Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

OBJECTIVES: To explore the mechanism of Circ-MYOCD back-splicing and its regulatory role in myocardial hypertrophy. METHODS: Sanger sequencing and RNase R assays were performed to verify the circularity and stability of Circ-MYOCD, whose subcellular distribution was determined by nuclear-cytoplasmic fractionation. Bioinformatics analysis and mass spectrometry from pull-down assays were conducted to predict the RNA-binding proteins (RBPs) interacting with Circ-MYOCD. In rat cardiomyocytes H9C2 cells, the effects of HNRNPH1 and HNRNPL knockdown and overexpression on Circ-MYOCD back-splicing were evaluated. In a H9C2 cell model of angiotensin II (Ang II)-induced myocardial hypertrophy, the expression of HNRNPH1 was detected, the effects of HNRNPH1 knockdown and overexpression on progression of myocardial hypertrophy were assessed, and the regulatory effect of HNRNPH1 on Circ-MYOCD back-splicing was analyzed. RESULTS: Sanger sequencing confirmed that the junction primers could amplify the correct Circ-MYOCD sequence. RNase R and nuclear-cytoplasmic fractionation assays showed that Circ-MYOCD was stable and predominantly localized in the cytoplasm. Bioinformatics analysis and mass spectrometry from the Circ-MYOCD pull-down assay identified HNRNPH1 and HNRNPL as the RBPs interacting with Circ-MYOCD. In H9C2 cells, HNRNPH1 knockdown significantly enhanced while its overexpression inhibited Circ-MYOCD back-splicing; HNRNPH1 overexpression obviously increased the expressions of myocardial hypertrophy markers ANP and BNP, while its knockdown produced the opposite effect. In Ang II-induced H9C2 cells, which exhibited a significant increase of HNRNPH1 expression and increased expressions of ANP and BNP, HNRNPH1 knockdown obviously increased Circ-MYOCD expression, decreased MYOCD expression and lowered both ANP and BNP expressions. CONCLUSIONS HNRNPH1 regulates Circ-MYOCD back-splicing to influence the progression of myocardial hypertrophy.
Animals ; Rats ; RNA, Circular/genetics* ; Cardiomegaly/metabolism* ; Myocytes, Cardiac/metabolism* ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H/metabolism* ; Cell Line ; RNA Splicing ; Angiotensin II ; RNA-Binding Proteins

Currently,emerging and re-emerging infectious diseases pose a serious threat to global health security,and have a huge impact on the economies and daily lives of countries around the world.Rapid detection and identification are crucial for monitoring,early warning,and prevention and control of infectious diseases.In recent years,with the rapid development of new materials and scientific technology,detection techniques have continued to innovate and be applied,progressively advancing towards automation,high throughput and real-time diagnosis.This article summarizes the research progress of new infectious disease diagnosis technologies,including CRISPR system,microfluidics technology,and nanoscale PCR,analyzes the advantages and limitations of various new detection technologies and their applications,and proposes prospects for the future develop-ment of detection technologies,in the hope of providing recommendations for monitoring human and animal diseases.

Objective To explore the neuroprotective effect of curcumin(Cur)on Parkinson's disease model and its mechanism.Methods Sprague-Dawley rats were randomly divided into the control(CON)group,the model(PD)group,and the low-,medium-,and highdose curcumin(Cur)groups,with ten rats in each group.Lipopolysaccharide was injected into the substantia nigra to establish a Parkinson's disease model.Rats in the Cur groups were administered Cur intraperitoneally at doses of 20 mg/kg,40 mg/kg,and 60 mg/kg daily for 21 days.α-synuclein(α-syn),nuclear transcription factor κB proteins(NF-κB,IKBα,p-NF-κB,p-IKBα)and the activation levels of astrocytes were detected in rat brain tissues by immunohistochemistry(IHC).mRNA levels of pro-inflammatory cytokines(TNF-α,IL-β,IFN-γ,IL-6),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),NADPH oxidase complex(gp47phox,gp91phox,gp67phox),and apoptosis-related factors(Bax,Bcl-2,Caspase-3,and Caspase-9)were measured by quantitative reverse transcription polymerase chain reaction(qRT-PCR).The rotarod and pole climbing tests were used to evaluate the motor coordination of the rats.Results Compared to the CON group,PD rats showed significantly increased levels of α-syn,p-NF-κB,p-IKBα proteins,activation of astrocytes,TNF-α,IL-β,IFN-γ,IL-6,iNOS,COX-2,Bax,Caspase-3,Caspase-9,gp47phox,gp91phox and gp67phox mRNA levels(P<0.05);while the Bcl-2 level was significantly decreased(P<0.05).Compared with the PD group,the medium-and high-dose Cur treatment groups inhibited the aggregation of α-syn protein,reduced the activation of the NF-κB pathway,and the expression of inflammatory and apoptosis-related factors(P<0.05).Moreover,medium and high doses of Cur significantly improved the motor coordination in rats,and compared with the PD group,the performance of rotarod and pole climbing tests was significantly improved(P<0.05).Conclusion cur may inhibit the aggregation of α-syn by suppressing neuroinflammation and oxidative stress responses,thereby improving motor coordination in Parkinson's disease rats and exerting neuroprotective effects.

