Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor (BCR) complex and block immune responses. The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens. Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies, which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions. Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies, and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P＜0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P＜0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric 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.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

Objective:To develop and test the intelligent model for automatically counting the number of vertebral ossification centers below the end of conus medullaris.Methods:From January 2021 to October 2022, 3 000 ultrasound images of the sacrococcygeal spinal middle sagittal plane were retrospectively selected from Shenzhen Maternal and Child Healthcare Hospital and Zhuhai People′s Hospital. The vertebral ossification center and spinal conus medullaris were artificially fine-marked in 2, 800 images for segmentation training. Yolov8 algorithm was used to build the segmentation model for segmentation training, and the fitting and automatic counting of vertebral ossification centers were carried out by post-processing. In the other 200 planes, the counting was performed by the artificial intelligence (AI) model, attending physician (D1), and junior physician (D2), and the accuracy of their performance were evaluated by a specialist physician. The accuracy and the time spent between D1, D2, and AI were compared.Results:The accuracy of AI model segmentation fitting and counting reached 95.00% (190/200) by the specialist physician evaluation, which was almost equal to 94.50%(189/200) by D1( P=0.823) and higher than that of 88.50% by D2(177/200)( P=0.012). The counting time spent for D1, D2, and AI model were 5.00 (4.25, 6.00)s, 7.00 (7.00, 8.00)s, 0.09 (0.08, 0.10)s, respectively, showing that the time spent by AI model was significantly shorter than that of doctors(all P<0.001). Conclusions:The trained artificial intelligence model can efficiently and accurately complete the vertebral ossification center counting below the end of conus medullaris, equivalent to the level of attending physicians. This study is expected to be further applied in the screening of fetal spina bifida and improve the automation and intelligence level of prenatal ultrasound screening.

The dental pulp is the only soft tissue structure within the tooth,serving functions such as sensation and nutrition.However,the dental pulp is highly susceptible to necrosis due to external factors.Currently,root canal therapy is the most commonly used treatment for pulp necrosis.Nevertheless,teeth treated with root canal therapy are prone to secondary infections and adverse outcomes like vertical root fractures.Regenerative endodontic therapy has emerged as a solution,aiming to replace damaged tooth structures,including dentin,root structure,and the pulp-dentin complex cells.This approach demonstrates significant advantages in addressing clinical symptoms and achieving regeneration of the root and even the pulp.Since the discovery of dental pulp stem cells,regenerative endodontic therapy has gained new momentum.Advances in cell transplantation and cell homing techniques have rapidly developed,showing promising potential for clinical applications.

Objective:To explore the effect and safety of local spraying tranexamic acid after thyroidectomy.Methods:Randomized double-blind placebo-controlled study method was used. Sixty-four patients underwent scheduled thyroidectomy from December 2022 to August 2023 in Baotou Cancer Hospital were selected. The patients were divided into tranexamic acid group and control group by random digits table method with 32 cases each. Before closing the wound during surgery, 16 ml of tranexamic acid injection with concentration of 25 mg/ml was used to wash the wound and 1 ml of tranexamic acid injection (tranexamic acid 100 mg) used to locally spray in tranexamic acid group; 16 ml of the sterile water for injection was used to wash the wound and 1 ml of sterile water for injection was used locally spray in control group, and then the drainage tube was clipped for 20 min. The neck drainage volume on the first to fourth day after surgery and complication were recorded; the C-reactive protein level before and after surgery was detected.Results:Two patients in each group withdrew from the study midway. The drainage volume on the first, second and third day and total drainage volume in tranexamic acid group were significantly lower than those in control group: (29.10 ± 8.04) ml vs. (38.50 ± 8.67) ml, (18.00 ± 7.33) ml vs. (27.20 ± 10.66) ml, (10.70 ± 5.75) ml vs. (14.60 ± 6.83) ml and (69.20 ± 24.48) ml vs. (96.70 ± 31.90) ml, and there was statistical difference ( P<0.01); there was no statistical difference in the drainage volume on the fourth day after surgery between two groups ( P>0.05). There was no statistical difference in C-reactive protein before and after surgery between two groups ( P>0.05). There was 1 case of fever (body temperature 37.5 ℃) in the control group, and there were no complications such as intermuscular thrombosis, venous thrombosis, incision infection and delayed wound healing in both groups. Conclusions:Local application of tranexamic acid after thyroidectomy can reduce postoperative drainage volume and does not increase the risk of thrombosis, infection and delayed healing.

