Publications by authors named "Zhi-Jun Li"

149 Publications

Three-dimensional digital measurement of the facet joint in normal and lumbar intervertebral disc herniation aged 13-18 years.

Asian J Surg 2021 Jun 19. Epub 2021 Jun 19.

Department of Physiatry, Changzhi People's Hospital, Changzhi, 046000, PR China. Electronic address:

Background: Lumbar facet joint is an important element of spinal "three-joint complex". Whether there is a relationship between strange structure of facet joint and adolescent lumbar disc herniation (ALDH) is nonetheless controversial, and the current research is mainly centered on adults.

Objective: To find out the normal lumbar facet joints between 13 and 18 years old to provide anatomical basis for early diagnosis and therapy of lumbar disc herniation.

Methods: CT imaging information of 32 sufferers with lumbar disc herniation aged from 13 to 18 years old in Inner Mongolia have been collected as the ALDH group, and 62 wholesome subjects in the equal period had been chosen as the normal group. Uncooked records of continuous scanning lumbar tomography pix were imported into MIMICS 21.0 for evaluation and size in DICOM format. The parameters include facet joint height, facet joint width, et al.

Results: 1. The left and right transverse angle of LS segment in the ALDH group were (52.41 ± 9.2) ° and (55.99 ± 10.91) ° (P < 0.05), and the differences were statistically significant. The right side is larger than the left side. 2. Facet joint thickness in L-L segment of the normal group was significantly higher than that of male (1.63 ± 0.32) mm than that of female (1.38 ± 0.25) mm; In 16-18 years old group, comparison of facet joint cross-sectional area was statistically significant (22.1 ± 3.04) mm in male than (18.92 ± 3.71) mm in female. 3. In comparison between normal and ALDH group, there was significant difference in L transverse angle (P < 0.05), L facet joint height and facet joint thickness (P < 0.05), LS facet joint thickness and transverse angle (P < 0.05).

Conclusion: When ALDH occurs in the LS segment, there is a substantial difference between the left and right sides of the transverse angle, and there is a difference in the thickness and the facet joint cross-sectional area between males and females, which is generally larger in males than in females. Facet joint height is larger, transverse angle of left and right is asymmetric, inferior articular process is larger, and facet joint thickness is smaller can indicate that lumbar disc herniation is effortless to occur.
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http://dx.doi.org/10.1016/j.asjsur.2021.05.028DOI Listing
June 2021

Zoledronic Acid in Osteoporotic Vertebral Compression Fractures Treated With Percutaneous Kyphoplasty: A Meta-Analysis.

Front Surg 2021 21;8:668551. Epub 2021 May 21.

Department of Traumatic Orthopedics, Tianjin Hospital, Tianjin, China.

We performed a meta-analysis to evaluate the efficacy and safety of zoledronic acid combined with percutaneous kyphoplasty (PKP) in treating osteoporotic vertebral compression fractures (OVCFs). Eligible scientific articles published prior to July 2020 were retrieved from the PubMed, Springer, ScienceDirect, and Cochrane Library databases. The statistical analysis was performed with RevMan 5.1. Three randomized controlled trials (RCTs) and 2 non-RCTs met the inclusion criteria. The present meta-analysis revealed that zoledronic acid combined with PKP is associated with a higher BMD, a better quality of life, less severe low back pain, and fewer additional vertebral body fractures than is percutaneous vertebral augmentation alone. Compared with PKP only, zoledronic acid combined with percutaneous vertebral augmentation is beneficial for OVCFs.
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http://dx.doi.org/10.3389/fsurg.2021.668551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176012PMC
May 2021

Comparison between Zip-Type Skin Closure Device and Staple for Total Knee Arthroplasty: A Meta-Analysis.

Biomed Res Int 2021 13;2021:6670064. Epub 2021 May 13.

Department of Orthopedics, Tianjin Hospital, No. 406, Jiefang Nan Road, Tianjin, China 300211.

Purpose: To compare the efficacy and safety of zip-type skin closure device (SCD) and staple in total knee arthroplasty (TKA).

Methods: Potential academic articles were identified from PubMed, Springer, ScienceDirect, and Cochrane Library from the inception of electronic databases to July 2020. The statistical analyses were performed with RevMan 5.1.

Results: One randomized controlled trial (RCT) and 5 non-RCTs met the inclusion criteria. Present meta-analysis reveals that SCD is associated with lower wound pain score, scar score, and readmission compared with a staple. No significant differences are identified in terms of wound total complications, dehiscence, blisters, and infection.

Conclusions: Comparing with a staple, zip-type SCD is a less painful skin closure method with fewer medical cost undergoing TKA.
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http://dx.doi.org/10.1155/2021/6670064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137286PMC
May 2021

Complete chloroplast genome sequence of (Leguminosae).

Mitochondrial DNA B Resour 2021 Feb 8;6(2):399-401. Epub 2021 Feb 8.

College of Life Sciences, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, South-Central University for Nationalities, Wuhan, China.

(Pall.) DC. is a perennial herbaceous plant belonging to the genus , Galegeae, Leguminosae, and is mainly distributed in dry areas in Central Asia and Northwest China. The complete chloroplast genome with a total size of 123,300 bp was reported in this study. Further annotation revealed the chloroplast genome contains 109 genes, including 76 protein coding genes, 29 tRNA genes, and four rRNA genes. A total of 107 simple sequence repeats (SSRs) from mononucleotide to hexa-nucleotide repeat motif were identified in the chloroplast genome. This information will be useful for study on the evolution and genetic diversity of in the future.
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http://dx.doi.org/10.1080/23802359.2020.1869618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872530PMC
February 2021

Complete chloroplast genome sequence of from PacBio Sequel platform.

