1665 Kongjiang Road, Shanghai, 200092, China.

We aimed to identify novel risk factors for the early prediction of coronary artery lesion (CAL) in children with Kawasaki disease (KD). We retrospectively analyzed data from hospitalized children newly diagnosed with KD between January 1, 2018, and December 31, 2020, with the following inclusion criteria: (1) diagnosis of KD, (2) first onset of CAL after admission, (3) with complete clinical records. Demographic and laboratory data were collected and analyzed. The independent risk factors of KD combined with CAL were identified by multivariate logistic regression analysis, followed by receiver operating characteristic (ROC) curve analysis to calculate the efficacy of identified risk factors in predicting KD combined with CAL. Among 241 initially recruited patients, 226 were eligible to be included in the study. Based on echocardiographic indications of CAL, 104 patients (46%) were assigned to the CAL (KD-CAL) group and 122 (54%) patients were assigned to the non-CAL (KD-nCAL) group. The levels of red blood cell count, red blood cell distribution width (RDW), C-reactive protein, tumor necrosis factor-α (TNF-α), and interleukin-6 were significantly higher in the KD-CAL group than those in the KD-nCAL group (all p < 0.05). RDW and TNF-α were found as independent risk factors of CAL occurrence. The sensitivity and specificity of RDW, TNF-α, and RDW + TNF-α in predicting KD with CAL were 67.31% and 79.51%, 74.04% and 73.77%, and 79.81% and 80.33%, respectively.Conclusion: In conclusion, alterations in RDW and TNF-α levels can be used as novel biomarkers for early prediction of CAL in KD patients, although the differences in their absolute values were small and might not give any added value to echocardiography. What is Known: •Known risk factors of CAL in children with KD include male gender and delayed use of intravenous immune globulin. What is New: •Our current study identified that red blood cell distribution width (RDW) and tumor necrosis factor-α (TNF-α) are novel independent risk factors for predicting CAL combined with KD among patients. •The combination of these RDW and TNF-α together shows higher sensitivity and specificity than either one used alone.
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http://dx.doi.org/10.1007/s00431-021-04252-3DOI Listing
September 2021

Low-Density Fluorinated Silane Solvent Enhancing Deep Cycle Lithium-Sulfur Batteries' Lifetime.

Adv Mater 2021 Aug 2:e2102034. Epub 2021 Aug 2.

Beijing Advanced Innovation Center for Materials Genome Engineering, Key Laboratory for Renewable Energy, Beijing Key Laboratory for New Energy Materials and Devices, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.

The lithium metal anode (LMA) instability at deep cycle with high utilization is a crucial barrier for developing lithium (Li) metal batteries, resulting in excessive Li inventory and electrolyte demand. This issue becomes more severe in capacity-type lithium-sulfur (Li-S) batteries. High-concentration or localized high-concentration electrolytes are noted as effective strategies to stabilize Li metal but usually lead to a high electrolyte density (>1.4 g mL ). Here we propose a bifunctional fluorinated silane-based electrolyte with a low density of 1.0 g mL that not only is much lighter than conventional electrolytes (≈1.2 g mL ) but also form a robust solid electrolyte interface to minimize Li depletion. Therefore, the Li loss rate is reduced over 4.5-fold with the proposed electrolyte relative to its conventional counterpart. When paired with onefold excess LMA at the electrolyte weight/cell capacity (E/C) ratio of 4.5 g Ah , the Li-S pouch cell using our electrolyte can survive for 103 cycles, much longer than with the conventional electrolyte (38 cycles). This demonstrates that our electrolyte not only reduces the E/C ratio but also enhances the cyclic stability of Li-S batteries under limited Li amounts.
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http://dx.doi.org/10.1002/adma.202102034DOI Listing
August 2021

Long-term low-dose oxytetracycline potentially leads to neurobehavioural changes.

Ecotoxicol Environ Saf 2021 Oct 27;223:112546. Epub 2021 Jul 27.

Department of Infectious Disease, Xinhua Children's Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address:

Trace levels of oxytetracycline (OTC)-a veterinary antibiotic and feed additive-are widespread in the environment. Studies revealed that OTC potentially impairs thyroid function, which may affect neurobehaviour; however, the impact of exposure to environmental concentrations of OTC on adult neurobehaviour is unknown. In this study, the effects of OTC on zebrafish after 30-day exposure were investigated. The total swimming distance was significantly increased under vibration and light/dark stimulation, while time spent in the white area was prolonged during the black/white preference test, indicating that the zebrafish became bolder and more impulsive under low OTC exposure. Additionally, monoamine neurotransmitter (5-hydroxytryptamine, dopamine, norepinephrine) levels were decreased and gene expression of monoamine oxidase (mao) involved in neurotransmitter metabolism was upregulated at the transcription level after OTC exposure. Because triiodothyronine (T3) levels were enhanced following exposure to OTC, we speculated that T3 may mediate OTC damage to the nervous system. Our simulated molecular docking analysis showed that OTC combined with the sodium iodide cotransporter protein may result in excessive T3 synthesis. We further exposed zebrafish to T3, and they exhibited similar behaviour to the OTC exposure group. In conclusion, environmental OTC may activate monoamine oxidase and enhance the metabolism of monoaminergic neurotransmitters via T3, thereby inducing abnormal neurobehaviour.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112546DOI Listing
October 2021

Dihydropyrimidinase Like 2 Promotes Bladder Cancer Progression via Pyruvate Kinase M2-Induced Aerobic Glycolysis and Epithelial-Mesenchymal Transition.

Front Cell Dev Biol 2021 6;9:641432. Epub 2021 Jul 6.

Department of Emergency Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Aerobic glycolysis and epidermal-mesenchymal transition (EMT) play key roles in the development of bladder cancer. This study aimed to investigate the function and the underlying mechanism of dihydropyrimidinase like 2 (DPYSL2) in bladder cancer progression.

Methods: The expression pattern of DPYSL2 in bladder cancer and the correlation of DPYSL2 expression with clinicopathological characteristics of bladder cancer patients were analyzed using the data from different databases and tissue microarray. Gain- and loss-of-function assays were performed to explore the role of DPYSL2 in bladder cancer progression and in mice. Proteomic analysis was performed to identify the interacting partner of DPYSL2 in bladder cancer cells.