Objective:To evaluate the clinical practice of intensive care unit (ICU) physicians at Hebei General Hospital in identifying patients meeting the diagnostic criteria for acute respiratory distress syndrome (ARDS) and the current status of invasive mechanical ventilation management and adjunctive therapy in these patients, and to analyze the incidence and clinical outcomes of ARDS.Methods:A retrospective cohort study was conducted. The patients who were hospitalized in the ICU of Hebei General Hospital from April 10, 2017 to June 30, 2022 and met the Berlin definition diagnostic criteria for ARDS were enrolled as study subjects. Artificial intelligence (AI) technology was applied to search the basic information (age, gender, height, body weight, etc.), auxiliary examination, electronic medical record, non-drug doctor's advice, drug doctor's advice, critical report, scoring system, monitoring master table and other data of the above medical records in the electronic medical record system of the hospital. The first set of laboratory indicators sequentially retrieved from the system daily from 05: 00 to 10: 00 and vital signs and mechanical ventilation-related parameters recorded in the "critical care report" at 06: 00 daily were extracted, and outcome indicators of the patients were collected.Results:After screening and analysis, a total of 255 patients who met the ARDS diagnostic criteria were finally enrolled. The overall incidence of ARDS in the ICU accounted for 3.4% (255/7?434) of the total number of ICU patients, of which mild, moderate and severe ARDS accounted for 22.4% (57/255), 49.0% (125/255), and 28.6% (73/255), respectively, while the recognition rates of clinical doctors were 71.9% (41/57), 58.4% (73/125) and 71.2% (52/73), respectively. During the ICU stay, 250 patients (98.0%) received only invasive mechanical ventilation, while 5 patients (2.0%) received both non-invasive and invasive mechanical ventilation. The tidal volume/ideal body weight of ARDS patients was 7.64 (6.49, 9.01) mL/kg, and the positive end-expiratory pressure (PEEP) was 8.0 (5.0, 10.0) cmH 2O (1 cmH 2O≈0.098 kPa). In addition, during the diagnosis and detection of ARDS, only 7 patients were recorded the platform pressure and 6 patients were recorded the drive pressure. Regarding adjunctive therapies, 137 patients (53.7%) received deep sedation, 26 patients (10.2%) underwent lung recruitment, 55 patients (21.6%) received prone ventilation, 42 patients (16.5%) were treated with high-dose steroids, 19 patients (7.5%) were treated with neuromuscular blockade, and 8 patients (3.1%) were treated with extracorporeal membrane oxygenation (ECMO). Finally, 70 patients (27.5%) were discharged automatically, while 50 patients (19.6%) died in the ICU, of which the ICU mortality of mild, moderate, and severe ARDS patients were 15.8% (9/57), 22.4% (28/125), and 17.8% (13/73), respectively. After follow-up, it was found that all 70 patients discharged automatically died within 28 days after discharge, and the overall ICU mortality adjusted accordingly was 47.1% (120/255). Conclusions:The overall incidence of ARDS in ICU patients at Hebei General Hospital is relatively low, with a high recognition rate by clinical physicians. Despite the high level of compliance and implementation of lung protective ventilation strategies and auxiliary treatment measures, it is still necessary to further improve the level of standardization in the implementation of small tidal volume and respiratory mechanics monitoring. For the implementation of auxiliary measures such as prone ventilation, it is necessary to further improve the enthusiasm of medical staff. The mortality in ICU is relatively low in ARDS patients, while the rate of spontaneous discharge is relatively high.

Objective: Excessive daytime sleepiness (EDS) and insomnia symptoms are common in patients with major depressive disorder (MDD), which might lead to a poor prognosis and an increased risk of depression relapse. The current study aimed to investigate the prevalence, and sociodemographic and clinical correlates of EDS and insomnia symptoms among adolescents with MDD. Methods: The sample of this cross-sectional study included 297 adolescents (mean age=15.26 years; range=12–18 years; 218 females) with MDD recruited from three general and four psychiatric hospitals in five cities (Hefei, Bengbu, Fuyang, Suzhou, and Ma’anshan) in Anhui Province, China between January and August, 2021. EDS and insomnia symptoms, and clinical severity of depressive symptoms were assessed using Epworth sleepiness scale, Insomnia Severity Index, and Clinical Global Impression-Severity. Results: The prevalence of EDS and insomnia symptoms in adolescents with MDD was 39.7% and 38.0%, respectively. Binary logistic regression analyses showed that EDS symptoms were significantly associated with higher body mass index (odds ratio [OR]=1.097, 95% confidence interval [CI]=1.027–1.172), more severe depressive symptoms (OR=1.313, 95% CI=1.028–1.679), and selective serotonin reuptake inhibitors use (OR=2.078, 95% CI=1.199–3.601). And insomnia symptoms were positively associated with female sex (OR=1.955, 95% CI=1.052–3.633), suicide attempts (OR=1.765, 95% CI=1.037–3.005), more severe depressive symptoms (OR=2.031, 95% CI=1.523–2.709), and negatively associated with antipsychotics use (OR=0.433, 95% CI=0.196–0.952). Conclusion EDS and insomnia symptoms are common among adolescents with MDD. Considering their negative effects on the clinical prognosis, regular screening and clinical managements should be developed for this patient population.