Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

Humans ; East Asian People ; Surveys and Questionnaires ; Vitiligo/epidemiology*

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg^-1·d^-1） or AAⅠ（5 mg·kg^-1·d^-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L^-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min^-1. Positive ion mode of electrospray ionization（ESI⁺） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MS^E was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.

Objective The metabolism and excretion of isochlorogenic acid B in rats were investigated by UHPLC-MS.Methods Feces,urine and plasma were individually collected before and at different time points after administration of 20 mg·kg-1.Post-prepared samples were analyzed by UHPLC-MS.Results According to the retention times,m/z,characteristic fragment ions and related literature,a total of 22 metabolites were detected,of which 18 metabolites were present in rat feces,3 metabolites in urine and one metabolite in plasma.The main metabolic pathways contain hydrolysis,hydrogenation,methylation,sulfation and so on.The cumulative excretion of isochlorogenic acid B and its main metabolite chlorogenic acid in feces and urine was further performed.Conclusion The metabolism and excretion of isochlorogenic acid B in rats were explored to provide experimental basis for its further research and development.

Purpose: This study aimed to investigate reproductive concerns among breast cancer patients of reproductive age, analyze the influencing factors, explore the relationship between coping styles, fear of progression (FOP), and reproductive concerns, and identify the multiple effects of coping styles on the relationship between FOP and reproductive concerns among Chinese breast cancer patients. Methods: A cross-sectional, descriptive study was conducted among breast cancer patients in four tertiary grade A hospitals in Fujian, China, from January 2022 to September 2022. A total of 210 patients were recruited to complete paper-based questionnaires, which included the general data questionnaires, the Reproductive Concerns After Cancer Scale (RCACS), the Fear of Progression Questionnaire-Short Form (FOP-Q-SF), and the Medical Coping Modes Questionnaire (MCMQ). Structural equation models were utilized to evaluate the multiple effects of coping styles on FOP and reproductive concerns. Results: Reproductive concerns in breast cancer patients had a mean score of 53.02 (SD, 10.69), out of a total score of 90, and coping styles for cancer (confrontation, avoidance) were closely associated with FOP and reproductive concerns. FOP showed a significant positive correlation with reproductive concerns (r = .52, p < .01). At the same time, confrontation was significantly negatively correlated with both FOP (r = −.28, p < .01) and reproductive concerns (r = −.39, p < .01). Avoidance was positively correlated to both FOP (r = .25, p < .01) and reproductive concerns (r = .34, p < .01). The impact of FOP on reproductive concerns is partially mediated by confrontation and avoidance, with effect sizes of .07 and .04, respectively. These mediating factors account for 22.0% of the total effect. Conclusions The FOP directly impacted reproductive concerns, while coping styles could partially mediate the association between FOP and reproductive concerns. This study illustrates the role of confrontation and avoidance in alleviating reproductive concerns, suggesting that it is necessary to focus on the changes in reproductive concerns among reproductive-age breast cancer patients. Healthcare professionals can improve disease awareness and reduce patients' FOP, thereby promoting positive psychological and coping behaviors and ultimately alleviating reproductive concerns.

Objective:To investigate the clinical significance of grip strength, three simple lung functions[functional volume capacity(FVC), forced expiratory volume in the first second(FEV1)and peak expiratory flow(PEF)], 6-minute walking distance test(6MWD)and left ventricular ejection fraction(LVEF)for assessing overall integrative function in elderly versus non-elderly patients with coronary artery disease(CAD).Methods:A total of 35 hospitalized CAD patients aged 70.4±10.6 years from January 2017 to December 2018 were retrospectively enrolled.Patients were divided into the non-elderly group(<65 years, n=8)and the elderly group(≥65 years, n=27). FVC, FEV1 and PEF were tested by a portable lung function machine.The grip strength, 6MWD, three simple lung functions(FVC, FEV1, PEF), LVEF and echocardiography were detected after admission.The above indexes were re-examined in outpatient clinic at 3 months after discharge.The results of above indexes were compared at admission versus at three months after discharge.The consistency and correlation between FVC, FEV1, PEF, 6MWD, grip strength and LVEF were analyzed.Results:The detected results of FVC, FEV1, PEF, 6MWD, left-hand grip strength, right-hand grip strength and LVEF showed no significant difference at admission versus at 3 months after discharge( P>0.05)in a total of 35 hospitalized CAD patients.Pearson bivariate correlation analysis showed that FVC, FEV1, PEF, left-hand and right-hand grip strength had pairwise correlation between them( P<0.01).6MWD had no correlation with LVEF.And LVEF was related with FVC and FEV( P<0.01), but not related with PEF, 6MWD and grip strength( P>0.05). The detective values of FVC, FEV1, PEF, 6MWD, left-hand and right-hand grip strength were lower in the elderly group than in the non-elderly group[(2.11±0.66 )L vs.(2.88±0.55) L, (1.74±0.46 )L vs.(2.62±0.49 )L, (5.50±1.79 )m/s vs.(8.22±1.59) m/s, (332.07±115.58)m vs.(446.14±99.81 )m, (25.14±7.87) vs.(35.15±8.30), (27.37±8.39 )kg vs.(38.37±10.20)kg, P<0.01]. LVEF had no significant difference between the two age groups. Conclusions:FVC, FEV1, PEF, 6MWD and grip strength are lower in elderly group than in non-elderly group.A comprehensive set of tests of grip strength, three simple lung function and 6MWT is helpful to evaluate the overall integrative function in elderly CHD patients.