Mitochondrial DNA B Resour 2021 Feb 8;6(2):378-380. Epub 2021 Feb 8.

Xinjiang Production & Construction Corps Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin, Tarim University, Alar, PR China.

Oliv., one of tall arbors growing in desert areas, has great stress resistance. The complete chloroplast genome was reported in this study using the PacBio Sequel Platform. The chloroplast genome with a total size of 157,881 bp consisted of two inverted repeats (IRs) (27,666 bp) separated by a large single-copy region (85,906 bp) and a small single-copy region (16,643 bp). Further annotation revealed the chloroplast genome contains 111 genes, including 77 protein-coding genes, 30 genes, and four genes. The information of the chloroplast genome will be useful for study on the evolution of in the future.
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http://dx.doi.org/10.1080/23802359.2020.1869605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872525PMC
February 2021

Complete chloroplast genome sequence of Schrenk from PacBio Sequel II Platform.

Mitochondrial DNA B Resour 2020 Sep 29;5(3):3452-3454. Epub 2020 Sep 29.

Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin Xinjiang Production and Construction Corps, Tarim University, Alar, China.

Schrenk plays an important role on ecological services in desert areas. The complete chloroplast genome was reported in this study using the PacBio Sequel II Platform. The chloroplast genome with a total size of 157,856 bp consists of two inverted repeats (IR, 27,673 bp) separated by a large single-copy region (LSC, 85,867 bp) and a small single-copy region (SSC, 16,645 bp). Further annotation revealed the chloroplast genome contains 111 genes, including 78 protein-coding genes, 29 tRNA genes, and 4 rRNA genes. A total of 151 simple sequence repeats (SSRs) were identified in the chloroplast genome. This information will be useful for study on the evolution and genetic diversity of in the future.
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http://dx.doi.org/10.1080/23802359.2020.1824593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782250PMC
September 2020

Osteochondroma of the pubic symphysis causing hematuria: a case report and literature review.

BMC Urol 2021 Jan 6;21(1). Epub 2021 Jan 6.

Department of Orthopaedic, Tianjin Medical University General Hospital, Anshan Road No. 154, Heping District, Tianjin, 300052, China.

Background: Osteochondroma is the most common benign bone neoplasm and is sometimes referred to as osteocartilaginous exostosis. The symptoms caused by osteochondroma are rare, especially the urogenital complications. Therefore, this tumour is sometimes misdiagnosed.

Case Presentation: This report described a 70-year-old woman with hematuria who was initially misdiagnosed with a bladder tumour in the outpatient department by a urologist. However, during cystoscopy, we found that the mass did not resemble a bladder tumor. Multidisciplinary approach with careful analysis of the imaging data suggested the diagnosis of osteochondroma. Open surgical excision of the mass was done and histology confirmed the diagnosis of benign osteochondroma. After 6 months of follow-up, the patient was still asymptomatic.

Conclusions: This case illustrates that hematuria is caused by not only urogenital disease but also osteochondroma. We present this case to draw the attention of clinicians to osteochondroma of the pubic symphysis.
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http://dx.doi.org/10.1186/s12894-020-00770-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789616PMC
January 2021

Rapid Onset of Efficacy of Baricitinib in Chinese Patients with Moderate to Severe Rheumatoid Arthritis: Results from Study RA-BALANCE.

Adv Ther 2021 01 25;38(1):772-781. Epub 2020 Nov 25.

Eli Lilly and Company, Shanghai, China.

Introduction: Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate.

Methods: This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4 mg once daily compared with placebo, based on data from a phase 3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks 1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4 weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively.

Results: Statistically significant (p ≤ 0.05) improvements were observed as early as week 1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week 4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24 weeks.

Conclusions: Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE.

Trial Registration: ClinicalTrials.gov identifier, NCT02265705.
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http://dx.doi.org/10.1007/s12325-020-01572-yDOI Listing
January 2021

Microstructure of the hyoid bone based on micro-computed tomography findings.

Medicine (Baltimore) 2020 Oct;99(44):e22246

Human Anatomy Teaching and Research Section (Digital Medical Center), Inner Mongolia Medical University Basic Medical College.

In this study, micro-CT was used to observe the microscopic anatomy of the hyoid bone, examine the variation of the trabecular bone inside the hyoid bone, and investigate the internal structure of the hyoid bone.A total of 22 hyoid bones were scanned using micro-CT. The changes in the internal bone trabeculae were assessed with 3D reconstructions, and the fine anatomical structure of the hyoid bone was further analyzed.Micro-CT images showed the microstructure of various parts of the hyoid bone. There were significant differences in total volume, bone volume, bone area, bone density, and volume fraction between the body and greater horns of the hyoid bone (P < .05), but no significant differences in the ratio of bone area/volume and bone surface density were found between the body and greater horns of the hyoid bone (P > .05). In addition, significant differences in the trabecular bone measurements, bone trabecular connectivity, and Euler number were found between the body and greater horns of the hyoid bone (P < .05). Other parameters, including bone trabecular thickness, number of trabecular bones, bone trabecular structure model index, and anisotropy of bone trabeculae, did not differ between the body and greater horns of the hyoid bone (P > .05). There was noticeably ossified healing at the joint between the body and greater horns of the hyoid bone.Micro-CT can adequately display the internal structure of the hyoid bone. The identified bone structure may help clarify the physiological function of the hyoid bone. The present findings provide a theoretical basis for further studies aimed at pathological changes due to hyoid injury in clinical and forensic medicine.
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http://dx.doi.org/10.1097/MD.0000000000022246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598853PMC
October 2020

Efficacy and Safety of Baricitinib in Chinese Rheumatoid Arthritis Patients and the Subgroup Analyses: Results from Study RA-BALANCE.

