HR-positive HER2-low breast cancer is a new hotspot therapeutic subtype, accounting for approximately 53.7% of all breast cancers. Patients with this type of cancer tend to have a high rate of lymph node metastasis and poor sensitivity to neoadjuvant chemotherapy and conventional anti-HER2 therapy, and exploring therapeutic strategies for this subtype of patient is a current clinical challenge. Therapeutic strategies for HR-positive HER2-low breast cancer are constantly being updated, including CDK4/6 inhibitors across the lines of therapy, and next-generation antibody-drug conjugates such as T-DXd. With the accumulation of high-level evidence-based evidence for HR-positive HER2-low breast cancer in the future, the research data will provide more practical support for precise diagnosis and treatment, thereby improving the prognosis of patients with HR-positive HER2-low breast cancer.

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.

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Objective:To establish a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of voliconazole (VRC), posaconazole (PCZ), and linazolam (LNZ) in human serum.Methods:This study is a methodological validation by LC-MS/MS. The blood concentration results of VRC, PCZ, and LNZ in our hospital′s anti-infection patients were collected. Voriconazole, Posaconazole, and Linezolid were accurately weighed and prepared. Linezolid-[2H3] was used as the internal standard. After gradient elution on the ACE PFP column, the residuals were analyzed by LC-MS/MS in the positive electrospray ionization mode and multiple reaction monitor (MRM) mode. The method′s linearity, precision, lower limit of detection, and recovery rate were validated according to standard guidelines.Results:The linear correlation coefficient ( r) of the standard curve was above 0.99 ( r>0.99). The linear range of VRC and PCZ were 0.10 mg/L~10.00 mg/L, and the lower limit of detection were 0.01 mg/L. The linear range of LNZ was 0.50 mg/L~50.00 mg/L, and the lower limit of detection was 0.05 mg/L. The recoveries of VRC, PCZ and LNZ were 90.96%-103.18%, 91.84%-99.17%, and 97.04%-100.41%, respectively. Intra-and inter-batch precision (% CV) for VRC were less than 8.30%. Intra-and inter-batch precision (% CV) for PCZ was less than 9.78%. Intra-and inter-batch precision (% CV) for LNZ was less than 7.14%. Drug concentrations in 155 cases of VRC, 44 cases of PCZ, and 59 cases of LNZ were detected. Conclusion:We have established an LC-MS/MS method for the rapid, accurate, highly specific determination of VRC, PCZ, and LNZ concentrations in human serum. This method is suitable for analyzing large clinical sample sets.

Currently, in precision cardiac surgery, there are still some pressing issues that need to be addressed. For example, cardiopulmonary bypass remains a critical factor in precise surgical treatment, and many core aspects still rely on the experience and subjective judgment of cardiopulmonary bypass specialists and surgeons, lacking precise data feedback. With the increasing elderly population and rising surgical complexity, precise feedback during cardiopulmonary bypass becomes crucial for improving surgical success rates and facilitating high-complexity procedures. Overcoming these key challenges requires not only a solid medical background but also close collaboration among multiple interdisciplinary fields. Establishing a multidisciplinary team encompassing professionals from the medical, information, software, and related industries can provide high-quality solutions to these challenges. This article shows several patents from a collaborative medical and electronic information team, illustrating how to identify unresolved technical issues and find corresponding solutions in the field of precision cardiac surgery while sharing experiences in applying for invention patents.

Objective     To establish a machine learning based framework to rapidly screen out high-risk patients who may develop atrial fibrillation (AF) from patients with valvular heart disease and provide the information related to risk prediction to clinicians as clinical guidance for timely treatment decisions. Methods     Clinical data were retrospectively collected from 1 740 patients with valvular heart disease at West China Hospital of Sichuan University and its branches, including 831 (47.76%) males and 909 (52.24%) females at an average age of 54 years. Based on these data, we built classical logistic regression, three standard machine learning models, and three integrated machine learning models for risk prediction and characterization analysis of AF. We compared the performance of machine learning models with classical logistic regression and selected the best two models, and applied the SHAP algorithm to provide interpretability at  the population and single-unit levels. In addition, we provided visualization of feature analysis results. Results    The Stack model performed best among all models (AF detection rate 85.6%, F1 score 0.753), while XGBoost outperformed the standard machine learning models (AF detection rate 71.9%, F1 score 0.732), and both models performed significantly better than the logistic regression model (AF detection rate 65.2%, F1 score 0.689). SHAP algorithm showed that left atrial internal diameter, mitral E peak flow velocity (Emv), right atrial internal diameter output per beat, and cardiac function class were the most important features affecting AF prediction. Both the Stack model and XGBoost had excellent predictive ability and interpretability. Conclusion    The Stack model has the highest AF detection performance and comprehensive performance. The Stack model loaded with the SHAP algorithm can be used to screen high-risk patients for AF and reveal the corresponding risk characteristics. Our framework can be used to guide clinical intervention and monitoring of AF.

