Publications by authors named "Jiping Zhao"

59 Publications

Clinical study on acupuncture treatment of hypertension with hyperactivity of liver yang.

Medicine (Baltimore) 2021 Apr;100(17):e25668

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine.

Introduction: Hypertension can lead to different degrees complications of cardiovascular and cerebrovascular, and increase the risk of sudden death. Acupuncture has become a complementary alternative therapy for hypertension because of its antihypertensive and nontoxic side effects. However, there is still lack of evidence-based medicine evidence for an effective acupuncture antihypertensive prescription. The purpose of this study is to evaluate the effect of a special acupuncture prescription on hypertension with hyperactivity of liver yang.

Methods: In this randomized controlled trial, we will recruit 56 hypertensive patients with hyperactivity of liver yang. Then the patients will be randomly divided into control group and experimental group. The control group will be treated with western medicine, and the experimental group will be treated with medicine combined with acupuncture. The intervention will last 4 weeks. The indices will be collected before acupuncture, after acupuncture, and 2 weeks after acupuncture. The primary outcome will be 24-hour ambulatory blood pressure. The secondary outcomes will be clinic blood pressure, anxiety and depression score, and the syndrome score of hyperactivity of liver yang. The auxiliary indicators will be blood pressure load values and salt sensitivity risk rate. The exploratory indicator will be acupoint diagnosis. The safety evaluation indicator will be incidence of adverse events.

Discussion: The results of this study will provide favorable evidence for the efficacy and safety of acupuncture in reducing blood pressure, and explore the positive reaction acupoints which related to hypertension.
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http://dx.doi.org/10.1097/MD.0000000000025668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084090PMC
April 2021

A wideband picosecond pulsed electric fields (psPEF) exposure system for the nanoporation of biological cells.

Bioelectrochemistry 2021 Aug 26;140:107790. Epub 2021 Feb 26.

Department of Biological Science and Bioengineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.

The effects and mechanisms of ultrashort and intense pulsed electric fields on biological cells remain some unknown. Especially for picosecond pulsed electric fields (psPEF) with a high pulse repetition rate, electroporation or nanoporation effects could be induced on cell membranes and intracellular organelle membranes. In this work, the design, implementation, and experimental validation of a wideband psPEF exposure system (WPES) is reported, comprising picosecond pulser and wideband biochip, for the in vitro exposure of suspended cells to high-intensity psPEF. Excited by repetitive picosecond pulses (the duration of 200 ps and the amplitude of a few kilovolts), the proposed biochip adopts grounded coplanar waveguide (GCPW) for a wide working bandwidth, which was fabricated with 160 μm thick electrodes for uniform distribution of psPEF in the cross-section. To ensure that only psPEF is generated in the biological medium containing cells except for ionic current, this work proposes to install capillary tubes in the electrode gaps for electrical insulation and cells delivery. By electrical measurements in the time domain and frequency domain, the exposure system is adapted for local generation of extremely high-intensity psPEF with the 3 dB bandwidth up to 4.2 GHz. Furthermore, biological experiments conducted on the developed exposure system verified its capability to permeabilize biological cells under the exposure of high-intensity psPEF.
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http://dx.doi.org/10.1016/j.bioelechem.2021.107790DOI Listing
August 2021

The characteristics of 527 discharged COVID-19 patients undergoing long-term follow-up in China.

Int J Infect Dis 2021 Mar 1;104:685-692. Epub 2021 Feb 1.

Respiratory Department, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China. Electronic address:

Background: Almost a year after the outbreak of coronavirus disease 2019 (COVID-19), many hospitalized COVID-19 patients have recovered. However, little is known about the long-term follow-up (> 2 months) of discharged patients.

Methods: This study enrolled 527 discharged COVID-19 patients from 05 February to 11 March 2020. Basic characteristics, imaging features, nucleic acid detection results, and antibody levels of these patients were retrospectively reviewed.

Results: Of the 527 discharged patients, 32 (6.1%) had re-detectable positive (RP) nucleic acid results for SARS-CoV-2 during follow-up examinations, with 11 and four detections entailing stool samples and anal swabs, respectively, rather than respiratory samples. Juveniles were more susceptible to "infection recurrence" than other age groups, with shorter time spans for re-detectable positive (RP) RNA tests (an average of 8.8 days [6.0-9.0 days]), while the reverse was true for the middle-aged group (17.5 days on average [14.0-17.5 days]). Similar improvements in the imaging features of both RP and no RP (NRP) groups were observed. Negative antibody detections in patients at 3 and 6 months after discharge were 14.2% and 25.0%, respectively. Cases evidencing negative antibodies were more common among juvenile patients (40% vs. 15.6%, P=0.03) 6 months post-discharge.

Conclusions: A total of 6.1% of 527 discharged patients showed RP status, which may be easier to be identified from stool samples than from other samples. Given the dropping rate of SARS-CoV-2 antibodies, reinfection may happen, especially in juvenile patients (aged<18 years). These findings have implications for the long-term management of recovered COVID-19 patients.
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http://dx.doi.org/10.1016/j.ijid.2021.01.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848496PMC
March 2021

FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy.

BMC Pulm Med 2021 Jan 28;21(1):45. Epub 2021 Jan 28.

Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, #16766, Jingshi Road, Jinan CityShandong Province, 250014, China.

Background: Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling.

Methods: Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1 mice and FSTL1 mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed.

Results: Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1 mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1 mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1 mice.

Conclusions: FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.
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http://dx.doi.org/10.1186/s12890-021-01409-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841997PMC
January 2021

Acupuncture for Hashimoto thyroiditis: study protocol for a randomized controlled trial.

Trials 2021 Jan 21;22(1):74. Epub 2021 Jan 21.

The Department of Acupuncture, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.

Background: The incidence rate of Hashimoto thyroiditis (HT) has gradually increased in recent years. There has been no specific etiological treatment for HT. Even though with normal level of thyroid hormone, the patients may still suffer from various clinical symptoms, such as anterior neck discomfort, fatigue, and mood swings, which seriously impair their quality of life. Acupuncture has long been used in the treatment of thyroid diseases, but there has been no related standardized clinical study as of today. This study aims to assess the feasibility, efficacy, and safety of acupuncture for HT.

