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PGE2 activates EP4 in subchondral bone osteoclasts to regulate osteoarthritis

Bone Research 2022年第2期10卷 378-393页

作者： Wenhao Jiang Yunyun Jin Shiwei Zhang Yi Ding Konglin Huo Junjie Yang Lei Zhao Baoning Nian Tao PZhong Weiqiang Lu Hankun Zhang Xu Cao karan mehul shah Ning Wang Mingyao Liu Jian Luo Yangzhi Rehabilitation Hospital(Sunshine Rehabilitation Centre) Tongji University School of MedicineShanghaiPR China Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghaiPR China Departments of Orthopaedic Surgery and Biomedical Engineering and Institute of Cell Engineering The Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Oncology and Metabolism The University of SheffieldSheffieldUK

Prostaglandin E2(PGE2), a major cyclooxygenase-2(COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis(OA) patients. However, NSAIDs, including COX-2 inhibitors, have severe side effects during OA treatment. Therefore, the identification of novel drug targets of PGE2 signaling in OA progression is urgently needed. Osteoclasts play a critical role in subchondral bone homeostasis and OA-related pain. However, the mechanisms by which PGE2 regulates osteoclast function and subsequently subchondral bone homeostasis are largely unknown. Here, we show that PGE2 acts via EP4 receptors on osteoclasts during the progression of OA and OA-related pain. Our data show that while PGE2 mediates migration and osteoclastogenesis via its EP2 and EP4 receptors, tissue-specific knockout of only the EP4 receptor in osteoclasts(EP4 Lys M) reduced disease progression and osteophyte formation in a murine model of OA. Furthermore, OA-related pain was alleviated in the EP4 Lys M mice, with reduced Netrin-1 secretion and CGRP-positive sensory innervation of the subchondral bone. The expression of plateletderived growth factor-BB(PDGF-BB) was also lower in the EP4 Lys Mmice, which resulted in reduced type H blood vessel formation in subchondral bone. Importantly, we identified a novel potent EP4 antagonist, HL-43, which showed in vitro and in vivo effects consistent with those observed in the EP4 Lys Mmice. Finally, we showed that the Gαs/PI3 K/AKT/MAPK signaling pathway is downstream of EP4 activation via PGE2 in osteoclasts. Together, our data demonstrate that PGE2/EP4 signaling in osteoclasts mediates angiogenesis and sensory neuron innervation in subchondral bone, promoting OA progression and pain, and that inhibition of EP4 with HL-43 has therapeutic potential in OA.

关键词： osteoclast homeostasis PGE2

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Augmentation cystoplasty in children with stages III and IV chronic kidney disease secondary to neurogenic bladder

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Asian Journal of Urology 2022年第3期9卷 313-317页

作者： Sanjay Sinha mehul shah Department of Urology Apollo HospitalsHyderabadIndia Department of Nephrology Apollo HospitalsHyderabadIndia

Objective:This study examines the outcome of augmentation cystoplasty(AC)in children with stages III and IV chronic kidney disease(CKD)secondary to neurogenic bladder in which transplantation was not ***:Hospital records of all children with CKD stages III and IV who underwent AC between 2008 and 2017 were retrieved to study outcome and complications including estimated glomerular filtration rate(eGFR,National Kidney Foundation Calculator),somatic growth(percentiles,compared with population data),and febrile urinary tract infections(fUTIs)requiring *** analysis was performed using ***:AC was performed in 13 children with CKD stages III and IV(10 girls;median 8.0 years)with median follow-up of 51 *** had incontinence(10/13),reflux(7/13),and hydronephrosis(13/13)despite antimuscarinics and intermittent *** capacity was 74%of expected and median compliance was 5 mL/cm H20(inter-quartile range 4 mL/cm H20).All underwent ileocystoplasty(25 cm bowel).One each had nephrectomy and mitrofanoff *** had resolution of *** had acute kidney injury that *** eGFR at presentation(24 mL/min/1.73 m2)improved with conservative management alone(52 mL/min/1.73 m2,p=0.004).This improved further 1 year following AC(61 mL/min/1.73 m2,p=0.036)with stable function at 7 *** was improvement in somatic growth,hydronephrosis,and fUTI despite no ureteric ***:AC carries acceptable morbidity in children with CKD stages III and IV secondary to neurogenic *** is effective with improvements in continence,eGFR,somatic growth,and propensity for *** re-implantation might not be necessary.

