OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVES: To investigate the role of activating transcription factor 3 (ATF3) in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis (AS) progression. METHODS: Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting. Apolipoprotein E-deficient (ApoE^-/-) mouse models of AS induced by high-fat diet (HFD) feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9 (AAV9) to knock down ATF3 expression. After an additional 5 weeks of HFD feeding, the mice were euthanized for analyzing structural changes of the aortic plaques, and the expression levels of ATF3, inflammatory factors (CD45, CD68, IL-1β, and TNF-α), and NF-κB pathway proteins (P-IKKα/β and P-NF-κB p65) were detected. In the cell experiment, THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF‑κB signaling. RESULTS: In human atherosclerotic plaques, ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE^-/- mice significantly increased aortic plaque volume, upregulated the inflammatory factors, enhanced phosphorylation of the NF‑κB pathway proteins, and increased the expressions of VCAM1, MMP9, and MMP2 in the plaques. In THP-1-derived foam cells, ATF3 silencing caused activation of the NF‑κB pathway, while ATF3 overexpression suppressed the activity of the NF-κB pathway. CONCLUSIONS AS promotes ATF3 expression, and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway, suggesting the potential of ATF3 as a therapeutic target for AS.
Animals ; Activating Transcription Factor 3/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Humans ; Mice ; Plaque, Atherosclerotic/metabolism* ; Inflammation/metabolism* ; Apolipoproteins E ; Atherosclerosis/metabolism* ; Diet, High-Fat

Objectives:To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district.Methods:Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods.Results:The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/10 5 and 597.51/10 5, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P＜0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P＞0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P＜0.05) and females showing a downward trend (AAPC=-1.67%, P＜0.05). Conclusions:The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.

Objectives:To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district.Methods:Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods.Results:The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/10 5 and 597.51/10 5, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P＜0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P＞0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P＜0.05) and females showing a downward trend (AAPC=-1.67%, P＜0.05). Conclusions:The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.

Objective To investigate the endoscopic ultrasonography(EUS)features of benign esophageal stenosis in children.Methods A retrospective analysis was conducted on the medical data of the children who were diagnosed with benign esophageal stenosis from February 2019 to February 2022.The clinical manifestations,EUS findings,and treatment outcome were analyzed to summarize the EUS features of benign esophageal stenosis in children.Results A total of 42 children with benign esophageal stenosis were included.Among these children,19(45% )had anastomotic stenosis after surgery for esophageal atresia,with unclear echogenic boundary of the esophageal walls and uneven thicknesses of the surrounding wall on EUS,and had 0-12 sessions of endoscopic treatment(average 2.1 sessions);5 children(12% )had corrosive esophageal stenosis and 1 child(2% )had physical esophageal stenosis,with unclear stratification of the esophageal walls on EUS,and they had 2-9 sessions of endoscopic treatment(average 5.3 sessions);1 child(2% )had patchy irregular hypoechoic areas of the esophageal walls on EUS and was diagnosed with tracheobronchial remnants with reference to pathology;16 children(38% )had unexplained esophageal stenosis and unclear stratification of the esophageal walls on EUS,among whom 6 received endoscopic treatment.During follow-up,95% (40/42)of the children had significant alleviation of the symptoms such as vomiting and dysphagia.Conclusions For benign esophageal stenosis in children,EUS can help to evaluate the degree of esophageal wall involvement in esophageal stenosis lesions,possible etiologies,and the relationship between the esophagus and the lesion and provide an important basis for selecting treatment modality and avoiding complications,thereby helping to optimize the treatment regimen.[Chinese Journal of Contemporary Pediatrics,2024,26(2):169-173]