Methods: This is a randomized, black-controlled assessor-blinded pilot trial. A total of 60 patients will be recruited and divided into the experimental group (n = 30) or the control group (n = 30). The experimental group will undergo acupuncture therapy (penetration needling of Hand-Yangming meridian, PNHM) for 16 weeks, followed by a 16-week follow-up period, and the control group will first go through an observation period for 16 weeks, followed by a 16-week compensation PNHM therapy. The primary outcome will be the change of the concentrations of anti-thyroperoxidase antibodies (TPOAb), antithyroglobulin antibodies (TgAb), and thyroid hormone, including total thyroxine (FT), free thyroxine (FT), and thyroid-stimulating hormone (TSH). The secondary outcome measurements include the thyroid-related quality of life questionnaire short-form (ThyPRO-39), The Mos 36-item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HAD). Data collection will be performed before the start of the study (the baseline assessment) and at weeks 8, 16, 24, and 32.

Discussion: The study is designed to assess the feasibility and effectiveness of PNHM in reducing the thyroid antibody level and improving the quality of life of HT patients with hypothyroidism or subclinical hypothyroidism. Results of this trial will assist further analyses on whether the acupuncture treatment can alleviate symptoms for patients with HT.

Trial Registration: Acupuncture-Moxibustion Clinical Trial Registry AMCTR-IOR-19000308 ( ChiCTR1900026830 ). Registered on 23 October 2019.
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http://dx.doi.org/10.1186/s13063-021-05036-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818748PMC
January 2021

Clinical Features for Severely and Critically Ill Patients with COVID-19 in Shandong: A Retrospective Cohort Study.

Ther Clin Risk Manag 2021 6;17:9-21. Epub 2021 Jan 6.

Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel pathogen, has caused an outbreak of coronavirus disease 2019 (COVID-19) that has spread rapidly around the world. Determining the risk factors for death and the differences in clinical features between severely ill and critically ill patients with SARS-CoV-2 pneumonia has become increasingly important.

Aim: This study was intended to provide insight into the difference between severely ill and critically ill patients with SARS-CoV-2 pneumonia.

Methods: In this retrospective, multicenter cohort study, we enrolled 62 seriously ill patients with SARS-CoV-2 pneumonia who had been diagnosed by March 12, 2020. Clinical data, laboratory indexes, chest images, and treatment strategies collected from routine medical records were compared between severely ill and critically ill patients. Univariate and multivariate logistic regression analyses were also conducted to identify the risk factors associated with the progression of patients with severe COVID-19.

Results: Of the 62 patients with severe or critical illness, including 7 who died, 30 (48%) patients had underlying diseases, of which the most common was cardiovascular disease (hypertension, 34%, and coronary heart disease, 5%). Compared to patients with severe disease, those with critical disease had distinctly higher white blood cell counts, procalcitonin levels, and D-dimer levels, and lower hemoglobin levels and lymphocyte counts. Multivariate regression showed that a lymphocyte count less than 10/L (odds ratio 20.92, 95% CI 1.76-248.18; p=0.02) at admission increased the risk of developing a critical illness.

Conclusion: Based on multivariate regression analysis, a lower lymphocyte count (<10/L) on admission is the most critical independent factor that is closely associated with an increased risk of progression to critical illness. Age, underlying diseases, especially hypertension and coronary heart disease, elevated D-dimer, decreased hemoglobin, and SOFA score, and APACH score also need to be taken into account for predicting disease progression. Blood cell counts and procalcitonin levels for the later secondary bacterial infection have a certain reference values.
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http://dx.doi.org/10.2147/TCRM.S280079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797329PMC
January 2021

Electroacupuncture vs Prucalopride for Severe Chronic Constipation: A Multicenter, Randomized, Controlled, Noninferiority Trial.

Am J Gastroenterol 2021 May;116(5):1024-1035

Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Introduction: This multicenter, randomized, noninferiority trial compared electroacupuncture with prucalopride for the treatment of severe chronic constipation (SCC).

Methods: Participants with SCC (≤ 2 mean weekly complete spontaneous bowel movements [CSBMs]) were randomly assigned to receive either 28-session electroacupuncture over 8 weeks with follow-up without treatment over 24 weeks or prucalopride (2 mg/d before breakfast) over 32 weeks. The primary outcome was the proportion of participants with ≥3 mean weekly CSBMs over weeks 3-8, based on the modified intention-to-treat population, with -10% as the noninferior margin.

Results: Five hundred sixty participants were randomized, 280 in each group. Electroacupuncture was noninferior to prucalopride for the primary outcome (36.2% vs 37.8%, with a difference of -1.6% [95% confidence interval, -8% to 4.7%], P < 0.001 for noninferiority); almost the same results were found in the per-protocol population. The proportions of overall CSBM responders through weeks 1-8 were similar in the electroacupuncture and prucalopride groups (24.91% vs 25.54%, with a difference of -0.63% [95% confidence interval, -7.86% to 6.60%, P = 0.864]). Except during the first 2-week treatment, no between-group differences were found in outcomes of excessive straining, stool consistency, and quality of life. Adverse events occurred in 49 (17.69%) participants in the electroacupuncture group and 123 (44.24%) in the prucalopride group. One non-treatment-related serious adverse event was recorded in the electroacupuncture group.

Discussion: Electroacupuncture was noninferior to prucalopride in relieving SCC with a good safety profile. The effects of 8-week electroacupuncture could sustain for 24 weeks after treatment. Electroacupuncture is a promising noninferior alternative for SCC (see Visual Abstract, http://links.lww.com/AJG/B776).
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http://dx.doi.org/10.14309/ajg.0000000000001050DOI Listing
May 2021

The effect of distal tibial tuberosity high tibial osteotomy on postoperative patellar height and patellofemoral joint degeneration.

J Orthop Surg Res 2020 Oct 9;15(1):466. Epub 2020 Oct 9.

Beijing University of Chinese Medicine, Beijing, 100029, China.

Background: Distal tibial tuberosity high tibial osteotomy (DTT-HTO) can prevent distalization of the tibial tuberosity and thus patellar infera. However, no studies on the clinical and radiological effects of DTT-HTO on the patellofemoral joint have been conducted. The purpose of the study was to evaluate the effect of DTT-HTO on patella height and patellofemoral joint congruity based on the severity of patellofemoral joint OA.

Methods: Twenty-nine patients (33 knees) who underwent DTT-HTO and second-look arthroscopy when implant was removed between January 2018 and May 2020 were eligible for the study. Among them, 6 were males, and 23 were females, with ages from 51 to 78 years old. The Caton-Deschamps index (CDI), congruence angle (CA), and lateral patellar tilt (LPT) were measured to evaluate the effect of surgery on patellar height and patellofemoral joint congruity. The weight-bearing line ratio (WBLR) was measured to assess lower limb alignment. The cartilage lesion in the patellofemoral joint was assessed arthroscopically during surgery and implant removal by the International Cartilage Repair Society (ICRS) grading system at 18-24 months after surgery. The Hospital for Special Surgery (HSS) scale was used to evaluate knee joint function.

