Objective To investigate the regularity of chronopharmacology of bruceolic oil emulsion ( BOE) in treating H22 tumor-bearing mice. Methods The KM mice model bearing H22 hepatocellular carcinoma was established. And then the model mice were divided into groups according to the condition of illumination and medicine intervention. After treatment for 10 days, the tumor-growth inhibitory rate, viscera indexes, and hepatic and renal function indexes were observed. Results Tumor mass and ratio of tumor mass to body mass were decreased in medication groups under the normal and disordered illumination. The tumor mass and ratio in mice treated with BOE before dark phase of normal illumination and disordered illumination, and during the dark phase of disordered illumination differed from those of the model group at the corresponding illumination phase (P<0.05) . Under normal illumination, BOE-treated mice at 10 pm of dark phase had lower liver index but higher thymus index than the model group (P < 0.05) . Under disordered illumination, BOE-treated mice at 7 am of dark phase had higher spleen index than the model group ( P < 0.05) . Conclusion BOE exerts certain inhibition of H22 hepatocellular carcinoma under both normal illumination and disordered illumination, and the effect will be better when medication is given in dark phase period.

Objective To investigate the need for and utilization of health services among six Zhiguo ethnic minority groups in Yunnan Province,aiming to provide further evidence for the improvement of healthcare.Methods Using stratified random sampling,1921 individuals from six Zhiguo ethnic minority groups,aged 15 and above,were investigated with a structured questionnaire between August and December 2022.A structured questionnaire was used to collect participants'information on health service needs and utilization.Results Am-ong the surveyed participants,the two-week prevalence rate was found to be 22.54%,while the prevalence rate of chronic diseases was 38.52%.Among the residents,the risk of two-week prevalence was higher for females(OR=1.564),individuals aged≥60 years(OR=1.727),and those who reported poorer health utility value(OR=5.277),while it was lower for residents of Keno(OR=0.470)and Lahu(OR=0.659)ethnicity,as well as those who reported higher EQ-VAS scores(OR=0.446/0.174).Meanwhile,residents aged≥45 years(OR=3.392/7.072)were at higher risk for chronic disease prevalence,while it was lower for Keno ethnicity(OR=0.409),unmarried individuals(OR=0.479),and those with higher education levels(OR=0.629/0.603),higher EQ-VAS scores(OR=0.208)P<0.05.Additionally,among the participants,the treat-ment rate for two-week illness was 14.32%,while the non-treatment rate stood at 36.49%.Furthermore,the one-year hospitalization rate was reported as 19.89%,with a corresponding rate of individuals who needed hospitalization but did not receive it being recorded at 15.86%.Among the residents,the likelihood of treatment for two-week illness was higher for females(OR=1.461)and residents aged≥45 years(OR=1.510/1.560),whereas it was lower for individuals with higher EQ-VAS scores(OR=0.445).The likelihood of hospitalization within one year was also higher for residents aged≥60 years(OR=2.029)and individuals of Nu(OR=1.599),Lisu(OR=1.688),and Keno(OR=1.968)ethnicity,whereas those with high EQ-VAS scores(OR=0.325)had a lower risk(P<0.05).Conclusion In Yunnan Province,the need for healthcare services among six Zhiguo ethnic minority groups in this study is relatively low;however,the high prevalence of chronic diseases raises concerns.The utilization of healthcare services appears to be relatively sufficient,but the utilization of outpatient services still needs to be improved.

Objective:To evaluate the efficacy of cerebral-placental-uterine ratio(CPUR)in predicting late-on-set fetal growth restriction(FGR).Methods:From May 2020 to May 2021,1255 women with singleton pregnancy who underwent prenatal examinations at the University of Hong Kong Shenzhen Hospital were selected for fetal growth and Doppler measurements at 35-37 +6 weeks of gestation.Pregnant women with birth weight of newbo-rns＜the 10th percentile were the FGR group.The pulsatility index(PI)of uterine artery(UtA),umbilical artery(UA)and fetal middle cerebral artery(MCA)were analyzed separately and in combination.ROC curve was used to analyze the cerebral-placental-uterine ratio(CPUR),cerebral-placental ratio(CPR),cerebral-uterine ratio(C-UtA)for predicting late-onset FGR;and to evaluate the sensitivity,positive and negative predictive value and of CPUR in the prediction of late-onset FGR.Results:The area under the curve(AUC)of CPUR,CPR,C-UtA and mean UtA-PI for FGR grope were 0.88,0.86,0.84 and 0.72.Under certain cut-off values and 87% specificity,the specificity of CPUR,CPR,C-UtA and mean UtA-Pifor predicting FGR group was 43.2%,46.6%,39.8% and 23.9%,respectively.The positive predictive values of CPUR,CPR,C-UtA and mean UtA-PI,UA-PI for predicting FGR group were 90.5%,71.9%,83.3%,63.6%and 5.2%,respectively.Conclusions:CPUR is more effective in predicting late onset FGR than CPR,C-UtA and mean UtA-PI.It can effectively increase the detection rate of fetal growth restrictionand reduce the FGR risk.

Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance. Herein, a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms. A disulfide bond-linked bispecific prodrug of NLG919 and JQ1 (namely NJ) was synthesized and self-assembled into a prodrug nanoparticle, which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ. Upon tumor accumulation via passive tumor targeting, the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug. NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond. JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1. In contrast, NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment, which thus restores robust antitumor immune responses. Photodynamic therapy (PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells. The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy.