Medical artificial intelligence （AI） is a new type of application formed by the combination of machine learning， computer vision， natural language processing， and other technologies with clinical medical treatment. With the continuous iteration and development of relevant technologies， medical AI has shown great potential in improving the efficiency of diagnosis and treatment， and service quality， but it also increases the possibility of triggering ethical issues. Ethical issues resulting from the clinical application of medical AI were analyzed， including the lack of algorithmic interpretability and transparency of medical AI， leading to information asymmetry and cognitive discrepancies； the concerning status of security and privacy protection of medical data； and the complex and unclear division of responsibilities due to the collaborative participation of multiple subjects in the clinical application of medical AI， resulting in increased difficulty in the identification of medical accidents and clarification of responsibilities. The paper proposed the principles of not harming patients’ interests， physician’s subjectivity， fairness and inclusiveness， and rapid response. It also explored the strategies and implementation paths for responding to the ethical issues of medical AI from multiple perspectives， including standardizing the environment and processes， clarifying responsibility attribution， continuously assessing the impact of data protection， guaranteeing data security， ensuring model transparency and interpretability， carrying out multi-subject collaboration， as well as the principles of being driven by ethical values and adhering to the “human health-centeredness.” It aimed to provide guidance for the healthy development of medical AI， ensuring technological progress while effectively managing and mitigating accompanying ethical risks， thereby promoting the benign development of medical AI technology and better serving the healthcare industry and patients.

OBJECTIVES: Rheumatoid arthritis (RA) imposes a heavy burden on individuals, families, and society. This study analyzed the incidence and mortality trends of RA in China from 1990 to 2023 to provide epidemiological evidence for precise prevention and control. METHODS: Data on RA incidence, age-standardized incidence rate (ASIR), deaths, and age-standardized mortality rate (ASMR) in China by sex and age group from 1900 to 2021 were extracted from the Global Burden of Disease (GBD) 2021 database. Joinpoint regression was used to analyze trends in ASIR and ASMR. An age-period-cohort model was constructed using R4.3.1 to evaluate longitudinal age trends and estimate relative risk (RR) values for period and cohort effects. RESULTS: In 2021, the number of RA cases, ASIR, deaths, and ASMR in China were 247 300, 13.70 per 100 000, 10 300, and 0.54 per 100 000, respectively. From 1990 to 2021, the ASIR of RA increased annually among both females and males, with average annual percentage changes (AAPCs) of 0.44% and 0.72%, respectively. Over the same period, ASMR declined in the total population and among females, with AAPCs of -0.78% and -1.19%, while the change in males was not statistically significant. Age-period-cohort analysis showed that the peak incidence occurred in women aged 60-64 years and men aged 75-79 years, and mortality increased with age. The period effect for incidence rose in both sexes, reaching 1.10 [95% confidence interval (CI) 0.94 to 1.27] for females and 1.14 (95% CI 1.02 to 1.27) for males during 2017 to 2021, compared with 2002 to 2006. The mortality period effect RR exhibited a downward-upward-downward pattern, decreasing to 0.56 (95% CI 0.52 to 0.61) in females and 0.75 (95% CI 0.68 to 0.82) in males in 2017 to 2021. Cohort analysis indicated that the highest incidence risk occurred in individuals born during 2012 to 2016, while the cohort effect RR for female RA mortality showed a continuous decline beginning with the 1922 to 1926 birth cohort. CONCLUSIONS The incidence and mortality risks of RA in China have continued to decline. However, with the aging of the population, the incidence and mortality risks among the elderly have increased. Middle-aged women and elderly men should receive focused attention. Health authorities should strengthen education, prevention, and screening among middle-aged women and enhance disease monitoring in elderly populations to reduce the national burden of RA.
