ObjectiveTo observe the protective effect of Erchentang （ECT） on SiO₂-induced lung injury in rats and to explore its underlying mechanism. MethodsA rat model of lung injury was established by a single intratracheal instillation of 50 mg·mL^-1 SiO₂ suspension. Thirty male Sprague-Dawley （SD） rats were randomly assigned to five groups： control， model， low and high-dose （4.5 g·kg^-1·d^-1 and 9 g·kg^-1·d^-1， respectively） ECT， and dexamethasone （0.2 mg·kg^-1·d^-1）. All the groups were treated for 4 consecutive weeks. Histopathological alterations in the lung tissue were examined by hematoxylin and eosin （HE） staining. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px） in the lung tissue were measured through biochemical assays. The expression of key molecules in the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway was determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunofluorescence assay. The primary active components of ECT were identified by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and their binding affinity to Nrf2/HO-1 was assessed by molecular docking. Untargeted metabolomics of the lung tissue was performed based on UPLC-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and correlation analysis was performed to identify differential metabolites and parameters closely associated with the Nrf2/HO-1 pathway. ResultsCompared with the control group， the model group exhibited a reduction in body weight gain， an increase in lung index， increased MDA content， weakened SOD and GSH-Px activities in the lung tissue， down-regulated mRNA and protein levels of Nrf2 and protein levels of HO-1 and GPX4， and an up-regulated protein level of Keap1 （P<0.05， P<0.01）. Treatment with ECT attenuated the SiO₂-induced decline in body weight （P<0.05）， alleviated inflammatory cell infiltration and silicotic nodule formation in alveoli， and reduced the MDA content and enhanced the SOD and GSH-Px activities in the lung tissue （P<0.05， P<0.01）. UPLC-MS/MS and molecular docking revealed that core components of ECT， such as hesperidin and glycyrrhizic acid， displayed strong binding affinity to Nrf2/HO-1. Molecular biological experiments demonstrated that ECT promoted nuclear translocation of Nrf2， up-regulated the mRNA and protein levels of HO-1 and GPX4， and down-regulated Keap1 expression （P<0.05， P<0.01）. Metabolomic analysis indicated that ECT reversed the SiO₂-induced aberrant expression of metabolites， including linoleic acid and glutamine （P<0.05， P<0.01）. Correlation analysis showed that Nrf2 and HO-1 were positively correlated with SOD and GSH-Px （P<0.05， P<0.01）， but negatively correlated with glutamine and serine （P<0.05， P<0.01）. ConclusionECT may activate the Nrf2/HO-1 pathway through its core active components， thereby regulating oxidative stress and metabolic disorders to ameliorate SiO₂-induced lung injury in rats. This study provides experimental evidence for ECT in the prevention and treatment of occupational lung injury.

Purpose To develop and validate an integrated model based on preoperative CT radiomic habitat analysis for predicting overall survival(OS)and progression-free survival(PFS)in patients with stage Ⅰ-ⅢA resectable non-small cell lung cancer(NSCLC).Materials and Methods A retrospective analysis was conducted on 341 NSCLC patients from the Second Affiliated Hospital of Naval Medical University from January 2016 to February 2023.Patients were randomly divided into training(n=238)and validation(n=103)cohorts.Tumor volumes of interest were manually delineated using 3D Slicer software.Habitat subregions were segmented via K-means clustering,and radiomic features were extracted using Pyradiomics.Key features were selected using LASSO-Cox regression.Integrated Cox proportional hazards models combining clinical factors and radiomic habitat features were constructed to predict OS and PFS.Model performance was evaluated using the concordance index,receiver operating characteristic curve and Kaplan-Meier analysis.Interpretability was explored via SHAP analysis.Results Habitat subregion analysis demonstrated superior prognostic predictive performance compared to conventional whole-tumor radiomic analysis.In the validation cohort,the integrated OS model and PFS model achieved the highest predictive accuracy,with concordance index 0.878 and 0.795,respectively.Receiver operating characteristic curve analysis showed that the integrated OS model predicted 1-,3-,and 5-year survival with areas under the curve of 0.781,0.878 and 0.881,respectively;while the integrated PFS model achieved areas under the curve of 0.786,0.725 and 0.715.Kaplan-Meier analysis confirmed significant survival differences between high-risk group and low-risk group(P<0.05).Conclusion The integrated model based on CT radiomic habitat analysis non-invasively and accurately predicts OS and PFS in stage Ⅰ-ⅢA NSCLC patients,providing critical insights for personalized treatment decision-making.