Findings: The results showed that DPYSL2 expression was upregulated in bladder cancer tissue compared with adjacent normal bladder tissue and in more aggressive cancer stages compared with lower stages. DPYSL2 promoted malignant behavior of bladder cancer cells , as well as tumor growth and distant metastasis in mice. Mechanistically, DPYSL2 interacted with pyruvate kinase M2 (PKM2) and promoted the conversion of PKM2 tetramers to PKM2 dimers. Knockdown of PKM2 completely blocked DPYSL2-induced enhancement of the malignant behavior, glucose uptake, lactic acid production, and epithelial-mesenchymal transition in bladder cancer cells.

Interpretation: In conclusion, the results suggest that DPYSL2 promotes aerobic glycolysis and EMT in bladder cancer via PKM2, serving as a potential therapeutic target for bladder cancer treatment.
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http://dx.doi.org/10.3389/fcell.2021.641432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291048PMC
July 2021

Preventive and Therapeutic Effects of a Novel JAK Inhibitor SHR0302 in Acute Graft-Versus-Host Disease.

Cell Transplant 2021 Jan-Dec;30:9636897211033778

Department of Hematology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Acute graft-versus-host disease (aGVHD) is one of the most common complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Janus kinase (JAK) inhibitors are considered as reliable and promising agents for patients with aGVHD. The prophylactic and therapeutic effects of SHR0302, a novel JAK inhibitor, were evaluated in aGVHD mouse models. The overall survival (OS), progression-free survival (PFS), bodyweight of mice, GVHD scores were observed and recorded. The bone marrow and spleen samples of diseased model mice or peripheral blood of patients were analyzed. SHR0302 could prevent and reverse aGVHD in mouse models with preserving graft-versus-tumor effect. Functionally, SHR0302 improved the OS and PFS, restored bodyweight, reduced GVHD scores, and reduced immune cells infiltrated in target tissues. SHR0302 treatment also enhanced the hematopoietic reconstruction compared to the control group. Mechanistically, our results suggested that SHR0302 could inhibit the activation of T cells and modulate the differentiation of helper T (Th) cells by reducing Th1 and increasing regulatory T (Treg) cells. In addition, SHR0302 decreased the expression of chemokine receptor CXCR3 on donor T cells and the secretion of cytokines or chemokines including interleukin (IL)-6, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), CXCL10, etc. thereby destroying the IFN-γ/CXCR3/CXCL10 axis which promotes the progression of GVHD. Besides, SHR0302 decreased the phosphorylation of JAK and its downstream STATs, AKT and ERK1/2, which ultimately regulated the activation, proliferation, and differentiation of lymphocytes. Experiments on primary cells from aGVHD patients also confirmed the results. In summary, our results indicated that JAK inhibitor SHR0302 might be used as a novel agent for patients with aGVHD.
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http://dx.doi.org/10.1177/09636897211033778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287347PMC
July 2021

Sodium Alginate Modulates Immunity, Intestinal Mucosal Barrier Function, and Gut Microbiota in Cyclophosphamide-Induced Immunosuppressed BALB/c Mice.

J Agric Food Chem 2021 Jun 21;69(25):7064-7073. Epub 2021 Jun 21.

Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, 116044 Dalian, PR China.

This study investigated the protective effects of sodium alginate (SA) on the gut microbiota, immunity, and intestinal mucosal barrier function in cyclophosphamide-induced immunosuppressed BALB/c mice. SA alleviated spleen tissue damage and restored impaired immune functions, such as increasing the immune organ index, decreasing splenic T lymphocytes, and markedly increasing the secretion of serum immunoglobulins and cytokines in immunosuppressed mice. In addition, SA reversed the intestinal mucosal injury and increased the intestinal permeability by upregulating the expression of tight junction proteins. Moreover, SA decreased gut inflammation by reducing serum d-lactic acid (D-LA) and lipopolysaccharide (LPS) concentrations and downregulating toll-like receptor 4 () and mitogen-activated protein kinase () pathway expression. Furthermore, SA significantly increased the abundance of beneficial bacteria (, , and Lachnospiraceae NK4A136) and decreased pathogenic bacteria (, , and ) in the intestine as determined by 16S rRNA gene high-throughput sequencing. In conclusion, our study provides a scientific basis for SA as a functional food in modulating gut microbiota and protecting against intestinal mucosal injury and indicates that SA has potential application for enhancing immunity.
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http://dx.doi.org/10.1021/acs.jafc.1c02294DOI Listing
June 2021

Overexpression of miR-874-3p alleviates LPS-induced apoptosis and inflammation in alveolar epithelial cell by targeting EGR3/NF-κB.

Acta Biochim Pol 2021 May;68(2):231-238

Department of Infection, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Objective: MicroRNA (miRNA) is implicated in the pathogenic mechanism of pneumonia. Role of miR-874-3p in pediatric pneumonia was therefore evaluated in this study.

Methods: Expression levels of miR-874-3p in the serum samples from pediatric patients with pneumonia and LPS-treated HPAEpiC were determined by RT-qPCR (reverse transcription quantitative real-time PCR). Secretion of inflammatory factors in LPS-treated HPAEpiC were determined by qRT-PCR and ELISA. Cell viability and apoptosis were evaluated by CCK8 and flow cytometry, respectively. HPAEpiC was used for the validation of binding target of miR-874-3p. Mechanism was determined by NF-κB promoter activity assay.

Results: MiR-874-3p was reduced in serum samples of pediatric patients with pneumonia, and LPS treatment dose-dependently decreased miR-874-3p expression in HPAEpiC. TNF-α and IL-1β expression levels were increased in HPAEpiC post LPS treatment. Over-expression of miR-874-3p attenuated LPS-induced increase of TNF-α and IL-1β and reversed LPS-induced decrease of cell viability and increase of cell apoptosis in HPAEpiC. EGR3 (early growth response 3), increased in LPS-induced HPAEpiC, was a target gene of miR-874-3p. EGR3 over-expression reversed miR-874-3p over-expression-induced increase of cell viability, decrease of cell apoptosis, TNF-α and IL-1β in LPS-induced HPAEpiC. Over-expression of miR-874-3p reduced p65 expression and NF-κB promoter activity in LPS-induced HPAEpiC, while EGR3 over-expression reversed these suppressive effects.