Rheumatol Ther 2020 Dec 2;7(4):851-866. Epub 2020 Sep 2.

Peking University People's Hospital, Beijing, China.

Introduction: Baricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2, which has demonstrated significant efficacy in patients with moderately to severely active rheumatoid arthritis (RA). This analysis aims to describe the efficacy and safety of baricitinib in Chinese RA patients with an inadequate response to methotrexate (MTX-IR), and to analyze the effects of baseline characteristics on the efficacy of baricitinib treatment.

Methods: In this 52-week, randomized, double-blind, placebo-controlled study, 231 Chinese patients with moderately to severely active RA who had MTX-IR were randomly assigned to placebo (n = 115) or baricitinib 4 mg once daily (n = 116). The primary endpoint was American College of Rheumatology 20% (ACR20) response at week 12. Other efficacy measures included ACR50, ACR70, Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, patient's assessment of pain, Disease Activity Score in 28 joints using high-sensitivity C-reactive protein, remission and low disease activity rates according to Simplified Disease Activity Index or Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, and mean duration and severity of morning joint stiffness, worst tiredness and worst joint pain were analyzed. Additionally, subgroup analyses were performed across baseline characteristics.

Results: Statistically significant improvement in ACR20 response was achieved with baricitinib at week 12 (53.4 vs. 22.6%, p = 0.001) in Chinese patients, compared to placebo. Most of the secondary objectives were met with statistically significant improvements. Efficacy of baricitinib was irrespective of patient demographics and baseline characteristics. Safety events were similar between the baricitinib and placebo groups.

Conclusions: The efficacy of baricitinib 4 mg in Chinese patients with moderately to severely active RA and prior MTX-IR was clinically significant compared to placebo regardless of baseline characteristics. Baricitinib was well tolerated with an acceptable safety profile during the full study period.

Trial Registration: NCT02265705.
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http://dx.doi.org/10.1007/s40744-020-00231-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695798PMC
December 2020

Kimura disease with a history of Budd-Chiari syndrome: a case report.

Chin Med J (Engl) 2020 Oct;133(19):2392-2394

Department of Rheumatology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China.

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http://dx.doi.org/10.1097/CM9.0000000000001008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546835PMC
October 2020

Ribosome Binding Protein 1 Correlates with Prognosis and Cell Proliferation in Bladder Cancer.

Onco Targets Ther 2020 7;13:6699-6707. Epub 2020 Jul 7.

The First Affiliated Hospital and College of Clinical Medicineof Henan University of Science and Technology, Luoyang, Henan 471003, People's Republic of China.

Introduction: Ribosome binding protein 1 (RRBP1) is reported to be correlated with tumor formation and progression. However, the role of RRBP1 in bladder cancer is unclear. In this study, we aimed to investigate the expression of RRBP1 and its influence on cell proliferation in bladder cancer.

Methods: Quantification real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to detect the expression levels of RRBP1 in 138 bladder cancer and matched adjacent normal bladder tissues. Then, the clinical significance of RRBP1 in bladder cancer was evaluated. The effect of RRBP1 on cell proliferation and its potential mechanism were further explored.

Results: Results show that the mRNA levels of RRBP1 in bladder cancer were significantly higher compared with those in normal tissues (< 0.001). IHC results show the high-expression rate of RRBP1 in bladder cancer was 68.8%, which was significantly greater than those in normal tissues (40.6%, < 0.001). RRBP1 high-expression was significantly associated with differentiation, T stage and lymph node metastasis in bladder cancer (< 0.05). The overall survival time of patients with RRBP1 high-expression was significantly reduced compared to those with RRBP1 low-expression. Moreover, RRBP1 overexpression significantly promoted cell proliferation, which was correlated with Smad1/Smad3/TGF-β1 signal pathway.

Conclusion: RRBP1 high-expression correlates with prognosis and promotes cell proliferation in bladder cancer, which could be a potential biomarker.
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http://dx.doi.org/10.2147/OTT.S252043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367924PMC
July 2020

Decoupling and Coupling of the Host-Dopant Interaction by Manipulating Dopant Movement in Core/Shell Quantum Dots.

J Phys Chem Lett 2020 Aug 14;11(15):5992-5999. Epub 2020 Jul 14.

Department of Chemistry, Syracuse University, Syracuse, New York 13244, United States.

Doping through the incorporation of transition metal ions allows for the emergence of new optical, electrical, and magnetic properties in quantum dots (QDs). While dopants can be introduced into QDs through many synthetic methods, the control of dopant location and host-dopant (H-D) coupling through directional dopant movement is still largely unexplored. In this work, we have studied dopant behaviors in Mn:CdS/ZnS core/shell QDs and found that dopant transport behavior is very sensitive to the temperature and microenvironments within the QDs. The migration of Mn toward the alloyed interface of the core/shell QDs, below a temperature boundary () at ∼200 °C, weakens the H-D interactions. At temperatures higher than the , however, dopant ejection and global alloying of CdS/ZnS QDs can occur, leading to stronger H-D coupling. The behavior of incorporated dopants inside QDs is fundamentally important for understanding doping mechanisms and the host-dopant interaction-dependent properties of doped nanomaterials.
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http://dx.doi.org/10.1021/acs.jpclett.0c01861DOI Listing
August 2020

Using internet search data to explore the global public concerns in ankylosing spondylitis.