Objective    To evaluate the use of machine learning algorithms for the prediction and characterization of cardiac thrombosis in patients with valvular heart disease and atrial fibrillation. Methods    This article collected data of patients with valvular disease and atrial fibrillation from West China Hospital of Sichuan University and its branches from 2016 to 2021. From a total of 2 515 patients who underwent valve surgery, 886 patients with valvular disease and atrial fibrillation were included in the study, including 545 (61.5%) males and 341 (38.5%) females, with a mean age of 55.62±9.26 years, and 192 patients had intraoperatively confirmed cardiac thrombosis. We used five supervised machine learning algorithms to predict thrombosis in patients. Based on the clinical data of the patients (33 features after feature screening), the 10-fold nested cross-validation method was used to evaluate the predictive effect of the model through evaluation indicators such as area under the curve, F1 score and Matthews correlation coefficient. Finally, the SHAP interpretation method was used to interpret the model, and the characteristics of the model were analyzed using a patient as an example. Results    The final experiment showed that the random forest classifier had the best comprehensive evaluation indicators, the area under the receiver operating characteristic curve was 0.748±0.043, and the accuracy rate  reached 79.2%. Interpretation and analysis of the model showed that factors such as stroke volume, peak mitral E-wave velocity and tricuspid pressure gradient were important factors influencing the prediction. Conclusion    The random forest model achieves the best predictive performance and is expected to be used by clinicians as an aided decision-making tool for screening high-embolic risk patients with valvular atrial fibrillation.

Objective:To evaluate the efficacy and safety of modified Atkins diet (MAD) in treating global growth retardation (GDD).Methods:A prospective multicenter clinical controlled study was conducted.The children were included from 8 departments of children′s rehabilitation in Henan Province from July 2017 to October 2017.A total of 154 children who met the inclusion criteria were randomly assigned into the routine treatment group (88 cases) and MAD therapy group (66 cases). A total of 62 children in MAD therapy group and 59 children in routine treatment group completed the study for 15 months.The routine treatment group was provided comprehensive rehabilitation training, and the MAD therapy group was given MAD treatment on the basis of rehabilitation training.Two-way repeated-measures ANOVA was used to compare the differences among datas at different time points. Results:After 3 months, there were significant differences in the scores of the Chinese Version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA)/Achenbach Children′s Behavior Scale (CBCL) between the 2 groups (all P<0.05). Significant improvement was seen in the MAD group.After 6 months, the MAD therapy group had significantly higher scores on the Gesell Developmental Scale for language and social behavior than the routine treatment group (all P<0.05). After 9 months, the scores of the children in the MAD therapy group were better than those in the routine treatment group in the Gesell Developmental Scale adaptive energy area and the infant-junior high school student social life scale (S-M scale), and the differences were statistically significant (all P<0.05). After 15 months, the fine motor in the MAD therapy group was better than that in the routine treatment group ( P<0.05). At the early stage of MAD therapy, 28 patients showed mild adverse reactions that were reversed after symptomatic treatment.No severe adverse reactions were observed. Conclusions:MAD therapy can improve the neuro-development, emotional and social behaviors, and adaptive behaviors with no severe adverse effects.

Objective: To quantitatively assess biochemical alterations in the cartilage of the subtalar and midtarsal joints in chronic lateral ankle instability (CLAI) patients with isolated anterior talofibular ligament (ATFL) injuries and combined calcaneofibular ligament (CFL) injuries using MRI T2 mapping. Materials and Methods: This study was performed according to regulations of the Committee for Human Research at our institution, and written informed consent was obtained from all participants. Forty CLAI patients (26 with isolated ATFL injuries and 14 with combined ATFL and CFL injuries) and 25 healthy subjects were recruited for this study. All participants underwent MRI scans with T2 mapping. Patients were assessed with the American Orthopedic Foot and Ankle Society (AOFAS) rating system. The subtalar and midtarsal joints were segmented into 14 cartilage subregions. The T2 value of each subregion was measured from T2 mapping images. Data were analyzed with ANOVA, the Student’s t test, and Pearson’s correlation coefficient. Results: T2 values of most subregions of the subtalar joint and the calcaneal facet of the calcaneocuboid joint in CLAI patients with combined CFL injuries were higher than those in healthy controls (all p < 0.05). However, there were no significant differences in T2 values in subtalar and midtarsal joints between patients with isolated ATFL injuries and healthy controls (all p > 0.05). Moreover, T2 values of the medial talar subregions of the posterior subtalar joint in patients with combined CFL injuries showed negative correlations with the AOFAS scores (r = -0.687, p = 0.007; r = -0.609, p = 0.021, respectively). Conclusion CLAI with combined CFL injuries can lead to cartilage degeneration in subtalar and calcaneocuboid joints, while an isolated ATFL injury might not have a significant impact on the cartilage in these joints.