Conclusion: MiR-874-3p negatively regulates EGR3 expression to promote cell viability and inhibit apoptosis as well as inflammation in LPS-treated HPAEpiC via suppression of NF-κB pathway, suggesting a potential therapeutic strategy for pneumonia.
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http://dx.doi.org/10.18388/abp.2020_5523DOI Listing
May 2021

Ultralight Electrolyte for High-Energy Lithium-Sulfur Pouch Cells.

Angew Chem Int Ed Engl 2021 Aug 23;60(32):17547-17555. Epub 2021 Jun 23.

Beijing Advanced Innovation Center for Materials Genome Engineering, Key Laboratory for Renewable Energy, Beijing Key Laboratory for New Energy, Material and Devices, Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Science, Beijing, 100190, China.

The high weight fraction of the electrolyte in lithium-sulfur (Li-S) full cell is the primary reason its specific energy is much below expectations. Thus far, it is still a challenge to reduce the electrolyte volume of Li-S batteries owing to their high cathode porosity and electrolyte depletion from the Li metal anode. Herein, we propose an ultralight electrolyte (0.83 g mL ) by introducing a weakly-coordinating and Li-compatible monoether, which greatly reduces the weight fraction of electrolyte within the whole cell and also enables Li-S pouch cell functionality under lean-electrolyte conditions. Compared to Li-S batteries using conventional counterparts (≈1.2 g mL ), the Li-S pouch cells equipped with our ultralight electrolyte could achieve an ultralow electrolyte weight/capacity ratio (E/C) of 2.2 g Ah and realize a 19.2 % improvement in specific energy (from 329.9 to 393.4 Wh kg ) under E/S=3.0 μL mg . Moreover, more than 20 % improvement in specific energy could be achieved using our ultralight electrolyte at various E/S ratios.
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http://dx.doi.org/10.1002/anie.202103303DOI Listing
August 2021

The lncRNA suppresses cervical cancer cell growth .

Open Med (Wars) 2020 29;15(1):1184-1192. Epub 2020 Nov 29.

Immunohematology Laboratory, Clinical Center of National Institutes of Health, Bethesda, Maryland, 20852, USA.

Purpose: This study explores the effects and mechanisms of the long noncoding RNA (lncRNA) activity in the cervical cancer development.

Methods: Thirty-four pairs of normal adjacent and cancer tissues were collected from cervical cancer patients. Pathology was evaluated by HE staining, and expression was evaluated by hybridization assays. HeLa and SiHa cells were respectively divided into negative control, pcDNA 3.1 vehicle control and lncRNA-expressing groups. Cell proliferation and apoptosis were measured by CCK8 expression and flow cytometry. The number of invading cells and the wound healing rate were measured by transwell and wound healing assays, respectively. Relative protein levels (caspase-3, caspase-8, MMP-2 and MMP-9) were measured by Western blot.

Results: Compared with adjacent normal tissues, expression was significantly suppressed in cancer tissues correlated with the increasing stage. suppressed cell proliferation and enhanced apoptosis, as well as decreased cell invasion and wound healing in cervical cancer cell lines. overexpression significantly upregulated caspase-3 and caspase-8 protein expressions and significantly downregulated MMP-2 and MMP-9 protein expressions by Western blot.

Conclusion: suppressed cervical cancer cell biological activities and might represent an antitumor factor in cervical cancer.
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http://dx.doi.org/10.1515/med-2020-0241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718647PMC
November 2020

Allogeneic uterus transplantation in a rhesus model: A short-term graft viability study.

PLoS One 2020 17;15(12):e0243140. Epub 2020 Dec 17.

Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, PR China.

Objective: This study examined the feasibility and safety of allogeneic uterus transplantation (UTx) from a living donor and assessed short-term graft viability in a rhesus model. This research is an important step towards further clinical application of UTx in humans.

Materials And Methods: Four female rhesus monkeys with regular menstrual cycles were used in this study, the animals were either donors or recipients depending on ABO blood type compatibility. Retrieval surgery was performed to connect the uterus and uterine arteries together with the ovarian uterine vein from the living donor, and the vagina of the recipient was excised. After the back table had been prepared, bilateral uterine arteries were anastomosed end-to-side with the iliac externa arteries, and bilateral ovarian uterine veins were anastomosed end-to-side with the iliac externa vena. The transplanted uterus was evaluated based on the conditions of arterial blood, and flow was evaluated by transabdominal ultrasonography one month post operation. The conditions of the transplanted uterus were examined by secondary laparotomy. The reproductive function of rhesus monkeys was evaluated on the basis of the menstrual cycle.

Results: All 4 rhesus monkeys received the transplantation surgery without any surgical complications. No injury occurred in the other organs, and no vascular injury was observed in the allogeneic uterus. All recipients survived after the surgery with a 100% short-term survival rate. All recipients resumed normal menstruation within two months after surgery.

Conclusions: Our short follow-up shows that allogeneic UTx surgery is a safe and feasible technology in the rhesus model. The arterial conditions and blood flow of the grafted uterus can be monitored by ultrasonography examination.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243140PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746281PMC
January 2021

Low-Dose Corticosteroid Treatment in Children With Pneumonia: A Retrospective Cohort Study.

Front Pediatr 2020 23;8:566371. Epub 2020 Nov 23.

Pediatric Infectious Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The clinical value of corticosteroid treatment in pneumonia (MPP) has been controversial. Our study aimed to identify the effects of low-dose corticosteroids on the recovery of children with MPP. In this retrospective cohort study, pediatric inpatients with MPP were included from the Shanghai Children's Mycoplasma pneumoniae pneumonia cohort study between August 2014 and July 2019. The multivariable logistic regression and propensity-score matching were used to investigate the effects of low-dose corticosteroid treatment on fever duration after admission, total fever duration, length of hospital stay, C-reactive protein recovery time, and imaging recovery time with the stratification of severe pneumonia, refractory pneumonia, inflammatory biomarkers, pulmonary images, and timing of corticosteroids. There were 548 patients in the corticosteroid group and 337 in the no-corticosteroid group. The corticosteroid group showed severe clinical parameters such as more severe and refractory cases, higher laboratory values, and more abnormal imaging manifestations. The corticosteroid group also showed longer fever duration after admission [odds ratio (OR) = 1.9 (95% CI, 1.2-3.1), = 0.008], longer total fever duration [OR = 1.6 (95% CI, 1.1-2.3), = 0.011], longer hospital stay [OR = 2.8 (95% CI, 1.9-4.0), < 0.001], and longer C-reactive protein (CRP) recovery time [OR = 2.1 (95% CI, 1.1-3.9), = 0.021] in the regression model after the adjustment for severity. Although low-dose corticosteroids were associated with shortened imaging recovery time in patients with high level laboratory values, pulmonary imaging could be completely recovered in both groups. The trend of these results was consistent even after stratifications and a propensity scores matching analysis. Low-dose corticosteroids may not be beneficial in children inpatients with MPP, and further studies on proper treatment modality are needed in the MRMP era.
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http://dx.doi.org/10.3389/fped.2020.566371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720903PMC
November 2020

A quantitative proteomics analysis for small molecule Stemazole's effect on human neural stem cells.

