Cushing's syndrome caused by giant Ewing's sarcoma of the kidney:A case report and review of literature

BACKGROUND Primary renal Ewing’s sarcoma(ES)is extremely rare,and only two cases causing Cushing’s syndrome(CS)have been reported to date.We report that the case of an 18-year-old patient is diagnosed primary renal ES with typical CS characterized by purple stripes,weight gain,and hypertension.CASE SUMMARY CS was first diagnosed by laboratory testing.A huge tumor was revealed in the kidney following an imaging examination.Moreover,brain and bone metastases were observed.After comprehensive treatment,primarily based on surgery,primary renal ES was pathologically diagnosed with a typical EWSR1-FLI1 genetic mutation through genetic testing.Furthermore,the glucocorticoid level returned to normal.By the ninth postoperative month of follow-up,the patient was recovering well.Cushing-related symptoms had improved,and a satisfactory curative effect was achieved.CONCLUSION Primary renal ES,a rare adult malignant tumor,can cause CS and a poor prognosis.

Diagnostic efficacy of virtual organ computer-assisted analysis in measuring the volume ratio of subchorionic hematoma with serum progesterone

BACKGROUND Subchorionic hematoma(SCH)is a common complication in early pregnancy characterized by the accumulation of blood between the uterine wall and the chorionic membrane.SCH can lead to adverse pregnancy outcomes such as miscarriage,preterm birth,and other complications.Early detection and accurate assessment of SCH are crucial for appropriate management and improved pregnancy outcomes.AIM To evaluate the diagnostic efficacy of virtual organ computer-assisted analysis(VOCAL)in measuring the volume ratio of SCH to gestational sac(GS)combined with serum progesterone on early pregnancy outcomes in patients with SCH.METHODS A total of 153 patients with SCH in their first-trimester pregnancies between 6 and 11 wk were enrolled.All patients were followed up until a gestational age of 20 wk.The parameters of transvaginal two-dimensional ultrasound,including the circumference of SCH(Cs),surface area of SCH(Ss),circumference of GS(Cg),and surface area of GS(Sg),and the parameters of VOCAL with transvaginal three-dimensional ultrasound,including the three-dimensional volume of SCH(3DVs)and GS(3DVg),were recorded.The size of the SCH and its ratio to the GS size(Cs/Cg,Ss/Sg,3DVs/3DVg)were recorded and compared.RESULTS Compared with those in the normal pregnancy group,the adverse pregnancy group had higher Cs/Cg,Ss/Sg,and 3DVs/3DVg ratios(P<0.05).When 3DVs/3DVg was 0.220,the highest predictive performance predicted adverse pregnancy outcomes,resulting in an AUC of 0.767,and the sensitivity,specificity were 70.2%,75%respectively.VOCAL measuring 3DVs/3DVg combined with serum progesterone gave a diagnostic AUC of 0.824 for early pregnancy outcome in SCH patients,with a high sensitivity of 82.1%and a specificity of 72.1%,which showed a significant difference between AUC.CONCLUSION VOCAL-measured 3DVs/3DVg effectively quantifies the severity of SCH,while combined serum progesterone better predicts adverse pregnancy outcomes.

40Hz闪烁频率对阿尔茨海默病影响的研究进展

阿尔茨海默病(Alzheimer's disease,AD)是目前影响人类生活的一大病症,探究AD病因、找寻治疗方法是该领域学者的重要工作。当前,一种闪烁刺激疗法——通过伽马振荡降低β-淀粉样蛋白含量以达到治疗AD的方案已取得初步进展,有望成为AD治疗的新方向。本研究介绍了闪烁频率治疗阿尔茨海默病的方案和原理,阐述了40 Hz闪烁刺激对大脑皮层活动的影响,并对该方案目前的局限进行分析,旨在为未来开展临床研究提供思路和参考。

Lignans from Seeds of Herpetospermum caudigerum Wall.Protect Against Alcoholic Liver Injury via TGF-β/Smads Pathway in Rats