【Objective】 To compare the enhancement effects of lean body weight （LBW） and total body weight （TBW） as indexes to calculate the contrast agent dosage under the condition of energy spectrum CT scanning. 【Methods】 A total of 218 patients who received liver enhancement CT from November 2018 to January 2019 were enrolled in this study. There were 101 patients in LBW group and 117 patients in TBW group. Both groups were scanned by energy spectrum CT， and the parameters of scanning and reconstruction were identical. The contrast agent dose was 500 mgI/kg （LBW） in LBW group and 450 mgI/kg （TBW） in TBW group， and the injection rate was 2.8 mL/s. Images were transferred to a GE AW4.7 workstation and the 50 keV monochromatic images were analyzed. We compared the dosage of contrast medium， CT value of aorta in arterial phase （HU-aorta）， hepatic enhancement CT value in venous phase （-liver）， the rate of reaching the enhancement standard and variability in the two groups. 【Results】 Compared with TBW group， LBW group had lower contrast agent dosage， HU-aorta and ∆-liver （P<0.05）， LBW and TBW group had no statistically different enhanced rate of HU-aorta as （91.09% vs. 90.60%） or ∆-liver （92.08% vs. 88.89%） （P>0.05）. The variation rate of HU-aorta and ∆-liver in LBW group was lower than that in TBW group. Using LBW as an index to calculate the dosage of liver enhanced CT also made the enhancement of liver parenchyma more consistent in different patients. 【Conclusion】 Even on the premise of energy spectrum CT scanning， using LBW-based contrast injection in liver enhanced CT can not only reduce contrast dose， but also make the enhancement in liver parenchyma more consistent among different patients.

Objective To explore the effects of NF-E2-related factor 2 (Nrf2) overexpression on mitochondrial biosynthesis and function in melanocytes.Methods An immortalized human vitiligo melanocyte cell line PIG3V was used in this study.An overexpression plasmid Nrf2-pEX-1 containing the full-length Nrf2 gene was constructed.PIG3V cells were divided into 3 groups:blank group receiving no treatment,control group transfected with the pEX-1 plasmid,overexpression group transfected with the Nrf2-pEX-1 plasmid.After transfection,real-time quantitative reverse transcription-PCR (RT-PCR) and Western blot were performed to determine the mRNA and protein levels of mitochondrial biosynthesis-related factors (including Nrf2,nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM)) respectively;RT-PCR was also conducted to measure the copy number of mitochondrial DNA (mtDNA),and flow cytometry to estimate mitochondial membrane potential (MMP);luciferase reporter system was used to estimate the intracellular adenosine triphosphate (ATP) level.Statistical analysis was carried out by using a two-sample t-test.Results After transfection,a significant increase was observed in the mRNA expression levels of Nrf2 and NRF1 at 24 hours (both P ＜ 0.001) and in those of Nrf2 and TFAM at 48 hours (both P ＜ 0.05),but no significant change was noted in the mRNA expression level of TFAM at 24 hours (P ＞ 0.05) or in that of NRF1 at 48 hours (P ＞0.05) in the overexpression group compared with the control group.In the case of Nrf2,NRF1 and TFAM protein levels,the overexpression group showed significant increases compared with the control group at 48 hours after transfection (all P ＜ 0.05),while no significant difference was noted between the two groups at 24 hours.Compared with the control group,MMP in the overexpression group increased by 2.313％ at 24 hours (t =5.546,P =0.005) and by 14.872％ at 48 hours (t =8.537,P =0.001) after transfection.Both the relative copy number of mtDNA and ATP level were similar between the overexpression group and control group at 24 hours after transfection (both P ＞ 0.05),but significantly higher in the overexpression group than in the control group at 48 hours (t =5.760,P =0.005;t =22.040,P =0.008).Conclusion Up-regulation of Nrf2 pathway can improve mitochondrial function and biosynthesis in PIG3V cells likely by promoting the expressions of mitochondrial biosynthesis-related genes and proteins.

