As the second part of this series, this article summarizes and synthesizes the key aspects of UK Serious Hazards of Transfusion (SHOT), SHOT’s continuous promotion of learning from excellent daily transfusion events over the past six years. This summary is based on an introduction to the holistic approach to improving patient safety—proactively learning from both failures and successes. The covered topics include an overview, definitions, case studies, implementation methods, safety culture, psychological safety in the workplace, civility in work, the use of neutral language, leading and lagging indicators, and compassionate governance. It is hoped that this article will assist domestic colleagues in understanding and studying the strategic significance of the transformation of transfusion safety governance in the UK, and inspire reflection on the strategic development direction of transfusion safety governance in China.

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

OBJECTIVES: To investigate the mechanism of DDX17 for regulating proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) during the development of pulmonary hypertension (PH). METHODS: In murine PASMCs cultured under normoxic or hypoxic conditions, the effects of transfection with si-Ddx17 and insulin treatment, alone or in combination, on cell proliferation and migration were evaluated using Ki-67 immunofluorescence staining, scratch assay and Transwell assay. Western Blotting was performed to detect the changes in protein expression levels of DDX17, 4EBP1, S6, p-4EBP1, and p-S6. In a mouse model of PH induced by intraperitoneal injection of monocrotaline (MCT), the changes in pulmonary vasculature were examined using HE staining following tail vein injection of AD-Ddx17i. RESULTS: The PASMCs in hypoxic culture exhibited significantly enhanced cell proliferation and migration and protein expressions of p-4EBP1 and p-S6, and these changes were obviously reversed by transfection with si-Ddx17. Treatment with insulin significantly attenuated the effect of si-Ddx17 against hypoxic exposure-induced changes in PASMCs. In the mouse model of MCT-induced PH, transfection with AD-Ddx17i obviously alleviated pulmonary vascular stenosis and intimal hyperplasia. CONCLUSIONS The expression of DDX17 is elevated in hypoxia-induced PASMCs and PH mice, and silencing DDX17 significantly inhibits PASMC proliferation and migration in vitro and pulmonary vascular remodeling in PH mice by reducing mTORC1 activity.
Animals ; Cell Proliferation ; Cell Movement ; DEAD-box RNA Helicases/metabolism* ; Myocytes, Smooth Muscle/metabolism* ; Mice ; Pulmonary Artery/cytology* ; Hypertension, Pulmonary/metabolism* ; Mechanistic Target of Rapamycin Complex 1 ; Cells, Cultured ; Muscle, Smooth, Vascular/cytology*

Objective:To explore the optimal duration of preoperative imatinib therapy in patients with locally advanced gastrointestinal stromal tumors (GIST) in order to optimize surgical timing and long-term survival benefits.Methods:A total of 171 patients with locally advanced GIST who received preoperative imatinib therapy and subsequent surgical resection between November 2012 and October 2024 at Fujian Cancer Hospital and Union Hospital of Fujian Medical University were retrospectively analyzed. Patients were divided into three groups according to the duration of preoperative imatinib treatment: short-term (≤6 months, n=50), intermediate-term (7-12 months, n=87), and long-term (>12 months, n=34). Imaging response, pathological efficacy, recurrence-free survival (RFS), and overall survival (OS) were compared among the groups. Univariate and multivariate Cox regression analyses were used to identify the optimal treatment duration. Results:The median duration of preoperative imatinib therapy was 9 (6, 12) months. After treatment, the average maximum tumor diameter decreased from (10.37±5.74) cm to (6.99±4.34) cm, with an average shrinkage of 31.5%. The objective response rates in the short-, intermediate-, and long-term groups were 50.0% (25/50), 58.6% (51/87), and 52.9% (18/34), respectively; high-grade pathological response rates were 28.0% (14/50), 37.9% (33/87), and 29.4% (10/34), with no statistically significant differences among groups (all P>0.05). With a median follow-up of 46 months, 39 patients experienced recurrence and 20 died. The intermediate-term group had 3- and 5-year RFS rates of 87.1% and 79.6%, respectively, significantly better than those of the short-term group (75.5% and 55.5%, P=0.004). The long-term group had 3- and 5-year RFS rates of 85.3% and 75.5%, which were between the other two groups, but not significantly different (all P>0.05). For OS, the intermediate-term group had 3- and 5-year rates of 97.3% and 92.7%, superior to the short-term group (84.4% and 72.4%, P=0.007), while the long-term group (88.2% and 79.4%) showed no significant advantage (all P>0.05). Stratified analysis revealed that among non-gastric primary tumor patients with c-Kit exon 11 mutations, partial response on imaging, or postoperative imatinib ≤24 months, the intermediate-term group had significantly better RFS and OS than the short-term group (all P<0.05), but had no differences compared to the long-term group ( P>0.05). Multivariate Cox regression analysis indicated that preoperative imatinib duration was not an independent factor for RFS ( P>0.05), but treatment for 7-12 months was an independent protective factor for OS ( HR=0.275, 95% CI: 0.089-0.851, P=0.025), while prolonging therapy beyond 12 months conferred no additional OS benefit ( P>0.05). Conclusions:In patients with locally advanced GIST, preoperative imatinib therapy for 7-12 months yielded the most favorable prognosis, with significantly improved RFS and OS compared to ≤6 months of treatment. Extending preoperative therapy beyond 12 months did not provide additional survival benefit.