Proteome Sci 2020 Dec 9;18(1):12. Epub 2020 Dec 9.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.

Background: Stemazole is a novel small molecule that has been suggested to have the ability to protect multiple stem cells. The proliferation-promoting activity and promising neuroprotective effects of stemazole make it a prospective drug for neurodegenerative disease treatment.

Methods: Since previous studies have shown that it protective effect in extreme conditions, to understand more aspects of stemazole, in this study, a systematic tandem mass tags (TMT)-labelled proteomics approach was used to address the whole proteome expression profile with or without stemazole in normal conditions instead of extreme conditions. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction (PPI) network analyses, were employed.

Results: The effect of stemazole on the expression profiles of neural stem cells was obtained. A total of 408 proteins with changes at the abundance level of two groups were identified: 178 proteins increase in abundance and 240 proteins decrease in abundance, respectively. Low abundance of some mitochondrial respiratory chain enzyme, overproduction of reactive oxygen species (ROS) and reduction of mitochondrial membrane potential may indicate stemazole has cytotoxicity.

Conclusions: It is the first proteomics research about stemazole, and the possible cytotoxicity of stemazole has been reported for the first time. The information about proteins that were affected by stemazole and more characteristics of stemazole will help obtain a complete picture of this small molecule drug. These findings provide a scientific basis for further stemazole treatment research.
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http://dx.doi.org/10.1186/s12953-020-00168-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724819PMC
December 2020

Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial.

J Immunother Cancer 2020 11;8(2)

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Background: Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response.

Methods: In this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m) and oxaliplatin (85 mg/m). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment.

Results: 54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28).

Conclusion: Camrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX.

Trial Registration Number: NCT03486678.
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http://dx.doi.org/10.1136/jitc-2020-001240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656907PMC
November 2020

R0026 Combined with R0179 Prevent Obesity-Associated Hyperlipidemia and Modulate Gut Microbiota in C57BL/6 Mice.

J Microbiol Biotechnol 2021 Feb;31(2):181-188

Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, P.R. China.

and are commonly used probiotics. This study aimed to identify the effect of live combined R0179 and R0026 (LCBE) on obesityassociated hyperlipidemia and gut microbiota in C57BL/6 mice. Forty male C57BL/6 mice were divided into four groups: normal group (N group), model group (M group), low-dose group (L group), and high-dose group (H group). Mice were gavaged with LCBE at 0.023 g/mice/day (L group) or 0.23 g/mice/day (H group) and fed with a high-fat diet for 8 weeks. In vitro R0026 showed an ability to lower the low-concentration of cholesterol by 46%, and the ability to lower the highconcentration of cholesterol by 58%. LCBE significantly reduced the body weight gain, Lee index, brown fat index and body mass index of mice on a high-fat diet. Moreover, LCBE markedly improved serum lipids (including serum triglyceride, total cholesterol, low-density lipoprotein and highdensity lipoprotein) while also significantly reducing liver total cholesterol. Serum lipopolysaccharide and total bile acid in L and H groups decreased significantly compared with M group. PCR-DGGE analysis showed that the composition of gut microbiota in the treatment groups was improved. was found in H group. The PCA result indicated a similar gut microbiota structure between LCBE treatment groups and normal group while the number of bands and Shannon diversity index increased significantly in the LCBE treatment groups. Finally, qPCR showed spp. increased significantly in H group compared with M group, LCBE alleviated liver steatosis and improved brown adipose tissue index.
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http://dx.doi.org/10.4014/jmb.2009.09005DOI Listing
February 2021

Prevalence and temporal trends of presarcopenia metrics and related body composition measurements from the 1999 to 2006 NHANES.

BMJ Open 2020 08 5;10(8):e034495. Epub 2020 Aug 5.

Clinical Research Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China

Objective: To evaluate the prevalence and temporal trends of presarcopenia and related body composition measurements.

Design: Cross-sectional study.

Setting: National Health and Nutrition Examination Survey (NHANES) 1999-2006.

Methods: Presarcopenia was defined according to the guidelines from the European Working Group on Sarcopenia. Logistic or linear regression models were used to evaluate the linear trend of the prevalence of presarcopenia, obesity and related body composition measurements.

Participants: A total of 29 947 participants aged 18-90 years from five waves of the NHANES were included in the analysis.

Outcome Measures: Presarcopenia was sex-specifically defined as having a skeletal mass index ≤7.26 kg/m in men and ≤5.5 kg/m in women. Body composition measurements, including total body fat percentage, total body fat mass, total lean body mass, appendicular skeletal muscle mass and bone mineral density, were obtained by dual-energy X-ray absorptiometry.

Results: The overall prevalence of presarcopenia ranged from 16.4% in 1999-2000 to 14.8% in 2005-2006 (p for trend=0.78). Presarcopenia was stable in both males (p for trend=0.36) and females (p for trend=0.20). The presarcopenia prevalence was significantly elevated among the age group of 18-39 years old (from 11.3% to 14.1%, p for trend=0.04) and among non-Hispanic blacks (p for trend <0.001). Adults aged ≥80 years old had the highest prevalence.

Conclusions: The prevalence of presarcopenia increased among young individuals over time. Non-Hispanic blacks also demonstrated an increasing trend in the prevalence over time.
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http://dx.doi.org/10.1136/bmjopen-2019-034495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410000PMC
August 2020

Neonatal hand, foot, and mouth disease due to coxsackievirus A6 in Shanghai.

BMC Pediatr 2020 08 3;20(1):364. Epub 2020 Aug 3.

Department of Pediatric Infectious Diseases, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Background: Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, pathogens, possible transmission routes, and prognosis of neonatal HFMD in Shanghai.

Methods: This was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus, and phylogenetic analysis based on the VP1 sequences of coxsackievirus A6 (CV-A6) was performed to investigate molecular and evolutionary characteristics. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical manifestations in the group of HFMD neonates and their paired siblings.

Results: There were 16 neonates among the 12,608 diagnosed patients with HFMD, accounting for 0.13%. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and were caused by CV-A6. CV-A6 was the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD experienced fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to age-matched controls. The clinical symptoms receded about 1 week after onset. None of the neonates had sequelae.

Conclusions: In our study, CV-A6 infection in neonates was benign, but had the character of family clustering. Due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.
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http://dx.doi.org/10.1186/s12887-020-02262-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397588PMC
August 2020

The Inhibitory Effect of Gut Microbiota and Its Metabolites on Colorectal Cancer.

Authors:
Chao Chen Huajun Li

J Microbiol Biotechnol 2020 Nov;30(11):1607-1613

Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.

Colorectal cancer (CRC) is regarded as one of the most common and deadly forms of cancer. Gut microbiota is vital to retain and promote several functions of intestinal. Although previous researches have shown that some gut microbiota have the abilities to inhibit tumorigenesis and prevent cancer from progressing, they have not yet clearly identified associative mechanisms. This review not only concentrates on the antitumor effects of metabolites produced by gut microbiota, for example, SCFA, ferrichrome, urolithins, equol and conjugated linoleic acids, but also the molecules which constituted the bacterial cell wall have the antitumor effect in the host, including lipopolysaccharide, lipoteichoic acid, β-glucans and peptidoglycan. The aim of our review is to develop a possible therapeutic method, which use the products of gut microbiota metabolism or gut microbiota constituents to help treat or prevent colorectal cancer.
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http://dx.doi.org/10.4014/jmb.2002.02032DOI Listing
November 2020

Ginsenoside Rb1 can ameliorate the key inflammatory cytokines TNF-α and IL-6 in a cancer cachexia mouse model.

BMC Complement Med Ther 2020 Jan 15;20(1):11. Epub 2020 Jan 15.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, 19 Xinjiekouwai Street, Haidian district, Beijing, China.

Background: Cancer cachexia is a severe condition that leads to the death of advanced cancer patients, and approximately 50~80% of cancer patients have cancer cachexia. Ginseng extract has been reported to have substantial anticancer and immune-enhancing effects; however, no study has reported the use of ginseng alone to treat cancer cachexia. Our study's purpose was to investigate the therapeutic effects of ginseng-related monomers or mixtures on a cancer cachexia mouse model.

Methods: We selected BALB/c mice and injected the mice subcutaneously with C26 colon cancer cells to construct a cancer cachexia experimental animal model. The water extract of ginseng (WEG), two types of ginseng extracts (ginsenosides at doses of 5 mg/kg (GE5) and 50 mg/kg (GE50)) and ginsenoside Rb1 (Rb1) were used to treat cancer cachexia mice. Enzyme-linked immunosorbent assays (ELISAs) were used to analyze the inhibitory effects on two key inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

Results: Our experimental results show that GE5, GE50 and Rb1 significantly reduced the levels of TNF-α (P < 0.01) and IL-6 (P < 0.01), which are closely related to cancer cachexia; however, WEG, GE5, GE50 and Rb1 did not significantly improve the gastrocnemius muscle weight or the epididymal fat weight of mice with cancer cachexia.

Conclusions: These results indicate that GE5, GE50 and Rb1 may be useful for reducing symptoms due to inflammation by reducing the TNF-α and IL-6 cytokine levels in cancer cachexia mice, thereby ameliorating the symptoms of cancer cachexia. Our results may be beneficial for future studies on the use of Chinese herbal medicines to treat cancer cachexia.
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http://dx.doi.org/10.1186/s12906-019-2797-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076885PMC
January 2020

Uncovering the Pharmacological Mechanism of Stemazole in the Treatment of Neurodegenerative Diseases Based on a Network Pharmacology Approach.

Int J Mol Sci 2020 Jan 9;21(2). Epub 2020 Jan 9.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

Stemazole exerts potent pharmacological effects against neurodegenerative diseases and protective effects in stem cells. However, on the basis of the current understanding, the molecular mechanisms underlying the effects of stemazole in the treatment of Alzheimer's disease and Parkinson's disease have not been fully elucidated. In this study, a network pharmacology-based strategy integrating target prediction, network construction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and molecular docking was adopted to predict the targets of stemazole relevant to the treatment of neurodegenerative diseases and to further explore the involved pharmacological mechanisms. The majority of the predicted targets were highly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. RAC-alpha serine/threonine-protein kinase (AKT1), caspase-3 (CASP3), caspase-8 (CASP8), mitogen-activated protein kinase 8 (MAPK8), and mitogen-activated protein kinase 14 (MAPK14) are the core targets regulated by stemazole and play a central role in its anti-apoptosis effects. This work provides a scientific basis for further elucidating the mechanism underlying the effects of stemazole in the treatment of neurodegenerative diseases.
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http://dx.doi.org/10.3390/ijms21020427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013392PMC
January 2020

3D Reconstruction of Slug Flow in Mini-Channels with a Simple and Low-Cost Optical Sensor.

Sensors (Basel) 2019 Oct 21;19(20). Epub 2019 Oct 21.

School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China.

The present work provides a new approach for 3D image reconstruction of gas-liquid two-phase flow (GLF) in mini-channels based on a new optical sensor. The sensor consists of a vertical and a horizontal photodiode array. Firstly, with the optical signals obtained by the vertical array, a measurement model developed by Support Vector Regression (SVR) was used to determine the cross-sectional information. The determined information was further used to reconstruct cross-sectional 2D images. Then, the gas velocity was calculated according to the signals obtained by the horizontal array, and the spatial interval of the 2D images was determined. Finally, 3D images were reconstructed by piling up the 2D images. In this work, the cross-sectional gas-liquid interface was considered as circular, and high-speed visualization was utilized to provide the reference values. The image deformation caused by channel wall was also considered. Experiments of slug flow in a channel with an inner diameter of 4.0 mm were carried out. The results verify the feasibility of the proposed 3D reconstruction method. The proposed method has the advantages of simple construct, low cost, and easily multipliable. The reconstructed 3D images can provide detailed and undistorted information of flow structure, which could further improve the measurement accuracy of other important parameters of gas-liquid two-phase flow, such as void fraction, pressure drop, and flow pattern.
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http://dx.doi.org/10.3390/s19204573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832154PMC
October 2019

Left ventricular remodeling and dysfunction in obstructive sleep apnea : Systematic review and meta-analysis.

