简介：AbstractImportance:The process of brain development in children with developmental delay is not well known. Amide proton transfer-weighted (APTw) imaging is a novel molecular magnetic resonance imaging (MRI) technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides involved in the myelination process, and may be useful for providing insights into brain development.Objective:To assess the contribution of amide proton transfer-weighted (APTw) imaging and magnetization transfer (MT) imaging to the evaluation of children with developmental delay (DD).Methods:Fifty-one patients with DD were recruited to this study. The patients were divided into two groups according to the state of myelination assessed on conventional magnetic resonance imaging (MRI). Thirty patients (10 girls, 20 boys; age range: 1-8 months; median age: 4 months) in group A showed delayed myelination on MRI , while 21 patients (3 girls, 18 boys; age range: 12-36months; median age: 25months) in group B showed normal myelination on MRI. Fifty-one age- and sex-matched children with normal developmental quotient (DQ) and normal MRI appearance were recruited as normal controls. Three-slice APTw/MT axial imaging was performed at the level of the centrum semiovale, the basal ganglia and the pons. Quantitative data of the MT ratio (MTR) and APTw were analyzed for multiple brain regions. Independent-sample t-tests were used to compare differences in APTw and MTR signals between the two DD groups and normal controls. Analysis of Covariance was conducted to correct the statistical results. The level of statistical significance was set to P < 0.05.Results:For group A, the MTR values were lower in all regions (P = 0.004-0.033) compared with the normal controls, while the APTw values were higher in the pons, middle cerebellar peduncle, corpus callosum, frontal white matter, occipital white matter and centrum semiovale (P = 0.004-0.040 ). For Group B, the MTR values were slightly reduced, and the APTw values were slightly increased compared with the normal controls, but the differences were not statistically significant (P > 0.05).Interpretation:For DD patients showing signs of delayed myelination on MRI, MTR and APTw imaging can help to diagnose myelination delay by quantifying semi-solid macromolecules and cytosolic endogenous mobile proteins and peptides at a molecular level, providing a new method for comprehensive evaluation of DD. For DD patients with normal myelination on MRI, the clinical values of MTR and APTw imaging remain to be explored.

简介：Thecurrentconceptof“AdoptiveTCellImmunotherapyofCancer”isquitedifferentfromhowitwasoriginallyconceived．Withthedevelopmentofmoderntechnologyinmolecularbiology,cellbiology，immunologyandbiochemistryduringthelasttwentyyearsorso，adoptiveimmunotherapyhasgrownfromitsinitialformofasimple“bloodcelltransfer”intoitspresentprocesswhichinvolveshostvauccination，effectorcellactivation／polarizationandgeneticmodification．Withtheuseofimmuneadjuvantsandtheidentification／characterizationoftumor-reactiveTcellsubsets，orincombinationwithothertherapeuticstrategies，adoptivelytransferredTcellshavebecomemuchmorepotentinmediatingtumorregression．Inaddition，studiesonthetraffickingofinfusedTcells，celltransferperformedinlymphopenicmodels，aswellasthediscoveryofnoveltechniquesinimmunemonitoringforthegenerationofeffectorcellsinvitroandaftercelltransferinvivohaveprovidedusefultoolstofurtherimprovethetherapeuticefficacyofthisapproach．ThisarticlewillreviewtheserelatedaspectsofadoptiveTcellimmunotherapyofcancerwithspecificcommentsoncertaincriticalareasintheapplicationofthisapproach．Withtherapidlyevolvingadvancesinthisarea，itishopedthatthiscellularimmunologictherapyasitwasconceptualizedinthepast，canbecomemoreusefulinthetreatmentofhumancancerinthenearfuture．

