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Prenatal amoxicillin exposure induces developmental toxicity in fetal mice and its characteristics

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Journal of Environmental Sciences 2024年第3期137卷 287-301页

作者： Yongguo Dai yu Peng wen Hu Yi Liu hui Wang Department of Pharmacology Wuhan University School of Basic Medical SciencesWuhan 430071China Department of Pharmacy Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Provincial Key Laboratory of Developmentally Originated Disease Wuhan 430071China

Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Currently,systematic studies about the developmental toxicity of amoxicillin are still lacking.We explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the midpregnancy.Meanwhile,PAmE altered multiple maternal/fetal serum phenotypes,especially in fetuses.Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>others.Further analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response relationship.In conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.

关键词： Amoxicillin Prenatal exposure Fetal development Organ function Developmental toxicity

Acetyl-11-keto-beta-boswellic acid promotes sciatic nerve repair after injury: molecular mechanism

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Neural Regeneration Research 2022年第12期17卷 2778-2784页

作者： Yao Wang Zong-Liang Xiong Xiang-Lin Ma Chong Zhou Mo-Han Huo Xiao-wen Jiang Wen-Hui yu Department of Veterinary Medicine Northeast Agricultural UniversityHarbinHeilongjiang ProvinceChina College of Life Sciences Northeast Agricultural UniversityHarbinHeilongjiang ProvinceChina Key Laboratory of Heilongjiang Education Department for Common Animal Disease Prevention and Treatment Northeast Agricultural UniversityHarbinHeilongjiang ProvinceChina Institute of Chinese Veterinary Medicine Northeast Agricultural UniversityHarbinHeilongjiang ProvinceChina

Previous studies showed that acetyl-11-keto-beta-boswellic acid(AKBA),the active ingredient in the natural Chinese medicine Boswellia,can stimulate sciatic nerve injury repair via promoting Schwann cell proliferation.However,the underlying molecular mechanism remains poorly understood.In this study,we performed genomic sequencing in a rat model of sciatic nerve crush injury after gastric AKBA administration for 30 days.We found that the phagosome pathway was related to AKBA treatment,and brain-derived neurotrophic factor expression in the neurotrophic factor signaling pathway was also highly up-regulated.We further investigated gene and protein expression changes in the phagosome pathway and neurotrophic factor signaling pathway.Myeloperoxidase expression in the phagosome pathway was markedly decreased,and brain-derived neurotrophic factor,nerve growth factor,and nerve growth factor receptor expression levels in the neurotrophic factor signaling pathway were greatly increased.Additionally,expression levels of the inflammatory factors CD68,interleukin-1β,pro-interleukin-1β,and tumor necrosis factor-αwere also decreased.Myelin basic protein-andβ3-tubulin-positive expression as well as the axon diameter-to-total nerve diameter ratio in the injured sciatic nerve were also increased.These findings suggest that,at the molecular level,AKBA can increase neurotrophic factor expression through inhibiting myeloperoxidase expression and reducing inflammatory reactions,which could promote myelin sheath and axon regeneration in the injured sciatic nerve.

关键词： AKBA axon genomics inflammatory injury and repair myelin sheath myeloperoxidase neurotrophic factor peripheral nerve phagosome pathway regeneration Sprague-Dawley rat

Statistical Inferences in a Partially Linear Model with Autoregressive Errors

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Acta Mathematicae Applicatae Sinica 2022年第4期38卷 822-842页

作者： Xiao-hui LIU yu WANG Ya-wen FAN yu-zi LIU School of Statistics Jiangxi University of Finance and EconomicsNanchang 330013China Key Laboratory of Data Science in Finance and Economics Jiangxi University of Finance and EconomicsNanchang 330013China

In this paper,we consider the statistical inferences in a partially linear model when the model error follows an autoregressive process.A two-step procedure is proposed for estimating the unknown parameters by taking into account of the special structure in error.Since the asymptotic matrix of the estimator for the parametric part has a complex structure,an empirical likelihood function is also developed.We derive the asymptotic properties of the related statistics under mild conditions.Some simulations,as well as a real data example,are conducted to illustrate the finite sample performance.

关键词： partially linear model autoregressive errors two-step procedure profile empirical likelihood

Meromorphic Functions of Finiteφ-order and Linear Askey-Wilson Divided Difference Equations

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Acta Mathematica Sinica,English Series 2022年第2期38卷 371-383页

作者： hui yu Janne HEITTOKANGAS Jun WANG Zhi Tao wen Department of Physics and Mathematics University of Eastern FinlandP.O.Box 11180101 JoensuuFinland School of Mathematical Sciences Fudan UniversityShanghai 200433P.R.China Department of Mathematics Shantou UniversityShantou 515063P.R.China

The growth of meromorphic solutions of linear difference equations containing Askey-Wilson divided difference operators is estimated.Theφ-order is used as a general growth indicator,which covers the growth spectrum b... 详细信息

关键词： Askey-Wilson divided difference operator Askey-Wilson divided difference equation lemma on the logarithmic

Primary Treatment for Clinically Early Cervical Cancer with Lymph Node Metastasis:Radical Surgery or Radiation?