Purpose To develop and validate an integrated model based on preoperative CT radiomic habitat analysis for predicting overall survival(OS)and progression-free survival(PFS)in patients with stage Ⅰ-ⅢA resectable non-small cell lung cancer(NSCLC).Materials and Methods A retrospective analysis was conducted on 341 NSCLC patients from the Second Affiliated Hospital of Naval Medical University from January 2016 to February 2023.Patients were randomly divided into training(n=238)and validation(n=103)cohorts.Tumor volumes of interest were manually delineated using 3D Slicer software.Habitat subregions were segmented via K-means clustering,and radiomic features were extracted using Pyradiomics.Key features were selected using LASSO-Cox regression.Integrated Cox proportional hazards models combining clinical factors and radiomic habitat features were constructed to predict OS and PFS.Model performance was evaluated using the concordance index,receiver operating characteristic curve and Kaplan-Meier analysis.Interpretability was explored via SHAP analysis.Results Habitat subregion analysis demonstrated superior prognostic predictive performance compared to conventional whole-tumor radiomic analysis.In the validation cohort,the integrated OS model and PFS model achieved the highest predictive accuracy,with concordance index 0.878 and 0.795,respectively.Receiver operating characteristic curve analysis showed that the integrated OS model predicted 1-,3-,and 5-year survival with areas under the curve of 0.781,0.878 and 0.881,respectively;while the integrated PFS model achieved areas under the curve of 0.786,0.725 and 0.715.Kaplan-Meier analysis confirmed significant survival differences between high-risk group and low-risk group(P<0.05).Conclusion The integrated model based on CT radiomic habitat analysis non-invasively and accurately predicts OS and PFS in stage Ⅰ-ⅢA NSCLC patients,providing critical insights for personalized treatment decision-making.

Objective:To investigate the association of exposure to PM 2.5 and its constituents during pregnancy and fetal growth and to further identify critical windows of exposure for fetal growth. Methods:We included 4 089 mother-child pairs from the Jiangsu Birth Cohort Study between January 2016 and October 2019. Data of general characteristics, clinical information, daily average PM 2.5 exposure, and its constituents during pregnancy were collected. Fetal growth parameters, including head circumference (HC), abdominal circumference (AC), and femur length (FL), were measured by ultrasound after 20 weeks of gestation, and then estimated fetal weight (EFW) was calculated. Generalized linear mixed models were adopted to examine the associations of prenatal exposure to PM 2.5 and its constituents with fetal growth. Distributed lag nonlinear models were used to identify critical exposure windows for each outcome. Results:A 10 μg/m 3 increase in PM 2.5 exposure during pregnancy was associated with a decrease of 0.025 ( β=-0.025, 95% CI: -0.048- -0.001) in HC Z-score, 0.026 ( β=-0.026, 95% CI: -0.049- -0.003) in AC Z-score, and 0.028 ( β=-0.028, 95% CI:-0.052--0.004) in EFW Z-score, along with an increased risk of 8.5% ( RR=1.085, 95% CI: 1.010-1.165) and 13.5% ( RR=1.135, 95% CI: 1.016-1.268) for undergrowth of HC and EFW, respectively. Regarding PM 2.5 constituents, prenatal exposure to black carbon, organic matter, nitrate, sulfate (SO 42-) and ammonium consistently correlated with decreased HC Z-score. SO 42- exposure was also associated with decreased FL Z-scores. In addition, we found that gestational weeks 2-5 were critical windows for HC, weeks 4-13 and 19-40 for AC, weeks 4-13 and 23-37 for FL, and weeks 4-12 and 20-40 for EFW. Conclusions:Our findings demonstrated that exposure to PM 2.5 and its constituents during pregnancy could adversely affect fetal growth and the critical windows for different fetal growth parameters are not completely consistent.