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简介：Bioluminescenceimagingisakindofemergingdetectiontechnologyatcellular,molecularandgeneticlevel.Themostpopularbioluminescenceimagingmodelisdiffusionapproximation(DA).However,becauseoftheill-posednessoftheDA-basedinverseproblemandtheinstabilityofreconstructionalgorithms,thelocationaccuracyofthereconstructedsourcesislow.Radiativetransferequation(RTE),whichconsidersthedirectionofthephotonmigrationandtheeffectofabsorptionandscatteringintissues,canaccuratelyexpressthetransmissionofbioluminescentphotonsthroughthetissues.Inthispaper,westudiedthebioluminescenceimagingbasedontheRTE.2Dsimulationswereperformed,andquantitativeevaluationwasgivenbytheabsolutesourcepositionerror,therelativesourceareaerrorandtheminimumboundingbox.TheresultsoftheexperimentshowedthattheimagingqualitybasedonRTEwasbetterthanthatonebasedonDA.

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简介：AbstractThis study aimed to describe a case of a patient with the spontaneous dissolution of zona pellucida (ZP) during cleavage embryo development after intracytoplasmic sperm injection (ICSI). This patient experienced early abortion due to fetal chromosome 8 abnormality and received ICSI at 31 years of age. Time-lapse monitoring of embryo cleavage and blastocyst culture was performed, and we found that the ZP of embryos 1, 2, 4, and 5 dissolved gradually during the cleavage stage of embryo development. Five blastocysts that developed from 2 pronuclear zygotes were analyzed using next-generation sequencing, and one frozen-thawed blastocyst was transferred, resulting in intrauterine pregnancy. The results of amniotic fluid puncture showed normal fetal chromosomes. To our knowledge, this is the first report of ZP dissolution during the cleavage-stage embryo; however, the exact mechanism remains unknown. The morphological changes inferred that the granular matter in the periocular space was related to the dissolution of ZP through time-lapse observation.

简介：AbstractPurpose:Osteochondral lesion of talus (OLT) is one of the common causes of ankle pain. This disorder is common in young athletes after ankle injury. There are various therapeutic options. One of the options is mosaic plasticizer. The purpose of this study was to investigate the effect of mosaicplasty on improvement of symptoms of patients with osteochondral lesions of talus.Methods:Nineteen patients with osteochondral lesions of talus participated in this study, who were treated with mosaicplasty. Before and after treatment, pain (visual analogue scale), function (American Orthopaedic Foot and Ankle Society), range of motion and radiographic signs were evaluated.Results:The results of this study showed that mosaicplasty could significantly reduce pain, increase function and improve radiographic symptoms. The range of motion increased after treatment, which was not significant.Conclusion:We can confirm the effect of mosaicplasty on the improvement of patients with osteochondral lesions of the ankle, suggesting it as a treatment option.

简介：AbstractBackground:Empiric therapy for patients with unexplained recurrent pregnancy loss (URPL) is not precise. Some patients will ask for assisted reproductive technology due to secondary infertility or advanced maternal age. The clinical outcomes of URPL patients who have undergone in vitro fertilization-embryo transfer (IVF-ET) require elucidation. The IVF outcome and influencing factors of URPL patients need further study.Methods:A retrospective cohort study was designed, and 312 infertile patients with URPL who had been treated during January 2012 to December 2015 in the Reproduction Center of Peking University Third Hospital were included. By comparing clinical outcomes between these patients and those with tubal factor infertility (TFI), the factors affecting the clinical outcomes of URPL patients were analyzed.Results:The clinical pregnancy rate (35.18% vs. 34.52% in fresh ET cycles, P = 0.877; 34.48% vs. 40.27% in frozen-thawed ET cycles, P = 0.283) and live birth rate (LBR) in fresh ET cycles (27.67% vs. 26.59%, P = 0.785) were not significantly different between URPL group and TFI group. URPL group had lower LBR in frozen-thawed ET cycles than that of TFI group (23.56% vs. 33.56%, P = 0.047), but the cumulative LBRs (34.69% vs. 38.26%, P = 0.368) were not significantly different between the two groups. The increased endometrial thickness (EMT) on the human chorionic gonadotropin day (odds ratio [OR]: 0.848, 95% confidence interval [CI]: 0.748-0.962, P = 0.010) and the increased number of eggs retrieved (OR: 0.928, 95% CI: 0.887-0.970, P = 0.001) were protective factors for clinical pregnancy in stimulated cycles. The increased number of eggs retrieved (OR: 0.875, 95% CI: 0.846-0.906, P < 0.001), the increased two-pronucleus rate (OR: 0.151, 95% CI: 0.052-0.437, P < 0.001), and increased EMT (OR: 0.876, 95% CI: 0.770-0.997, P = 0.045) in ET day were protective factors for the cumulative live birth outcome.Conclusion:After matching ages, no significant differences in clinical outcomes were found between the patients with URPL and the patients with TFI. A thicker endometrium and more retrieved oocytes increase the probability of pregnancy in fresh transfer cycles, but a better normal fertilization potential will increase the possibility of a live birth.

