Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

OBJECTIVES: To investigate the mechanism mediating the regulatory effect of miR-155-5p on proliferation of human submandibular gland epithelial cells (HSGECs) in primary Sjogren's syndrome (pSS). METHODS: Dual luciferase reporter assay was used to verify the targeting relationship between miR-155-5p and the PI3K/AKT pathway. In a HSGEC model of pSS induced by simulation with TRAIL and INF-γ, the effects of miR-155-inhibitor-NC or miR-155 inhibitor on cell viability, cell cycle, apoptosis and proliferation were evaluated using CKK8 assay, flow cytometry and colony formation assay. ELISA and RT-PCR were used to detect the expressions of inflammatory cytokines and miR-155-5p mRNA in the cells; Western blotting was performed to detect the expressions of proteins in the PI3K/AKT signaling pathway. RESULTS: Dual luciferase assay showed that miR-155-5p targets the PI3K/AKT pathway via PIK3R1 mRNA. The HSGEC model of pSS showed significantly decreased cell viability, cell clone formation ability and expressions IL-10 and IL-4 and increased cell apoptosis, cell percentage in G2 phase, expressions of TNF‑α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-Akt/AKT ratio, and PIK3R1 protein expression. Treatment of the cell models with miR-155 inhibitor significantly increased the cell viability, G1 phase cell percentage, colony formation ability, and expressions of IL-10 and IL-4 levels, and obviously reduced cell apoptosis rate, G2 phase cell percentage, expressions of TNF-α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-AKT/AKT ratio, and PIK3R1 protein expression. CONCLUSIONS In HSGEC model of pSS, inhibition of miR-155-5p can promote cell proliferation and reduced cell apoptosis by targeting PI3K1 mRNA to negatively regulate the overexpression of PI3K/AKT signaling pathway.
Humans ; MicroRNAs/genetics* ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Sjogren's Syndrome/pathology* ; Epithelial Cells/cytology* ; Submandibular Gland/cytology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Apoptosis ; Class Ia Phosphatidylinositol 3-Kinase ; Cells, Cultured

BACKGROUND:Previous studies have shown that puerarin can inhibit the differentiation of osteoclasts,and the expression of Notch signaling pathway-related proteins such as Notch1,HES1,and Jagged1 is decreased.However,the specific mechanism of the Notch1 signaling pathway for the inhibition of osteoclast differentiation by puerarin is not clear. OBJECTIVE:To explore the effect of Notch signaling pathway on puerarin inhibiting the differentiation of mouse macrophage Raw264.7 into osteoclasts. METHODS:Raw264.7 cells were divided into seven groups for intervention culture.Blank control group was cultured in high-sugar DMEM medium;the osteoclast induction group was cultured in osteoclast induction medium;the puerarin intervention group was cultured with 50 μmol/L puerarin at the same time of osteoclast induction;Notch1 siRNA control group,Notch1 siRNA group,Notch1 overexpression control group and Notch1 overexpression group were transfected with Notch1 siRNA control sequence,Notch1 siRNA,Notch1 overexpression control plasmid and Notch1 overexpression plasmid,respectively,and then cultured with osteoclast induction medium and puerarin.The number and size of osteoclasts were observed by tartrate-resistant acid phosphatase staining,the skeleton formation of osteoclasts was observed by F-actin staining,and the gene expression level of osteoclast formation markers was detected by RT-PCR. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining results showed that puerarin intervention could inhibit the generation of osteoclasts,Notch1 silencing could further reduce the number of osteoclasts,while the number of osteoclasts in the osteoclast-induced group increased significantly after Notch1 overexpression.The results of F-actin showed that Raw264.7 cells could form a well-defined F-actin ring after osteoclast induction.Puerarin intervention would inhibit the formation of cytoskeleton,and Notch1 silencing could aggravate the inhibitory effect of cytoskeleton formation,while Notch1 overexpression could alleviate this inhibitory effect of puerarin.RT-PCR results showed that puerarin could inhibit the mRNA expression levels of tartrate-resistant acid phosphatase,Cathepsin K and c-Fos,the expression of the above-mentioned three factors decreased significantly after Notch1 gene silencing,and Notch1 overexpression could upregulate the expression of these factors.These finding indicate that puerarin inhibits the differentiation of Raw264.7 cells into osteoclasts through the Notch signaling pathway.