Herz 2020 Dec 25;45(8):726-738. Epub 2019 Sep 25.

Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China.

Background: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular mortality and morbidity. Several studies have reported that it affects the left ventricle; however, large randomized controlled trials are lacking. The current study aimed to summarize the association between OSAS and left ventricular (LV) structure and function.

Methods: Electronic databases (PubMed, Embase, and Cochrane) and references were searched for articles published until March 2018. A systematic review and meta-analysis were performed to assess LV structure and function in OSAS patients based on echocardiography.

Results: In total, 17 studies with 747 OSAS patients and 426 control participants were included. Patients with OSAS showed an increase in LV diastolic diameter (weighted mean difference [WMD], 95% CI: 1.24 [0.68, 1.80]; p < 0.001), LV systolic diameter (WMD, 95% CI: 1.14 [0.47, 1.81]; p = 0.001), and LV mass (WMD, 95% CI: 35.34 [20.67, 50.00]; p < 0.001). In addition, left ventricular ejection fraction (LVEF) significantly decreased in the OSAS group compared with the controls (WMD, 95% CIs: -1.82 [-2.76, -0.87]; p < 0.001), and the reduction in LVEF was consistent with the severity of OSAS. The OSAS group also showed an increase in left atrial diameter (WMD, 95% CI: 2.13 [1.48, 2.77]; p < 0.001) and left atrial diameter volume index (WMD, 95% CIs: 3.96 [3.32, 4.61]; p < 0.001).

Conclusion: Obstructive sleep apnea syndrome leads to atrial dilatation, left ventricular hypertrophy, enlargement, mass increase and reduction of systolic function. Treatments for OSAS might be beneficial for the preservation of left cardiac structure and function.
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http://dx.doi.org/10.1007/s00059-019-04850-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695673PMC
December 2020

Pharmacokinetics and absolute oral bioavailability of stemazole by UPLC-MS/MS and its bio-distribution through tritium labeling.

Drug Test Anal 2020 Jan 12;12(1):101-108. Epub 2019 Sep 12.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.

The small molecule, stemazole, has significant therapeutic effects on neurodegenerative diseases, such as Alzheimer's disease (AD), due to its neuroprotective effects and remarkable survival-promoting activity in stem cells. However, pharmacokinetic properties of stemazole were unclear. In this study, a rapid and effective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to detect stemazole. The detector was operated in the positive-ion mode with an electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) mode. Chromatographic separation was performed on an Acquity UPLC BEH C column with gradient elution. Stemazole was extracted from plasma following a one-step protein precipitation method. The method was fully validated for its selectivity, specificity, and sensitivity. The calibration curve range of 5-1125 ng/mL showed good linearity for stemazole. Intra-day and inter-day precision rates were less than 10%, and accuracy ranged from 95.87% to 105.23%. The pharmacokinetic profiles were illustrated through the newly developed method for the first time. The absolute oral bioavailability of stemazole is 32.10%. Therefore, it is feasible as an oral medication, which greatly facilitates its broad application. The biological distribution of tritium-labeled stemazole in mice was studied, and the results showed that stemazole was absorbed rapidly and distributed widely, mainly in the liver and kidneys. A specific amount was also detected in the brain, which provides a prerequisite for the use of stemazole to treat neurodegenerative diseases. This work represents first description of the pharmacokinetics, bioavailability, and tissue distribution of stemazole and will lay the foundation for further investigation and drug development.
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http://dx.doi.org/10.1002/dta.2694DOI Listing
January 2020

Secreted TGF-beta-induced protein promotes aggressive progression in bladder cancer cells.

Cancer Manag Res 2019 25;11:6995-7006. Epub 2019 Jul 25.

The Third Clinical College of Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.

Transforming growth factor-beta-induced (TGFBI) is an exocrine protein, which has been found to be able to promote the development of nasopharyngeal carcinoma, glioma, pancreatic cancer, and other tumors. However, there is currently no report concerning the relationship between TGFBI and invasive progression of bladder cancer (BCa). IHC staining, qRT-PCR and Western blot were used to analyze TGFBI and EMT markers levels. In vivo tumorigenesis was performed by xenograft tumor model. In this study, we found that both mRNA and protein levels of TGFBI were significantly up-regulated in muscle invasive bladder cancer (MIBC) tissues compared with non-muscle-invasive bladder cancer (NMIBC) tissues. The high expression level of TGFBI was positively correlated with high histological grade and advanced clinical stage, and BCa patients with high TGFBI levels exhibited poor prognoses. We further confirmed that high expression level of TGFBI can promote proliferation, invasive progression, and epithelial-to-mesenchymal transition (EMT) of BCa cells in vitro, as well as promote tumor growth and EMT in vivo, while silencing of TGFBI inhibited these malignant phenotypes. TGFBI was involved in the up-regulation of EMT by inducing the expression level of Slug, Vimentin, Snail, MMP2, and MMP9 genes, while it down-regulated the expression level of E-cadherin. Moreover, Western blot analysis was carried out to demonstrate that BCa cell lines stably transfected with expression of TGFBI, a secreted protein. Furthermore, conditional medium containing TGFBI protein also resulted in enhanced EMT and malignant phenotype of BCa cells. Our results indicate that high expression level of TGFBI promotes EMT, proliferation, and invasive progression of BCa cells, and TGFBI is a potential therapeutic target and prognostic marker for BCa.
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http://dx.doi.org/10.2147/CMAR.S208984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6664251PMC
July 2019

Association between prenatal exposure to perfluoroalkyl substances and asthma-related diseases in preschool children.

Environ Sci Pollut Res Int 2019 Oct 10;26(29):29639-29648. Epub 2019 Aug 10.

Department of Pediatrics Infectious Diseases, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.

