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简介：比较支持者天赋杀手(A-NK)的增长和cytotoxicity之间的差别与没有浆液的中等AIMV和标准有教养的房间在vitro的包含浆液的媒介，并且也在激活和IL-2-treatedA-NK房间的形态学特性上观察IL-12的帮助效果，细胞的增长被MTT方法在vitro评估。A-NK房间打死的目标房间的形态学通过验电器被观察。所有能很快在没有浆液的中等AIMV有教养的A-NK房间增殖并且在标准包含浆液的媒介与那相比使cytotoxicity高。中等剂量的IL-2和IL-12激活的A-NK房间比高剂量的IL-2-treatedA-NK房间优异。这些数据显示没有浆液的中等AIMV能为culturingA-NK房间代替标准包含浆液的媒介，并且中等剂量的IL-2和IL-12能减少高剂量的IL-2引起的副作用。学习为A-NK房间的试验性、临床的准备提供了一个新试验性的基础。

简介：AbstractBackground:The genetic central dogma (GCD) has been demonstrated its essential function in many biological processes and diseases. However, its roles in the process of osteogenic differentiation of mesenchymal stem cells (MSCs) remain unclear.Methods:In this project, we analyzed an online database of osteogenic differentiation of MSCs after 14 days and 28 days by osteoinductive medium (GSE83770). The differentially expressed genes were screened by GEO2R, with further conducting of KEGG pathways using DAVID. In addition, protein-protein interactions of the enriched pathways were performed using STRING with marked hub genes measured by the CytoHubba. Hub genes were verified by quantitative reverse-transcription polymerase chain reaction.Results:Results showed that six pathways related to GCD, including DNA replication, Aminoacyl-tRNA biosynthesis, Mismatch repair, Ribosome, Spliceosome, and RNA degradation pathways enriched in the early stage (14 days vs. undifferentiated MSCs) of osteogenesis. The Lysosome pathway was highly enriched in the late stage (28 vs. 14 days) of osteogenesis, and Ribosome pathway plays a key role throughout the entire process (28 days vs. undifferentiated MSCs) of osteogenesis.Conclusion:Both DNA replication and protein translation were functionally worked in the early stage of osteogenesis, whereas the Lysosome pathway was the only GCD-related one in the late stage of osteogenesis. The GCD-related Ribosome pathway occupied the entire process of osteogenesis.

简介：NocathiacinI,aglycosylatedthiopeptideantibiotic,displaysexcellentantibacterialactivitiesagainstmultidrugresistantbacterialpathogens.Previously,anovelnocathiacinIformulationforintravenousadministrationhasbeensuccessfullydevelopedanditsaqueoussolubilityisgreatlyenhancedforclinicalapplication.ThepurposeofthepresentstudywastoincreasethefermentationtiterofnocathiacinIandreduceoreliminateanalogousimpuritiesbyscreeningthemediumingredientsusingresponsesurfacemethodology.Afterasysmaticoptimization,awater-solublemediumcontainingquality-controllablecomponentswasdevelopedandvalidated,resultinginanincreaseintheproductionofnocathiacinIfrom150to405.8mg·L-1at150-Lscale.Meanwhile,theanalogousimpuritiesexistedinreportedprocessesweregreatlyreducedoreliminated.Usingoptimizedmediumforfermentation,nocathiacinIwithpharmaceuticallyacceptablequalitywaseasilyobtainedwitharecoveryof67%.Inconclusion,theresultsfromthepresentstudyofferapracticalandefficientfermentationprocessfortheproductionofnocathiacinIasatherapeuticagent.

简介：AbstractPurpose:The COVID-19 pandemic has caused 1.4 million deaths globally and is associated with a 3-4 times increase in 30-day mortality after a fragility hip fracture with concurrent COVID-19 infection. Typically, death from COVID-19 infection occurs between 15 and 22 days after the onset of symptoms, but this period can extend up to 8 weeks. This study aimed to assess the impact of concurrent COVID-19 infection on 120-day mortality after a fragility hip fracture.Methods:A multi-centre prospective study across 10 hospitals treating 8% of the annual burden of hip fractures in England between 1st March and 30th April, 2020 was performed. Patients whose surgical treatment was payable through the National Health Service Best Practice Tariff mechanism for "fragility hip fractures" were included in the study. Patients’ 120-day mortality was assessed relative to their perioperative COVID-19 status. Statistical analysis was performed using SPSS version 27.Results:A total of 746 patients were included in this study, of which 87 (11.7%) were COVID-19 positive. Mortality rates at 30- and 120-day were significantly higher for COVID-19 positive patients relative to COVID-19 negative patients (p < 0.001). However, mortality rates between 31 and 120-day were not significantly different (p = 0.107), 16.1% and 9.4% respectively for COVID-19 positive and negative patients, odds ratio 1.855 (95% CI 0.865-3.978).Conclusion:Hip fracture patients with concurrent COVID-19 infection, provided that they are alive at day-31 after injury, have no significant difference in 120-day mortality. Despite the growing awareness and concern of "long-COVID" and its widespread prevalence, this does not appear to increase mediumterm mortality rates after a hip fracture.