简介：Toevaluatetheeffectofadenovirus-mediatedp53gene(Adp53)onapoptosisandradiosensitivityofhumangastriccarcinomacelllines.Methods:Recombinantadenovirusexpressingwild-typep53lineswithdifferentp53geneticstatus.p53proteinexpressionwasdetectedbyimmunohistochemistryassayandwesternblotassay.Cellsurvivalwasassessedusingaclonogenicassay.TUNELassaywasusedindeterminationofapoptosis.FourhumangastriccarcinomacellsinfectedwithAdp53wereirradiatedwith4GyandcellcycledistributionandSub-G1peakwereassayedbyflowcytometry.Results:G2/Marrest,apoptosisandinhibitionoftumorcellproliferationwereinducedbyinfectionatAdp53at100MOIwhichcausedhightransferrateofwild-typep53andstrongexpressionofp53proteininfourhumangastriccarcinomacells.Theradio-enhancementratioofAdp53at4Gywere3.0forWcell,3.6forMcell,2.2forneocelland2.5for823cellinvitro.Conclusion:ThisstudydemonstratedthatAdp53transferincreasedcellularapoptosisandradiosensitivityofhumangastriccarcinomacelllinesinvitroindependentlyoncellularintrinsicp53statusthussupportingthecombinationofp53genetherapywithradiotherapyinclinicaltrials.

简介：ObjectiveTopresentanexperimentalmethodthatallowsisolationofgreaterepithelialridge(GER)andlesserepithelialridge(LER)cellsfrompostnatalratcochleaeusingacombinatorialapproachofenzymaticdigestionandmechanicalseparationandtoinvestigatearetrovirus-mediatedgenetransfertechniqueforitspossibleutilityinimmortalizationoftheGERandLERcelllines,inanefforttoestablishaninvitromodelsystemofhaircelldifferentiation.MethodsGERandLERcellsweredissectedfrompostnatalratcochleaeandimmortalizedbytransferringtheSV40largeTantigenusingaretrovirus.Theestablishedcelllineswereconfirmedthroughmor-phologyobservation,immunnocytochemicalstainingandRT-PCRanalysis.TheHath1genewastransferredintothecelllinesusingadenovirus-mediatedtechniquestoexploretheirpotentialtodifferentiateintohaircells.ResultsTheestablishedcelllineswerestablymaintainedformorethan20passagesanddisplayedmanyfeaturessimilartoprimaryGERandLERcells.Theygrewinpatchesandassumedapolygonalmorphology.ImmunostainingshowedlabelingbySV40largeTantigenandIslet1(aspecificmarkerforGERandLER).AllpassagesofthecelllinesexpressedSV40largeTantigenonRT-PCRanalysis.Thecellsalsoshowedthecapabilitytodifferentiateintohaircell-likecellswhenforcedtoexpressHath1.ConclusionRetrovirus-mediatedgenetransfercanbeusedinestablishingimmortalizedprogenitorhaircelllinesinnewbornrat,whichmayprovideaninvaluablesystemforstudyinghaircelldifferentiationandregenerationfornewtreatmentofsensoryhearinglosscausedbyhaircellloss.