This study aims to analyze the main drug resistance mechanism of Salmonella enteritidis induced by polymyxin in vitro.In this study,the resistance of Salmonella enteritidis CMCC(B)50335(ZK)to polymyxin was induced in vitro,and the growth characteristics,exercise ability,ul-trastructure and sensitivity to 16 antimicrobial agents before and after induction were determined by turbidimetry,semi-solid agar method,transmission electron microscope and disk diffusion method,and the whole genome and single nucleotide polymorphism(SNP)were detected by Illu-mina NovaSeq PE150 method.RT-qPCR was used to detect the differences in the expression levels of six drug-resistant related genes.The recombinant strain △phoPE1-128-1,which induced drug-resistant strain E1-128-1,was constructed by homologous recombination of Red Escherichia coli,and its sensitivity to polymyxin was detected.The results showed that three strains of induced drug-resistant bacteria E1-128-1,E1-128-3 and E2-128-3 were screened out,and the MIC increased by 128,64 and 64 times respectively after drug resistance stability test.Induced drug resistance had no significant effect on the growth ability of the tested bacteria and the sensitivity of 16 antibacte-rial drugs.The exercise ability of E1-128-1was significantly increased,and the cell wall and plasma membrane obviously thicken.There was no significant difference in the genome components of E1-128-1 before and after induction,but eight missense mutations of six drug-resistance related genes,including phoP/phoQ,cpxP,lptD,csrA and acrB,were detected,including four missense mutation sites of phoP,namely Leu185Trp,His189Ser,Thr190Tyr and Ile191His.The corresponding genes were sequenced by PCR,and the results were consistent with those of SNP.RT-qPCR results showed that the expression levels of mutant genes of the three induced strains increased signifi-cantly.Compared with E1-128-1,the MIC of △phoP E1-128-1 decreased to 1 mg/L.It is sug-gested that the mutation and increased expression of phoP gene are important factors for inducing polymyxin resistance of Salmonella CMCC(B)50335 in vitro.

Objective To analyze the prevalence,burden and risk factors of mental disorders in Chinese population from 1990 to 2019.Methods Data on disease burden of mental disorders in China from 1990 to 2019 was obtained from the Global Burden of Disease(GBD)in 2019.The prevalence,disability adjusted of life years(DALY)and burden attributable to risk factors of mental disorders were analyzed.Joinpoint was used to estimate the annual percent change average(APC)and the annual percent change(AAPC)of DALY rate of mental disorders and analyze the trend of disease burden.Results In 2019,the prevalence of mental disorders was 11260.42/100000.Among mental disorders,depressive disorder(3519.26/100000)and anxiety disorder(3363.60/100000)had the highest prevalence.In 2019,the DALY rate of females(1564.22/100000)was higher than that of males(1294.51/100000).Depressive disorder(531.65/100000),anxiety disorder(321.60/100000)and schizophrenia(250.99/100000)had the highest DALY rates,accounting for 37.26%,22.54%and 17.59%of the total DALY rates of mental disorders respectively.From 1990 to 2019,the DALY rate of mental disorders in China increased from 1321.15/100000 to 1426.78/100000,the age-standardized DALY rate decreased with an average annual decrease of 0.19%(95%CI:-0.22%～-0.15%),and the age-standardized DALY rate of eating disorders increased the most(AAPC=1.94%,95%CI:1.85%～2.02%).The DALY rate of depressive disorder attributable to intimate partner violence was the highest in China in 2019(26.72/100000).The DALY rate of male depression attributed to childhood sexual abuse increased significantly from 1990 to 2019(AAPC=0.68%,95%CI:0.26%～1.09%).Conclusion Attention should be paid to the prevention and treatment of mental disorders,screening and intervention measures should be carried out among high risk populations,and etiological prevention should be carried out according to risk factors to reduce the burden of mental disorders.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.
Humans ; COVID-19 ; Sleep Initiation and Maintenance Disorders ; Crisis Intervention ; Psychosocial Intervention ; SARS-CoV-2 ; Mental Health ; Depression/epidemiology* ; Health Personnel/psychology* ; Anxiety/etiology*