简介：目的探讨MesenPRORSMedium对人脂肪干细胞增殖与分化的影响。方法应用MesenPRORSMedium与DMEM＋10％FBS两种培养基培养人脂肪干细胞，比较两者在细胞形态、体外增殖能力、成纤维细胞集落形成（CFU—F）能力及多向分化潜能的差异。结果MesenPRORSMedium培养的人脂肪干细胞具有良好的细胞形态，在增殖速度、细胞集落，以及成脂、成骨及成软骨能力等方面均优于DMEM＋10％FBS。结论MesenPRORSMedium是人脂肪干细胞优良的培养基。

简介：BackgroundPrematureventricularcontractions(PVCs)arefrequentlyseeninchildren.However,therearelesssystematicandlongerfollowing-upstudiesexaminingtheprognosisofPVCsinchildren.TheaimofthisstudywastoevaluatethemediumtolongtermprognosisofPVCsinchildhoodandwhetherthereisadifferentialprognosisindifferentprimarydiseasesofPVCs.MethodsThisstudyreviewedthedataof106pediatricpatients(49F/57M,7.5±3.8years)seenattheAffiliatedHospitalofQingdaoUniversitywiththediagnosisofPVCsbetween1999and2005.Dataondemographics,clinicalpresentation,laboratorytests,andechocardiogramsofpatientswereextractedfromtheavailableclinicalrecords.ResultsAtotalof35(33.0%)childrenpresentedwithPVCsduetomyocarditis,7(6.6%)duetocardiomyopathies,7(6.6%)duetomitralvalveprolapse(MVP),10(9.4%)duetooperationforcongenitalheartdisease(O-CHD),16(15.2%)duetoleftventricularfalsetendons(LVFT),and31(29.2%)duetounknowncause.HolterdidnotshowPVCsduringfollow-upperiodin100%ofmyocarditispatients,57%ofcardiomyopathypatients,71%ofMVPpatients,60%ofO-CHDpatients,88%ofLVFTpatients,87%ofunknowncausepatients.ThePVCsdisappearedin93%ofpatientswhodidnotuseanti-arrhythmicdrugsandin76%ofpatientswhousedantiarrhythmicdrugs.Therewasnoasignificantdifferenceinprognosisbetweenmyocardialnutritioncombinedwithintravenousinjectionofimmunoglobulin(IVIG)groupandpropafenonegroup.ConclusionsPVCscausedbydifferentprimarydiseaseshasafavorableprognosisinchildren.Usually,thePVCswillreduceevendisappearduringfollow-up.ThepatientswithPVCsduetomyocarditisshouldbepreferredusemyocardialnutrientcombinedwithIVIG.

简介：TheeffectofTPA,apotenttumorpromoter,onSSV-NIH3T3cellsinserum-freemediumwasinvestigated.TPAstimulatedDNAsynthesisofSSV-NIH3T3cellsonthethirddayofcultureinSFM.InSDS-PAGFofmediumconditionedbyTPA-treatedSSV-NIH3T3cells(inSFM+TPA),theamountsoffourproteinsof31.0Kd,28.5Kd,25.5Kdand13.5Kdstrikinglyincreasedoverthatofnon-TPA-treatedcounterpart(inSFM).ThePDGF-likeactivitywasalsodetectedinCMofSFM+TPA.WheninsulinandEGFweredrownofftheSFM+TPA(SFM-Ins-EGF+TPA),TPAlostitsabilitytostimulateDNAsynthesisofSSV-NIH3T3cellsonthethirddayandSDS-PAGEoftheconditionedmediumshowedthattheamountsofthefourproteinsnotedabovegratelyreduced.However,cellsinSFM-Ins-EGF+TPAwereinalmostthesamegrowthconditionascellsincompleteSFM+TPAonthethirddayofculture.Resultswerediscussedinthepaper.