Results: Twenty-nine patients were followed up for 18-28 months. The preoperative CDI, CA, and LPT changed from 0.92 ± 0.16 to 0.89 ± 0.14, from 5.52 ± 2.19 to 5.44 ± 2.27, and from 6.95 ± 2.88 to 6.54 ± 2.42, respectively, and the differences were not statistically significant (p > 0.05). The preoperative WBLR significantly increased from 16.72 ± 6.77 to 58.77 ± 7.69% (p < 0.001). The cartilage lesions in the patella and femoral trochlea did not progress significantly from the first- to the second-look arthroscopy, according to the ICRS grades (p > 0.05). The HSS score significantly improved from 50.64 ± 19.18 preoperatively to 67.33 ± 14.72, 81.63 ± 11.92, and 82.73 ± 8.05 at the 3-month, 12-month, and last follow-up after surgery (p < 0.001).

Conclusion: DTT-HTO can effectively prevent patellar infera, and its effects on postoperative patellofemoral joint congruity and patellofemoral joint OA progression are inconspicuous. It can be recommended as a treatment of varus knee combined with patellar infera or patellofemoral joint OA.
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http://dx.doi.org/10.1186/s13018-020-01996-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547468PMC
October 2020

Study of the effects of 3.1 THz radiation on the expression of recombinant red fluorescent protein (RFP) in .

Biomed Opt Express 2020 Jul 22;11(7):3890-3899. Epub 2020 Jun 22.

Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, Shaanxi, China.

In recent years, many studies have been conducted to investigate the non-thermal effects of THz radiation on different organisms, but further studies are needed to fully elucidate the effects, especially on the molecular level. In this study, we explored the effects of at 3.1 THz radiation on protein expression in ) using red fluorescent protein as a reporter molecule. After 8 hours of continuous THz irradiation of bacteria on LB (Luria-Bertani) solid plates at an average power of 33 mW/cm and 10 Hz pulse repetition frequency, we found that the plasmid copy number, protein expression and fluorescence intensity of bacteria from the irradiated area were 3.8-, 2.7-, and 3.3 times higher than in bacteria from the un-irradiated area, respectively. These findings suggest that plasmid replication changed significantly in bacteria exposed to 3.1 THz radiation, resulting in increased protein expression as evidenced by increased fluorescence intensity of the RFP reporter.
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http://dx.doi.org/10.1364/BOE.392838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510898PMC
July 2020

CT texture analysis for the differentiation of papillary renal cell carcinoma subtypes.

Abdom Radiol (NY) 2020 11;45(11):3860-3868

Department of Radiology, The Affiliated Hospital of Qingdao University, No. 1677, Wu Tai Shan Road, Huangdao District, Qingdao, Shandong, China.

Purpose: The objective of this study was to investigate whether computed tomography texture analysis can be used to differentiate papillary renal cell carcinoma (PRCC) subtypes.

Method: Sixty-two PRCC tumors were retrospectively evaluated, with 30 type 1 tumors and 32 type 2 tumors. Texture parameters quantified from three-phase contrast-enhanced CT images were compared with least absolute shrinkage and selection operator (LASSO) regression. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curve (AUC) was calculated for each parameter. The selected texture parameters of each phase were used to generate support vector machine (SVM) classifiers. Decision curve analysis (DCA) of the classification was performed.

Results: The two texture parameters with the top two AUC values were - 333-7 Correlation (AUC = 0.772) and 45-7 Entropy (AUC = 0.753) in the corticomedullary phase, 333-4 Correlation (AUC = 0.832) and 45-7 Entropy (AUC = 0.841) in the nephrographic phase, and 135-7 Entropy (AUC = 0.858) and - 333-1 InformationMeasureCorr2 (AUC = 0.849) in the excretory phase. Entropy and Correlation have a high correlation with the two types of PRCC and are increased in type 2 PRCC. A model incorporating the texture parameters with the top two AUC values in each phase produced an AUC of 0.922 with an accuracy of 84% (sensitivity = 89% and specificity = 80%). The nephrographic-phase model and the model combining the texture parameters of the three phases can differentiate the two types with the largest net benefit.

Conclusions: Computed tomography texture analysis can be used to distinguish type 2 PRCC from type 1 with high accuracy, which may be clinically important.
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http://dx.doi.org/10.1007/s00261-020-02588-2DOI Listing
November 2020

Macrophage Colony-stimulating Factor Mediates the Recruitment of Macrophages in Triple negative Breast Cancer.

Int J Biol Sci 2019 8;15(13):2859-2871. Epub 2019 Nov 8.

Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, 030006, China. 13934565188.

Triple negative breast cancer (TNBC) is characterized by aggressive malignant tumor, poor prognosis and lack of targeted treatment. Several studies have established that macrophages are closely associated with the progression of TNBC. Through immunohistochemical analysis, we found that the infiltration of macrophage in TNBC tissue was more than that in non-triple negative breast cancer (nTNBC) tissue. Furthermore, the conditioned medium (CM) of MDA-MB-231 and HCC1937, the TNBC cell lines, had significant migration-promoted effect on macrophages. However, the macrophages migration-promoted ability of nTNBC cell line MCF-7 was weaker than that of MDA-MB-231 and HCC1937 cells. Mechanistically, MDA-MB-231 and HCC1937 cells secreted more macrophage colony-stimulating factor (M-CSF) than MCF-7, which is the main inducer of macrophage migration, and the secreted M-CSF promoted the increase in actin and the elongation of pseudopodia. When M-CSF was neutralized by antibody, the elongation of macrophage pseudopodia was disappeared and the migration was inhibited. , there were more macrophages in tumors induced by MDA-MB-231 than MCF-7 did. Therefore, M-CSF specially secreted by TNBC was the important cause of macrophages aggregation in TNBC, which further promoted the aggressiveness of TNBC.
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http://dx.doi.org/10.7150/ijbs.39063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909971PMC
June 2020

Functionalized polyhydroxyalkanoate nano-beads as a stable biocatalyst for cost-effective production of the rare sugar d-allulose.

Bioresour Technol 2019 Oct 19;289:121673. Epub 2019 Jun 19.