关键词： Neurogenic bladder Chronic kidney disease Augmentation cystoplasty Vesicoureteric reflux Urodynamics

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Effect of transverse compression on the residual tensile strength of ultrahigh molecular weight polyethylene(Dyneema~? SK-76) yarns

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Defence Technology（防务技术） 2020年第1期16卷 35-42页

作者： karan shah Subramani Sockalingam McNAIR Center for Aerospace Innovation and Research University of South CarolinaSCUSA Department of Mechanical Engineering University of South CarolinaSCUSA

Ballistic impact induces complex stress states on fiber-based armor *** impact fibers undergo multiaxial loading which includes axial tension,axial compression,transverse compression,and transverse *** co mpression induced by the projectile leads to permanent defo rmation and fibrillation of fibers resulting in degradation of material tensile *** work(Sockalingam et *** Res.J 2018) has shown a reduction of 20% in the tensile strength of Dyneema~? SK76 single fibers subjectet to 77% nominal transverse compressive *** investigation of quasistatic transverse compression on Dyneema~? SK-76 yarns,unconstrained in the lateral direction,indicate an average of 4% reduction in tensile strength of yarns compressed to 77% nominal *** this work we use finite element modeling techniques to understand the difference in residual tensile strength between single fibers and yarns observed in laterally unconstrained transverse compression *** element study of the transverse compression response of single fibers and yarns indicate that local strains developed in fibers within the yarn are much lower than the local strains developed in single fibers subjected to a given nominal strain and may explain the less reduction in strength observed in yarns.

关键词： Polymer fibers Compression Tensile strength

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GPRC5B protects osteoarthritis by regulation of autophagy signaling

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药学学报:英文版 2023年第7期13卷 2976-2989页

作者： Liang He Ziwei Xu Xin Niu Rong Li Fanhua Wang Yu You Jingduo Gao Lei Zhao karan M.shah Jian Fan Mingyao Liu Jian Luo Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center) Tongji University School of MedicineShanghai 201613China Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Oncology and Metabolism the Medical Schoolthe University of SheffieldSheffield S102TNUK Department of Orthopedics Tongji HospitalTongji University School of MedicineShanghai 200092China

Osteoarthritis(OA)is one of the most common chronic diseases in the ***,current treatment modalities mainly relieve pain and inhibit cartilage degradation,but do not promote cartilage *** this study,we show that G protein-coupled receptor class C group 5 member B(GPRC5B),an orphan G-protein-couple receptor,not only inhibits cartilage degradation,but also increases cartilage regeneration and thereby is protective against *** observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression,along with downregulation of anabolic genes in ***,mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus(DMM)induced OA mouse model,with upregulation of cartilage catabolic factors and downregulation of anabolic factors,consistent with our in vitro *** of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting *** also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B(AKT)-mammalian target of rapamycin(m TOR)-autophagy signaling ***,we demonstrate an integral role of GPRC5B in OA pathogenesis,and activation of GPRC5B has the potential in preventing the progression of OA.

关键词： Osteoarthritis GPRC5B Cartilage Chondrocyte Cartilage anabolism and catabolism Cartilage regeneration Autophagy Drug target

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Plasma Pulse Technology: An uprising EOR technique

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Petroleum Research 2018年第2期3卷 180-188页

作者： karan Patel Manan shah Anirbid Sircar School of Petroleum Technology Pandit Deendayal Petroleum UniversityGandhinagarGujaratIndia

Conventionally oil recovery factor is too low,which leaves great prospects for the application of enhanced oil recovery(EOR)methods to increase recovery *** methods are capital intensive and few are environmentally *** the paper discusses on the alternate enhanced oil recovery technique which has tremendous potential to curb the challenges of conventional EOR *** pulse technology(PPT)aided EOR treatment is administered with an electric wireline conveyed plasma pulse generator tool that is run in the well and positioned alongside the *** energy stored in the generator's capacitors,a plasma arc is created that emits a tremendous amount of heat and pressure for a fraction of a *** in turn creates a broad band of hydraulic impulse acoustic waves that are powerful enough to clean perforations and near wellbore *** waves continue to resonate deep into the reservoir,exciting the fluid molecules and increasing the reservoirs natural resonance to the degree that it can break larger hydrocarbon molecules to smaller one and simultaneously reducing adhesion tension which results in increased mobility of *** plasma pulse technology has been successfully used on production as well as injection *** has been used often as a remedial procedure to increase well's productivity that has been on production for a period of *** paper throws light on fundamentals of this advancing plasma pulse technology,contrasting it with recent EOR *** of treatment in increasing oil recovery,it's applicability to different reservoir types and results achieved so far are also covered in the paper.