Humans ; China/epidemiology* ; Arthritis, Rheumatoid/epidemiology* ; Incidence ; Male ; Female ; Middle Aged ; Adult ; Aged ; Cohort Studies ; Mortality/trends* ; Age Distribution ; Age Factors ; Aged, 80 and over ; Adolescent

OBJECTIVE To prepare hyaluronic acid （HA）-modified emodin （EMD）-contained multi-walled carbon nanotubes （MWCNTs） drug delivery system （HA-MWCNTs-EMD） and explore its in vitro inhibitory effect on breast cancer cells. METHODS EMD was loaded onto MWCNTs to prepare a drug delivery system MWCNTs-EMD； subsequently， the system was further modified with HA to obtain the drug delivery system HA-MWCNTs-EMD. The two drug delivery systems mentioned above were characterized. With free EMD as the reference， the drug release in vitro of the above two drug delivery systems was investigated； the uptake of EMD by two breast cancer cells （MCF-7， MDA-MB-231 cells） was detected. The impacts of the above two drug delivery systems on the expression of surface glycoprotein differentiation group 44 （CD44）， activity， apoptosis and lactate dehydrogenase （LDH） release of two breast cancer cells were detected. RESULTS The encapsulation efficiencies of MWCNTs-EMD and HA-MWCNTs-EMD were both （63.52±2.74）%， with drug loading rates of （25.01±1.83）% and （12.13± 1.96）%， particle sizes of （865.95±2.16） and （351.86±1.68） nm， polydispersity indexes of 0.54±0.02 and 0.23±0.01， and Zeta potentials of （23.87±0.14） and （－42.79±0.39） mV， respectively. The 2， 4， 6， 8， 10， 12 and 24-hour cumulative release rates of EMD in MWCNTs-EMD and HA-MWCNTs-EMD were significantly lower than those in free EMD， while the cumulative release rate of HA-MWCNTs-EMD was significantly higher than that of MWCNTs-EMD （P＜0.05）； the EMD uptakes of MWCNTs-EMD and HA-MWCNTs-EMD by the two types of breast cancer cells were significantly higher than their uptake of free EMD （P＜0.05）. Compared with the free EMD group， the MWCNTs-EMD and MWCNTs-EMD groups showed significantly higher apoptosis rate and LDH release， significantly lower surface CD44 expression （except for the MWCNTs-EMD group） and cell viability in both cell types， and the effect of HA-MWCNTs-EMD was more pronounced （P＜0.05）. CONCLUSIONS A novel drug delivery system HA-MWCNTs- EMD loaded with EMD is developed successfully； the drug delivery system has a certain slow-release effect， which can significantly reduce the activity of breast cancer cells， promote their apoptosis and increase the release of LDH， and the above anti- breast cancer effect is significantly stronger than that of free EMD and MWCNTs-EMD.

OBJECTIVE To explore the effects of Tianma xiongling zhixuan tablet on autophagy in vascular endothelial cells of rats and its potential mechanism. METHODS The rat aortic endothelial cells （RAECs） were divided into normal group， model group， blank serum group， traditional Chinese medicine （TCM） medicated serum group， autophagy blocker group， autophagy agonist group， and TCM combined with autophagy agonist group. Except for normal group， other groups were given 10 μg/mL lipopolysaccharide for 24 hours to induce RAECs inflammation injury model. Blank serum group was treated with 10% blank serum； TCM medicated serum group received 10% medicated serum derived from Tianma xiongling zhixuan tablet； autophagy blocker group was treated with 20 μmol/L of PD98059； autophagy agonist group was administered 50 μmol/L Honokiol. Lastly， the TCM combined with autophagy agonist group was given both 10% medicated serum derived from Tianma xiongling zhixuan tablet and 50 μmol/L Honokiol. The morphological characteristics of RAECs in each group were observed. The cell viability of each group， the contents of endothelin-1 （ET-1） and nitric oxide （NO）， mitochondrial reactive oxygen species， mitochondrial membrane potential， and the expression levels of PTEN-induced kinase 1 （PINK1）， Parkin， ubiquitin-binding protein （p62）， and microtubule-associated protein 1 light chain 3 （LC3） were detected. RESULTS Compared with model group， the levels of ET-1， mitochondrial reactive oxygen species， and the relative expressions of PINK1， Parkin， and LC3 proteins in the autophagy blocker group and TCM medicated serum group were decreased or down-regulated significantly （P＜0.05 or P＜0.01）； the cell viability rate （only autophagy blocker group）， NO level， mitochondrial membrane potential， and the E-mail：46164660@qq.com relative expression level of p62 protein were increased or up-regulated significantly （P＜0.05 or P＜0.01）； the pathological damage of RAECs was significantly improved， the number