The prospects for bioprinting tumor models:recent advances in their applications

Three-dimensional(3D)tumor models prepared from patient-derived cells have been reported to imitate some of the biological development processes of in situ tumors in vitro.These 3D tumor models share several important characteristics with their in vivo tumor counterparts.Accordingly,their applications in tumor modeling,drug screening,and precision-targeted treatment are promising.However,the establishment of tumormodels is subject to several challenges,including advancements in scale size,repeatability,structural precision in time and space,vascularization,and the tumor microenvironment.Recently,bioprinting technologies enabling the editorial arrangement of cells,factors,and materials have improved the simulation of tumormodels in vitro.Among the 3D bioprinted tumor models,the organoidmodel has been widely appreciated for its advantages of maintaining high heterogeneity and capacity for simulating the developmental process of tumor tissues.In this review,we outline approaches and potential prospects for tumor model bioprinting and discuss the existing bioprinting technologies and bioinks in tumor model construction.The multidisciplinary combination of tumor pathology,molecular biology,material science,and additive manufacturing will help overcome the barriers to tumor model construction by allowing consideration of the structural and functional characteristics of in vitro models and promoting the development of heterogeneous tumor precision therapies.

Knowledge, attitudes and practices related to seeking medical eyecare services by adults with moderate-to-severe visual impairment in rural Yueqing, Wenzhou, China: a cross-sectional survey

AIM:To evaluate the knowledge,attitudes,and practices regarding eye-care seeking practices of visually impaired adults in a rural area Yueqing,and explore factors influencing their behavior.METHODS:A stratified sampling method was used to select 48 villages in Yueqing,from which 2400 people were selected to receive vision screenings conducted by oculists during a household visit.Those presenting visual acuity≥0.5 log MAR in either eye completed a self-designed questionnaire investigating their knowledge about medical eye-care seeking,attitudes about eye health and eye-careseeking behavior.RESULTS:Totally 165 people with moderate-to-severe visual impairment were identified(6.9%,165/2400),and 146 eligible participants were recruited(response rate:88.4%,mean age:68.6±15.0 y),among which 88(60.3%)were female.They had 82(56.2%)and 64(43.8%)monocular and binocular visual impairments respectively.A total of 67(45.9%)subjects demonstrated a high knowledge level about medical eye-care seeking and 88(60.3%)had self-rated poor vision,with 23(15%)receiving regular vision checks.The 105(71.9%)subjects had never been to hospital for an eye examination."No need"and"schedule conflicts"were the main reasons for not seeking eye care.Having extensive knowledge of medical eye-care seeking was positively associated with high education levels(OR=3.73,P=0.045)and negatively correlated with older age(OR=0.97,P=0.043).Both the self-perceived vision condition(OR=2.59,P=0.03)and regular vision check behavior(OR=6.50,P<0.01)were related with seeking eye care services.CONCLUSION:In rural Yueqing,intervention is required to increase public knowledge about seeking medical eye care among people with moderate-to-severe visual impairment,especially for the elderly and poorly education.Regular vision checks may be useful to promote their medical eye-care utilization.

Effect of TACE combined with radiotherapy on the expression of serum tumor markers and malignant molecules in patients with primary large liver cancer

Objective:To investigate the effect of TACE combined with radiotherapy on the expression of serum tumor markers and malignant molecules in patients with primary large liver cancer.Methods:A total of 90 patients with primary large liver cancer who were treated in our hospital between September 2016 and September 2018 were retrospectively analyzed and divided into the control group(n=51)who received radiotherapy and the TACE group(n=39)who received TACE combined with radiotherapy.The expression levels of serum tumor markers,angiogenesis indexes and apoptosis molecules were compared between the two groups before and after treatment.Results:Before treatment,there were no statistically significant differences in the expression levels of serum tumor markers,angiogenesis indexes or apoptotic molecules between the two groups.After treatment,the serum levels of tumor markers AFP,AFu,CGT,CEA and CA19-9 in the TACE group were lower than those in the control group;the serum levels of angiogenesis indexes HGF,VEGF,MMP-9 and EGFR were lower than those in the control group;the serum levels of apoptosis molecules Bax,Caspase-4 and Caspase-10 were higher than those in the control group,while the levels of Bcl-2 and Survivin were lower than those in the control group.Conclusion:TACE on the basis of radiotherapy can further reduce the tumor malignancy in primary large liver cancer patients.

Cuproptosis mediates copper-induced testicular spermatogenic cell death

Cuproptosis,a novel mechanism of programmed cell death,has not been fully explored in the context of spermatogenic cells.Thisstudy investigated the potential involvement of cuproptosis in spermatogenic cell death using a mouse model of copper overload.Sixty male Institute of Cancer Research(ICR)mice were randomly divided into four groups that received daily oral gavage withsodium chloride(control)or copper sulfate(CuSO_(4))at 50 mg kg^(−1),100 mg kg^(−1),or 200 mg kg^(−1),for 42 consecutive days.Micesubjected to copper overload exhibited a disruption in copper homeostasis.Additionally,significant upregulated expression of keycuproptosis factors was accompanied by a significant rise in the rates of testicular tissue cell apoptosis.Immunohistochemicalanalysis revealed the presence of ferredoxin 1(Fdx1)in Sertoli cells,Leydig cells,and spermatogenic cells at various stages oftesticular development,and the Fdx1-positive staining area was significantly increased in copper-overloaded mice.Mitochondrialdysfunction and decreased adenosine triphosphate levels were also observed,further implicating mitochondrial damage undercuproptosis.Further analyses revealed pathological lesions and blood−testis barrier destruction in the testicular tissue,accompaniedby decreased sperm concentration and motility,in copper-overloaded mice.In summary,our results indicate that copper-overloadedmice exhibit copper homeostasis disorder in the testicular tissue and that cuproptosis participates in spermatogenic cell death.These findings provide novel insights into the pathogenic mechanisms underlying spermatogenic cell death and provide initialexperimental evidence for the occurrence of cuproptosis in the testis.

Effectiveness and Safety of Moxibustion Robots on Primary Dysmenorrhea:A Randomized Controlled Pilot Trial

Objective To conduct a pilot trial to explore the effectiveness and safety of moxibustion robots in treating primary dysmenorrhea(PD)and evaluate its feasibility in clinic.Methods A total of 70 participants with PD were allocated to either moxibustion robot(MR)group(35 cases)or manual moxibustion(MM)group(35 cases)using computer-generated randomization.One acupoint Guanyuan(CV 4)was selected to receive moxa heat stimulation.Two groups of participants were given 3 menstrual cycles of MM and MR treatment respectively(once a day,5 days a session)and received another 3 menstrual cycles follow-up.The degree of pain was evaluated by short-form McGill pain questionnaire(SF-MPQ)and the symptoms of dysmenorrhea were evaluated by Cox Menstrual Symptom Scale(CMSS).The safety was measured by the occurrence rate of adverse events(AEs),including burns(blisters,red and swollen),itching,bowel changes,menstrual cycle disorder,menorrhagia and fatigue,etc.Results A total of 62 patients completed the trial,32 in MR group and 30 in MM group.Compared with baseline,scores of SF-MPQ and CMSS significantly decreased in both groups(P<0.05),and no significant difference was observed between the two groups in the 3rd and 6th menstrual cycles(P>0.05).The total occurrence rate of AEs in MR group was 2.1%,which was significantly lower than MM group(7.2%,P<0.05).Conclusions MR has the same effect as MM at SF-MPQ and CMSS in patients with PD.However,MR is safer than MM(Trial registration No.ChiCTR1800018236).