Department of Biological Science and Bioengineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, Shaanxi, People's Republic of China. Electronic address:

d-Allulose is a promising low-calorie sweetener especially for diabetes and obesity patients. The functionalized polyhydroxyalkanoate (PHA) nano-beads decorated with d-tagatose 3-epimerase (DTE) was produced in recombinant endotoxin-free ClearColi, whereby the expression, purification, and immobilization of the active DTE were efficiently combined into one step. The immobilized DTE exhibited remarkable enzyme activity of 649.3 U/g beads and extremely high stability at a harsh working condition (pH 7.0-8.0, 65 °C). When DTE-PHA beads were subjected to enzymatic synthesis of d-allulose, a maximum conversion rate of 33% can be achieved at pH 7.0 and 65 °C for 3 h, and DTE-PHA beads retained about 80% of its initial activity after 8 continuous cycles. Moreover, the d-allulose/d-fructose binary mixture can be simply separated by a single cation exchange resin-equipped chromatography. Taken together, DTE-PHA beads are promising and robust nano-biocatalysts that will remarkably simplify the production procedures of d-allulose, contributing to its cost-effective production.
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http://dx.doi.org/10.1016/j.biortech.2019.121673DOI Listing
October 2019

Poly(3-hydroxybutyrate--3-hydroxyhexanoate) Biopolyester Based Nanoparticles as NVP-BEZ235 Delivery Vehicle for Tumor Targeting Therapy.

Biomacromolecules 2019 09 26;20(9):3313-3323. Epub 2019 Jun 26.

Department of Biological Science and Bioengineering , Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University , Xi'an 710049 , Shaanxi , People's Republic of China.

As a biopolyester with excellent properties, the potential biomedical applications of poly(3-hydroxybutyrate--3-hydroxyhexanoate) (PHBHHx) have gained extensive attention. In this research, PHBHHx was fabricated into nanoparticles (NPs) to encapsulate NVP-BEZ235 (BEZ), an efficient kinase inhibitor/antitumor agent, for tumor targeting therapy. The resulting BEZ-NPs displayed a regularly spherical form with an appropriate diameter at 76.0 ± 3.6 nm. The encapsulation efficiency of BEZ was 83.7 ± 3.6%, and the sustained release profiles showed that almost 97% of BEZ could be gradually unrestricted from PHBHHx NPs within 72 h. The nanotoxicity studies revealed a satisfactory biosafety of PHBHHx NPs. PHBHHx NPs presented significantly improved cellular uptake in human prostate cancer cell line PC3, thereby enhancing the antiproliferation ability and kinase inhibitory activity of BEZ . More importantly, the real-time imaging demonstrated the adequate tumor targeting and accumulation capability of PHBHHx NPs. The remarkably delayed tumor growth, increased tumor necrosis, and reduced tumor proliferation in PC3 tumor xenograft mice further confirmed the antitumor efficacies of BEZ-loaded PHBHHx NPs. The above results suggest that PHBHHx NPs might be a promising drug delivery vehicle, safe and effective, for tumor targeting therapy.
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http://dx.doi.org/10.1021/acs.biomac.9b00505DOI Listing
September 2019

IL33/ST2 contributes to airway remodeling via p-JNK MAPK/STAT3 signaling pathway in OVA-induced allergic airway inflammation in mice.

Exp Lung Res 2019 Apr - May;45(3-4):65-75. Epub 2019 May 21.

a Department of Pulmonary Diseases , Qilu Hospital, Shandong University , Jinan , Shandong , People's Republic of China.

Airway remodeling, which encompasses structural changes in airway is a main feature of asthma. Interleukin-33 (IL-33) has been reported to be a vital cytokine in airway remodeling in asthma, but the underlying mechanisms are not clear yet. This study focused on discussing the role of IL-33 in airway remodeling in asthma. Female BALB/c mice were divided into a control group, an OVA induced allergic airway disease group and an anti-ST2 antibody intervention group. Immunohistochemistry and western blot were performed to detect IL-33, ST2 expression in addition to airway remodeling markers a-smooth muscle actin (a-SMA) and type 1 collagen in OVA-induced mice model. Levels of p-JNK and p-STAT3 activation in mice were detected by western blot. Human lung fibroblast (HLF) were stimulated with rhIL-33, anti-ST2 antibody and JNK inhibitor sp600125 and levels of JNK and STAT3 activation were determined via western blot and immunofluorescence staining. Anti-ST2 treatment inhibited JNK/STAT3 phosphorylation and airway remodeling in OVA-induced mouse model. IL-33 induced a-SMA and collagen 1 expression was inhibited by anti-ST2 antibody and sp600125 treatment via decreased JNK/STAT3 phosphorylation in human lung fibroblast. IL-33 promoted airway remodeling by interacting with ST2 to activate the JNK/STAT3 signaling pathway in asthma.
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http://dx.doi.org/10.1080/01902148.2019.1611972DOI Listing
April 2020

Differentiation Researches on the Meningioma Subtypes by Radiomics from Contrast-Enhanced Magnetic Resonance Imaging: A Preliminary Study.

World Neurosurg 2019 Jun 1;126:e646-e652. Epub 2019 Mar 1.

GE Healthcare, Shanghai, China.

Background: Meningioma subtypes are one of the most common key points to the treatment and prognosis of patients. The purpose of this study was to investigate the differential diagnostic value of radiomics features on meningioma.

Methods: A total of 241 patients with meningioma who had undergone tumor resection were randomly selected including 80 with meningothelial meningioma, 80 with fibrous meningioma, and 81 with transitional meningioma. These meningiomas were divided into 4 groups including: meningothelial versus fibrous (group 1), fibrous versus transitional (group 2), meningothelial versus transitional (group 3), and meningothelial versus fibrous versus transitional (group 4). All patients were examined using the same magnetic resonance scanner (GE 3.0 T) and the preoperative contrast-enhanced T1-weighted images were available. Radiomics features from the contrast-enhanced T1-weighted images of 241 patients were evaluated by 2 experienced radiology specialists.

Results: A total of 385 radiomics features were extracted from the images of each patient. Several preprocessing methods were applied on the radiomics dataset to reduce the redundancy and highlight differences between different meningioma before the Fisher discrimination analysis was adopted and leave one out cross validation methods were used for the model validation. The differentiation accuracies of the Fisher discriminant analysis model for groups 1, 2, 3, and 4 were 99.4%, 98.8%, 100% and 100%, respectively; leave one out cross validation method was achieved for group 1, 2, 3, and 4 with the accuracies of 91.3%, 95.0%, 100%, and 94.2%, respectively.

