ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 （ACSL4） signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group， sham-operation group， model group， trimetazidine group （5.4 mg·kg^-1）， low-， medium-， and high-dose group （3.51， 7.02，14.04 g·kg^-1） of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome， and continuous treatment for 7 d was conducted， while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed， and indicators such as electrocardiogram， echocardiography， and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin （HE） staining， and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid （12-HETE） and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe²⁺， lipid peroxidation （LPO）， glutathione （GSH）， and T-GSH/glutathione disulfide （GSSG） in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species （ROS）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， ACSL4， and ly-sophosphatidylcholine acyltransferase3 （LPCAT3） in myocardial tissue. ResultsCompared with those in the normal group， the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage， bow-back elevation of the ST segments， elevated T waves， J-point elevation， and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）. Blood rheology showed that the viscosity of the whole blood （low， medium， and high rate of shear） was significantly increased （P<0.01）. HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken， and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles， and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased （P<0.01）. The content of Fe²⁺， LPO， and ROS in myocardial tissue was significantly increased （P<0.01）. The content of GSH was significantly decreased （P<0.01）， and T-GSH/GSSG was decreased （P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased （P<0.05， P<0.01）， while those of ACSL4 and LPCAT3 increased significantly （P<0.01）. Compared with the model group， the general macroscopic symptoms and electrocardiogram results of rats in low-， medium- and high-dose groups of Xuefu Zhuyutang were alleviated， and the differences in LVEF/LVFS ratios were all significantly increased （P<0.05， P<0.01）. The differences in whole-blood viscosity （low， medium， and high rate of shear） were all significantly decreased （P<0.01）. The results of HE staining and transmission electron microscopy showed that the morphology， structure， and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. The content of Fe²⁺， LPO， and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and the content of GSH and T-GSH/GSSG was significantly increased （P<0.05， P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and ACSL4 and LPCAT3 were decreased to different degrees in the low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway， thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To analyze differential metabolites (DMs) in the urine of workers with occupational nickel exposure using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 30 nickel exposed workers were selected as the exposure group, and 30 administrative staff from the same factory were selected as the control group using the judgment sampling method. Urine samples of the individuals from the two groups were collected. The ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and non-targeted metabolomics were used to detect and identify metabolites. The differential metabolic profiles were compared between workers of the two groups, and key differential metabolic pathways and potential biomarkers were screened. The association of DMs and urinary nickel level were evaluated by Spearman correlation coefficients. The sensitivity and specificity of biomarkers were assessed by receiver operating characteristic (ROC) curve analysis. Results A total of 418 metabolites were identified in the urine of worker in the exposure and control groups. The result of principal component analysis and orthogonal partial least squares analysis showed that there were 128 DMs in the urine of workers in the exposure group compared with the control group. These DMs were mainly enriched in glutathione metabolism, carnitine synthesis, and amino acid and nucleotide metabolism pathways, including glycine and serine metabolism. The result of correlation analysis and ROC curve analysis revealed that 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid could be the potential biomarkers for nickel exposure (all area under the ROC curve >0.800). Conclusion There were significant differences in the urinary metabolic profiles of workers with occupational nickel exposure. The five DMs including 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid. These DMs could be potential biomarkers of occupational nickel exposure.

The aim of this study was to investigate the virulence determinants and genetic diversity of foodborne Yersinia enterocolitica from Wenzhou.A total of 71 strains of Yersinia enterocolitica were isolated from food and foodborne diarrhea ca-ses in Wenzhou,and their biotypes,serotypes,and drug resistance were analyzed.On the basis of whole genome sequencing,we assessed virulence gene profiles,and performed multilocus sequence typing(MLST)and core gene multilocus sequence typ-ing(cgMLST).A total of 94.4％(67/71)of isolates belonged to biotype 1A,and the highest proportion had serotype lA/O∶5(29.6％,21/71).The sensitivity rates of the isolates to 14 antibiotics exceeded 95.8％.A total of 16 categories and 126 viru-lence genes were identified,with two strains carrying the pYV plasmid and chromosome-related virulence genes.ST3(31.6％,12/38)was the most widespread MLST type,and cgMLST analysis revealed no dense clusters of genotypes except for strains sharing the same ST.In conclusion,pathogenic strains were identified from foodborne Yersinia enterocolitica in Wenzhou and were found to exhibit high genetic polymorphism.Enhanced regulatory supervision is essential to prevent the outbreak of food-borne diseases caused by Yersinia enterocolitica.