of cells increased significantly， and the typical paving stone-like characteristics were restored. The levels of ET-1， mitochondrial reactive oxygen species， and the relative expression levels of Parkin and LC3 proteins in the autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while cell viability rate was decreased significantly （P＜0.05）， the damage of RAECs was aggravated. Compared with the autophagy agonist group， the cell viability rate and the relative expression level of p62 protein in TCM combined autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while the levels of ET-1， the relative expression levels of PINK1， Parkin， and LC3 proteins were down-regulated significantly （P＜ 0.01）， the damage of RAECs was reversed to a certain extent. CONCLUSIONS Tianma xiongling zhixuan tablet protects vascular endothelial function by regulating mitochondrial autophagy， the mechanism of which may be associated with the regulation of PINK1/Parkin signaling pathway and the inhibition of mitochondrial autophagy.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

OBJECTIVE: To explore the role of CDGSH iron-sulfur domain 2 (CISD2) in patients with sepsis-related myocardial injury (SMI) and its predictive value for 28-day prognosis and myocardial damage through clinical studies and cell experiments. METHODS: A retrospective study was conducted. Adult patients diagnosed with sepsis admitted to the critical care medicine of Third Affiliated Hospital of Qiqihar Medical University from January 2023 to January 2024 were enrolled. The clinical data, laboratory indicators, expression level of CISD2 mRNA in peripheral blood mononuclear cells (PBMC) 24 hours after admission, and 28 days prognosis were collected. Patients were divided into SMI group [left ventricular ejection fraction (LVEF) < 0.50 or LVEF decreased by ≥ 10% from baseline] and sepsis non-myocardial injury group based on LVEF. The expression levels of CISD2 mRNA were compared between the two groups, and the correlation between CISD2 and myocardial injury was analyzed. Patients were divided into the low-expression group (CISD2 mRNA < 0.5 copy/μL) and the high-expression group (CISD2 mRNA ≥ 0.5 copy/μL) based on the expression of CISD2 mRNA, and into the survival group and the death group based on the prognosis at 28 days. The clinical characteristics were analyzed between the groups. Multivariate Logistic regression was used to analyze the independent predictors of 28-day mortality in patients with sepsis. The predictive value of CISD2 for myocardial damage and 28-day prognosis in patients with sepsis were evaluated by using the receiver operator characteristic curve (ROC curve). In addition, in vitro experiments using human AC16 cardiomyocytes was conducted. The cells were divided into control group, lipopolysaccharide (LPS) group, the LPS+transfection group with overexpression of CISD2 plasmid (LPS+p-CISD2 group), and the LPS + transfection group with negative control plasmid (LPS+p-NC group). The mRNA expression of CISD2 in cells were detected by real-time quantitative polymerase chain reaction (RT-qPCR), the protein expression of CISD2 in cells were detected by Western blotting, and the cell viability was determined by cell counting kit-8 (CCK-8). RESULTS: A total of 85 sepsis patients were included, with 32 developing myocardial injury and 53 without myocardial injury. There were 40 cases of low expression of CISD2 and 45 cases of high expression of CISD2. At 28 days, 60 cases survived and 25 cases died. The mRNA expression of CISD2 in the SMI group was significantly lower than that in the sepsis non-myocardial injury group (copy/μL: 0.41±0.09 vs. 0.92±0.13, P < 0.05). CISD2 was significantly correlated with myocardial injury in patients with sepsis (r = 0.729, P < 0.05). The proportion of LVEF < 0.50 (67.50% vs. 11.11%), sequential organ failure score (SOFA: 15.63±2.15 vs. 11.12±1.52), and acute physiology and chronic health evaluation II (APACHEII: 29.49±3.51 vs. 22.41±2.61) in the CISD2 low-expression group were significantly higher than those in the CISD2 high-expression group (all P < 0.05), while there were no significantly differences in other indicators. The Kaplan-Meier survival curve showed that the 28-day survival time of sepsis patients with in the CISD2 low-expression group was significantly shorter than that in the CISD2 high-expression group (Log-rank test: χ ² = 5.601, P < 0.05). The proportion of CISD2 low-expression and the proportion of LVEF < 0.50 in the survival group were both higher than