Conclusions: Radiomics features and the combined Fisher discriminant analysis could provide satisfactory performance in the preoperative differential diagnosis of meningioma subtypes and enable the potential ability for clinical application.
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http://dx.doi.org/10.1016/j.wneu.2019.02.109DOI Listing
June 2019

[Professor 's thoughts and methods of penetration needling].

Zhongguo Zhen Jiu 2018 Nov;38(11):1201-5

Department of Acupuncture and Moxibustion, Dongzhimen Hospital of Beijing University of CM, Beijing 100700.

As a vital part of acupuncture and moxibustion,the theory of penetration needling obviously lags behind the practice. This article summarizes the thoughts andmethods of penetration needling by professor . Based on the three basic elements of penetrating acupuncture, including the acupoint, needle and manipulation, the academic origins, the application of penetrating acupuncture at present and the clinical cases are reviewed; the essential content and the extension meaning of needle penetration are summarized, which is based on the identification of the location, pathology and characteristics of disease, combined with the characteristics of acupoints and the tissue structure of the part, we quantify the intensity of stimulation, so as to provide featured reference clinical practice.
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http://dx.doi.org/10.13703/j.0255-2930.2018.11.016DOI Listing
November 2018

Electroacupuncture Versus Pelvic Floor Muscle Training Plus Solifenacin for Women With Mixed Urinary Incontinence: A Randomized Noninferiority Trial.

Mayo Clin Proc 2019 01;94(1):54-65

Guang'an Men Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address:

Objective: To evaluate the efficacy and safety of electroacupuncture vs pelvic floor muscle training (PFMT) plus solifenacin for women with mixed urinary incontinence (MUI).

Patients And Methods: This randomized controlled noninferiority trial was conducted at 10 hospitals in China between March 1, 2014, and October 10, 2016. Participants were randomized 1:1 to receive electroacupuncture (36 sessions) over 12 weeks with 24 weeks of follow-up or PFMT-solifenacin (5 mg/d) over 36 weeks. The primary outcome was percentage change from baseline to week 12 in mean 72-hour incontinence episode frequency (IEF) measured by the 72-hour bladder diary. It was analyzed in the per-protocol set with a prespecified noninferiority margin of 15%.

Results: Of 500 women with MUI who were randomized, 467 (239 in the electroacupuncture group and 228 in the PFMT-solifenacin group) completed treatment per protocol and were included in the primary outcome analysis. At weeks 1 through 12, the percentage of reduction from baseline in mean 72-hour IEF was 37.83% in the electroacupuncture group and 36.49% in the PFMT-solifenacin group (between-group difference, -1.34% [95% CI, -9.78% to 7.10%]; P<.001 for noninferiority), which demonstrates noninferiority; the treatment effect persisted throughout follow-up. Statistically significant improvements were found for secondary outcomes in both groups, with no meaningful difference between treatments.

Conclusion: In women with moderate to severe MUI, electroacupuncture was not inferior to PFMT-solifenacin in decreasing the 72-hour IEF and shows promise as an effective alternative for the treatment of MUI.

Trial Registration: clinicaltrials.gov Identifier: NCT02047032.
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http://dx.doi.org/10.1016/j.mayocp.2018.07.021DOI Listing
January 2019

TSLP promotes asthmatic airway remodeling via p38-STAT3 signaling pathway in human lung fibroblast.

Exp Lung Res 2018 08 14;44(6):288-301. Epub 2018 Nov 14.

a Department of Pulmonary Diseases , Qilu Hospital, Shandong University , Jinan , Shandong , People's Republic of China.

Purpose: Thymic stromal lymphopoietin (TSLP) acts as a critical cytokine involved in asthmatic airway remodeling. Our study aimed to characterize the crosstalk between airway epithelial cells and fibroblasts regulated by TSLP through the signaling pathways of Mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3).

Materials And Methods: Human biopsy specimens and lung tissues from mice were stained with hematoxylin and eosin (H&E) and immunohistochemistry. Human lung fibroblasts were stimulated with human recombinant TSLP. The protein expression of phosphorylation of STAT3 (p-STAT3) and phosphorylation of MAPK as well as the expression of collagen I and alpha-smooth muscle actin (α-SMA) were detected by Western blotting and immunofluorescence. Co-culture was performed to detect the influence of TSLP secreted by airway epithelial cells on fibroblasts. An ovalbumin (OVA)-induced asthmatic murine model was established with or without intraperitoneal injection of SB203580 (inhibitor of p-38). Protein expression in lung tissue was detected by immunohistochemistry and western blotting.

Result: TSLP could activate MAPK in HLF-1. SB203580 could inhibit the activation of p38, attenuate phosphorylation of STAT3, and decrease the expression of collagen I and α-SMA consequently in human fibroblasts. Co-culture demonstrated that TSLP secreted by epithelial cells could promote the expression of collagen I and α-SMA and aggravates airway remodeling in fibroblasts. In vivo, expression of TSLP, collagen I, α-SMA, p-p38 and p-STAT3 was upregulated in airway tissue of OVA-challenged mice and downregulated in mice which were treated by SB203580. The tissue staining showed that airway structure change was attenuated by SB203580 compared with OVA challenged mice as well.

Conclusions: TSLP might promote asthmatic airway remodeling via p38 MAPK-STAT3 axis activation and the crosstalk between airway epithelial cells and fibroblasts could aggravate remodeling. Blockade of p38 could alleviate airway remodeling which might provide a new therapeutic target for asthma.
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http://dx.doi.org/10.1080/01902148.2018.1536175DOI Listing
August 2018

The Function of in Airway Epithelial Cell Senescence in a Rat COPD Model.

Can Respir J 2018 1;2018:6080348. Epub 2018 Apr 1.

Department of Respiratory Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.

() seems to be able to alleviate airway epithelial cell senescence in chronic obstructive pulmonary disease (COPD). The objective of the study is to evaluate the effect of on airway epithelial senescence in the COPD model both in vitro and in vivo. We observed the expression of P16 and P21 in the airway epithelia of 30 patients with COPD. The optimal concentration of and exposure time of the cigarette smoke extract (CSE) were determined in vitro, and senescence-associated -galactosidase (SA--gal) and 5-bromodeoxyuridine (BrdU) were used to evaluate the senescence and proliferation of human bronchial epithelial (16HBE) cells pretreated with by staining kits. COPD model rats were treated with at various concentrations to determine the changes in P16 and P21 expression in airway epithelial tissues. It was found that the expression levels of P16 and P21 were higher in the airway epithelia of COPD patients than those in the control group based on immunohistochemical staining, real-time quantitative PCR, and western blotting. The CSE could induce 16HBE cell senescence, and could alleviate CSE-induced senescence and promote the proliferation of 16HBE cells. The expression levels of P16 and P21 were also higher in the airway epithelia of COPD model rats; however, the levels of P16 and P21 in the groups treated with all concentrations of were obviously lower than those in the COPD model group based on real-time quantitative PCR and western blotting. In conclusion, the CSE can induce airway epithelium senescence, and can inhibit CSE-induced cellular senescence, both in vitro and in vivo.
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http://dx.doi.org/10.1155/2018/6080348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902013PMC
April 2019

Y-chromosome polymorphisms of the domestic Bactrian camel in China.