Objective:To evaluate the long-term outcomes and predictors of coronary atherosclerotic lesions deemed functionally non-ischemic (quantitative flow ratio(QFR)>0.80) and deferred from intervention.Methods:This study is a post-hoc analysis of the FAVOR Ⅲ China trial, which enrolled 3 825 patients with stable or unstable angina pectoris or with myocardial infarction occurring at least 72 hours prior to screening, between December 5, 2018 and January 9, 2020 from 26 research centers in China. Coronary vessels with QFR>0.80 and without interventional treatment were analyzed in this study. The primary endpoint was 3-year target vessel revascularization. Vessels with revascularization (revascularized group) during follow-up were matched 1∶1 using propensity score matching to comparable vessels without revascularization (non-revascularized group). Multivariate Cox regression analysis was used to identify the risk factors for target vessel revascularization (TVR).Results:A total of 6 212 functionally negative vessels with deferred intervention were included in the final analysis, among which 153 vessels (2.5%) underwent TVR during a 3-year follow-up. Prior to propensity score matching, 6 059 vessels comprised the non-revascularized group. At the vessel level, compared to the non-revascularized group, the revascularized group exhibited a significantly higher proportion of males (79.1% (121/153) vs. 70.2% (4 253/6 059), P=0.018), higher body mass index ((25.6±4.0) kg/m2 vs. (24.3±5.2) kg/m2, P=0.003), and a higher prevalence of hypertension (73.9% (113/153) vs. 65.1% (3 944/6 059), P=0.025). And 152 pairs of vessels were successfully matched. Multivariate Cox regression analysis identified in-stent restenosis lesions ( HR=2.59, 95% CI 1.28-5.23, P=0.008) as an independent risk factor for target vessel revascularization. Conclusions:Coronary lesions classified as functionally non-ischemic at baseline are not entirely stable and may progress to lesions that requiring revascularization over time. In-stent restenosis emerges as a critical independent predictor of revascularization.