Postgrad Med J 2021 Feb 24;97(1144):93-96. Epub 2020 Feb 24.

Department of Rheumatology and Immunology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China

Objective: This study explored the changes of global public interest in internet search of ankylosing spondylitis (AS) based on Google Trends (GT) data, in order to reflect the characteristics of AS itself.

Methods: GT was used to obtain the search popularity scores of the term 'AS' on a global scale, between January 2004 and December 2018, under the 'health' classification. Based on the global search data of AS provided by GT, the cosinor analysis was used to test whether there was seasonality in AS.

Results: In general, AS related search volume demonstrated a decreasing trend from January 2004 to December 2014 and then remain stable from January 2015 to December 2018. No obvious seasonal variations were detected in AS related search volume (amplitude=1.54; phase: month=3.9; low point: month=9.9; p>0.025), which peaked in April and bottomed out in October. The top 17 rising topics were adalimumab, spondylolisthesis, Morbus, Vladimir Mikhailovich Bekhterev, autoimmune disease, rheumatoid arthritis, ankylosis, HLA- B27 positive, Crohn's disease, rheumatology, spondylosis, arthritis, uveitis, rheumatism, sacroiliac, psoriatic arthritis and spondylitis.

Conclusions: Globally, there is no significant seasonal variation in GT for AS. The top fast-growing topics related to AS may be beneficial for doctors to provide targeted health education of the disease to patients and their families.
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http://dx.doi.org/10.1136/postgradmedj-2019-137407DOI Listing
February 2021

Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis.

Chin Med J (Engl) 2019 Dec;132(24):2899-2904

Department of Rheumatology and Immunology, Hebei General Hospital, Shijiazhuang, Hebei 050051, China.

Background: Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.

Methods: We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.

Results: A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017, 95% confidence interval: 5.803-55.938; P < 0.001).

Conclusion: As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.
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http://dx.doi.org/10.1097/CM9.0000000000000570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964957PMC
December 2019

Insights into the Effect of Reactive Oxygen Species Regulation on Photocatalytic Performance via Construction of a Metal-Semiconductor Heterojunction.

J Nanosci Nanotechnol 2020 06;20(6):3478-3485

Shandong Institute of Scientific and Technical Information, Jinan, 250101, China.

Reactive oxygen species (ROS), as primary intermediates formed during photocatalytic reactions, are critical for a photocatalyst to realize high activity. The major objective of this study was to investigate the regulation of ROS involved in the photocatalytic degradation process via constructing a typical metal-semiconductor hybrid heterojunction using Ag nanoparticles/anatase TiO₂ as an example. Based on radical capturing, electron paramagnetic resonance, and electron spin resonance experiments, an increase in the available ROS can be achieved in the Ag/TiO₂ heterojunction due to the fast separation of photogenerated carriers. In addition, due to the change in the electron transfer pathway, superoxide radicals (·O₂) are the dominant reactive species responsible for dye degradation using Ag/TiO₂ rather than hydroxyl radicals (·OH) as the main free radicals in pristine TiO₂. This study offers fresh insight into the regulation of ROS in photodegradation via the construction of a Ag/TiO₂ heterojunction.
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http://dx.doi.org/10.1166/jnn.2020.17405DOI Listing
June 2020

Dual-Functionalized Fluorescent Cationic Organic Network: Highly Efficient Detection and Removal of Dichromate from Water.

ACS Appl Mater Interfaces 2019 Dec 26;11(49):46197-46204. Epub 2019 Nov 26.

College of Chemistry and Chemical Engineering , Longdong University , Qingyang , Gansu 745000 , P. R. China.

Dichromate is a widespread contaminant in wastewater, threatening the health of humans and other organisms. Therefore, effective detection and removal of dichromate from water is of great significance. Herein, a tetraphenylethylene functionalized cationic organic network () was constructed via a facile quaternization reaction. was successfully integrated with both detection and removal functionalities toward dichromate. On the one hand, benefiting from the strong fluorescence, was employed as a chemosensor, it could efficiently and selectively probe CrO in water with "turn-off" fluorescent response. On the other hand, the cationic skeleton and free anions inside framework make an excellent adsorbent for CrO, it could capture CrO from water with rapid kinetics and high capacity. The kinetic constant for adsorption of CrO can reach up to 1.784 g mg min, while the capacity is determined as 325 mg g. Furthermore, displayed good recyclability and can be reused for at least 5 cycles. Therefore, can serve as an ideal candidate not only in detection but also in removal of CrO in water medium.
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http://dx.doi.org/10.1021/acsami.9b17074DOI Listing
December 2019

Association of Urinary Plasminogen-Plasmin with Edema and Epithelial Sodium Channel Activation in Patients with Nephrotic Syndrome.

Am J Nephrol 2019 3;50(2):92-104. Epub 2019 Jul 3.

Department of Nephrology, The Central Hospital of Putuo District, Shanghai, China,

Background: Previous animal experiments and small human studies suggest that urinary plasmin can activate the epithelial sodium channel (ENaC) and contribute to sodium retention in nephrotic syndrome (NS), but this however is not well studied in clinical settings, and its relevance to edema formation is not well characterized in humans. We have investigated the association between urinary plasmin and clinical phenotypes in a large group of patients with NS from multiple etiologies, aiming to assess the role of urinary plasmin in sodium handling and edema formation.

Methods: Two hundred and three NS patients with urine and blood samples were divided into mild and severe symptom groups based on their edema severity. Twenty six of them had serial samples collected during the course of immunosuppressive therapy. The plasminogen-plasmin level and other key parameters were assayed, and their association with clinical manifestations were analyzed.