简介：AbstractObjective:To explore the best timing for frozen embryo transfer (FET) after ovarian stimulation and egg retrieval using the clomiphene citrate (CC) + human menopausal gonadotropin (hMG) ovulation induction regimen through a retrospective analysis.Methods:Data of patients who underwent CC + hMG ovulation induction and FET from January 2014 to December 2019 were analyzed retrospectively. The patients were divided into three groups according to the interval from egg retrieval to FET: CC1 (within 1 menstrual cycle), CC2 (2 menstrual cycles), and CC3 (≥ 3 menstrual cycles). Indicators such as hormone levels and pregnancy outcomes were recorded to explore the effect of different intervals on pregnancy outcome.Results:A total of 1,082 transfer cycles were included in this retrospective analysis. The implantation, clinical pregnancy, and live birth rates in the CC1 group were significantly lower than those in the CC2 and CC3 groups (P < 0.05). The E2/P4 ratio on progesterone injection day (3 days before thawed embryo transfer) was lower in the CC1 group than in the other groups (P < 0.05). After adjusting for all factors using multifactor regression analysis, the interval between egg retrieval and FET was found to be an independent predictor of the implantation, pregnancy, and live birth rates.Conclusion:An interval of more than one menstrual cycle between the day of egg retrieval after ovarian stimulation with the CC + hMG ovulation induction regimen and the day of FET can result in high implantation, clinical pregnancy, and live birth rates, which can lead to an improved pregnancy outcome.

简介：瞄准：调查影响他我有教养的老鼠小岛的生存能力和功能上的oxygenase-1(HO-1)基因转移在试管内。方法：小岛被管内胶原酶消化从Sprague-Dawley老鼠的胰孤立，并且由不连续的Ficoll密度坡度远心沉淀净化了。净化的老鼠小岛是有包含人的HO-1基因(Ad-HO-1)的adenoviral向量的transfected或提高了绿荧光灯的蛋白质基因(Ad-EGFP)，然后为七天有教养。Transfection被萤光显微镜检查和西方的污点证实。小岛生存能力被氮蒽orange/propidium碘化物评估荧光灯的染色。刺激葡萄糖的胰岛素版本用胰岛素放射性免疫测定工具包被检测并且被用来估计小岛的功能。刺激索引(SI)被在低葡萄糖刺激之上由胰岛素版本在高葡萄糖刺激之上划分胰岛素版本计算。结果：在七种天文化以后，有教养的老鼠小岛的生存能力显著地减少了(92%+/-6%对52%+/-13%，P<0.05)，并且刺激葡萄糖的胰岛素版本也显著地减少了(6.47+/-0.55mIU/L/30IEQ对4.57+/-0.40mIU/L/30IEQ，14.93+/-1.17mIU/L/30IEQ对9.63+/-0.71mIU/L/30IEQ，P<0.05)。有在20的MOI的adenoviral向量的老鼠小岛的Transfection是有效的，并且没损害小岛功能。在7dpost-transfection，Ad-HO-1transfected小岛的生存能力比控制小岛的高(71%+/-15%对52%+/-13%，P<0.05)。在Ad-HO-1transfected组之中在在低葡萄糖刺激(2.8mmol/L)之上的胰岛素版本没有有效差量，Ad-EGFPtransfected组织，并且控制组织P>0.05)，当时当由高葡萄糖(16.7mmol/L)刺激了时答案，在Ad-HO-1transfected组的胰岛素版本比在Ad-EGFP，transfected组织并且控制组显著地高，分别地(12.50+/-2.17mIU/L/30IEQ对8.87+/-0.65mIU/L/30IEQ；12.50+/-2.17mIU/L/30IEQ对9.63+/-0.71mIU/L/30IEQ，P<0.05)。Ad-HO-1transfected组的SI比Ad-EGFP，transfected组织并且控制组也显著地高，分