Objective:To explore the risk factors for complications related to internal fixation after Inter-Tan intramedullary nail fixation in the treatment of intertrochanteric fractures in elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 314 elderly patients with intertrochanteric fractures admitted to the Seventh Medical Center of the Chinese PLA General Hospital from January 2016 to December 2020, including 100 males and 214 females, aged 60-98 years [(80.2±8.2)years]. All the patients underwent Inter-Tan intramedullary nail fixation. According to the 2018 AO/OTA classification, 103 patients were with stable fractures and 211 with unstable fractures. The patients were further divided into complication groups and non-complication groups according to the presence of the complications during the follow-up. Six patients (5.8%) with stable fractures had the complications including nonunion in 4 and cut-out in 2. Twenty-eight patients (13.3%) with unstable fractures developed the complications, including nonunion in 5, cut-out in 20, cut-through in 1, and broken nails in 2. With the internal fixation-related complications after surgery as dependent variables, and gender, age, complications [hypertension, coronary heart disease, arrhythmia, pulmonary infection, chronic obstructive pulmonary disease (COPD), renal insufficiency, diabetes], bone density, waiting time for surgery, anesthesia method, reduction method, reduction quality, tip-apex distance, head screw displacement and other influencing factors as independent variables, univariate and multivariate Logistic regression analyses were conducted on the patients with stable fractures and unstable fractures separately to screen the independent risk factors of internal fixation-related complications.Results:For the patients with stable fractures, the univariate analysis indicated significant differences in bone density and reduction quality between the complication group and non-complication group ( P<0.05 or 0.01); the multivariate Logistic regression analysis showed that bone density T value ≤-3.0 SD ( OR=33.17, 95% CI 2.40, 457.82, P<0.01) and poor reduction quality ( OR=71.38, 95% CI 3.58, 1 422.02, P<0.01) were significantly correlated with the incidence of the postoperative complications. For the patients with unstable fractures, the univariate analysis indicated significant differences in age, reduction quality, bone density, tip-apex distance, and screw displacement between the complication group and non-complication group ( P<0.05 or 0.01); the multivariate Logistic regression analysis showed that age >80 years ( OR=2.82, 95% CI 1.01, 7.93, P<0.05), bone density T value ≤-3.0 SD ( OR=6.10, 95% CI 2.06, 17.51, P<0.01), poor reduction quality ( OR=12.25, 95% CI 2.90, 51.79, P<0.01), tip-apex distance ≥25 mm ( OR=3.65, 95% CI 1.20, 11.08, P<0.05), and head screw displacement <4 mm ( OR=7.26, 95% CI 2.54, 20.81, P<0.01) were significantly correlated with the postoperative complications. Conclusion:For Inter-Tan intramedullary nail fixation of intertrochanteric fractures in elderly patients, low bone density and poor reduction quality are independent risk factors for the postoperative complications in patients with stable intertrochanteric fractures; old age, low bone density, poor reduction quality, tip-apex distance, and head screw displacement are independent risk factors for the postoperative complications in patients with unstable fractures.