Results: One hundred and one of the 203 patients had renal biopsies performed, the results of which had included all the common types of primary NS and various types of secondary NS. Quantitative comparison and multivariate logistic regression analysis identified urinary plasminogen-plasmin to creatinine ratio (uPLG-PL/C), serum albumin, D-Dimer, and cardiac dysfunction history, but not albuminuria or 24-h urine protein, as independent risk factors for edema (p < 0.01). In patients who were treated and had serial samples, a decrease in uPLG-PL/C was identified as an independent influencing factor of edema remission (p < 0.01). Finally, the urinary fractional excretion of sodium (FENa) in patients was inversely correlated with the fractional excretion of potassium (FEK; p< 0.001), and FEK/FENa ratio was positively correlated with uPLG-PL/C (p < 0.001), suggesting a close association between uPLG-PL and ENaC activation.

Conclusions: Our study identifies uPLG-PL abundance as an independent influencing factor of edema in adult NS patients, and supports the conclusion that plasmin-dependent ENaC activation is an important pathophysiological mechanism of sodium retention and edema formation in humans with NS.
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http://dx.doi.org/10.1159/000501059DOI Listing
August 2020

NADPH Oxidase Isoforms Are Involved in Glucocorticoid-Induced Preosteoblast Apoptosis.

Oxid Med Cell Longev 2019 27;2019:9192413. Epub 2019 Mar 27.

The Department of Orthopedics, Tianjin Medical University General Hospital, Heping District, Tianjin, China.

Oxidative stress induced by long-term glucocorticoid (GC) use weakens the repair capacity of bone tissue. Nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase (NOX) is a superoxide-generating enzyme that plays an important role in regulating bone metabolism. To clarify the role of nonphagocytic NOX isoforms in osteoblast reactive oxygen species (ROS) generation and apoptosis, dexamethasone was used to establish a high-dose GC environment . A dose-dependent increase in intracellular ROS generation was demonstrated, which was accompanied by increased osteoblastic MC3T3-E1 cell apoptosis. Addition of the ROS inhibitor NAC (-acetyl-L-cysteine) or NOX inhibitor DPI (diphenyleneiodonium) reversed this effect, indicating that NOX-derived ROS can induce osteoblast apoptosis under high-dose dexamethasone stimulation. NOX1, NOX2, and NOX4 are NOX homologs recently identified in bone tissue. To clarify the NOX isoforms that play a role in osteoblast ROS generation, , , and mRNA expression and NOX2 and NOX4 protein expression were analyzed. and mRNA expression was elevated in a dose-dependent manner after culture in 100 nM, 250 nM, 500 nM, or 1000 nM dexamethasone, and the increased expression of NOX1 mRNA was more significant compared with NOX4 mRNA. Small interfering RNAs (siRNAs) were used to confirm the role of NOX1 and NOX4 in ROS generation. To clarify the signaling pathway in ROS-induced osteoblast apoptosis, mitogen-activated protein kinase (MAPK) signaling molecules were analyzed. Phosphorylated ASK1 and p38 levels were significantly higher in the 1000 nM dexamethasone group, which NAC or DPI markedly attenuated. However, the total mRNA and protein levels of ASK1 and p38 between the dexamethasone group and control were not significantly different. This is related to ROS regulating the posttranslational modification of ASK1 and p38 in MC3T3-E1 cell apoptosis. Altogether, NOX1- and NOX4-derived ROS plays a pivotal role in high-dose dexamethasone-induced preosteoblast apoptosis by increasing phosphorylated ASK1 and p38 and may be an important mechanism in steroid-induced avascular necrosis of the femoral head (SANFH).
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http://dx.doi.org/10.1155/2019/9192413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458927PMC
August 2019

Susceptible Surface Sulfide Regulates Catalytic Activity of CdSe Quantum Dots for Hydrogen Photogeneration.

Adv Mater 2019 Feb 20;31(7):e1804872. Epub 2018 Dec 20.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Semiconducting quantum dots (QDs) have recently triggered a huge interest in constructing efficient hydrogen production systems. It is well established that a large fraction of surface atoms of QDs need ligands to stabilize and avoid them from aggregating. However, the influence of the surface property of QDs on photocatalysis is rather elusive. Here, the surface regulation of CdSe QDs is investigated by surface sulfide ions (S ) for photocatalytic hydrogen evolution. Structural and spectroscopic study shows that with gradual addition of S , S first grows into the lattice and later works as ligands on the surface of CdSe QDs. In-depth transient spectroscopy reveals that the initial lattice S accelerates electron transfer from QDs to cocatalyst, and the following ligand S mainly facilitates hole transfer from QDs to the sacrificial agent. As a result, a turnover frequency (TOF) of 7950 h can be achieved by the S modified CdSe QDs, fourfold higher than that of original mercaptopropionic acid (MPA) capped CdSe QDs. Clearly, the simple surface S modification of QDs greatly increases the photocatalytic efficiency, which provides subtle methods to design new QD material for advanced photocatalysis.
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http://dx.doi.org/10.1002/adma.201804872DOI Listing
February 2019

Three-dimensional digitizing and anatomic study of lumbar vertebral canal and pedicle in children.

Wideochir Inne Tech Maloinwazyjne 2018 Dec 8;13(4):518-524. Epub 2018 Aug 8.

Teaching and Researching Institute of Human Anatomy, School of Basic Medicine, Hohhot, China.