[Objectives]This study aimed to investigate the effects of lignans from seeds of Herpetospermum caudigerum Wall.(SHC)on expression of TGF-β/Smads in liver tissue of hepatic alcohol-injuried rats,and to explore its protective mechanism.[Methods]A total of 60 SD rats were randomly divided into six groups.The rats in all the groups except those in the normal group were given with white spirit by gavage for 8 weeks to establish alcoholic liver injury models.After rat models were established successfully,they were administered intragastrically with 400,200 and 100 mg/kg of lignans,respectively.The rats in the normal group were administered intragastrically with 50 mg/kg of silymarin.The administration lasted for 8 weeks,once a day.The changes in the general state,liver tissue pathology and collagen deposition of the rats were observed.The expression of TGF-β,TGF-β1 receptor 1(TβR-I),TGF-β1 receptor 2(TβR-II),Smad2/p-Smad2 and Smad3/p-Smad3 in the hepatic tissue was detected.[Results]The expression levels of TGF-β1,Smad2,p-Smad2,and p-Smad3 significantly declined,and the expression levels of TβR-I,TβR-II and Smad3 did not change significantly in the liver tissue of rats in the lignans groups and the expression levels of TGF-β,Smad2,and p-Smad3 significantly declined.Meanwhile,the expression levels of TβR-I,TβR-II,p-Smad2 and Smad3 did not change significantly in the silymarin group.[Conclusions]The lignans from SHC have significant intervention effects on alcoholic livery injury.The mechanism may be related to the inhibition of hepatic stellate cell(HSC)activation,TGF-βsecretion and p-Smad2,p-Smad3 expression in the signaling pathway.

The Spatial and Electronic Effects of Substituent Groups on the Thermal Curing of Bio-Based Benzoxazines

To explore the influence of substituent groups on thermally induced curing,eight new bio-based benzoxazines containing different substituent groups with different electron negativity and volumes were synthesized.The thermal curing of these bio-based benzoxazines was studied in detail.Combined with the curing reaction kinetics,simulation and calculation of Highest Occupied Molecular and Lowest Unoccupied Molecular values,the spatial and electronic effects of different substituent groups on the curing of benzoxazine was explored.It was found that when the substituent was located at the position directly connected to the N atom,the steric hindrance effect of the group was dominant.When the substituent group was located on the benzene ring connected to the O atom,both the electronic effect and the spatial effect influenced the curing of benzoxazine.When an electron-withdrawing group was connected ortho position to the O atom,the curing reaction was promoted due to the decreased electron cloud density of O-on the oxazine ring,making the C-O bond easier to break.When an electron-donating group was connected to the meta position of the O atom it also promoted the curing reaction,possibly because it increased the electron cloud density of the+CH2 reaction site and thereby facilitated electrophilic substitution via attack of+CH2 on the cross linking reaction centre.This work provides a deeper understanding of how spatial and electronic effects of substituents affect the curing of benzoxazine.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer

Objective:Real-word data on long-acting luteinizing hormone-releasing hormone(LHRH)agonists in Chinese patients with prostate cancer are limited.This study aimed to determine the real-world effectiveness and safety of the LHRH agonist,goserelin,particularly the long-acting 10.8-mg depot formulation,and the follow-up patterns among Chinese prostate cancer patients.Methods:This was a multicenter,prospective,observational study in hormone treatment-na?ve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen.The patients had follow-up evaluations for 26 weeks.The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen(PSA)levels.The secondary outcomes included testosterone and PSA levels,attainment of chemical castration(serum testosterone<50 ng/d L),and goserelin safety.The exploratory outcome was the monitoring pattern for serum testosterone and PSA.All analyses were descriptive.Results:Between September 2017 and December 2019,a total of 294 eligible patients received≥1 dose of goserelin;287 patients(97.6%)were treated with goserelin 10.8-mg depot.At week 24±2,the changes from baseline[standard deviation(95%confidence interval)]in serum testosterone(n=99)and PSA(n=131)were-401.0 ng/d L[308.4 ng/d L(-462.5,-339.5 ng/d L)]and-35.4 ng/m L[104.4 ng/m L(-53.5,-17.4 ng/m L)],respectively.Of 112 evaluable patients,100(90.2%)achieved a serum testosterone level<50 ng/d L.Treatment-emergent adverse events(TEAEs)and severe TEAEs occurred in 37.1%and 10.2%of patients,respectively.The mean testing frequency(standard deviation)was 1.6(1.5)for testosterone and 2.2(1.6)for PSA.Conclusions:Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

An integrated micromachined flexible ultrasonicinductive sensor for pipe contaminant multiparameter detection