关键词： Enhanced oil recovery Plasma pluse technology Reservoir natural resonance Effective viscosity Oil production Reservoir deliverability and intake

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Comprehensive geochemical/hydrochemical and geo-thermometry analysis of Unai geothermal field, Gujarat, India

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Acta Geochimica 2019年第1期38卷 145-158页

作者： Manan shah Anirbid Sircar Nahid Shaikh karan Patel Darshan Sharma Dwijen Vaidya School of Petroleum Technology Pandit Deendayal Petroleum University Wipro Limited Centre of Excellence for Geothermal Energy Pandit Deendayal Petroleum University

The knowledge of water temperature produced from a geothermal reservoir and its composition is of utmost importance in designing utilization strategies, the surface production facilities and in selecting the material to be used. Unai hot springs are located in the southern part of Gujarat, India with discharge temperatures varying from 51 to 56 ℃. With the aim of developing Unai as a potential geothermal field and exploiting it in the future, geochemical and geothermometrical study was undertaken. The samples were collected from various Unai geothermal location and analysis of chemical composition of water obtained from different wells was done. The concentration of Silica, carbonate and ions like Na and Cl have been analyzed to delineate the path of water movement in the subsurface and classify the reservoir based on the *** ratio of the concentration of ions like Na^+ and K^+ and the relative proportions of various sets of ions were also used to characterize the geothermal reservoir and the reservoir fluid by the use of ternary diagrams. Na–K–Ca,Chalcedony, quartz, and Silica geo-thermometers have been studied. The present study also envisages the importance of graphical representations like Piper diagram,Scholler etc. to determine variation in hydrochemical facies and to understand the evolution of hydrochemical processes in the Unai geothermal field respectively. The study yields the conclusion that the reservoir under consideration is a low enthalpy reservoir with temperature ranging from 60 to 80 ℃.

关键词： Geothermal energy Hydrochemical Geochemical Geothermometery Renewable energy

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Distribution and Habitat Preference of Red Panda (<i>Ailurus fulgens fulgens</i>) in Jumla District, Nepal

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Open Journal of Ecology 2014年第15期4卷 989-1001页

作者： Manoj Bhatta karan Bahadur shah Bhupendra Devkota Rajiv Paudel Saroj Panthi Amrit Science Campus Kathmandu Nepal Natural History Museum Tribhuvan University Kathmandu Nepal College of Applied Science Kathmandu Nepal Winrock International Lalitpur Nepal Department of Forests District Forest Office Darchula Nepal

Reliable and sufficient information regarding status, distribution and habitat preference of red panda (Ailurus fulgens fulgens) is lacking in Nepal. The research activities on red panda in the mid-western Nepal are very limited, so the status of red panda in the region is quite unknown. The study conducted during May, 2013 in three Village Development Committees (VDCs) namely Godhemahadev, Malikathata and Tamti of Jumla district was an important step for providing vital information including distribution and habitat preference of this species. The study included the reconnaissance, key informants survey, interviews and consultation for the most potential area identification, opportunistic survey comprising the direct observation and indirect sign count method for the presence and distribution, habitat assessment consisting vegetation sampling and ocular estimation. The study revealed the presence of red panda in three forests namely Bahirepatan, Imilchadamar and Tyakot of Godhemahadev, Tamti and Malikathata VDCs respectively. The species was found distributed between 2880 and 3244 m with an average dropping encounter rate of 1.04 per hour of searching effort and 12 pellets per dropping. Red panda mostly preferred the habitat in the elevation range of 2900 - 3000 m with southwest facing steep slopes (36? - 45?), associated with water sources at the distance of ≤100 m. Trees such as Acer spp., Betula utilis and Quercus semecarpifolia, shrub species of Elaeagnus parvifolia, Drepanostachyum spp. and Jasminum humile, and the herbs like Polygonatum cirrhifolium, Fragaria nubicola and Galium asperifolium were found to be the most preferred species by red panda. The red panda preferred the habitat with dense crown coverage (>20% - 100%) and 31% - 50% ground cover. Fallen logs (39%) were the most preferred substrate used for defecation.

关键词： Distribution Habitat Preference Jumla Red Panda Sign

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Factors Affecting Visual Outcome Following Surgical Treatment of Cataracts in Children

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Open Journal of Ophthalmology 2012年第4期2卷 131-139页

作者： mehul A. shah Shreya M. shah Khushboo A. Shikhangi Pramod R. Upadhyay Geetopam B. Bardoloi Drashti Netralaya Dahod India