Objective To explore the distribution and drug resistance of pathogen in hospitalized tumor patients and to provide reference for the clinical reasonable use of antibiotics and strengthening the hospital infection control. Methods 6 500 clinical speciments were tested in hospitalized tumor patients from January to December,2013.The drug susceptibilities were tested by automated microbiology system or Kirby-Bauer disk dilution method.Drug susceptibility tests were evaluated according to CLSI standard 2012.WHONET5.6 software data were used to analyze the data.The clinical distribution and the resistance results of bacterial were analyzed retrospectively. Results A total of 2 093 strains of pathogens were isolated from 6 500 clinical speciments,among these strains, the gram-negative bacteria accounted for 55.23%,the gram-positive bacteria accounted for 11.08%,and the fungi accounted for 33.68%.Klebsiella pneumoniae,Escherichia coli,Pseudomonas aeruginosa ranked the top three species of pathogens, accounting for 16.63%, 9.60%, and 7.98%, respectively. Staphylococcus aureus, Candidaalbicans ranked the first place of gram-positive bacteria and fungi,respectively.The antibiotic resistance of Escherichia coli was strong in Enterobacteriaceae, and its resistance rates to penicillins,cephalosporins, and quinolones were more than 60%.Of the Staphylococcus,the methicillin-resistant Staphylococcus aureus(MRSA) accounted for 10.00% and the coagulase-negative Staphylococcus (MRCNS)accounted for 87.10%.There was no vancomycin resistant Staphylococcus aureus and coagulase-negative Staphylococcus detected. Enterobacteriaceae strains were found most sensitive to imipenem;gram-positive bacteria were found most sensitive to vancomycin. Conclusion The hospitalized tumor patients are susceptible to pathogens, and the gram-negative bacteria are the predominant isolated pathogen.Etiology inspection and monitoring of antibiotics sensitivity provide experimental basis for clinical infection control and prevention.

Objective To identify the pathogen of an acute epidemic gastroenteritis outbreak in newborn room. Methods Forty five samples were collected from 38 newborn patients at the peak of a diarrhea outbreak, which happened in a newborn room in Inner Mongolia Autonomous Region during December 2008 to February 2009. The presence of rotavirus antigen, Adeno-like virus antigen and Astrovirus antigen were detected by enzyme-linked immunosorbent assay (ELISA). The presence of Astrovirus RNA were detected by reverse transcriptase polymerase chain reaction (RT-PCR) with universal primer of Astrovirus. Thirteen samples positive for Astrovirus nucleic acid were analyzed by sequencing and phylogenetic tree. Four samples positive for both Astrovirus antigen and Astrovirus nucleic acid were observed by immune electron microscopy. Results Both rotavirus antigen and Adeno-like virus antigen were negative in 45 faecal samples. Thirty samples were positive for Astrovirus antigen when checked by ELISA, which resulted in a positive rate of 66.7%. Thirty-one samples were positive for Astrovirus RNA when check by RT-PCR, which resulted in a positive rate of 68.9%. The genotype results confirmed all patients were infected with genotype 1 Astrovirus. The gene sequences of thirteen samples were compared with reference strains of Astrovirus type 1 in GeneBank and the homology rate of nucleotide sequence was 90.9 %- 96.3 %. The homology rate of intra these thirteen sample was 94.7%-100.0%. Four positive samples were randomly selected and observed by immune electron microscopy and a large amount of Astrovirus particles were found in two of these samples. Conclusion Genotype 1 Astrovirus is the pathogen of this diarrhea outbreak in newborn.