Pipe contaminant detection holds considerable importance within various industries,such as the aviation,maritime,medicine,and other pertinent fields.This capability is beneficial for forecasting equipment potential failures,ascertaining operational situations,timely maintenance,and lifespan prediction.However,the majority of existing methods operate offline,and the detectable parameters online are relatively singular.This constraint hampers real-time on-site detection and comprehensive assessments of equipment status.To address these challenges,this paper proposes a sensing method that integrates an ultrasonic unit and an electromagnetic inductive unit for the real-time detection of diverse contaminants and flow rates within a pipeline.The ultrasonic unit comprises a flexible transducer patch fabricated through micromachining technology,which can not only make installation easier but also focus the sound field.Moreover,the sensing unit incorporates three symmetrical solenoid coils.Through a comprehensive analysis of ultrasonic and induction signals,the proposed method can be used to effectively discriminate magnetic metal particles(e.g.,iron),nonmagnetic metal particles(e.g.,copper),nonmetallic particles(e.g.,ceramics),and bubbles.This inclusive categorization encompasses nearly all types of contaminants that may be present in a pipeline.Furthermore,the fluid velocity can be determined through the ultrasonic Doppler frequency shift.The efficacy of the proposed detection principle has been validated by mathematical models and finite element simulations.Various contaminants with diverse velocities were systematically tested within a 14mm diameter pipe.The experimental results demonstrate that the proposed sensor can effectively detect contaminants within the 0.5−3mm range,accurately distinguish contaminant types,and measure flow velocity.

Study on the Protective Effect and Mechanism of Tibetan Medicine Ershiwuwei Songshi Pill on Acute Alcoholic Liver Injury in Rats

[Objectives]To investigate the protective effect and mechanism of Ershiwuwei Songshi Pill on acute alcoholic liver injury in rats.[Methods]Sixty male SD rats were randomly divided into normal control group,model group,polyene phosphatidylcholine(82.08 mg/kg)positive control group and Ershiwuwei Songshi Pill high(180 mg/kg),medium(90 mg/kg)and low(45 mg/kg)dose groups.The rats in each group were given corresponding drugs by intragastric administration for 3 d and fed normally.From the 4th d,all groups except the normal control group were fed with 15 mL/kg liquor(56%vol)for 7 d after 2 h of administration.After the last modeling,the levels of AST,ALT,TC,TG,SOD,GSH in serum and IL-1β,IL-6,TNF-αin liver tissue were measured.The protein expressions of Bax,Bcl-2 and Caspase3 were determined by Western blotting.HE staining was used to observe the pathological changes of liver tissue under light microscope.[Results]Compared with the model group,the body weight and the levels of SOD and GSH in the treatment group were significantly higher than those in the model group;liver index,serum ALT,AST,TC,TG,IL-1β,IL-6 and TNF-αlevels decreased significantly(P<0.01 or P<0.05);HE staining showed that there was a small amount of collagen proliferation and lymphocyte infiltration in connective tissue around the hepatic portal area in the model group,multiple inflammatory foci could be seen in the lobules,and round fat vacuoles could be seen in the cytoplasm;in each administration group,the pathological condition of the liver was mild.[Conclusions]Ershiwuwei Songshi Pill had a certain protective effect on acute alcoholic liver injury in rats,and its mechanism might be related to reducing enzyme,promoting lipid metabolism and anti-inflammation.

GhAP1-D3 positively regulates flowering time and early maturity with no yield and fiber quality penalties in upland cotton

Flowering time(FTi)is a major factor determining how quickly cotton plants reach maturity.Early maturity greatly affects lint yield and fiber quality and is crucial for mechanical harvesting of cotton in northwestern China.Yet,few quantitative trait loci(QTLs)or genes regulating early maturity have been reported in cotton,and the underlying regulatory mechanisms are largely unknown.In this study,we characterized 152,68,and 101 loci that were significantly associated with the three key early maturity traits—FTi,flower and boll period(FBP)and whole growth period(WGP),respectively,via four genome-wide association study methods in upland cotton(Gossypium hirsutum).We focused on one major early maturity-related genomic region containing three single nucleotide polymorphisms on chromosome D03,and determined that GhAP1-D3,a gene homologous to Arabidopsis thaliana APETALA1(AP1),is the causal locus in this region.Transgenic plants overexpressing GhAP1-D3 showed significantly early flowering and early maturity without penalties for yield and fiber quality compared to wild-type(WT)plants.By contrast,the mutant lines of GhAP1-D3 generated by genome editing displayed markedly later flowering than the WT.GhAP1-D3 interacted with GhSOC1(SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1),a pivotal regulator of FTi,both in vitro and in vivo.Changes in GhAP1-D3 transcript levels clearly affected the expression of multiple key flowering regulatory genes.Additionally,DNA hypomethylation and high levels of H3K9ac affected strong expression of GhAP1-D3 in early-maturing cotton cultivars.We propose that epigenetic modifications modulate GhAP1-D3 expression to positively regulate FTi in cotton through interaction of the encoded GhAP1 with GhSOC1 and affecting the transcription of multiple flowering-related genes.These findings may also lay a foundation for breeding early-maturing cotton varieties in the future.