简介：Objective:ToprovideahighlyefficientadenoviralvectorAd-CMV-hTGFβ1forthestudyofgenetherapyforreversionoftheintervertebraldiscdegeneration.Methods:Anewlydevelopedrecombinantadenoviralvectorconstructionsystemwasusedinthestudy.ThecDNAofhTGFβ1wasfirstsubclonedintoashuttleplasmidpShuttle-CMV.TheresultantplasmidwaslinearizedbydigestingwithrestrictionendonucleasePmeI,andsubsequentlytransformedintoE.coll.BJ5183cellswithanadenoviralbackboneplasmidpAdEasy-1.Recombinantswereselectedbykanamycinresistanceandconfirmedbyrestrictionendonucleaseanalysis.Finally,therecombinantplasmidlinearizedbyPmeIwastransfectedinto293cells.Recombinantadenovirusesweregeneratedwithin2weeks.Results:TherecombinantadenoviralplasmidswerecutbyBamHIandPacIrespectively,andthediagnosticfragmentsappearedin0.8%agaroseelectrophoresis.Theinfected293cellsshowedevidentcytopathlceffect(CPE).TheproductionsofPCRconfirmedthepresenceofrecombinantadenovirus.TheexpressionofhTGFβ1wasverifiedbyimmunohistochemicalstaining.Conclusions:ThesuccessfulgenerationoftheadenoviralvectorAd-CMV-hTGFβ1andtheconfirmationoftheinterestgeneexpressionmakeitpossiblefortheexperimentalstudyofthereversionoftheintervertebraldiscdegenerationbygenetherapy.

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简介：瞄准：为了阐明，在在各种各样的铁地位下面的含铁锡，转铁蛋白和转铁蛋白受体之中的铁的顺序的转移调节。方法：进粘膜、钠的蛋白质的59Fe的加入在控制WKY老鼠被执行。在含铁锡，转铁蛋白和转铁蛋白受体之中的铁的顺序的转移在铁被执行缺乏，控制和铁过载了老鼠。十二指肠的蛋白质被microautoradiography和免疫组织化学被特定的ELISA和原位本地化在双人脚踏车受到免疫降水和quantitation十二指肠的节。人的十二指肠的活体检视(n=36)从有不同的铁的题目镇定地位也为这些蛋白质被染色。结果：铁蛋白作为主要蛋白质被识别在十二指肠的粘膜以一种时间依赖者方式合并了铁。粘膜含铁锡的集中在与控制相比的铁过量组是显著地更高的，熨缺乏的组(731.5+/-191.96对308.3+/-123.36，731.5+/-191.96对256.0+/-1.19，P<0.005)，当比粘膜显著地高的钠转铁蛋白的没在这些组之中不同时(10.9+/-7.6对0.87+/-0.79，11.1+/-10.3对0.80+/-1.20，6.8+/-4.7对0.61+/-0.63，P<0.001)。蛋白质和熨斗分级的原位，和他们的重迭，建议了铁的顺序的转移的出现。这被表明然后通过铁的起始的绑定发生到钠转铁蛋白到吸收性的房间表面转铁蛋白受体。这些蛋白质的染色的紧张在人根据铁营养变化了，与在铁观察的转铁蛋白受体的强烈染色缺乏的题目。结论：肠通过包含钠转铁蛋白，transferrin-transferrin受体和含铁锡的相互作用的顺序的转移收起铁，这被结束。