those in the death group (80.00% vs. 33.33%, 64.00% vs. 26.67%, both P < 0.05), while there were no significantly differences in other indicators. Multivariate Logistic regression analysis showed that CIDS2 and LVEF were independent predictive factors for 28-day mortality in patients with sepsis [CIDS2: odds ratio (OR) = 3.400, 95% confidence interval (95%CI) was 1.026-11.264, P = 0.045; LVEF: OR = 2.905, 95%CI was 1.029-8.199, P = 0.044]. ROC curve analysis showed that when CISD2 was expressed at a low level, patients with sepsis were at high risk of death within 28 days and myocardial injury. The sensitivity of CISD2 in predicting the 28-day mortality of patients with sepsis was 80.00%, and the specificity was 66.67%, and the area under the curve (AUC) was 0.733 (95%CI was 0.626-0.823). The sensitivity of CISD2 in predicting myocardial injury in patients with sepsis was 83.87%, the specificity was 74.07%, and the AUC was 0.790 (95%CI was 0.688-0.871). In addition, compared with the control group, the mRNA and protein expressions of CISD2 as well as the cell activity in the LPS group were significantly decreased. The mRNA and protein expressions of CISD2 and the activity of cardiomyocytes transfected with p-CISD2 were significantly increased. CONCLUSIONS CISD2 plays a protective role in sepsis-associated myocardial injury and has good predictive value for 28-day prognosis and myocardial injury.
Humans ; Sepsis/metabolism* ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; RNA, Messenger/genetics* ; Aged ; Myocardium/metabolism*

Objective:To investigate the effect of methylene blue (MB) on motor dysfunction and its mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse models.Methods:Forty healthy male C57BL/6 mice were randomly divided into 4 groups: control group, model group, low-dose treatment group and medium-dose treatment group ( n=10); PD mouse models were established by intraperitoneal injection of 25 mg/kg/d MPTP for a consecutive 7 d; low-dose treatment group and medium-dose treatment group were pretreated intraperitoneally with MB 2 mg/kg/d or MB 10 mg/kg/d for a consecutive 3 d, respectively; and then, MPTP 25 mg/kg/d+MB 2 mg/kg/d or MPTP 25 mg/kg/d+MB 10 mg/kg/d were injected intraperitoneally into the low-dose treatment group or medium-dose treatment group for a consecutive 7 d (MPTP and MB were given at 12 h of interval). Eight d after modeling, open field experiment, pole climbing experiment and rod rotating experiment were carried out to evaluate the spontaneous movement, coordination, endurance and motor ability. And then, the mice were sacrificed; immunofluorescent staining was used to observe tyrosine hydroxylase (TH) expression in the substantia nigra; Western blotting was used to detect the expressions of TH, α-synuclein, nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-Caspase-1 and Gasdermin D (GSDMD) in the striatum and substantia nigra of mice. Contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-18 in the substantia nigra and striatum of mice were detected by ELISA. Results:Compared with the control group, the model group had shortened residence time in rod rotating, prolonged descent time in rod climbing, reduced total movement distance in open field, decreased number of TH-positive cells in the substania nigra, decreased TH protein levels in the substania nigra and striatum, and increased NLRP3, ASC, cleaved-Caspase-1, GSDMD and GSDMD-N protein levels in the substania nigra and striatum, and increased TNF-α, IL-1β and IL-18 contents in the substania nigra and striatum, with significant differences ( P<0.05). Compared with the model group, low-dose treatment group and medium-dose treatment group had prolonged residence time in rod rotating, shortened descent time in rod climbing, increased total movement distance in open field, increased number of TH-positive cells in the substania nigra, and increased TH protein levels in the substania nigra and striatum, decreased NLRP3, ASC, and cleaved-Caspase-1 levels in the substania nigra and striatum, and decreased TNF-α, IL-1β and IL-18 contents in the substania nigra and striatum, with significant differences ( P<0.05). No statistical differences in the above indexes were noted between the low-dose treatment group and medium-dose treatment group ( P>0.05). Conclusion:Low-/medium-dose MB can ameliorate motor dysfunction in PD mouse models, whose mechanism may be related to downregulate NLRP3 inflammasome and inhibit neuroinflammatory response to reduce dopaminergic neuron pyroptosis.