Noninvasive fluid bubble detection based on capacitive micromachined ultrasonic transducers

Ultrasonic fluid bubble detection is important in industrial controls,aerospace systems and clinical medicine because it can prevent fatal mechanical failures and threats to life.However,current ultrasonic technologies for bubble detection are based on conventional bulk PZT-based transducers,which suffer from large size,high power consumption and poor integration with ICs and thus are unable to implement real-time and long-term monitoring in tight physical spaces,such as in extracorporeal membrane oxygenation(ECMO)systems and dialysis machines or hydraulic systems in aircraft.This work highlights the prospect of capacitive micromachined ultrasonic transducers(CMUTs)in the aforementioned application situations based on the mechanism of received voltage variation caused by bubble-induced acoustic energy attenuation.The corresponding theories are established and well validated using finite element simulations.The fluid bubbles inside a pipe with a diameter as small as 8 mm are successfully measured using our fabricated CMUT chips with a resonant frequency of 1.1 MHz.The received voltage variation increases significantly with increasing bubble radii in the range of 0.5–2.5 mm.Further studies show that other factors,such as bubble positions,flow velocities,fluid medium types,pipe thicknesses and diameters,have negligible effects on fluid bubble measurement,demonstrating the feasibility and robustness of the CMUT-based ultrasonic bubble detection technique.

Reasons for diagnostic delay in patients with out-of-hospital acute ischemic stroke

BACKGROUND： Time window is a common problem in various therapies of acute ischemic stroke, and diagnostic duration plays an important role in prognosis. OBJECTIVE： To analyze the main reasons for out-of-hospital diagnostic delay of patients with acute ischemic stroke. DESIGN ： Survey and analysis SETTING： Department of Neurology, the First Affiliated Hospital of Jinan University PARTICIPANTS： A total of 116 patients with acute ischemic stroke were selected from the Department of Neurology, the First Affiliated Hospital of Jinan University from December 2002 to December 2005, including 79 males and 37 females aged from 35 to 90 years with the mean age of （65±10） years. All patients met the diagnostic criteria of ＂mainly diagnostic points of various cerebrovascular diseases＂ established by the 4^th National Cerebrovascular Diseases Meeting in 1995. Patients having acute ischemic stroke in hospital were excluded. Moreover, 32 nurses received questionnaires of partial items. All patients and nurses provided informed consent. METHODS： （1） Information, such as social position, educational level and incomes, was added up based on questionnaires. （2） Out-of-hospital diagnostic delay was surveyed based on the recorded time of patients treated in emergency department and out-patient clinic or during hospitalization. （3） Ability of patients and nurses to identify symptoms of stroke during an early period was evaluated; meanwhile, understanding concapt of stroke and using emergent system of social medicine by patients were surveyed. Especially, whether patients understood the emergent number ＂120＂ or not and how they used it practically were investigated further. （4）Attitude and behavior of patients to stroke were surveyed. （5） Whether patients were able to identify the symptoms of stroke or not was investigated; furthermore, identification of stroke by patients and nurses was dealt with semi-quantitative analysis. The scores ranged from -10 to 10. The higher the scores were, the better the identification was. （6） All factors which was possibly related to stroke were dealt with one-way Logistic regression analysis. MAIN OUTCOME MEASURES ： （1） Out-of-hospital diagnostic delay; （2） evaluating results of general knowledge of stroke; （3） attitude and behavior to stroke; （4） identification of symptoms of stroke; （5） results of relative factors with regression analysis. RESULTS ： All 116 patients with stroke were involved in the survey of out-of-hospital diagnostic delay. Among them, 81 patients and 32 nurses finished the questionnaires of general knowledge of stroke. （1） Out-of-hospital diagnostic delay： A total of 26 patients directly received the treatment in local hospitals, and the median was 4.00 hours. Another 73 patients directly received the treatment in emergency department of our hospital. The diagnostic rate was 26% within 3 hours and 7% from 3 hours to 6 hours. （2） Evaluating results of general knowiedge of stroke： About 57% （46/81） patients and 81% （26/32） nurses knew how to use emergent number. In addition, after the onset of stroke, 26% （21/81） people knew how to call the first aid; however, only 19% （15/18） cases gave a telephone call of first aid. Among them, about 53% （43/81） patients and 81% （26/32） nurses cleady understood what stroke was. Only 22% （18/81） patients realized that the best time for treating stroke was within 6 hours after its onset. （3） Attitude and behavior to stroke： Once stroke was occurred, about 47% （38/81） patients directly received the treatment in some famous hospital; meanwhile, 25% （20/81） patients waited for observing whether the symptoms disappeared or not; however, 27% （22/81） patients did not know what to do at the phase of onset of stroke; furthermore, 26% （21/81） patients received regular review in local clinics. （4） Identification of symptoms of stroke： Patients and nurses in this survey ware poorly able to identify symptoms of stroke. The minimal scores of patients were 6, the maximal was 9 and the median was 2; moreover, among 31 nurses, scores ranged from 0 to 8 and the median was 3. （5） Results of relative factors with regression analysis： Educational level was the basic factor for symptom identification and diagnostic delay for patient at the phase of onset of stroke （OR value = 0.466, 0.225, 9.831, P 〈 0.05）. CONCLUSION ： Patients and nurses are poorly able to identify the symptoms of stroke. Out-of-hospital diagnostic delay is related to educational level, delay treatment in local hospital or medical community, and poorly common information of stroke.