Objective:To compare the failure risks between restricted and unrestricted cephalomedullary nail sliding during InterTAN intramedullary nail fixation for intertrochanteric fractures in the elderly patients.Methods:A retrospective study was conducted to analyze the data of 192 elderly patients with intertrochanteric fracture who had been admitted to Department of Orthopaedics, The Seventh Medical Center, General Hospital of the People's Liberation Army from January 2021 to December 2022. The patients were divided into 2 groups based on whether the set screws were tightened or not during surgery. In the observation group of 78 cases, there were 31 males and 47 females with an age of (80.2±7.7) years, and 23 cases of type 31-A1 and 55 cases of type 31-A2 by the AO classification. Their set screws were not tightened during surgery to allow the cephalomedullary nail sliding. In the control group of 114 cases, there were 40 males and 74 females with an age of (81.6±7.8) years, and 42 cases of type 31-A1 and 72 cases of type 31-A2. Their set screws were tightened during surgery to restrict the cephalomedullary nail sliding. The incidence of postoperative fixation complications and sliding distances of the cephalomedullary nail within 1 year after surgery were compared between the 2 groups in the total fractures and in the stable and unstable fractures as well.Results:There was no statistically significant difference in the preoperative general data between the 2 groups of patients, indicating comparability ( P>0.05). The incidence of fixation complications within 1 year after surgery was 5.1% (4/78) for the observation group and 12.3% (14/114) for the control group, showing no statistically significant difference between the 2 groups ( P>0.05). The sliding distance of the cephalomedullary nail in the observation group [7.05 (6.00, 8.25) mm] was significantly larger than that in the control group [5.65 (3.55, 7.00) mm] ( P<0.05). For stable fractures, the incidence of fixation complications within 1 year after surgery was 7.1% (2/28) for the observation group and 7.0% (3/43) for the control group, showing no statistically significant difference ( P>0.05), and the sliding distance of the cephalomedullary nail in the observation group [6.00 (5.25, 7.00) mm] was significantly greater than that in the control group [3.05 (2.00, 5.00) mm] ( P<0.05). For unstable fractures, the incidence of fixation complications within 1 year after surgery for the observation group patients [4.0% (2/50)] was significantly lower than that for the control group patients [15.5% (11/71)], and the sliding distance of the cephalomedullary nail in the observation group [8.00 (6.70, 10.00) mm] was significantly greater than that in the control group [6.00 (4.87, 7.57) mm] ( P<0.05). Conclusions:In the InterTAN intramedullary nail fixation for intertrochanteric fractures in the elderly patients, tightening of set screws is crucial because it not only increases the stability but also limits compression at the fracture site. It is recommended not to tighten the set screws for unstable fractures, but further observation is needed before it can be determined whether the set screws should be tightened or not for stable fractures.

Objective:To investigate the prevalence and mortality of dementia and assess the impact of geriatric syndromes (GS) on the risk for dementia and death in elderly population in Beijing.Methods:A cross-sectional survey was conducted in the elderly population aged ≥65 years and selected by a multi-stage sampling in Beijing during 2013-2015. Cognitive function was screened using the Chinese Revised Version of the Mini-Mental State Examination (MMSE). Then, neurological examination and psychiatric assessment were performed for those with the MMSE score lower than the cut-off value. The information about GS prevalence was also collected. The study also collected death records for all individuals from baseline until December 31, 2019. Based on the age and gender distribution from Beijing data of the 2010 Six th National Population Census, the dementia prevalence in the study population was directly standardized. Logistic regression analysis was used to evaluate the association of different forms of dementia with GS, and Cox proportional hazards regression model was used to estimate the hazard ratio ( HR) and 95% CI of death. Results:During 2013-2015, a total of 2 935 individuals completed dementia assessments, of which 167 were diagnosed with dementia. The standardized prevalence of dementia was 5.9% (95% CI: 5.0%-17.4%). The individuals with Alzheimer's disease (AD) and vascular dementia (VaD) accounted for 58.7% and 28.1% of total individuals with dementia, respectively. Aging, lower education level, urinary incontinence, and fall were risk factors for AD, while disability of activity of daily life dependence, hypertension, and stroke were found to be risk factors for VaD. After a median follow-up of 5.44 person-years, 399 deaths were recorded. The 5-year mortality risk was 2.87 (95% CI: 1.92-4.17) times and 4.93 (95% CI: 3.23-7.53) times higher for the elderly individuals with AD and VaD, respectively, compared to non-demented individuals. After adjusting for demographic, GS, and cardiovascular risk factors, the mortality risk in the elderly individuals with AD showed no significant difference compared with non-demented individuals ( HR=1.32, 95% CI: 0.89-1.97), while the mortality risk in those with VaD was 2.46 (95% CI: 1.49-4.05) times higher than that in non-demented individuals. Conclusions:The prevalence of dementia in Beijing increased significantly in the context of population aging, especially the prevalence of AD. The presence of GS increased the risks for AD and VaD, as well as the risk for death. Close attention needs to be paid to GS management in dementia prevention in elderly population.