Thus far, the few studies on the associations between perfluoroalkyl substances (PFASs) and asthma in children have yielded inconsistent results. In this study, we aimed to evaluate whether and to what extent prenatal PFASs exposure is associated with childhood asthmatic diseases. Eight PFASs were measured in cord blood drawn from 358 children in the Shanghai Allergy Birth Cohort, and a 5-year follow-up plan was completed. Asthma was diagnosed and reported by pediatric respiratory physicians via repeated symptoms (wheezing and coughing) and laboratory examination (Immunoglobulin E level test and skin prick test). A total of 26.6% and 17.4% subjects were diagnosed with wheezing and asthma, respectively. Multivariable logistic regression and piecewise linear regression were applied, and no association was found between PFASs and asthma or wheezing. However, cord serum PFOA, PFOS, and PFDA were positively correlated with serum total IgE in 5-year-old children as the level of the former beyond the turning point (4.37 ng/mL, 2.95 ng/mL, and 0.42 ng/mL, respectively), but negatively with IgE before it reach turnning point.
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http://dx.doi.org/10.1007/s11356-019-05864-xDOI Listing
October 2019

Anisotropic Vibration Tactile Model and Human Factor Analysis for a Piezoelectric Tactile Feedback Device.

Micromachines (Basel) 2019 Jul 3;10(7). Epub 2019 Jul 3.

School of Mechanical Engineering, Yanshan University, Qinhuangdao 066004, China.

Tactile feedback technology has important development prospects in interactive technology. In order to enrich the tactile sense of haptic devices under simple control, a piezoelectric haptic feedback device is proposed. The piezoelectric tactile feedback device can realize tactile changes in different excitation voltage amplitudes, different excitation frequencies, and different directions through the ciliary body structure. The principle of the anisotropic vibration of the ciliary body structure was analyzed here, and a tactile model was established. The equivalent friction coefficient under full-coverage and local-coverage of the skin of the touch beam was deduced and solved. The effect of system parameters on the friction coefficient was analyzed. The results showed that in the full-coverage, the tactile effect is mainly affected by the proportion of the same directional ciliary bodies and the excitation frequency. The larger the proportion of the same direction ciliary body is, the smaller the coefficient of friction is. The larger the excitation frequency is, the greater the coefficient of friction is. In the local-coverage, the tactile effect is mainly affected by the touch position and voltage amplitude. When changing the touch pressure, it has a certain effect on the change of touch, but it is relatively weak. The experiment on the sliding friction of a cantilever touch beam and the experiment of human factor were conducted. The experimental results of the sliding friction experiment are basically consistent with the theoretical calculations. In the human factor experiment, the effects of haptic regulation are mainly affected by voltage or structure of the ciliary bodies.
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http://dx.doi.org/10.3390/mi10070448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680780PMC
July 2019

Fucoidan and galactooligosaccharides ameliorate high-fat diet-induced dyslipidemia in rats by modulating the gut microbiota and bile acid metabolism.

Nutrition 2019 09 11;65:50-59. Epub 2019 Mar 11.

Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China. Electronic address:

Objectives: Dyslipidemia is an important risk factor for cardiovascular diseases. Fucoidan (FUC) is a polysaccharide extracted from brown marine algae with various biological activities. Galactooligosaccharides (GOS) are important prebiotics that exert benefits on the intestinal microbiota. The aim of this study was to investigate the effects of FUC and GOS on dyslipidemia in rats by modulating the gut microbiota and bile acid metabolism.

Methods: Twenty-four male inbred Sprague-Dawley (SD) rats aged 8 wk were fed a normal or high-fat diet (HFD) for 8 wk. During the feeding period, rats were gavaged with normal saline solution, FUC solution (100 mg/kg),or GOS solution (800 mg/kg), or a combination of both once daily. Serum biochemical parameters were determined, and the gut microbiota were analyzed via 16S rRNA gene sequencing. Bile salt hydrolase (BSH) activity in the small intestinal contents was also analyzed. The effects of FUC and GOS on Lactobacillus casei DM8121 were analyzed in vitro.

Results: In rats, GOS and FUC supplementation significantly improved serum total cholesterol, low-density lipoprotein cholesterol, lipopolysaccharide, serum total bile acid, hepatic tissue steatosis, aortic arch injury, gut microbiota, serum high-density lipoprotein cholesterol, cholesterol 7-alpha hydroxylase expression in the liver, and BSH activity in the small intestinal contents. In an in vitro experiment, GOS and FUC supplementation significantly increased L. casei DM8121's BSH activity.

Conclusions: In rats, FUC and GOS supplementation improved serum dyslipidemia, gut microbiota, BSH activity, and bile acid metabolism-related pathways. In vitro, GOS and FUC supplementation increased L. casei DM8121's BSH activity.
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http://dx.doi.org/10.1016/j.nut.2019.03.001DOI Listing
September 2019

Clinical characteristics and managements of severe hand, foot and mouth disease caused by enterovirus A71 and coxsackievirus A16 in Shanghai, China.

BMC Infect Dis 2019 Mar 27;19(1):285. Epub 2019 Mar 27.

Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.

Background: Hand, foot and mouth disease (HFMD) is a transmissible infectious disease caused by human enteroviruses (EV). Here, we described features of children with severe HFMD caused by EV-A71 or coxsackievirus A16 (CV-A16) in Shanghai, China.

Methods: Severe EV-A71 or CV-A16 caused HFMD children admitted to the Xinhua Hospital from January 2014 and December 2016, were recruited retrospectively to the study. Symptoms and findings at the time of hospitalization, laboratory tests, treatments, length of stay and residual findings at discharge were systematically recorded and analyzed.

Results: Of 19,995 children visited clinic service with probable HFMD, 574 children (2.87%) were admitted, 234 children (40.76%) were confirmed with EV-A71 (90/574) or CV-A16 (144/574) disease. Most (91.02%) of the patients were under 5 years. Initial clinical symptoms of EV-A71 and CV-A16 cases were: fever > 39 °C in 81 (90%) and 119 (82.63%), vomiting in 31 (34.44%) and 28 (19.44%), myoclonic twitching in 19 (21.11%) and 11(7.64%), startle in 21 (23.33%) and 20 (13.69%), respectively. Serum levels of interleukin-1β (IL-1β), IL-2, IL-6, IL-8, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) were significantly upregulated in severe HFMD subjects. Forty-seven children (20.08%) treated with intravenous gamma globulin (IVIG) showed decreased duration of illness episodes. All children were discharged without complications.

