Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

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

Objective:To investigate the impact of early invasive arterial blood pressure (IBP) monitoring on survival and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR).Methods:This retrospective cohort study analyzed 44 OHCA patients receiving ECPR between January 2021 and January 2023. Patients were divided into: Early intervention group : IBP established within 3 min of ECMO initiation; Late intervention group : IBP established after ICU admission. Baseline characteristics, ECMO parameters, and clinical outcomes were compared. Multivariable logistic regression (adjusted for age, initial rhythm, etc.) and Spearman's correlation were used.Results:This study included a total of 44 patients treated with OHCA and ECPR, divided into an early intervention group of 23 cases and a late intervention group of 21 cases. The early intervention group showed significantly higher: Survival to discharge (43.5% vs. 9.5%, P<0.05), Good neurological recovery (CPC 1-2: 34.8% vs. 9.5%, P<0.05).Early intervention independently predicted survival (adjusted OR=18.84, 95% CI:1.97-179.98, P=0.01). Stratified analysis by pH (cutoff 7.0) demonstrated consistent benefits in both pH>7.0 ( aOR=0.392, 95% CI:0.106-0.678) and pH≤7.0 subgroups ( aOR=0.385, 95% CI: 0.075-0.695; interaction P=0.183). Early IBP positively correlated with CPC scores ( ρ=0.40, P=0.007). Conclusions:Early IBP monitoring significantly improves survival and neurological outcomes in OHCA-ECPR patients, supporting its integration into standardized protocols.

21-hydroxylase deficiency (21-OHD) is a rare disease caused by insufficient adrenocortical hormone synthesis and hyperandrogen due to enzyme deficiency during steroid synthesis.Glucocorticoid and mineralocorticoid replacement therapies are main treatment method for 21-OHD.Currently, there are guidelines for the specific dosage and usage of the glucocorticoid replacement therapy, but no detailed evidence is offered for mineralocorticoid dose adjustment.Insufficient mineralocorticoid replacement can lead to an increase in the dose of glucocorticoids and further iatrogenic Cushing′s syndrome.Excessive dosage can result in sodium and water retention and further drug-induced hypertension.Therefore, the dose adjustment and treatment monitoring of Fludrocortisone still need to be further explored.In this article, the progress in mineralocorticoid treatment and monitoring for 21-OHD will be reviewed.

21-hydroxylase deficiency (21-OHD) is a rare disease caused by insufficient adrenocortical hormone synthesis and hyperandrogen due to enzyme deficiency during steroid synthesis.Glucocorticoid and mineralocorticoid replacement therapies are main treatment method for 21-OHD.Currently, there are guidelines for the specific dosage and usage of the glucocorticoid replacement therapy, but no detailed evidence is offered for mineralocorticoid dose adjustment.Insufficient mineralocorticoid replacement can lead to an increase in the dose of glucocorticoids and further iatrogenic Cushing′s syndrome.Excessive dosage can result in sodium and water retention and further drug-induced hypertension.Therefore, the dose adjustment and treatment monitoring of Fludrocortisone still need to be further explored.In this article, the progress in mineralocorticoid treatment and monitoring for 21-OHD will be reviewed.

With the whole life involvement，21-hydroxylase deficiency（21-OHD）affects the quality of life，and the death rate of salt wasting form is high，thus the timely diagnosis and standardized treatment are needed. Traditionally，17-hydroxyprogesterone（17-OHP）is an indicator for screening，diagnosis and monitoring of 21-OHD. However，17-OHP has some limitations，such as high false-positive rate in neonatal screening，high fluctuation，and interference of puberty and menstrual cycle，etc. Therefore，attempts have been made to find better indicators to help guide clinical practice. Recently，several studies have suggested that 21-deoxycortisol（21-DF）may be a more specific marker for 21-OHD，which has the following advantages：no elevation is observed in premature infants or patients with other forms of congenital adrenal hyperplasia，and the blood sample timing doesn't affect the detection of 21-DF；21-DF is a reliable diagnostic marker of non-classical 21-OHD；adrenal gland is the only source of 21-DF. Therefore，this article reviews the limitations of 17-OHP and the relative advantages of 21-DF.

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To explore the factors influencing clinicians'adoption of new medical technologies and provide data and strategic support to promote the clinical application of innovative medical technologies.Methods:Based on the Unified Theory of Acceptance and Use of Technology ( UTAUT),a model was constructed to examine the factors influencing clinicians'adoption of new medical technologies.The model was revised through expert interviews,and data were collected via a survey questionnaire.Structural equation modeling ( SEM) was conducted using AMOS software to test both the direct and mediating effects.Results:Clinical performance expectancy ( P<0.001 ),DRG/DIP policy impact ( P=0.009 ),patient willingness ( P<0.001 ),and facilitating conditions ( P<0.001 ) had significant direct effects on usage intention.Usage intention ( P=0.005 ),patient willingness ( P=0.021 ),and facilitating conditions ( P<0.001 ) had significant direct effects on usage behavior.Usage intention mediated the relationship between clinical performance expectancy ( P<0.001 ),DRG/DIP policy impact ( P=0.030 ),patient willingness ( P<0.001 ),facilitating conditions ( P<0.001 ),and usage behavior.Conclusions:Clinical performance expectancy is the primary factor influencing clinicians'willingness to adopt new medical technologies.DRG/DIP payment methods somewhat reduce usage intention,while facilitating conditions are the key factor influencing usage behavior.Policy recommendations should focus on these key factors to promote the clinical application of innovative medical technologies.

Objective:To explore the factors influencing clinicians'adoption of new medical technologies and provide data and strategic support to promote the clinical application of innovative medical technologies.Methods:Based on the Unified Theory of Acceptance and Use of Technology ( UTAUT),a model was constructed to examine the factors influencing clinicians'adoption of new medical technologies.The model was revised through expert interviews,and data were collected via a survey questionnaire.Structural equation modeling ( SEM) was conducted using AMOS software to test both the direct and mediating effects.Results:Clinical performance expectancy ( P<0.001 ),DRG/DIP policy impact ( P=0.009 ),patient willingness ( P<0.001 ),and facilitating conditions ( P<0.001 ) had significant direct effects on usage intention.Usage intention ( P=0.005 ),patient willingness ( P=0.021 ),and facilitating conditions ( P<0.001 ) had significant direct effects on usage behavior.Usage intention mediated the relationship between clinical performance expectancy ( P<0.001 ),DRG/DIP policy impact ( P=0.030 ),patient willingness ( P<0.001 ),facilitating conditions ( P<0.001 ),and usage behavior.Conclusions:Clinical performance expectancy is the primary factor influencing clinicians'willingness to adopt new medical technologies.DRG/DIP payment methods somewhat reduce usage intention,while facilitating conditions are the key factor influencing usage behavior.Policy recommendations should focus on these key factors to promote the clinical application of innovative medical technologies.