J Genet 2018 Mar;97(1):3-10

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People's Republic of China.

Single-nucleotide polymorphisms (SNPs), microsatellites and copy number variation (CNV) were studied on the Y chromosome to understand the paternal origin and phylogenetic relationships for resource protection, rational development and utilization of the domestic Bactrian camel in China. Our sample set consisted of 94 Chinese domestic Bactrian camels from four regions (Inner Mongolia, Gansu, Qinghai and Xinjiang), we screened 29 Y-chromosome-specific loci for SNPs, analysed 40 bovine-derived microsatellite loci and measured CNVs of HSFY and SRY through Sanger sequencing, automated fluorescence-based microsatellite analysis and quantitative real-time PCR, respectively. A multicopy gene, SRY, was first found, and sequence variation was only detected in SRY in a screen of 29 loci in 13 DNA pools of individual camels. In addition, a TG repeat in the USP9Y gene was identified as the first polymorphic microsatellite in the camel Y chromosome, whereas microsatellite based on bovine sequences were not detected. The frequency of each allele varied among different populations. For the Nanjiang, Hexi and Alashan populations, a 243-bp allele was found. For the Sunite population, 241-bp, 243-bp and 247-bp alleles were detected, and the frequencies of these alleles were 22.2%, 44.5% and 33.3%, respectively; 241-bp and 243-bp alleles were found in other populations. Finally, CNVs in two Y-chromosomal genes were detected; CNV for HSFY and SRY ranged from 1 to 3 and from 1 to 9, respectively.
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March 2018

inhibits airway remodeling in rats with chronic obstructive pulmonary disease.

Exp Ther Med 2018 Mar 19;15(3):2731-2738. Epub 2018 Jan 19.

Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.

is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of s on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated. treatment significantly ameliorated airway wall thickening, involving collagen deposition, airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in model rats with COPD. Additionally, administration in rats with COPD reduced inflammatory cell accumulation and decreased inflammatory cytokine production, including tumor necrosis factor-α, interleukin-8 and transforming growth factor (TGF)-β1 in bronchoalveolar lavage fluid. Meanwhile, the increased levels of α-smooth muscle actin and collagen I in the COPD group were also markedly decreased by treatment. Furthermore, compared with untreated rats with COPD, reduced the expression level of phosphorylated (p)-Smad2, p-Smad3, TGF-β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD. These results indicated that treatment with may be a useful approach for COPD therapy.
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http://dx.doi.org/10.3892/etm.2018.5777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795554PMC
March 2018

[Discussion on the acupuncture and moxibustion thoughts of diagnosis and treatment for secondary dysmenorrhea of adenomyosis on the basis of disease location and pathogenesis].

Zhongguo Zhen Jiu 2017 Oct;37(10):1108-12

Department of Acupuncture and Moxibustion, Dongzhimen Hospital of Beijing University of CM, Beijing 100700, China.

To discuss the acupuncture and moxibustion thoughts of diagnosis and treatment for secondary dysmenorrhea of adenomyosis on the basis of disease location and pathogenesis. In clinic, we take the "principle, method, prescription, acupoint and technic" as the outline, paying attention to identify disease location and establishing the method of "promoting blood to remove stasis, regulating thoroughfare vessel and conception vessel" on the basis of the pathogenesis of "stasis obstructing uterus, disharmony of thoroughfare vessel and conception vessel". The prescription combines "dredging" with "conditioning", and the emphasis should be different in different periods. In menstrual period, we put emphasis on activating the circulation of and blood as well as clearing meridians to relieve pain and choose the acupoints on the spleen meridian of foot- and experimental points, such as Diji (SP 8), Sanyinjiao (SP 6), Ciliao (BL 32), Shiqizhui (EX-B 8). In the intermenstrual period, we regulate the and blood of thoroughfare vessel and conception vessel, and the function of viscera. The acupoints for the disease root are mainly at spleen meridian of foot- and conception vessel, such as Sanyinjiao (SP 6), Guanyuan (CV 4), Zigong (EX-CA 1), Zusanli (ST 36). And the reinforcing and reducing technic are applied accordingly.
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http://dx.doi.org/10.13703/j.0255-2930.2017.10.022DOI Listing
October 2017

[Analysis on the laws of acupoint selection and therapeutic operations with acupuncture based on the characteristics of postherpetic neuralgia].

Zhongguo Zhen Jiu 2017 Apr;37(4):429-431

Department of Acupuncture and Moxibustion, Dongzhimen Hospital, Beijing University of CM, Beijing 100700, China.

Postherpetic neuralgia is manifested as drastic lingering pain, which seriously impacts the survival quality of patient. In the paper, focusing on the time of postherpetic neuralgia and in association with the characteristics of symptoms such as the location and nature of pain and skin lesion, the etiology, location of sickness, nature of sickness and pathogenesis were differentiated, and the laws of acupoint selection and therapeutic operations were explored in the treatment with acupuncture. Regarding the apparent pain at night, especially during 23:00 to 3:00, Ashi points (Extra) and Jiaji (EX-B 2) were selected in terms of location differentiation. The acupoints on the liver and gallbladder meridians were specially selected and the supplementary acupoints were used according to general symptoms based on syndrome and symptom differentiation to improve the therapeutic effects. Regarding the therapeutic operation, the bloodletting puncture was used in terms of blood stagnation in collaterals. Additionally, the other operations were selected individually, such as filiform needle therapy, fire needling therapy, plum-blossom needle therapy and bleeding and cupping therapy.
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http://dx.doi.org/10.13703/j.0255-2930.2017.04.020DOI Listing
April 2017

[Herbal-partitioned moxibustion for moderate to severe persistent allergic rhinitis with spleen- deficiency syndrome].

Zhongguo Zhen Jiu 2017 Jun;37(6):603-607

Department of Acupuncture-Moxibustion, Dongzhimen Hospital, Beijing University of CM, Beijing 100700, China.