Introduction: Spinal pedicle screw internal fixation has been widely used in adult spine injury fixation. Due to being in a period of continuous growth and development, the spine of children at different ages shows different characteristics from adults in terms of anatomy, physiological function, and biomechanics. Furthermore, because the pedicle of children is small, has large anatomic variation, and has complex adjacent relationships, the surgical risk is extremely high. How to improve the screwing accuracy is the key to the success of children's pedicle internal fixation. Therefore, applying the concept of digitized and individualized screwing will be of great significance to children's pedicle screwing.

Aim: To investigate the morphologies, development patterns, and aging characteristics of the lumbar vertebral pedicle (LVP) in children aged 6-11 years, and to provide a theoretical basis for screw implantation and related biomechanical studies.

Material And Methods: A total of 60 children aged 6-11 years were selected for the intergroup measurement and statistical analysis of their lumbar diameter, pedicle diameter, screw canal length (SCL), etc.

Results: Generally, the vertebral foramen diameter (ID), sagittal diameter (SD), pedicle width (PW), and SCL as well as the pedicle height (PH) exhibited an increasing trend with age and increasing vertebral sequence among children aged 6-11 years.

Conclusions: By observing the LVP in children using 3D digital reconstruction technology, the morphology of the spinal canal and pedicles at different lumbar segments showed obvious development patterns, and the best treatment protocol should be selected according to the LVP characteristics in clinical applications.
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http://dx.doi.org/10.5114/wiitm.2018.77554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280084PMC
December 2018

The role and clinical significance of programmed cell death- ligand 1 expressed on CD19B-cells and subsets in systemic lupus erythematosus.

Clin Immunol 2019 01 28;198:89-99. Epub 2018 Nov 28.

Department of Rheumatology and immunology, the First Affiliated Hospital to Bengbu Medical college, Bengbu 233004, China. Electronic address:

Background: Programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1)-targeted therapies have enhanced T-cell response and demonstrated efficacy in the treatment of multiple cancers. However, the role and clinical significance of PD-L1 expression on CD19 B-cells and their subsets, with particular reference to systemic lupus erythematosus (SLE), have not yet been studied in detail.

Objective: The present study aimed to investigate PD-L1 expression on CD19+ B-cells and their subsets, in addition to exploring its possible role in Tfh-cell activation and B-cell differentiation in SLE.

Methods: Frequencies of CD19 B-cells, their subsets, PD-L1 and Tfh cells in the peripheral blood of SLE patients and healthy controls (HCs) were determined using cytometry. The clinical data of SLE patients were recorded in detail, and the correlation between their laboratory parameters, clinical parameters and disease activity indices was statistically analyzed. CD19PD-L1B-cells and CD19PD-L1 B-cells were sorted and cultured with a stimulant, following which the supernatants were collected for immunoglobulin G and anti-double stranded DNA detection via enzyme-linked immunosorbent assay.

Results: In SLE patients, CD19B-cells and partial subgroups were enriched in peripheral blood. Also, the observed increase in the frequency of CD19PD-L1B-cells was significantly associated with a higher disease activity index. An in vitro culture test demonstrated that the amounts of anti-dsDNA and immunoglobulin G secreted by the CD19PD-L1B-cells of SLE patients and HCs were vastly different. In addition, a strong correlation existed between the frequencies of CD19PD-L1B-cells and defined Tfh cells of SLE patients.

Conclusion: This study demonstrated that the expression of CD19PD-L1B-cells in the peripheral blood of SLE patients was abnormal, and that disease-related laboratory parameters and clinical indicators were correlated. CD19PD-L1B-cells were enriched and played a critical role in activating the pathogenic T-cell and B-cell responses in patients with SLE.
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http://dx.doi.org/10.1016/j.clim.2018.11.015DOI Listing
January 2019

Intramedullary versus extramedullary alignment guides on total knee arthroplasty: a meta-analysis.

J Comp Eff Res 2018 12 28;7(12):1181-1193. Epub 2018 Nov 28.

Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, PR China.

Aim: A meta-analysis concentrated on the effect of intramedullary and extramedullary systems on total knee arthroplasty.

Method: Potential academic articles were identified from Cochrane Library, Medline, PubMed, Embase, ScienceDirect, CNKI, WanFang, VIP and other databases. The STATA version was used to analyze the pooled data.

Results: There are obvious significant differences in drainage volume and transfusion rate. There was no significant difference in lower limb coronal alignment, coronal and sagittal alignment of the femoral component, operation time, postoperative knee score and complications.

Conclusion: Our meta-analysis shows that the alignment of the extramedullary distal femur osteotomy is as accurate as intramedullary systems. Furthermore, extramedullary distal femur osteotomy without invading the femoral medullary cavity could reduce postoperative bleeding and the transfusion rate. Furthermore, research is required to test the robustness of our findings when more data is available and by undertaking both Bayesian and frequentist methods. When more data are available, the heterogeneity can be further explored through sensitivity analysis, and the available data can be combined to verify the hypothesis.
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http://dx.doi.org/10.2217/cer-2018-0064DOI Listing
December 2018

TRPM7 overexpression enhances the cancer stem cell-like and metastatic phenotypes of lung cancer through modulation of the Hsp90α/uPA/MMP2 signaling pathway.

BMC Cancer 2018 Nov 26;18(1):1167. Epub 2018 Nov 26.

Department of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qing Chun Road, Zhejiang Province, 310016, Hangzhou, China.

Background: Waixenicin A, a bioactive extract of soft coral Sarcothelia edmondsoni, has been shown to be anti-neoplastic. However, its mechanisms of action remain unclear. Cancer stem cells (CSCs) and associated stemness factors are implicated in lung cancer. Here, we investigated the role of Waixenicin A on CSCs-like and metastatic lung cancer cells.