Conclusions: EV-A71 and CV-A16 accounted 40.76% of admitted HFMD during 2014 to 2016 in Xinhua Hospital. IVIG appeared to be beneficial in shortening the duration of illness episodes of severe HFMD.
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http://dx.doi.org/10.1186/s12879-019-3878-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438032PMC
March 2019

Clinical characteristics and antimicrobial resistance of pneumococcal isolates of pediatric invasive pneumococcal disease in China.

Infect Drug Resist 2018 26;11:2461-2469. Epub 2018 Nov 26.

Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,

Purpose: causes serious infections globally, including invasive pneumococcal disease (IPD). We analyze clinical features of pediatric IPD cases identified in China and antibiotic susceptibility of isolated pneumococcal strains.

Methods: Confirmed pediatric IPD patients were prospectively recruited to the study. Symptoms at the time of hospitalization, laboratory tests, antimicrobial susceptibility of pneumococcal isolates, treatments, hospital stay, and residual findings at discharge were analyzed systematically.

Results: From January 2008 to December 2017, a total of 123 hospitalized children diagnosed with IPD were enrolled: 68 from pediatric departments of Xinhua Hospital, and 55 from Lanzhou University Second Hospital. Of these pediatric IPD patients, 81 (65.86%) were male, and 98 (79.67%) <5 years old. Most cases (96, 78.05%) were diagnosed during the cold season between September and February. Sepsis was observed in 82 (66.67%) patients, 48 (39.02%) children were diagnosed with meningitis, 41 (33.33%) with pneumonia, 30 (24.39%) with pleurisy, and 4 (3.25%) with osteomyelitis. Underlying diseases were noted in 35 (28.45%) patients and concurrent infections in 45 (36.58%). The overall mortality rate was 2.44%. IPD children who developed sepsis and necrotizing pneumonia showed higher proportions of intensive care-unit admission, intravenous γ-globulin, glucocorticoid use, hemofiltration and ventilator, and longer duration of fever, hospital stay, and antibiotic use than nonsepsis and pneumonia subjects. Antimicrobial resistance of showed a highly unsusceptible rate for erythromycin (96.75%), trimethoprim-sulfamethoxazole (79.67%), and tetracycline (77.23%). All isolates were sensitive to vancomycin, linezolid, and levofloxacin.

Conclusion: Clinical symptoms were severe in the majority of pediatric IPD patients. More intensive treatments were demanded for IPD children with sepsis and necrotizing pneumonia. High resistance rates for erythromycin, trimethoprim-sulfamethoxazole, and tetracycline were found.
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http://dx.doi.org/10.2147/IDR.S183916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263219PMC
November 2018

Dienogest for Treatment of Endometriosis in Women: A 28-Week, Open-Label, Extension Study.

J Womens Health (Larchmt) 2019 02 21;28(2):170-177. Epub 2018 Nov 21.

1 Peking Union Medical College Hospital , Beijing, People's Republic of China .

Background: Dienogest provided significantly greater reduction in endometriosis-associated pelvic pain (EAPP) than placebo in a 24-week, randomized, double-blind study of Chinese women with endometriosis. The current open-label extension study investigated the efficacy and safety of dienogest for 28 additional weeks in this population.

Patients And Methods: Women with endometriosis were eligible to enroll at completion of the 24-week, placebo-controlled study (n = 220). All women, regardless of prior study treatment, received dienogest 2 mg once daily for up to 28 weeks. Absolute change in EAPP from baseline on a 1-100 mm visual analog scale (VAS), bleeding pattern, adverse events (AEs), laboratory parameters, and bone mineral density (BMD) were evaluated.

Results: The open-label study was completed by 203 (92.3%) women. At the end of open-label study, mean (SD) change from baseline in EAPP score on VAS was -43.1 mm (26.54 mm) and -39.8 mm (31.15 mm) in the prior-dienogest and prior-placebo groups, respectively. Other assessments confirmed that dienogest maintained or enhanced efficacy after 28 weeks of additional treatment. Dienogest initiation was associated with longer, but fewer, spotting/bleeding episodes. Bleeding frequency and intensity decreased progressively during continued treatment. Treatment-emergent AEs, generally mild or moderate, led to withdrawal in 2 (0.9%) patients during the open-label study. Dienogest had no effect on BMD.

Conclusions: Dienogest 2 mg once daily is effective and safe in the long-term management of EAPP in Chinese women with endometriosis, with progressive decreases in EAPP and bleeding irregularities during continued treatment. Efficacy and safety results of this study were consistent with previous studies in Caucasian patients.
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http://dx.doi.org/10.1089/jwh.2018.7084DOI Listing
February 2019

[Separation and purification of iopamidol using preparative high-performance liquid chromatography].

Authors:
Huajun Li Qian Chen

Se Pu 2018 Oct;36(10):1061-1066

Zhejiang Starry Pharmaceutical Co. Ltd., Taizhou 317300, China.

The development and optimization of separation and purification methods for high-purity iopamidol were performed based on preparative high-performance liquid chromatography (prep-HPLC). In this study, a reversed-phase separation method for the analysis of iopamidol was developed first. The effects of chromatographic parameters, including two kinds of stationary phase with different bonded amounts, column temperature, and sample loading capacity, on the retention, resolution, and peak shape of iopamidol were investigated. The results showed that good retention and resolution of iopamidol were realized on a C18-1 column (250 mm×4.6 mm, 10 μm) of which the bonded amount was 13.7%. Retention of iopamidol was weakened with increasing column temperature, resulting in a low resolution between iopamidol and impurities. Thus, the column temperature was adjusted to 20-30℃. Meanwhile, the increasing of loading capacities was also detrimental to retention of iopamidol or removal of impurities. Prep-HPLC was performed on the C18-1 column (270 mm×50 mm, 10 μm) with the mobile phase of water-methanol at a column temperature of 20℃. After preparation, the chromatographic purity of the iopamidol sample was 98.97% with recovery of 93.44%, and its related substances all met limited requirements. This method can reduce the impurity level effectively with a high recovery rate, which is helpful for the development of separation and purification of iopamide.
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http://dx.doi.org/10.3724/SP.J.1123.2018.06001DOI Listing
October 2018
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