Objective: To explore the clinical efficacy of herbal-partitioned moxibustion on moderate and severe persistent allergic rhinitis (AR) with spleen- deficiency syndrome.

Methods: With prospective case series study method, forty-seven patients of moderate and severe persistent AR with spleen- deficiency syndrome were treated with herbal-partitioned moxibustion at Yintang (GV 29), Shenque (CV 8), Hegu (LI 4) and Zusanli (ST 36), once every two days, three treatments a week, continuously for 8 weeks. The visual analogue scale (VAS), rhinoconjunctivitis quality of life questionnaire (RQLQ) and scores of spleen- deficiency syndrome were recorded before treatment, 2 weeks, 4 weeks and 8 weeks into treatment as well as 4 weeks after treatment; in addition, the improvement rate of each index was compared before and after treatment.

Results: Compared before treatment, the VAS, RQLQ and scores of spleen- deficiency syndrome were significantly reduced 2 weeks, 4 weeks and 8 weeks into treatment as well as 4 weeks after treatment (<0.05, <0.01). The efficacy was gradually increased 2 weeks, 4 weeks and 8 weeks into treatment (all <0.01). On the 8 weeks into treatment, the improved and markedly effective rate was 59.6% (28/47) for VAS, 19.1% (9/47) for RQLQ and 14.9% (7/47) for scores of spleen- deficiency syndrome; the total effective rate was all 85.1% (40/47). Compared with 4 weeks after treatment, there was no significant difference (all >0.05).

Conclusions: The herbal-partitioned moxibustion has superior efficacy for moderate and severe persistent allergic rhinitis with spleen- deficiency syndrome.
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http://dx.doi.org/10.13703/j.0255-2930.2017.06.008DOI Listing
June 2017

Comparison of the Therapeutic Effects of Acupuncture at PC6 and ST36 for Chronic Myocardial Ischemia.

Evid Based Complement Alternat Med 2017 16;2017:7358059. Epub 2017 Aug 16.

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.

We aimed to compare the differences of the effects on chronic myocardial ischemia (MI) of acupuncture at PC6 and ST36. The chronic MI model of minipigs was created by implanting an Ameroid constrictor on the left anterior descending coronary artery (LAD) and then two weeks' acupuncture was stimulated at PC6 or ST36, respectively. The results showed that both acupoints' stimulation decreased the serous cardiac troponin T (cTnT) and ischemia modified albumin (IMA) significantly and improved the ischemic ECG changes. The amplitude of pathological Q wave in the PC6 group decreased more significantly than that of the ST36 group. The cardiovascular magnetic resonance imaging (cMRI) results showed that the decreased left ventricular ejection fraction (LVEF) was not improved obviously in both groups. The left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) enlarged progressively even after acupuncture. The left ventricular wall mass (LVWM) in the ST36 group increased more obviously than that of the PC6 group, which paralleled the decreasing angiotensin II (Ang II) concentration in the plasma. These results suggested that acupuncture at PC6 or ST36 was effective for protecting the myocardium from chronic ischemic injury, and the effect of PC6 seemed to be better.
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http://dx.doi.org/10.1155/2017/7358059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576407PMC
August 2017

The Correlation between FSTL1 Expression and Airway Remodeling in Asthmatics.

Mediators Inflamm 2017 3;2017:7918472. Epub 2017 Aug 3.

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

Background: Asthma is characterized by airway remodeling. Follistatin-like protein 1 (FSTL1) is an extracellular glycoprotein. Recent studies suggest that FSTL1 may participate in the pathogenesis of asthma.

Objectives: To analyze the association between FSTL1 and some parameters and inspect the role of FSTL1 in asthma.

Methods: We examined FSTL1 levels in 32 asthmatics and 25 controls. All subjects enrolled had routine blood tests, spirometry, and impulse oscillometry performed. Additionally, 15 of the 32 asthmatics underwent fibre optic bronchoscopy. Spearman rank analysis was performed to detect the correlation between FSTL1 and other parameters.

Results: Plasma FSTL1 levels were higher in asthmatics (130.762 ± 46.029 ng/mL) than in controls (95.408 ± 33.938 ng/mL) ( = 0.009). Plasma FSTL1 levels were associated with fibrosis levels around the airways (rs = 0.529, = 0.043) and -smooth muscle actin (-SMA) (rs = 0.554, = 0.032). FSTL1 levels in bronchoalveolar lavage fluid were associated with collagen I (rs = 0.536, = 0.040), -SMA (rs = 0.561, = 0.029), fibrosis levels (rs = 0.779, = 0.001), and the thickness of the airway reticular basement membrane (RBM) (rs = 0.660, = 0.007).

Conclusions: FSTL1 levels in asthmatics were linked with increased smooth muscle mass and thickened RBM. FSTL1 may contribute to airway remodeling in asthmatics.
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http://dx.doi.org/10.1155/2017/7918472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560092PMC
May 2018

Effect of Electroacupuncture on Urinary Leakage Among Women With Stress Urinary Incontinence: A Randomized Clinical Trial.

JAMA 2017 06;317(24):2493-2501

Guang'an Men Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Importance: Electroacupuncture involving the lumbosacral region may be effective for women with stress urinary incontinence (SUI), but evidence is limited.

Objective: To assess the effect of electroacupuncture vs sham electroacupuncture for women with SUI.

Design, Setting, And Participants: Multicenter, randomized clinical trial conducted at 12 hospitals in China and enrolling 504 women with SUI between October 2013 and May 2015, with data collection completed in December 2015.

Interventions: Participants were randomly assigned (1:1) to receive 18 sessions (over 6 weeks) of electroacupuncture involving the lumbosacral region (n = 252) or sham electroacupuncture (n = 252) with no skin penetration on sham acupoints.

Main Outcomes And Measures: The primary outcome was change from baseline to week 6 in the amount of urine leakage, measured by the 1-hour pad test. Secondary outcomes included mean 72-hour urinary incontinence episodes measured by a 72-hour bladder diary (72-hour incontinence episodes).

Results: Among the 504 randomized participants (mean [SD] age, 55.3 [8.4] years), 482 completed the study. Mean urine leakage at baseline was 18.4 g for the electroacupuncture group and 19.1 g for the sham electroacupuncture group. Mean 72-hour incontinence episodes were 7.9 for the electroacupuncture group and 7.7 for the sham electroacupuncture group. At week 6, the electroacupuncture group had greater decrease in mean urine leakage (-9.9 g) than the sham electroacupuncture group (-2.6 g) with a mean difference of 7.4 g (95% CI, 4.8 to 10.0; P < .001). During some time periods, the change in the mean 72-hour incontinence episodes from baseline was greater with electroacupuncture than sham electroacupuncture with between-group differences of 1.0 episode in weeks 1 to 6 (95% CI, 0.2-1.7; P = .01), 2.0 episodes in weeks 15 to 18 (95% CI, 1.3-2.7; P < .001), and 2.1 episodes in weeks 27 to 30 (95% CI, 1.3-2.8; P < .001). The incidence of treatment-related adverse events was 1.6% in the electroacupuncture group and 2.0% in the sham electroacupuncture group, and all events were classified as mild.