Objective To analyze the disease burden and change trend of breast cancer mortality among Chinese women from 2013 to 2021.Methods The indicators of breast cancer-related mortality (MR),age-standardized mortality rate (ASMR),deaths,and urban-rural deaths in the Chinese Cause of Death Surveil-lance Dataset from 2013 to 2021 were collected and collated,and the trend changes of MR,ASMR,and years lost in life of premature death (YLL) were analyzed,annual percentage change (APC) was used for trend a-nalysis,and Fisher substitution test was used to compare APC in different regions.Results From 2013 to 2021,a total of 88112 cases of breast cancer died,with an average annual MR of 7.56/100000 and an ASMR of 6.34/100000.From 2013 to 2021,the MR rate of breast cancer (APC=2.12%,t=5.414,P<0.001),MR in rural areas (APC=2.84%,t=7.581,P<0.001),and YLL in rural areas (APC=1.61%,t=3.588,P=0.009) showed an upward trend in China.MR at 40-<45 years old showed a downward trend (APC=-2.76%,t=-4.689,P=0.002),and at 70-<75 years old (APC=1.41%,t=2.494,P=0.041),75-<80 years old (APC=3.05%,t=3.690,P=0.008),and 80-<85 years old (APC=1.82%,t=2.909,P=0.023).There was a statistically significant difference in APC between MR and ASMR in urban and rural areas (P<0.001).There was no significant difference in the trend of other indicators (P>0.05).Conclusion From 2013 to 2021,the disease burden of breast cancer mortality in Chinese women showed an upward trend,and the comprehensive prevention and treatment of breast cancer should be strengthened to reduce the risk of breast cancer death.

Objective:Based on the health ecological model, this paper systematically explores the influencing factors of mild cognitive impairment among the elderly herders in Nanshan pastoral area of Xinjiang, and provides the basis for local medical institutions to formulate prevention and control strategies for mild cognitive impairment among the elderly herders.Methods:A total of 1 145 valid questionnaires were collected, all of them were permanent herdsmen aged over 60 years in Nanshan pastoral area of Xinjiang were selected from June 2022 to February 2023 by stratified cluster random sampling method in a cross-sectional survey. Under the guidance of health ecological model, the research variables were included from five dimensions: physiology, psychology, behavioral lifestyle, social network and medical and health environment, and questionnaires were conducted. SPSS 23.0 was used for chi-square test and binary Logistic regression to analyze the influencing factors of mild cognitive impairment in elderly herders.Results:There were 564 males and 581 females with age of (70.84 ± 5.69) years old in the study. The prevalence rate of mild cognitive impairment among elderly herdsmen in Nanshan pastoral area of Xinjiang was 36.1%(413/1 145). Binary Logistic regression analysis showed that: personal monthly income (1 000-2 999 yuan)( OR = 0.583, 95% CI 0.366 - 0.926, P<0.05), education level (junior high school and above)( OR = 0.479, 95% CI 0.315 - 0.728, P<0.01) were the protective factors for mild cognitive impairment among the elderly herdsmen in Nanshan pastoral area. Hypertension ( OR = 1.842, 95% CI 1.256 - 2.702, P<0.01), dyslipidemia ( OR = 1.449, 95% CI 1.069 - 1.964, P<0.05) and chronic pain ( OR = 1.549, 95% CI 1.082 - 2.216, P<0.05) were the risk factors of mild cognitive impairment in elderly herders in Nanshan pastoral area. Conclusions:The prevalence rate of mild cognitive impairment among elderly herders in Nanshan pastoral area of Xinjiang is high, so it is necessary to carry out mild cognitive impairment screening as soon as possible, especially focusing on people suffering from hypertension, dyslipidemia and chronic pain, and making intervention plans to delay the occurrence and development of mild cognitive impairment and improve the quality of life of elderly herders.

Objective:To analyze the biological characteristics, phylogeny and the taxonomic status of strain 7712 (=CGMCC 1.17031=NBRC 113783=KCTC 15766) isolated from a clinical blood sample.Methods:Strain 7712 was identified by the cultural properties, cellular and colonial morphology, physiological and biochemical reactions, matrix-assisted laser desorption ionization time-of-flight mass spectrometry system, and genome correlation index analysis. The genomic phylogenetic tree was construct to analyze the taxonomic position. The virulence factors and resistance genes of strain 7712 and related strains were then compared by the online virulence factor database and online comprehensive antibiotic research database respectively.Results:Strain 7712 was urease negative, gram-negative nonfermenters, which was identified as Ochrobactrum anthropi by VITEK GN card. The 16S rRNA gene analysis showed that the strain was closely related to the members of genera Ochrobactrum and Brucella. The phylogenetic tree showed that strain 7712 was clustered together with Ochrobactrum teleogrylli LCB8 T and Ochrobactrum haematophilum CCUG 38531 T, along with genus Brucella and other Ochrobactrum species. The genome relatedness indexes analysis showed that the average nucleotide identity between strain 7712 and Ochrobactrum teleogrylli LCB8 T was 98.16%, which was higher than the threshold for prokaryotic species. Genetic prediction showed that strain 7712 carried several virulence-related genes and resistance-related genes, of which the existence of OCH gene might be responsible to the resistance to cephalosporin. Conclusions:A case of human infection caused by Ochrobactrum teleogrylli is identified, which would help promote the understanding of biodiversity of genus Ochrobactrum.