Sonographic Alteration of Basal Ganglia in Different Forms of Primary Focal Dystonia： A Cross-sectional Study

Background：Few studies have addressed whether abnormalities in the lenticular nucleus （LN） are characteristic transcranial sonography （TCS） echo features in patients with primary dystonia.This study aimed to explore alterations in the basal ganglia in different forms of primary focal dystonia.Methods：A cross-sectional observational study was performed between December 2013 and December 20 1 4 in 80 patients with different forms of primary focal dystonia and 55 neurologically normal control subjects.TCS was performed in patients and control subjects.Multiple comparisons of multiple rates were used to compare LN hyperechogenicity ratios between control and patient groups.Results：Thirteen individuals were excluded due to poor temporal bone windows,and two subjects were excluded due to disagreement in evaluation by sonologists.Totally,70 patients （cervical dystonia,n =30;blepharospasm,n =30;oromandibular dystonia,n =10） and 50 normal controls were included in the final analysis.LN hyperechogenicity was observed in 51% （36/70） of patients with primary focal dystonia,compared with 12% （6/50） of controls （P 〈 0.001）.Substantia nigra hyperechogenicity did not differ between the two groups.LN hyperechogenicity was observed in 73% （22/30） of patients with cervical dystonia,a greater prevalence than in patients withblepharospasm （33%,10/30,P =0.002） and oromandibular dystonia （40%,4/10,P =0.126）.LN hyperechogenicity was more frequently observed in patients with cervical dystonia compared with controls （73% vs.12%,P 〈 0.001）;however,no significant difference was detected in patients with blepharospasm （33% vs.12%,P =0.021） or oromandibular dystonia （40% vs.12%,P =0.088）.Conclusions：LN hyperechogenicity is more frequently observed in patients with primary focal dystonia than in controls.It does not appear to be a characteristic TCS echo feature in patients with blepharospasm or oromandibular dystonia.

Progresses in pharmaceutical and surgical management of premature ejaculation

Objective:Premature ejaculation(PE)is regarded as one of the most common male sexual dysfunctions.This review introduced several pharmaceutical and surgical methods for the management of PE.The definition,etiology,behavioral,and psychological therapy of PE were also discussed.Data sources:"Premature,""ejaculation,"or"sexual dysfuction"were used as the medical subject headings(MeSH)to obtain relevant articles before June 2019 on Pubmed,Google Scholar and CNKI.Most articles used were written in English and several Chinese articles were also cited.Study selection:Full-text articles of retrospective/prospective/randomized controlled trials were analyzed.Animal experiments and letters were excluded.Results:There are four PE sub-types:lifelong PE,acquired PE,natural variable PE,and subjective PE.Behavioral therapy,psychotherapy,medication,topical anesthetics,and surgery are currently used for the treatment of PE.However,all the above treatments have limitations.Therefore,novel ways should be investigated to more efficiently control PE.Conclusions:The pharmaceutical therapy that is currently being used in clinical practice for the management of PE is still the main choice globally due to its good efficacy.Surgery may be a choice for patients who are resistant to medication.However,it should be performed cautiously.