Conclusions And Relevance: Among women with stress urinary incontinence, treatment with electroacupuncture involving the lumbosacral region, compared with sham electroacupuncture, resulted in less urine leakage after 6 weeks. Further research is needed to understand long-term efficacy and the mechanism of action of this intervention.

Trial Registration: clinicaltrials.gov Identifier: NCT01784172.
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http://dx.doi.org/10.1001/jama.2017.7220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815072PMC
June 2017

Autophagy plays a role in FSTL1-induced epithelial mesenchymal transition and airway remodeling in asthma.

Am J Physiol Lung Cell Mol Physiol 2017 07 4;313(1):L27-L40. Epub 2017 May 4.

Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, China;

Asthma is a chronic disease related to airway hyperresponsiveness and airway remodeling. Airway remodeling is the important reason of refractory asthma and is associated with differentiation of airway epithelia into myofibroblasts via epithelial-mesenchymal transition (EMT) to increase the process of subepithelial fibrosis. There is growing evidence that autophagy modulates remodeling. However, the underlying molecular mechanisms of these effects are still unclear. In this study, we hypothesized that Follistatin-like 1 (FSTL1) promotes EMT and airway remodeling by intensifying autophagy. With the use of transmission electron microscopy (TEM), double-membrane autophagosomes were detected in the airways of patients and mice. More autophagosomes were in patients with asthma and OVA-challenged mice compared with healthy controls. The expression of FSTL1 and beclin-1 was upregulated in the airways of patients with asthma and OVA-challenged mice, accompanied by airway EMT and remodeling. In OVA-challenged mice, the degree of airway remodeling and autophagy was decreased compared with control mice. The effects of FSTL1 on autophagy and EMT were also tested in 16HBE cells in vitro. Additionally, inhibition of autophagy by using LY-294002 and siRNA-ATG5 reduced the FSTL1-induced EMT in 16HBE cells, as measured by E-cadherin, N-cadherin, and vimentin expression. In line herewith, administration of LY-294002 reduced the expression of autophagy, EMT, and airway remodeling markers in FSTL1-challenged WT mice. Taken together, our study suggests that FSTL1 may induce EMT and airway remodeling by activating autophagy. These findings may provide novel avenues for therapeutic research targeting the autophagy and FSTL1 pathway, which may be beneficial to patients with refractory asthma.
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http://dx.doi.org/10.1152/ajplung.00510.2016DOI Listing
July 2017

Immobilization of alkaline polygalacturonate lyase from Bacillus subtilis on the surface of bacterial polyhydroxyalkanoate nano-granules.

Appl Microbiol Biotechnol 2017 Apr 20;101(8):3247-3258. Epub 2017 Jan 20.

Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, Shaanxi, People's Republic of China.

Alkaline polygalacturonate lyase (PGL), one of the pectinolytic enzymes, has been widely used for the bioscouring of cotton fibers, biodegumming, and biopulp production. In our study, PGL from Bacillus subtilis was successfully immobilized on the surface of polyhydroxyalkanoate (PHA) nanogranules by fusing PGL to the N-terminal of PHA synthase from Ralstonia eutropha via a designed linker. The PGL-decorated PHA beads could be simply achieved by recombinant fermentation and consequent centrifugation. The fused PGL occupied 0.985% of the total weight of purified PHA granules, which was identified by mass spectrometer-based quantitative proteomics. The activity of immobilized PGL (184.67 U/mg PGL protein) was a little lower than that of the free PGL (215.93 U/mg PGL protein). The immobilization process did not affect the optimal pH and the optimal temperature of the PGL, but it did enhance the thermostability as well as the pH stability at certain conditions, which will extend the practicability of the immobilized PGL-PHA beads in the alkaline and generally harsh bioscouring process. Furthermore, the immobilized PGL still retained more than 60% of its initial activity after 8 cycles of reuse. Our study provided a novel and promising approach for cost-efficient in vivo PGL immobilization, contributing to wider commercialization of this environmental-friendly biocatalyst.
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http://dx.doi.org/10.1007/s00253-016-8085-4DOI Listing
April 2017

Protective effect of suppressing STAT3 activity in LPS-induced acute lung injury.

Am J Physiol Lung Cell Mol Physiol 2016 11 16;311(5):L868-L880. Epub 2016 Sep 16.

Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama;

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are diseases with high mortality. Macrophages and neutrophils are responsible for inflammatory responses in ALI and ARDS, which are characterized by excessive production of proinflammatory mediators in bronchoalveolar lavage fluid (BALF) and plasma. Aberrant activation of the JAK/STAT pathway is critical for persistent inflammation in many conditions such as infection and autoimmunity. Given the importance of the STAT3 transcription factor in activating macrophages and neutrophils and augmenting inflammation, we investigated the therapeutic potential of inhibiting STAT3 activity using the small-molecule STAT3 inhibitor, LLL12. Our results demonstrate that LPS induces STAT3 activation in macrophages in vitro and in CD45CD11b cells from BALF in the LPS-induced ALI model in vivo. LLL12 treatment inhibits LPS-induced lung inflammation in the ALI model, which is accompanied by suppression of LPS-induced STAT3 activation and an inhibition of macrophage and inflammatory cell infiltration in lung and BALF. LLL12 treatment also suppresses expression of proinflammatory genes including IL-1β, IL-6, TNF-α, iNOS, CCL2, and MHC class II in macrophages and inflammatory cells from BALF and serum as determined by ELISA. Furthermore, hyperactivation of STAT3 in LysMCre-SOCS3 mice accelerates the severity of inflammation in the ALI model. Both pre- and post-LPS treatment with LLL12 decrease LPS-induced inflammatory responses in mice with ALI. Importantly, LLL12 treatment attenuates STAT3 phosphorylation in human peripheral blood mononuclear cells induced by plasma from patients with ARDS, which suggests the feasibility of targeting the STAT3 pathway therapeutically for patients with ALI and ARDS.
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http://dx.doi.org/10.1152/ajplung.00281.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130536PMC
November 2016