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:To explore application effect of early respiratory training schemes based on 4E mode (Engage, Educate, Execute, Evaluate) in children with bronchiolitis obliterans (BO) and provide evidence for the clinical implementation of early respiratory rehabilitation in children with BO.Methods:This was a quasi-experimental study. The children with BO who were admitted to 2 wards of the Department of Respiratory Medicine of Hunan Children's Hospital from January 1 to December 31, 2021 were selected as the research objects. They were randomly divided into the control group and the experimental group, with 23 cases in each group. The control group received routine treatment, nursing and rehabilitation guidance. The experimental group established a multidisciplinary team based on the control group, and used the early respiratory training program based on the 4E model to implement intervention. The clinical symptom severity scale was used to evaluate the improvement of the clinical symptoms of the children within 24 hours of being diagnosed as BO, the day of discharge, and 1 and 3 months after discharge for re-examination, and the hospitalization time of the children and the incidence of adverse events related to respiratory training were counted by using medical records and questionnaires.Results:The clinical symptom severity scores of the experimental group within 24 hours of admission diagnosis and the day of discharge were (20.00 ± 2.51) and (11.30 ± 2.46)points respectively, while those of the control group were (20.57 ± 2.21) and (11.70 ± 2.42) points respectively, with no statistically significant difference ( t=0.81, 0.54, both P>0.05). The clinical symptom severity scores of the experimental group were(10.52 ± 2.31) and (8.55 ± 1.06) points, lower than (12.32 ± 1.39) and (12.45 ± 2.19) points of the control group when they returned to the hospital for re-examination 1 and 3 months after discharge, with a statistically significant difference ( t=3.14, 7.25, both P<0.05). The experimental group was hospitalized for (11.78 ± 1.17) days, which was showter than (13.74 ± 1.63) days in the control group, with a statistically significant difference ( t=4.68, P<0.05). No respiratory training-related adverse events occurred in both groups of children during hospitalization. During home respiratory training after discharge, 1 and 2 respiratory training-related adverse events occurred in the experimental group 1 and 3 months after discharge, respectively, compared with 6 and 9 in the control group. The difference was statistically significant ( χ2=4.64, 5.94, both P<0.05). Conclusions:Early respiratory training solutions based on the 4E mode can improve the clinical symptoms of BO children, shorten the hospitalization time, reduce the number of adverse events related to respiratory training, and promote the recovery of children.

Objective:To study the short-term clinical outcomes of different courses of antenatal corticosteroids (ACS) for preterm twins.Methods:From January 2017 to December 2021, preterm twins with gestational age (GA) 24-34 weeks admitted to the neonatal ward of our hospital and received ACS were retrospectively studied. The infants were assigned into single-course group, partial-course group and multiple-course group according to ACS courses. The short-term clinical outcomes were compared among the groups. SPSS software version 25.0 was used for statistical analysis.Results:A total of 286 infants were enrolled in this study, including 128 in single-course group, 89 in partial-course group and 69 in multiple-course group. Compared with single-course group, the risks of neonatal respiratory distress syndrome (RDS) in both partial-course group ( OR=2.332, 95% CI 1.028-5.293, P=0.043) and multiple-course group ( OR=3.872, 95% CI 1.104-13.584, P=0.034) were higher. The birth length in multiple-course group ( β=-0.016, 95% CI -0.029 - -0.002, P=0.024) was lower than single-course group. Conclusions:The risks of neonatal RDS in preterm twins are higher in partial-course and multiple-course of ACS. A full course of ACS should be used to prevent neonatal RDS until further evidence of effectiveness is available.

Objective:To investigate the epidemiology of pathogens of acute respiratory tract infection (ARTI) in children in Guangzhou area.Methods:A total of 13 610 hospitalized children with ARTI in Guangzhou Women and Children′s Medical Center from January 2018 to December 2021 were enrolled. Throat swab specimens were collected, and fluorescent quantitative polymerase chain reaction (PCR) was performed to detect 11 respiratory pathogens, including respiratory syncytial virus (RSV), adenovirus (ADV), parainfluenza virus (PIV), human rhinovirus (HRV), human bocavirus (HBoV), human metapneumovirus (HMPV), enterovirus (EV), influenza A virus (IFA), influenza B virus (IFB), Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP). Grouping according to age (< one year group, one to < three years group, three to < six years group, six to 14 years group) and season. Chi-square test was used for statistical analysis. Results:At least one pathogen was detected in 6 331 cases among 13 610 patients, and the overall positive rate was 46.52%. The detection rates from high to low were as follows: RSV (13.75%(1 872/13 610)), ADV (4.82%(656/13 610)), PIV (4.82%(656/13 610)), MP (4.54%(618/13 610)), HRV (3.39%(462/13 610)), HBoV (2.64%(359/13 610)), HMPV (2.59%(352/13 610)), EV (1.76%(239/13 610)), IFA (1.29%(176/13 610)), IFB (0.90%(122/13 610)) and CP (0.30%(41/13 610)). The positive rate of viral detection showed significant differences among different age groups ( χ2=49.91, P<0.001), and the highest positive rate was in the age group of one to