Objectives:To explore the feasibility of a coronary angiography-based method developed with artificial intelligence which was able to automatically and quickly calculate coronary volumetric blood flow and coronary flow reserve (CFR), and explore the differences in CFR after injection of different vasodilators.Methods:This was a observational study screening patients with suspected coronary artery disease who underwent coronary angiography From June to September 2022 in Fuwai Hospital, Chinese Academy of Medical Sciences. Patients without obstructive coronary artery disease in the left anterior descending artery (<50% diameter stenosis by visual) and accompanied by coronary slow flow phenomenon (Thrombolysis in Myocardial Infarction flow grade ≤2) were enrolled. According to pre-specified coronary angiography acquisition protocol, one angiographic image in optimal projection was acquired for each of the following five states: baseline when none of the vasodilators was injected (resting state), intracoronary injection of 200 μg nitroglycerin (nitroglycerin-induced hyperemia), intracoronary injection of 100 μg adenosine (adenosine-induced hyperemia), 5 minutes after cessation of adenosine injection (resting state 2), and intracoronary injection of 4 mg nicorandil (nicorandil-induced hyperemia). Coronary volumetric blood flow and CFR were assessed in a fully automatic manner at an independent core laboratory. One-way repeated measures ANOVA was used to detect the differences in coronary volumetric blood flow at five states and the differences in CFR after injection of different vasodilators.Results:A total of 21 eligible patients were included. The age was (62±9) years, and 5 (24%) were female. Coronary volumetric blood flow at five states and CFR after injection of different vasodilators were successfully calculated in all patients, with a feasibility of 100% (21/21) for CFR. Resting coronary volumetric blood flow was (80.6±12.4) ml/min. Using this as a reference, the volumetric blood flow increased to (167.7±30.5) ml/min under nitroglycerin-induced hyperemia (adjusted P<0.001), and remained at (171.5±23.1) ml/min under adenosine-induced hyperemia (adjusted P<0.001). The volumetric blood flow under resting state 2 was (83.8±15.6) ml/min, returning to baseline level (adjusted P=0.94). Under nicorandil-induced hyperemia, the coronary volumetric blood flow increased again to (182.9±28.3) ml/min (adjusted P<0.001). CFR was 2.09±0.29, 2.15±0.27, and 2.29±0.29 after injection of nitroglycerin, adenosine, and nicorandil, respectively( P=0.034). Using CFR after adenosine injection as a reference, CFR after nicorandil injection was higher (adjusted P=0.044). Using the coronary volumetric blood flow under resting state 2 as the baseline flow for CFR calculation, there was no statistically significant difference compared to the CFR calculated using the volumetric blood flow under resting state (all P>0.05). Conclusions:Preliminary findings confirm the high feasibility of rapid, automated assessment of coronary volumetric blood flow and CFR from a single angiographic projection, as well as good reproducibility in calculating baseline volumetric blood flow. In patients with coronary slow flow, the CFR after nicorandil injection is significantly higher than that after adenosine injection.

BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Room temperature stored platelets are associated with a higher risk of sepsis and related fatality. The risk of bacterial contamination of platelets is a leading risk of infection from blood transfusion. U.S. Food and Drug Administration recently issued a guidance on bacterial risk control strategies for blood collection establishments and transfusion services to enhance the safety and availability of platelets for transfusion. The prevention and control strategies in the guidance would be informative and instructive for further development of risk control strategies of platelet bacterial contamination in China.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

Objective To investigate the prevalence and influencing factors of work-related musculoskeletal disorders (WMSDs) among bus drivers. Methods A total of 962 drivers from a bus company in Shenzhen City were selected as the research subjects using the judgment sampling method. The Musculoskeletal Disorders Questionnaire for Bus Drivers was used to investigate the prevalence of WMSDs among the research subjects. Results The prevalence of WMSDs was 37.8% in the bus drivers. The prevalence of WMSDs was higher in the low back/waist, neck, and shoulder compared with other body parts, with prevalence of 24.0%, 20.2%, and 14.8%, respectively. The prevalence of single-site and multi-site WMSDs was 18.5% and 19.3%, respectively. The results of the multivariable logistic regression analysis showed that longer job tenure and higher alcohol consumption frequency were associated with higher WMSDs risks (all P<0.01). Weekly work time >48 hours, insufficient rest, work-related fatigue, uncomfortable auxiliary lenses, non-upright trunk posture, prolonged static trunk posture, prolonged wrist flexion, and habitual staying up late were risk factors of WMSDs in the bus drivers (all P<0.05). Conclusion The prevention and treatment of WMSDs among the bus drivers cannot be ignored. Personal characteristics, work organization, work environment, working posture and sleeping habits are the factors that influence the development of WMSDs.