Methods: We demonstrated and compared TRPM7 expression in the non-tumor lung tissues or bronchial epithelial 16-HBE cell line. TRPM7 was aberrantly expressed in the cancer tissues and SPCA-1, NCI-H520, SK-MES-1, A549 and 95D cell lines.

Results: Increased TRPM7 expression was associated with enhanced SOX2, KLF4, and CD133, Hsp90α, uPA, and MMP2 expression in lung cancer cells. TRPM7-silencing inhibited epithelial-to-mesenchymal transition (EMT), suppressed stemness markers and phenotypes, concomitantly suppressed Hsp90α/uPA/MMP2 axis. Coincidently, Waixenicin A treatment downregulated TRPM7 and oncogenic markers; Waixenicin A also attenuated the ability of lung cancer cells to form tumorspheres, in vitro. In validation, our clinicopathological analyses showed that a higher TRPM7 expression was positively correlated with the larger tumor size (p = 0.007), positive lymph node metastasis (p = 0.005) and disease grade (p = 0.003).

Conclusions: Through its ability to inhibit Hsp90α/uPA/MMP2 signaling and suppress TRPM7 expression, we showed that Waixenicin A is a potential anticancer therapeutic agent for treating malignant lung cancer.
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http://dx.doi.org/10.1186/s12885-018-5050-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258145PMC
November 2018

Corticosteroids as adjunctive therapy with antibiotics in the treatment of children with septic arthritis: a meta-analysis.

Drug Des Devel Ther 2018 23;12:2277-2284. Epub 2018 Jul 23.

Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, China,

Purpose: We performed a meta-analysis to systematically assess the effect of adjunctive administration of dexamethasone with antibiotic therapy in the clinical course of septic arthritis (SA) in children.

Method: Potential academic articles were identified from the Cochrane Library, Medline, PubMed, Embase, ScienceDirect, and other databases. The time range we retrieved from was from the inception of electronic databases to January 2018. The reference lists of identified studies were manually checked to identify other potentially eligible trials. The STATA version 11.0 (Stata Corporation, College Station, TX, USA) was used to analyze the pooled data.

Results: Three randomized controlled trials, and one retrospective cohort study were included in the meta-analysis. There were significant differences in the days of hospitalization (mean difference [MD] = -4.226, 95% CI: -4.785 to -3.667, =0.001), the days of intravenous antibiotics treatment (MD = -3.593, 95% CI: -4.825 to -2.361, =0.001), the days of oral antibiotics treatment (MD = -1.658, 95% CI: -2.539 to -0.777, =0.001), and the days to normalization of C-reactive protein (MD = -3.075, 95% CI: -3.362 to -2.788, =0.001).

Conclusion: The present meta-analysis base points strongly toward a beneficial effect for corticosteroids in SA. Corticosteroids as adjunctive therapy with antibiotics in the treatment of children with SA could shorten the number of days of hospitalization, the days of intravenous antibiotics treatment, the days of oral antibiotics treatment, and the days to normalization of C-reactive protein. We recommend corticosteroids as adjunctive therapy with antibiotics in the treatment of children with SA.
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http://dx.doi.org/10.2147/DDDT.S163560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061407PMC
January 2019

Incidence and risk factors of postoperative delirium in the elderly patients with hip fracture.

J Orthop Surg Res 2018 Jul 27;13(1):186. Epub 2018 Jul 27.

Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, 300052, People's Republic of China.

Background: To investigate the incidence and related risk factors of delirium in elderly patients with hip fracture.

Methods: This is a retrospective study, performed in a medical center from October 2014 to February 2017, which enrolled all subjects aged over 65 years who were admitted for hip surgeries (hip arthroplasty, proximal femoral nail fixation). Univariate and multivariate logistic analysis was used to determine the incidence and risk factors of delirium. Delirium was assessed according to the Confusion Assessment Method (CAM).

Results: Overall, 19.29% of total 306 patients (mean age 81.9 ± 5.4 years) were identified as delirium. The delirium was significantly associated (p < 0.05) with the factors of age, hospitalization, diabetes, preoperative hematocrit (HCT), perioperative protein consumption, transfusion volume, preoperative leukocyte level, albumin level, American Society of Anesthesiologists (NYHA) classification, American Society of Anesthesiologists (ASA) classification, blood loss, coronary heart disease, and cerebral infarction. Multivariate analysis of the variables confirmed that age (> 75 years old), diabetes, and ASA classification (> 2 level) are the independent risk factors of postoperative delirium (POD). In addition, patients in delirium had prolonged hospitalization and high perioperative albumin infusion.

Conclusion: The elderly patients over the age of 75 years with the history of diabetes or ASA classification > 2 level were at higher risk of POD. Delirium is an important postoperative complication, which had prolonged hospitalization and high perioperative albumin infusion.

Level Of Evidence: III.
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http://dx.doi.org/10.1186/s13018-018-0897-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063011PMC
July 2018

[The Study of Protective Effect of Paeoniflorin on Lung Injury in MRL/lpr Mice].

Sichuan Da Xue Xue Bao Yi Xue Ban 2018 May;49(3):394-398

Department of Histology and Embryology,Bengbu Medical College,Bengbu 233000,China.

Objective: To investigate the protective effects of paeoniflorin on the lung injury in systemic lupus erythematosus with mouse model.