Objective To investigate the causes of a cluster of suspected neonatal carbapenem-resistant Klebsiella pneumoniae(CRKP)bloodstream infection(BSI)in the neonatal department of a hospital,and provide references for the effective control of the occurrence of healthcare-associated infection(HAI).Methods Epidemiological in-vestigation on 3 neonates with CRKP BSI in the neonatal department from January 31 to February 6,2023 was per-formed.Specimens from environmental object surfaces were taken for environmental hygiene monitoring,and effec-tive control measures were taken according to the risk factors.Results From January 31 to February 6,2023,a to-tal of 60 neonates were admitted in the neonatal department,including 16 with peripherally inserted central venous catheter(PICC).Three neonates had CRKP BSI,with a incidence of 5.00％.There were 33 hospitalized neonates on the day(February 7)when the cluster of HAI was reported,with a prevalence rate of 9.09％(3/33).CRKP BSI rate in the neonatal department of this hospital from January 31 to February 6,2023 was higher than that in 2022(P＜0.001).The incubators of the 3 neonates with CRKP BSI were in the same ward and adjacent to each other.The first neonate with CRKP BSI(who developed BSI on January 31)underwent PICC maintenance on Feb-ruary 4,and the other 2 neonates with PICC maintenance immediately following the first one also developed CRKP BSI.CRKP were isolated from blood culture of all 3 neonates,and antimicrobial susceptibility testing results were consistent.Conclusion The occurrence of the cluster event of neonatal CRKP BSI may be related to the failure of strict implementation of aseptic procedures during PICC maintenance and cross contamination among items.

Aim To explore the feasibility of the cloud exposure system for in vitro exposure experiments on inhalation toxicology.Methods Calu-3 cells cultured at the air-liquid interface(ALI)were exposed to three concentrations of lipopolysaccha-ride(LPS):high,medium,and low(800,400,200 mg·L-1)by the cloud exposure system,and phosphate buffer solu-tion(PBS)was used as a negative control group for one expo-sure,while the high concentration of LPS was used to expose Calu-3 cells for five times.Calu-3 cells were exposed to phos-phate buffer solution(PBS)once as negative control group and to high concentration of LPS solution for five times,and the ac-tivity of Calu-3 cells,the release of lactate dehydrogenase(LDH),TEER,mucin MUC5AC,and the expression of inflam-matory factors IL-6,IL-8 and TNF-α were detected 3 h and 24 h after the end of the exposure,respectively.Results Compared with the PBS-negative control group,after exposure to the Calu-3 cell model at the air-liquid interface with three concentrations of LPS,high,medium,and low,there were no significant changes in the activity and LDH release,but the cellular electrical resist-ance value was reduced,and the barrier function of the cells was impaired;with the increase of the exposure concentration,the LPS promoted the expression of the cellular mucin MUC5AC,which led to a decrease in the expression of cellular IL-6,IL-8,and a decrease in the expression of TNF-α.Expression of IL-6 and IL-8 decreased and TNF-α expression increased;as the fre-quency of exposure increased,LPS inhibited the expression of mucin and increased the expression of IL-6;an increase in the frequency of exposure along with a prolongation of post-exposure assay time resulted in an increase in the expression of cellular IL-8 and TNF-a.Conclusions The ALI cloud exposure ap-proach can effectively reflect the cellular response to positive subjects,and this in vitro exposure can be used in subsequent exposure experiments to evaluate the inhalation toxicity of com-pounds.