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当代医学科学(英文) 2023年第3期43卷 551-559页

作者： Xin-yi LI Jia-yi wen yu-hui HUANG wen-wen WANG Zheng WEI yu-jia MA Xiang KANG Ze-hua WANG Department of Obstetrics and Gynecology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Pathology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Gynecology the Sixth Afiliated HospitalSun Yat-sen UniversityGuangzhou 510655China

Objective To compare survival outcomes between primary radical surgery and primary radiation in early cervical cancer.Methods Patient information was extracted from the Surveillance,Epidemiology,and Results database.Patients diagnosed with early cervical cancer of stage T1a,T1b,and T2a(American Joint Committee on Cancer,7th edition)from 1998 to 2015 were included in this study after propensity score matching.Overall survival(OS)was analyzed using the Kaplan-Meier method.Results Among the 4964 patients included in the study,1080 patients were identified as having positive lymph nodes(N1),and 3884 patients were identified as having negative lymph nodes(N0).Patients with primary surgery had significantly longer 5-year OS than those with primary radiotherapy in both the N1 group(P<0.001)and N0 group(P<0.001).In the subgroup analysis,similar results were found in patients with positive lymph nodes of stage T1a(100.0%vs.61.1%),T1b(84.1%vs.64.3%),and T2a(74.4%vs.63.8%).In patients with T1b1 and T2a1,primary surgery resulted in longer OS than primary radiation,but not in patients with T1b2 and T2a2.In multivariate analysis,the primary treatment was identified as an independent prognostic factor in both N1 and N0 patients(HR_(N1)=2.522,95%CI=1.919–3.054,PN1<0.001;HR_(N0)=1.895,95%CI=1.689–2.126,PN0<0.001).Conclusion In early cervical cancer stage T1a,T1b1,and T2a1,primary surgery may result in longer OS than primary radiation for patients with and without lymph node metastasis.

关键词： early cervical cancer overall survival primary treatment lymph node status radical surgery radiation

Effect of non-stationary accretion on spectral state transitions:An example of a persistent neutron star LMXB 4U 1636–536

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Research in Astronomy and Astrophysics 2018年第3期18卷 91-98页

作者： hui Zhang wen-Fei yu Key Laboratory for Research in Galaxies and Cosmology Shanghai Astronomical ObservatoryChinese Academy of Sciences

Observations of black hole and neutron star X-ray binaries show that the luminosity of the hard-to-soft state transition is usually higher than that of the soft-to-hard state transition,indicating additional parameters other than mass accretion rate are required to interpret spectral state transitions.It has been found in some individual black hole or neutron star soft X-ray transients that the luminosity corresponding to the hard-to-soft state transition is positively correlated with the peak luminosity of the following soft state. In this work,we report the discovery of the same correlation in the single persistent neutron star low mass X-ray binary（LMXB） 4 U 1636–536 based on data from the All Sky Monitor（ASM） on board RXTE,the Gas Slit Camera（GSC） on board MAXI and the Burst Alert Telescope（BAT） on board Swift. We also found such a positive correlation holds in this persistent neutron star LMXB in a luminosity range spanning about a factor of four. Our results indicate that non-stationary accretion also plays an important role in driving X-ray spectral state transitions in persistent accreting systems with small accretion flares,which is much less dramatic compared with the bright outbursts seen in many Galactic LMXB transients.

关键词： accretion accretion disks - X-rays binaries - stars neutron

Optimal Control Policy of M/G/1 Queueing System with Delayed Randomized Multiple Vacations Under the Modified Min(N,D)-Policy Control

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Journal of the Operations Research Society of China 2023年第4期11卷 857-874页

作者： Le Luo Ying-hui Tang Miao-Miao yu wen-Qing Wu School of Mathematical Sciences Sichuan Normal UniversityChengdu610068SichuanChina Nanchong Vocational and Technical College Nanchong637000JiangsuChina Visual Computing and Virtual Reality Key Laboratory of Sichuan Province Sichuan Normal UniversityChengdu610068SichuanChina

Based on the number of customers and the server’s workload,this paper proposes a modified Min(N,D)-policy and discusses an M/G/1 queueing model with delayed randomized multiple vacations under such a policy.Applying the well-known stochastic decomposition property of the steady-state queue size,the probability generating function of the steady-state queue length distribution is obtained.Moreover,the explicit expressions of the expected queue length and the additional queue length distribution are derived by some algebraic manipulations.Finally,employing the renewal reward theorem,the explicit expression of the long-run expected cost per unit time is given.Furthermore,we analyze the optimal policy for economizing the expected cost and compare the optimal Min(N,D)-policy with the optimal N-policy and the optimal D-policy by using numerical examples.