简介：AbstractThere is increasing evidence that cell-free DNA (cfDNA) in spent culture media (SCM) can be amplified for genetic testing. Therefore, this paper reviews the characteristics of cfDNA, including its fragment size, amount, origin, as well as some factors affecting the success rate of its amplification, together to provide researchers with a more comprehensive perspective on embryonic cfDNA. The origin of cfDNA in SCM is complicated and poses challenges to the interpretation of genetic test results. Advanced molecular techniques should distinguish between embryonic and contaminated DNA to maximize the success rate of amplification and analysis. Recent data showed that the type of culture medium, assisted hatching or not, the type of amplification kit, and fresh or thawed embryos were not related to the success rate of amplification, but the length of culture time might affect the success rate. The longer culture time, the more cfDNA is available in the SCM. Then we focused on the concordance between trophectoderm (TE), inner cell mass, whole embryo, and embryonic cfDNA. Despite successful amplification, the concordance between TE and embryonic cfDNA was low. In summary, non-invasive genetic testing using SCM could represent a major advance in future single embryo selection, however, contamination and timing for media collection are key factors affecting the results, and current non-invasive cfDNA testing should not be directly applied to clinical practice. Further research is needed to improve the methods used for testing techniques and genetic analysis to achieve greater accuracy and trace its origins before it can be used in the clinics.

简介：AbstractBackground:Total ankle replacement (TAR) is a viable option for the treatment of end-stage ankle arthritis. In China, the INBONE-II implant is the only total ankle prosthesis approved since 2016. The purpose of this study is to report a large sample of findings for the TAR with INBONE-II prosthesis.Methods:A total of 64 patients with end-stage ankle arthritis, who underwent primary TAR using INBONE-II by the same surgeon from 2016 to 2019, at a single institution were included in this retrospective, single-center study. Clinical data, radiographic findings, survival rate, and complications were recorded and assessed pre-operatively and at the most recent follow-up.Results:A total of 64 patients were available for follow-up at least 2 years after surgery; the mean follow-up duration for clinical outcomes was 37.9 months (24–59 months), and for radiographic findings was 22.8 months (12–59 months). There were significant improvements (P < 0.01) in the American Orthopedic Foot and Ankle Society hindfoot scale, the visual analog scale for pain, and the Short Form-36. There were statistically significant differences between pre-operative and post-operative comparisons of the talar tilt angle (TT) and the tibial lateral surface angle (TLS) in the radiographic findings (TT from 4.7 ± 4.3° to 1.3 ± 1.3°, TLS from 80.4 ± 7.7° to 87.4 ± 2.3°, P < 0.01). There was no statistically significant difference in improvement of the tibial anterior surface angle (P = 0.14). Ten complications (all low grade) were recorded according to the Glazebrook classification system. The survivorship of the prosthesis was 100% (64/64).Conclusion:Patients who underwent TAR with INBONE-II prosthesis demonstrated significant improvements in all measures of pain and function as well as in radiographic findings. High survival and a low incidence of complications were observed in this study.

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.