Purpose: To assess treatment results in pediatric patients with cataracts, to evaluate the efficacy of various surgical interventions, and to determine the factors that affect visual outcomes. Methods: This is aProspective cohort study. We studied a consecutive series of pediatric patients with congenital, developing, or traumatic cataracts who underwent surgery between January, 1999 and April, 2012 at Drashti Netralaya, Dahod. Patient demographics, cataract type, presenting symptoms, surgical intervention, postoperative visual acuity, and follow-up refractive changes were recorded. Results: In total, 1305 eyes of 1047 children were included: unilateral cataracts were present in 786 (60.2%) eyes. There were 610 (46.7%) traumatic and 695 (53.3%) non-traumatic cases. Ages at surgery ranged from 1 to 215 months. Eyes were grouped by the surgical intervention performed: Group 1, pars plana approach including 366 (28%) eyes that underwent lensectomies, and Group 2, anterior approach, including 939 (71.9%) eyes that underwent phacoemulsification ± IOL placement or small incision cataract surgery ± IOL placement. The mean follow-up time was 117 days. Ultimately, 113 (30.9%) Group 1 and 503 (53.6%) Group 2 patients achieved a visual acuity better than 20/60 (P < 0.001). Age at intervention, laterality, sensory nystagmus, pretreatment vision, IOL insertion, and etiology were all significantly related (all P < 0.001) to visual outcome. Conclusions: Surgical treatment with intraocular lens implantation for children with congenital, developmental, or traumatic cataracts is an effective treatment for visual rehabilitation. Visual outcome was significantly better in cases of traumatic cataracts versus non-traumatic cataracts.

关键词： Pediatric Cataract Visual Outcome Traumatic Cataract Developmental Cataract Congenital Cataract

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Strabismus in Cases of Cataract in Pediatric Age Group

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Open Journal of Ophthalmology 2013年第1期3卷 19-23页

作者： Shreya M. shah mehul A. shah Pramod R. Upadhyay Geetopam B. Bardoloi Drashti Netralaya Drashti Netralaya Dahod India Drashti Netralaya Dahod India.

Purpose: To investigate the epidemiology of strabismus in cases of pediatric cataracts. To assess visual outcome following orthoptic treatment for amblyopia in cases of cataracts in the pediatric age group. Methods: This was a retrospective cohort study. We investigated a consecutive series of pediatric patients with congenital, developing, or traumatic cataracts who underwent surgery between January 1999 and April 2012 at our center. Patient demographics, cataract type, presenting symptoms, surgical intervention, postoperative visual acuity, and follow-up refractive changes were recorded. Results: In total, 1331 eyes of 1043 children were included: unilateral cataracts were present in 785 (59%) eyes. There were 605 (45.5%) traumatic and 726 (54.5%) non-traumatic cases. Ages at surgery ranged from 1 to 215 months. All eyes were examined for ocular alignment;66 (5%) were found to manifest strabismus. Deviation was significantly associated with age at intervention (p p < 0.001), and etiology of cataracts (p 0.001). We found significant differences in visual outcome following amblyopia therapy (p 0.001). Conclusions: Surgical treatment with intraocular lens implantation in children with congenital, developmental, or traumatic cataracts is effective for visual rehabilitation. Orthoptic treatment made a significant difference in visual outcome (p < 0.001).

关键词： Pediatric Cataract Visual Outcome Traumatic Cataract Developmental Cataract Congenital Cataract

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Assessment of quadriceps muscle thickness using bedside ultrasonography by nurses and physicians in the intensive care unit:Intra- and inter-operator agreement

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World Journal of Critical Care Medicine 2019年第7期8卷 127-134页

作者： Rohit Kumar Tajamul Hussain shah Vijay Hadda Pawan Tiwari Saurabh Mittal karan Madan Maroof Ahmad Khan Anant Mohan Department of Pulmonary Critical Care and Sleep MedicineAll India Institute of Medical SciencesNew Delhi 110029India Department of Biostatistics All India Institute of Medical SciencesNew Delhi 110029India

BACKGROUND Data regarding the agreement among multiple operators for measurement of quadriceps muscle thickness by bedside ultrasonography(USG)are *** To statistically assess the agreement among 5 operators for measurement of quadriceps muscle thickness on bedside *** This was a cross-sectional observational *** 5 operators of varied experience(comprised of 1 critical care consultant,2 fellows,and 2 nurses)independently measured quadriceps muscle thickness in triplicate for 45 critically ill patients each,using ***-and interrater agreement rates among the 5 operators were assessed using intraclass correlation coefficient(ICC)and expressed with 95%confidence interval(CI).RESULTS The 5 operators produced a total of 135 readings and 675 observations for ICC calculations to determine the intraoperator and interoperator variations *** intraoperator agreement,the overall ICC(95%CI)was 0.998(0.997,0.999)for operator 1,0.998(0.997,0.999)for operator 2,0.997(0.995,0.999)for operator 3,0.999(0.998,0.999)for operator 4,and 0.998(0.997,0.999)for operator *** interoperator agreement,the overall ICC(95%CI)was 0.977(0.965,0.986;P<0.001)for reading 1,0.974(0.960,0.984;P<0.001)for reading 2,and 0.975(0.961,0.985;P<0.001)for reading *** USG measurement of quadriceps muscle thickness was not dependent on clinical experience,supporting training for nurses in it.

关键词： Agreement Intensive care unit Critical illness Muscle thickness Quadricepsmuscle Ultrasonography

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