Objective To explore the potential category characteristics of self-management behavior in patients with lung cancer based on potential profile analysis,and to analyze the characteristic differences and influencing factors of self-management behavior in patients with different categories of lung cancer.Methods A total of 260 patients with lung cancer who had completed the main treatment program and were about to enter the follow-up period in a tertiary A general hospital in Zhejiang Province from July 2022 to May 2023 were selected by convenience sampling method as the investigation subjects.General Information Questionnaire,Lung Cancer Survivor Self-management Behavior Assessment Scale,Strategies Used by People to Promote Health,Hospital Anxiety and Depression Scale and Social Support Rating Scale were used for investigation.Potential profile analysis was used to explore the potential categories of self-management behavior in lung cancer patients and analyze its influencing factors.Results 252 patients were finally included.The results of potential profile analysis showed that lung cancer patients'self-management behavior could be divided into 3 potential categories,namely low self-management behavior-low emotion management group(11.90％),medium self-management behavior-low resource management group(45.24％),and high self-management behavior-low hope management group(42.86％).Logistic regression analysis showed that education level,previous surgery,tumor stage,anxiety level,depression level,self-efficacy level and social support level were the influencing factors of lung cancer patients'self-management behavior(P＜0.05).Conclusion The self-management behavior of lung cancer patients is at a moderate level,and there are obvious classification characteristics.It is suggested that medical staff should carry out personalized intervention measures according to the characteristics of self-management behavior of patients of various categories,so as to improve the level of self-management behavior of lung cancer survivors.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Objective: Polyethylene glycol-modified gold nanostar particles (GNS-PEG) were constructed to investigate whether the degradation of extracellular matrix in triple-negative breast cancer could improve the tumor delivery of GNS-PEG and enhance the efficacy of photothermal therapy. Methods: GNS-PEG were constructed and characterized for physicochemical properties as well as photothermal properties. At the cellular level, the cytotoxicity of halofuginone (HF) and the effect of photothermal therapy were detected. Mouse model of triple negative breast cancer was established by subcutaneous inoculation of 4T1 cells in BALB/c nude mice. Five injections of HF were given via tail vein (HF group), and tumor sections were stained with Masson stain and immunohistochemical staining for transforming growth factor β1 (TGFβ1), α-smooth muscle actin (α-SMA) and CD31 to observe the effect of tumor stromal degradation. Five injections of HF via tail vein followed by GNS-PEG (HF+ GNS-PEG group) were applied to determine the content of gold in tumor tissues by inductively coupled plasma mass spectrometry. The tumor sites of the mice in the GNS-PEG and HF+ GNS-PEG groups were irradiated with NIR laser and the temperature changes were recorded with an IR camera. The tumour growth and weight changes of mice in each group were observed. Ki-67 immunohistochemical staining, TdT-mediated dUTP nick-end labeling and HE staining were performed on tumor tissue sections from each group to observe tumor proliferation, apoptosis and necrosis. HE staining was performed on heart, liver, spleen, lung and kidney tissues from each group to observe the morphological changes of cells. Results: GNS-PEG nanoparticles showed a multi-branched structure with a particle size of 73.5±1.4 nm. The absorption peak of GNS was 810 nm, which is in the near infrared region. The photothermal conversion rate of GNS-PEG was up to 79.3%, and the photothermal effect could be controlled by the laser energy. HF has a concentration-dependent cytotoxicity, with a cell survival rate being as low as (22.8±2.6)% at HF concentration of up to 1 000 nmol/L. The photothermal effect of GNS-PEG was significant in killing tumor cells, with a cell survival rate of (32.7±5.2)% at the concentration of 25 pmol/L. The collagen area fraction, TGFβ1 integrated optical density and α-SMA integrated optical density in the tumor tissues of mice in the HF group were (2.1±0.2)%, 3.1±0.4 and 5.2±1.9, respectively, which were lower than those of the control group (all P<0.01), and the vessel diameter was 8.6±2.9 μm, which was higher than that of the control group (P<0.05). In the HF+ GNS-PEG group, the concentration of gold in tissues was 52.4 μg/g, higher than that in the GNS-PEG group (15.9 μg/g, P<0.05). After laser irradiation, the temperature of the tumor site in the HF+ GNS-PEG group was significantly higher than that in the GNS-PEG group. At the 4th minute, the temperatures of the tumor site in the GNS-PEG and HF+ GNS-PEG groups were 51.5 ℃ and 57.7 ℃ respectively; the tumor volume in the HF+ GNS-PEG group was effectively suppressed. The body weights of the mice in each group did not change significantly during the monitoring period. No significant abnormalities were observed in the main organs of the mice in the GNS-PEG group, but some hepatocytes in the HF and HF+ GNS-PEG groups showed edema and degeneration. Conclusion: The remodeling of extracellular matrix in triple-negative breast cancer could significantly improve the intratumoral delivery of GNS-PEG and thus achieve better photothermal therapy effect.
Humans ; Animals ; Mice ; Phototherapy/methods* ; Photothermal Therapy ; Triple Negative Breast Neoplasms/pathology* ; Hyperthermia, Induced/methods* ; Mice, Nude ; Gold/chemistry* ; Cell Line, Tumor