Angiosarcoma around Hip Joint Prosthesis

Angiosarcoma,a rare and malignant tumor,is known to be associated with prosthesis and trauma.Up to now,only a few cases related to knee prosthesis and fewer cases related to hip prosthesis have been reported.

Point-defect-driven flattened polar phonon bands in fluorite ferroelectrics

The scale-free ferroelectric polarization of fluorite MO_(2)(M=Hf,Zr)due to flat polar phonon bands are promising for nonvolatile memories.Defects are also widely introduced to improve the emergent ferroelectricity.However,their roles are still not fully understood at the atomic-level.Here,we report a significant effect of point-defect-driven flattening of polar phonon bands with more polar modes and polarization contribution in doped MO_(2).The polar phonon bands in La-doped MO_(2)(M=Hf,Zr)can be significantly flattened,compared with pure ones.However,the lower energy barrier with larger polarization of VO-only doped MO_(2) compared with La-doped cases suggest that VO and local lattice distortion should be balanced for high-performance fluorite ferroelectricity.The work is believed to bridge the relation between point defects and the generally enhanced induced ferroelectricity in fluorite ferroelectrics at the atomic-level and inspire their further property optimization via defect-engineering.

Genetic and biological characteristics of the globally circulating H5N8 avian influenza viruses and the protective efficacy offered by the poultry vaccine currently used in China

The H5N8 avian influenza viruses have been widely circulating in wild birds and are responsible for the loss of over 33 million domestic poultry in Europe, Russia, Middle East, and Asia since January 2020. To monitor the invasion and spread of the H5N8 virus in China, we performed active surveillance by analyzing 317 wild bird samples and swab samples collected from 41,172 poultry all over the country. We isolated 22 H5N8 viruses from wild birds and 14 H5N8 viruses from waterfowls. Genetic analysis indicated that the 36 viruses formed two different genotypes: one genotype viruses were widely detected from different wild birds and domestic waterfowls;the other genotype was isolated from a whopper swan. We further revealed the origin and spatiotemporal spread of these two distinct H5N8 virus genotypes in 2020 and 2021. Animal studies indicated that the H5N8 isolates are highly pathogenic to chickens, mildly pathogenic in ducks, but have distinct pathotypes in mice. Moreover, we found that vaccinated poultry in China could be completely protected against H5N8 virus challenge. Given that the H5N8 viruses are likely to continue to spread in wild birds, vaccination of poultry is highly recommended in high-risk countries to prevent H5N8 avian influenza.

Three-dimensional Printed Scaffolds with Gelatin and Platelets Enhance In vitro Preosteoblast Growth Behavior and the Sustained-release Effect of Growth Factors

Background：Three-dimensional （3D） printing technology holds great promise for treating diseases or injuries that affect human bones with enhanced performance over traditional techniques.Different patterns of design can lead to various mechanical properties and biocompatibility to various degrees.However,there is still a long way to go before we can fully take advantage of 3D printing technologies.Methods：This study tailored 3D printed scaffolds with gelatin and platelets to maximize bone regeneration.The scaffolds were designed with special internal porous structures that can allow bone tissue and large molecules to infiltrate better into the scaffolds.They were then treated with gelatin and platelets via thermo-crosslinking and freeze-drying,respectively.Vascular endothelial growth factor （VEGF） and transforming growth factor （TGF）-β1 were measured at different time points after the scaffolds had been made.Cell proliferation and cytotoxicity were determined via cell counting kit-8 （CCK-8） assay.Results：There was a massive boost in the level of VEGF and TGF-β1 released by the scaffolds with gelatin and platelets compared to that of scaffolds with only gelatin.After 21 days of culture,the CCK-8 cell counts of the control group and treated group were significantly higher than that of the blank group （P 〈 0.05）.The cytotoxicity test also indicated the safety of the scaffolds.Conclusions：Our experiments confirmed that the 3D printed scaffolds we had designed could provide a sustained-release effect for growth factors and improve the proliferation of preosteoblasts with little cytotoxicity in vitro.They may hold promise as bone graft substitute materials in the future.