关键词： M/G/1 queue Modified Min(N,D)-policy Randomized multiple vacations Queue length generating function Optimal joint control policy

Acetyl-11-keto-β-boswellic acid extracted from Boswellia serrata promotes Schwann cell proliferation and sciatic nerve function recovery

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Neural Regeneration Research 2018年第3期13卷 484-491页

作者： xiao-wen jiang bin-qing zhang lu qiao lin liu xue-wei wang Wen-Hui yu Department of Veterinary Medicine Northeast Agricultural University Harbin Helongjiang Province China

Frankincense can promote blood circulation. Acetyl-11-keto-β-boswellic acid （AKBA） is a small molecule with anti-inflammatory properties that is derived from Boswellia serrata. Here, we hypothesized that it may promote regeneration of injured sciatic nerve. To address this hypothesis, we established a rat model of sciatic nerve injury using a nerve clamping method. Rats were administered AKBA once every 2 days at doses of 1.5, 3, and 6 mg/kg by intraperitoneal injection for 30 days from the 1st day after injury. Sciatic nerve function was evaluated using the sciatic functional index. Degree of muscle atrophy was measured using the triceps surae muscle Cuadros index.Neuropathological changes were observed by hematoxylin-eosin staining. Western blot analysis was used to detect expression of phospho-extracellular signal-regulated kinase 1 and 2 （p-ERK1/2） in injured nerve. S100 immunoreactivity in injured nerve was detected by immunohistochemistry. In vivo experiments showed that 3 and 6 mg/kg AKBA significantly increased sciatic nerve index, Cuadros index of triceps muscle, p-ERK1/2 expression, and S100 immunoreactivity in injured sciatic nerve of sciatic nerve injury model rats. Furthermore,for in vitro experiments, Schwann cells were treated with AKBA at 0–20 μg/mL. Proliferation of Schwann cells was detected by Cell Counting Kit-8 colorimetry assay. The results showed that 2 μg/mL AKBA is the optimal therapeutic concentration. In addition, ERK phosphorylation levels increased following 2 μg/mL AKBA treatment. In the presence of the ERK1/2 inhibitor, PD98059 （2.5 μL/mL）, the AKBA-induced increase in p-ERK1/2 protein expression was partially abrogated. In conclusion, our study shows that AKBA promotes peripheral nerve regeneration with ERK protein phosphorylation playing a key role in this process.

关键词： nerve regeneration acetyl-11-keto-β-boswellic acid peripheral nerve injury repair sciatic nerve crush injury Schwann cells cell proliferation ERK signaling pathway PD98059 neural regeneration

Treatment status of extremely premature infants with gestational age<28 weeks in a Chinese perinatal center from 2010 to 2019

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World Journal of Pediatrics 2022年第1期18卷 67-74页

作者： wen-wen Zhang Yong-hui yu Xiao-yu Dong Simmy Reddy Department of Neonatology Shandong Provincial Hospital Afliated to Shandong First Medical UniversityJinan 250021China Department of Neonatology Shandong Maternal and Child Health HospitalJinan 250021China Cheeloo College of Medicine Shandong UniversityJinanChina

Background There is a paucity of studies conducted in China on the outcomes of all live-birth extremely premature infants(EPIs)and there is no unifed recommendation on the active treatment of the minimum gestational age in the feld of perinatal medicine in China.We aimed to investigate the current treatment situation of EPIs and to provide evidence for formulating reasonable treatment recommendations.Methods We established a real-world ambispective cohort study of all live births in delivery rooms with gestational age(GA)between 24+0 and 27+6 weeks from 2010 to 2019.Results Of the 1163 EPIs included in our study,241(20.7%)survived,while 849(73.0%)died in the delivery room and 73(6.3%)died in the neonatal intensive care unit.Among all included EPIs,862(74.1%)died from withholding or withdrawal of care.Regardless of stratifcation according to GA or birth weight,the proportion of total mortality attributable to withdrawal of care is high.For infants with the GA of 24 weeks,active treatment did not extend their survival time(P=0.224).The survival time without severe morbidity of the active treatment was signifcantly longer than that of withdrawing care for infants older than 25 weeks(P<0.001).Over time,the survival rate improved,and the withdrawal of care caused by socioeconomic factors and primary nonintervention were reduced signifcantly(P<0.001).Conclusions The mortality rate of EPIs is still high.Withdrawal of care is common for EPIs with smaller GA,especially in the delivery room.It is necessary to use a multi-center,large sample of real-world data to fnd the survival limit of active treatment based on our treatment capabilities.

关键词： Active treatment Extremely premature Infants Mortality rate Withdrawal of care