Objective: To analyze the emotional and behavioral problems and associated factors of the only and non only child, and to provide some clues for further monitoring and intervention of psychological and behavioral development among preschool children. Methods: Using a convenience sampling method, a total of 45 065 children enrolled in 153 kindergartens in 23 districts and counties of Chengdu were selected from May to June 2021 to investigate demographic characteristics and children s psycho behavioral development through online questionnaires filled out by their guardians. The Chi square tests were used to analyze whether the differences in abnormality rates of each dimension were statistically significant between the only and non only children. The emotional and behavioral problems of only children and non only children were analyzed by propensity score measurement. Results: The detection rate of abnormal emotional behavior problems in children was 6.10%, including 6.34% in the only child group and 5.84 % in the non only child group. After matching, total difficulty score, and scores of emotional symptoms, conduct problems, hyperactive attention deficit, peer interaction, and social behavior differed between the only child group and the non only child group ( t =9.91, 8.97, 3.91, 15.57, -5.46, 4.08, P <0.01). Conclusion In terms of the total score of difficulties, emotional symptoms, moral problems, and hyperactivity attention defects, the non only child is better than the only child，but the opposite is true in terms of peer interaction and social behavior. Mental health conditions among the only child should be paid more attention. Whether or not the only child should be taken as an important consideration for preschool children s mental health care.

Circadian rhythm is a phenomenon of diurnal changes in life activities formed by a transcription-translation feedback loop of biological clock genes affected by external environmental conditions. The circadian rhythm system controls almost all physiological processes in the organism, and these processes will change as the external environment changes. Previous studies have shown that the hypothalamic-pituitary-thyroid axis in mammals is regulated by the central diurnal pacemaker of the suprachiasmatic nucleus of the hypothalamus, so part of the thyroid function is controlled by the biological clock, and the secretion of thyroid hormones in blood can present a circadian rhythm. However, the molecular mechanism of the biological clock's regulatory effect on thyroid is still unclear. Whether circadian rhythm interference is related to the disorder of thyroid function or the occurrence of thyroid diseases is worthy of attention. This paper focused on the research progress of biological clock, circadian rhythm, and thyroid function, specifically the characteristics of circadian rhythm of thyroid physiological function and the effects of sleep deprivation, light at night, and night shift work on thyroid function, elaborated the relationships of circadian rhythm disorder with thyroid function and thyroid diseases represented by thyroid malignant tumors. The review summarized that circadian rhythm disorder may disrupt the rhythmic secretion of thyroid hormones, but no clear conclusion is reached yet on any effect on thyroid diseases, especially thyroid malignant tumors, so it is necessary to further strengthen the relevant epidemiological and molecular mechanism research.

Objective:To evaluate the left ventricular myocardial strain in patients with light chain cardiac amyloidosis (AL-CA) with normal left ventricular ejection fraction (LVEF) by three-dimensional speckle tracking imaging(3D-STI), and to explore the clinical value of 3D-STI in predicting the prognosis of AL-CA patients with normal LVEF.Methods:A total of 80 patients with AL-CA and LVEF≥50% were retrospectively analyzed in the Xijing Hospital of Air Force Military Medical University from October 2014 to May 2020.According to whether the patients had endpoint events, they were divided into endpoint event group and non-endpoint event group. The clinical data, conventional echocardiographic parameters, 3D-STI related parameters and follow-up results were collected. Cox regression proportional hazards model was used to analyze the survival status of AL-CA patients with univariate and multivariate regression analyses, in order to find the relevant indicators of conventional echocardiography and 3D-STI to predict adverse events.Results:All patients were followed up for 20(7.3, 40.8) months. At the end of follow-up, 25 patients had all-cause deaths. Compared with the non-endpoint group, the endpoint event group had significantly increased left ventricular end diastolic maximum wall thickness (MLVWT), peak early diastolic flow velocity/peak early diastolic velocity at mitral annulus(E/e′) (all P<0.05), and decreased LVEF, left ventricular global longitudinal strain (GLS) and basal segment longitudinal strain (LS) (all P<0.05). Multivariate cox regression analysis after adjusting for age and gender showed that basal segment LS ( HR=0.812, 95% CI=0.675-0.976, P=0.026) was an independent predictor of end-point events in patients with AL-CA. Kaplan-Meier survival curve showed that AL-CA patients with basal segment LS≤13.07% were more likely to have endpoint events. Conclusions:Basal segment LS can be used as a predictor of endpoint events in patients with AL-CA.