Clinical outcomes and predictive model of platelet reactivity to clopidogrel after acute ischemic vascular events

Background:High on-treatment platelet reactivity (HTPR) has been suggested as a risk factor for patients with ischemic vascular disease.We explored a predictive model of platelet reactivity to clopidogrel and the relationship with clinical outcomes.Methods:A total of 441 patients were included.Platelet reactivity was measured by light transmittance aggregometry after receiving dual antiplatelet therapy.HTPR was defined by the consensus cutoff of maximal platelet aggregation >46% by light transmittance aggregometry.CYP2C19 loss-of-function polymorphisms were identified by DNA microarray analysis.The data were compared by binary logistic regression to find the risk factors.The primary endpoint was major adverse clinical events (MACEs),and patients were followed for a median time of 29 months.Survival curves were constructed with Kaplan-Meier estimates and compared by logrank tests between the patients with HTPR and non-HTPR.Results:The rate of HTPR was 17.2%.Logistic regression identified the following predictors of HTPR:age,therapy regimen,body mass index,diabetes history,CYP2C19^*2,or CYP2C19^*3 variant.The area under the curve of receiver operating characteristic for the HTPR predictive model was 0.793 (95% confidence interval:0.738–0.848).Kaplan-Meier analysis showed that patients with HTPR had a higher incidence of MACE than those with non-HTPR (21.1% vs.9.9%;χ^2 = 7.572,P = 0.010).Conclusions:Our results suggest that advanced age,higher body mass index,treatment with regular dual antiplatelet therapy,diabetes,and CYP2C19^*2 or CYP2C19^*3 carriers are significantly associated with HTPR to clopidogrel.The predictive model of HTPR has useful discrimination and good calibration and may predict long-term MACE.

Hip Squeaking after Ceramic-on-ceramic Total Hip Arthroplasty

Objective： The present study aimed to review the characteristics and influencing factors of squeaking after ceramic-on-ceramic （CoC） total hip arthroplasty （THA） and to analyze the possible mechanisms of the audible noise. Data Sources： The data analyzed in this review were based on articles from PubMed and Web of Science. Study Selection： The articles selected for review were original articles and reviews found based on the following search terms： “total hip arthroplasty”, “ceramic-on-ceramic”, “hip squeaking”, and “hip noise.” Results： The mechanism of the squeaking remains unknown. The possible explanations included stripe wear, edge loading, a third body, fracture of the ceramic liner, and resonance of the prosthesis components. Squeaking occurrence is influenced by patient, surgical, and implant factors. Conclusions： Most studies indicated that squeaking after CoC THA was the consequence of increasing wear or impingement, caused by prosthesis design, patient characteristics, or surgical factors. However, as conflicts exist among different articles, the major reasons for the squeaking rernain to be identified.

Colorectal cancer cell growth inhibition by linoleic acid is related to fatty acid composition changes

Polyunsaturated fatty acids （PUFAs） possess anti-cancer action both in vitro and in vivo. In the present study, we detected cell viability with methyl thiazolyl tetrazolium （MTT） assay and cell membrane permeability with propidium iodide （PI） fluorescence dyeing, and calculated cell membrane fluidity change as fluorescence anisotropy. Fatty acid content in cells was measured by gas chromatography/mass spectroscopy （GC/MS）, and the relationship between fatty acid composition and cell viability was studied. We observed that n-6 PUFA linoleic acid （LA） inhibited tumor cell growth at high concentrations （〉300 μmol/L）, while low concentrations （100-200 μmol/L） seemed to promote cell proliferation. Analyses of cell membrane permeability, cell membrane fluidity, and cell fatty acid composition suggested that the anti-cancer action of LA could be related to changes in the ratio of n-6 to n-3 PUFAs. We observed that pre-incubation of cancer cells with 100 μmol/L LA for 24 h enhanced cell sensitivity to the cytotoxic action of LA, whereas undifferentiated cell line LoVo seemed to have a distinct path in LA-induced death. These results showed that one of the mechanisms by which supplementation of LA induces cancer cell death could be altering the ratio of n-6/n-3 PUFAs, and this may be related to celt differentiation status.