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简介：AbstractBackground:Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis, partially by activating lung fibroblasts. However, how macrophages communicate with lung fibroblasts is largely unexplored. Exosomes can mediate intercellular communication, whereas its role in lung fibrogenesis is unclear. Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis.Methods:In vivo, bleomycin (BLM)-induced lung fibrosis model was established and macrophages infiltration was examined. The effects of GW4869, an exosomes inhibitor, on lung fibrosis were assessed. Moreover, macrophage exosomes were injected into mice to observe its pro-fibrotic effects. In vitro, exosomes derived from angiotensin II (Ang II)-stimulated macrophages were collected. Then, lung fibroblasts were treated with the exosomes. Twenty-four hours later, protein levels of α-collagen I, angiotensin II type 1 receptor (AT1R), transforming growth factor-β (TGF-β), and phospho-Smad2/3 (p-Smad2/3) in lung fibroblasts were examined. The Student’s t test or analysis of variance were used for statistical analysis.Results:In vivo, BLM-treated mice showed enhanced infiltration of macrophages, increased fibrotic alterations, and higher levels of Ang II and AT1R. GW4869 attenuated BLM-induced pulmonary fibrosis. Mice with exosomes injection showed fibrotic features with higher levels of Ang II and AT1R, which was reversed by irbesartan. In vitro, we found that macrophages secreted a great number of exosomes. The exosomes were taken by fibroblasts and resulted in higher levels of AT1R (0.22 ± 0.02 vs. 0.07 ± 0.02, t = 8.66, P = 0.001), TGF-β (0.54 ± 0.05 vs. 0.09 ± 0.06, t= 10.00, P < 0.001), p-Smad2/3 (0.58 ± 0.06 vs. 0.07 ± 0.03, t= 12.86, P < 0.001) and α-collagen I (0.27 ± 0.02 vs. 0.16 ± 0.01, t = 7.01, P = 0.002), and increased Ang II secretion (62.27 ± 7.32 vs. 9.56 ± 1.68, t= 12.16, P < 0.001). Interestingly, Ang II increased the number of macrophage exosomes, and the protein levels of Alix (1.45 ± 0.15 vs. 1.00 ± 0.10, t = 4.32, P = 0.012), AT1R (4.05 ± 0.64 vs. 1.00 ± 0.09, t = 8.17, P = 0.001), and glyceraldehyde-3-phosphate dehydrogenase (2.13 ± 0.36 vs. 1.00 ± 0.10, t = 5.28, P = 0.006) were increased in exosomes secreted by the same number of macrophages, indicating a positive loop between Ang II and exosomes production.Conclusions:Exosomes mediate intercellular communication between macrophages and fibroblasts plays an important role in BLM-induced pulmonary fibrosis.

简介：AbstractObjective:Collected human cumulus-oocyte complexes (COCs) are usually inseminated after 4 to 6 hours in in vitro fertilization (IVF) laboratories. The purpose of this study was to determine the effect of short-term pre-IVF incubation in culture medium on subsequent oocyte maturation, fertilization, and embryonic development, as well as clinical outcomes.Methods:Sixty patients were divided randomly into 2 groups, pre-IVF incubation for 5 hours: 1) with (+) the designed oocyte maturation medium; 2) without (-) the designed oocyte maturation medium (transferred directly to fertilization medium for 5 hours before insemination). Oocyte maturation and fertilization were assessed, and the rate of cleavage and good quality embryos were evaluated between the 2 groups on days 2 and 3, respectively. Blastocyst development was based on the remaining number of embryos on day 3, continuously cultured to day 5 after embryo transfer or frozen on day 3, and was compared between the 2 groups. Clinical pregnancy, implantation, and miscarriage rates were also compared.Results:Oocyte maturation rates did not differ between groups (85.8 ± 14.1% vs. 90.7 ± 9.1%). However, the range of oocyte maturation rates (58.3%-100.0%) for each patient was significantly higher in the (-) group than in the (+) pre-incubation group (71.4%-100.0%). There were no differences in fertilization rates (89.9 ± 10.0% vs. 86.5 ± 12.2%) and good quality embryos (70.8 ± 19.1% vs. 62.1 ± 23.7%) between groups; however, the blastocyst development rates were significantly different between groups (73.1 ± 20.1% vs. 58.8 ± 18.2%, P <0.05). Nevertheless, clinical pregnancy (62.5% vs. 61.1%) and implantation (46.9% vs. 47.2%) rates did not differ between groups.Conclusions:These results indicate that a short pre-IVF incubation time in the designed culture medium promotes oocyte maturation and embryonic development, suggesting that short pre-IVF incubation of COCs in the designed culture medium may be important for subsequent final oocyte maturation and early embryonic development.