Methods: Ten wild type mice and 40 MRL/lpr mice were used in this study. MRL/lpr mice were randomly assigned to MRL/lpr group,MRL/lpr + dexamethasone (1.5 mg/kg) group,MRL/lpr + paeoniflorin (20 mg/kg) group,and MRL/lpr + paeoniflorin (40 mg/kg). The levels of malondialdehyde (MDA) , superoxide dismutase (SOD) ,catalase (CAT) ,glutathione peroxidase (GSH-Px) in serum were detected. The serum levesl of inflammatory cytokines were measured. Lung pathological changes were determined by HE staining. The protein level of phospho-phosphatidylinositol-3 kinase (P-PI3K),phospho-serine-threonine kinase B(P-Akt) ,phospho-nuclear factor kappa B (P-NF-κB),phospho-inhibitor of nuclear factor kappa Bα (P-IκBα) were detected by Western blot.

Results: Paeoniflorin decreased serum level of MDA and increased the levels of SOD,CAT,GSH-PX,and decreased the levels of inflammatory cytokines. Paeoniflorin improved lung pathological changes and inhibited the protein levels of P-PI3K,P-Akt,P-NF-κBp65,and P-IκBα in the lung tissue of MRL/lpr mice.

Conclusion: Paeoniflorin may be beneficial for the prevention of lung injury in systemic lupus erythematosus.
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May 2018

Establishment of animal model of gastroesophageal reflux disease by per-oral endoscopic tunneling: a preliminary study.

J Thorac Dis 2018 Mar;10(3):1607-1613

Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.

Background: Although a variety of antireflux procedures and medications are used to treat gastroesophageal reflux disease (GERD), reliable large-animal models of GERD that can be used to objectively compare the efficacy of these treatments are lacking. We developed a method to establish large animal models of GERD by endoscopic sphincterotomy to develop an endoscopic treatment for GERD.

Methods: In this study six flesh swine carcasses were used. A full thickness incision was made at the esophageal site 5 cm above the dentate line by per-oral endoscopic tunneling. Esophageal radiography was conducted before and after surgery to observe changes at the site of the lower esophagus 5 cm above the dentate line and in the cardia.

Results: There was no significant change in the diameter of the esophageal site 5 cm above the dentate line before and after surgery, while the cardiac orifice significantly relaxed after surgery and enabled the contrast agent to smoothly travel through. The difference in diameter was statistically significant (P<0.05).

Conclusions: Our experiments showed that it is a minimally invasive and mature technology of establishing GERD animal models by using the per-oral endoscopic tunneling technique, and might be a new method to establishing GERD large animal models.
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http://dx.doi.org/10.21037/jtd.2018.02.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906314PMC
March 2018

Peroral endoscopic cardial constriction in gastroesophageal reflux disease.

Medicine (Baltimore) 2018 Apr;97(15):e0169

Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing Department of Gastroenterology and Hepatology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.

Gastroesophageal reflux disease (GERD) is a major digestive health problem with a high and increasing incidence worldwide. Peroral endoscopic cardial constriction (PECC) was developed by our group to provide a less invasive treatment for GERD.In this preliminary follow-up study, 16 patients were enrolled and 13 patients with GERD were targeted for analysis according to the Los Angeles classification of reflux esophagitis. The GERD health-related quality of life (GERD-HRQL) scale and esophageal pH monitoring were applied to assess clinical efficiency at 3 and 6 months after PECC treatment, respectively.All GERD patients successively received PECC, and no severe treatment-related complication was reported. Before PECC treatment, the GERD-HRQL scale was 19.92 ± 7.89. At 3 and 6 months after treatment, the GERD-HRQL scale was 4.46 ± 4.31 and 5.69 ± 5.07, respectively. DeMeester score was 125.50 ± 89.64 before PECC treatment, and 16.97 ± 12.76 and 20.32 ± 15.22 at 3 and 6 months after PECC treatment. Furthermore, the fraction time of a pH below 4 significantly decreased at 3 and 6 months after PECC treatment. Fraction time at pH <4 was 35.55 ± 26.20 before PECC treatment and 7.96 ± 13.03 and 4.72 ± 3.78 at 3 and 6 months after PECC treatment, respectively. These results suggest that PECC treatment could significantly reduce the GERD-HRQL scale and DeMeester score (P < .01).PECC is a feasible, safe, and effective method to treatment GERD through narrowing the diameter of the cardia and preventing the reflux of stomach contents.
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http://dx.doi.org/10.1097/MD.0000000000010169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908561PMC
April 2018

Intra-articular platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: a meta-analysis.

Drug Des Devel Ther 2018 5;12:445-453. Epub 2018 Mar 5.

Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

Purpose: Platelet-rich plasma (PRP) and hyaluronic acid (HA) have been increasingly used in recent years to treat knee osteoarthritis (OA). However, whether PRP is superior to HA is controversial.

Methods: We conducted an electronic search of PubMed, Embase, ScienceDirect, and Cochrane library. The pooled data were analyzed using RevMan 5.1.

Results: Three prospective and ten randomized trials were identified. PRP injections reduced pain more effectively than HA injections in OA of the knee at 6 months (mean difference [MD]=-14.18; 95% confidence interval [CI]: -26.12 to -2.23; =0.02; =95%) and 12 months (MD=-15.25; 95% CI: -22.17 to -8.32; <0.01; =81%) of follow-up evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, while the VAS showed no significant difference at 3 months (MD=-0.98; 95% CI: -2.55 to 0.59; =0.22; =90%) and 6 months (MD=-0.82; 95% CI: -1.80 to 0.16; =0.1; =83%). Additionally, similar results were observed for the function recovery according to the WOMAC function score and EuroQol-visual analog scales.

Conclusion: The intra-articular injection of PRP was not obviously superior to HA in knee OA. Due to the limited quality and data of the evidence currently available, more high-quality randomized controlled trials are required.
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http://dx.doi.org/10.2147/DDDT.S156724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842781PMC
September 2018
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