简介：AbstractBackground:Pharmacological factors used to induce insulin resistance (IR) in in vitro models may not mimic the full in vivo features of type 2 diabetes mellitus (T2DM). This study aimed to examine the ability of diabetic serum (DS) to induce IR and investigate whether adipose-derived mesenchymal stem cell conditioned medium (ADMSC-CM) reverses DS-induced IR.Methods:DS was obtained from newly diagnosed T2DM patients. IR was induced in differentiated 3T3-L1 cells by employing dexamethasone, tumor necrosis factor alpha (TNF-α), palmitate and DS. Glucose uptake (2-[N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino]-2-deoxyglucose(2-NBDG) uptake assay), intracellular levels of reactive oxygen species (ROS), and superoxide radicals (O2-) (fluorescence microscopy and fluorometry) were analyzed in control and experimental samples. mRNA expression of key genes involved in glucose transport and inflammation were analyzed by using reverse transcription polymerase chain reaction (RT-PCR). Pro-inflammatory cytokines and phospho-insulin receptor substrate (IRS) (Ser-307) protein expression were analyzed by fluorescence activated cell sorter analysis. Statistical significance was determined by using one-way ANOVA followed by Tukey's multiple comparison tests.Results:ADMSC-CM significantly increased the DS-mediated decrease in 2-NBDG uptake (11.01 ± 0.50 vs. 7.20 ± 0.30, P < 0.01) and reduced DS-driven ROS (fluorescence count, 6.35 ± 0.46 vs. 9.80 ± 0.10, P < 0.01) and O2- (fluorescence count, 3.00 ± 0.10 vs. 4.60 ± 0.09, P < 0.01) production. Further, the ADMSC-CM restored DS-induced down regulation GLUT4 (1.52- fold, P < 0.05) as well as the up-regulation of PPARγ (0.35-fold, P < 0.01), and IKKβ (0.37-fold, P < 0.01) mRNA, and phospho-IRS (Ser-307) protein expression compared to the baseline (median fluorescence intensity, 88,192 ± 2720 vs. 65,450 ± 3111, P < 0.01). DS induced IR, similar to the traditionally used pharmacological factors, namely dexamethasone, TNF-α, and palmitate, which can be attributed to the significantly higher pro-inflammatory cytokines levels (TNF-α (2.28 ± 0.03 pg/mL vs. 2.38 ± 0.03 pg/mL, P < 0.01), interleukin 6 (IL)-6 (1.94 ± 0.02 pg/mL vs. 2.17 ± 0.04 pg/mL, P < 0.01), IL-17 (2.16 ± 0.02 pg/mL vs. 2.22 ± 0.002 pg/mL, P < 0.05), and interferon gamma (IFN-γ) (2.07 ± 0.02 pg/mL vs. 2.15 ± 0.04 pg/mL, P < 0.05)) in DS.Conclusions:DS can be explored as a novel inducer of IR in in vitro studies with further standardization, substituting the conventionally used pharmacological factors. Our findings also affirm the validity of ADMSC-CM as a prospective insulin sensitizer for T2DM therapy.

简介：调查在在hypoxic下面的gliomaangiogenesis的受体(u-PA/u-PAR)系统调节的尿激类型plasminogenactivator/urokinase-typeplasminogen的角色的目的，我们在导致的组织缺氧上学习了调节glioma的媒介的效果在人的象endothelial一样ECV304房间增长，apoptosis，在vitro的绳索形成和u-PA/u-PAR表示的变化。方法MTT试金被用来在房间增长检验变化。房间apoptosis被染色的Hoechst33258分析。Matrigel像绳索的形成试金被用来在vitro评估ECV304房间的angiogenesis能力。u-PA/u-PARmRNA的表情被量的即时RT-PCR检测。结果组织缺氧禁止了ECV304房间增长并且导致了房间apoptosis。当不normoxic调节了部分堵住的U251glioma房间的媒介(N厘米)时，Hypoxic调节了媒介(H厘米)ECV304房间增长和apoptosis上的组织缺氧的效果。U251glioma房间的H厘米也支持了在matrigel上播种的ECV304房间的绳索形成。当u-PA或u同等monoclonal抗体被增加进ECV304房间culturing媒介时，绳索形成能力部分被禁止。U251glioma房间的H厘米在ECV304房间导致了uPA和uPAR表示。这些建议那个u-PA/u-PAR系统的结论被hypoxicmicroenviroment涉及gliomaangiogenesistrigged。

简介：AbstractObjectives:To investigate the prevalence of ACADM pathogenic variants, c.985A>G and c.199T>C, for medium chain acyl CoA dehydrogenase deficiency (MCADD) in a healthy population in the southern region of Brazil.Methods:This was an observational cross-sectional study with a convenience sampling strategy. The participants were recruited from the blood bank of the Hospital de Clínicas of Porto Alegre, Brazil. A total of 1000 healthy individuals from the state of Rio Grande do Sul were included. Genotyping for the c.199T>C and c.985A>G variants was performed using real-time polymerase chain reaction (PCR) and the PCR-restriction fragment length polymorphism (RFLP) technique, respectively. Individuals considered heterozygous for c.985A>G were subjected to additional acylcarnitine profile analysis using tandem mass spectrometry. Carrier frequency was obtained by calculating the ratio of heterozygous individuals to the total number of individuals analyzed and reported with a 95% confidence interval. Allele and genotype frequencies were calculated based on the Hardy-Weinberg equilibrium.Results:The c.985A>G variant was detected as heterozygotes in three individuals (frequency of the heterozygous genotype = 1:333, allele frequency= 0.0015, minimum frequency of MCADD= 1:444,444) whose acylcarnitine profiles were within normal limits. The c.199T>C variant was not identified.Conclusions:Considering the small sample size and associated allelic heterogeneity with MCADD, these findings are believed to denote the rarity or underdiagnosis of MCADD in southern Brazil. This study provides evidence for the need for further investigation to ascertain the contribution of these diseases to child morbidity and mortality in the country.