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 clinical features and surgical outcomes of greater trochanteric fractures of the femoral neck in children.Methods:A retrospective study was conducted to analyze the 5 children with greater trochanteric fracture of the femoral neck who had been treated at Department of Pediatric Orthopaedics, Fuzhou Second General Hospital from January 2011 to December 2020. There were 1 boy and 4 girls, with an age of (11.0±1.9) years. By the Delbet classification, all were type Ⅲ fractures. The time from injury to operation was (4.4±2.1) days. The children were treated with cannulated screws (1 case) or fixation with a pediatric hip plate (4 cases). The clinical features of such fractures were analyzed; the fracture union time and hip function and complications at the last follow-up were recorded.Results:The clinical features of greater trochanteric fractures of the femoral neck in children were: (1) involvement of 2 anatomic sites in a narrow region, (2) comminuted fractures, and (3) all Delbet type Ⅲ fractures. The follow-up time was (22.8±6.0) months. All the 5 children obtained bony union. The union time was (5.2±1.8) weeks for greater trochanteric fractures, and 8.0 (8.0,10.0) weeks for femoral neck fractures. Follow-up observed no necrosis of the femoral head, premature closure of the femoral head epiphysis, hip varus deformity, or length disparity between the lower limbs. Premature closure of the greater trochanteric epiphysis occurred in 2 children after surgery. According to the Ratliff scoring, the hip function was excellent in 3 cases and good in 2.Conclusions:Greater trochanteric fractures of the femoral neck in children are a special kind of proximal femoral comminuted fractures that affect 2 anatomic sites in a narrow region and belong all to Delbet type Ⅲ fractures. Open reduction and internal fixation with cannulated screws or a pediatric hip plate is a safe and effective treatment for such fractures.

Objective:To evaluate the relationship between the mechanism underlying electroacupuncture-induced reduction of postoperative cognitive dysfunction and microglial nuclear factor kappa B (NF-κB)/NOD-like receptor protein 3 (NLRP3) signaling pathway in aged mice.Methods:Sixty SPF healthy male C57BL/6 mice, aged 18 months, weighing 27-30 g, were allocated into 4 groups ( n=15 each) using a random number table method: control group (C group), operation group (O group), operation plus sham electroacupuncture group (O+ SE group) and operation plus electroacupuncture group (O+ Egroup). In O+ E group, the mice received electrical stimulation at the Baihui and Shenting acupoints for a duration of 30 min. The electroacupuncture entailed the utilization of a continuous wave with a frequency of 10 Hz, an intensity of 1 mA, and a daily application for 5 consecutive days. The mice in Y group underwent the same procedure as O+ E group, except that no electrical stimulation was administered. Laparotomy was performed on the mice following a 3% isoflurane anesthesia in O, O+ SE, and O+ E groups. The open field test was conducted in the morning of 6th day after surgery to assess the spontaneous activity and anxiety-like behavior. The novel object recognition test was subsequently performed in the afternoon of 6th day after surgery. The fear conditioning test was performed on 7th day postoperatively. The mice were sacrificed under deep anesthesia at the end of behavioral testing, and the hippocampal tissue was extracted for determination of the expression of phosphorylated NF-κB p65 (p-NF-κB p65), NLRP3, postsynaptic density protein-95 (PSD-95), and synaptic vesicle protein (SYN) (by Western blot) and the co-staining area of NLRP3 and ionized calcium-binding adapter molecule 1 (Iba1, a specific marker for microglia) (by immunofluorescence staining) and for measurement of the dendritic length and dendritic spine density of neurons in the hippocampal CA1 region (using Golgi staining). Results:No statistically significant differences were observed in terms of movement speed, distance traveled, and time of center stay during the open field test among the four groups ( P>0.05). Compared to C group, the percentage of novel object exploration and discrimination index were significantly decreased, the freezing time was prolonged, the expression of p-NF-κB p65 and NLRP3 in the hippocampal tissue was up-regulated, the co-staining area of NLRP3 and Iba1 was increased, the expression of PSD-95 and SYN was down-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were decreased in O, O+ SE and O+ E groups ( P<0.05). Compared to O group, the percentage of novel object exploration and discrimination index were significantly increased, the freezing time was shortened, the expression of p-NF-κB p65 and NLRP3 in the hippocampal tissue was down-regulated, the co-staining area of NLRP3 and Iba1 was decreased, the expression of PSD-95 and SYN was up-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were increased in O+ E group ( P<0.05), and no significant change was found in each parameter in O+ SE group ( P>0.05). Compared to O+ SE group, the percentage of novel object exploration and discrimination index were significantly increased, the freezing time was shortened, the expression of p-NF-κB p65 and NLRP3 in the hippocampal tissue was down-regulated, the co-staining area of NLRP3 and Iba1 was decreased, the expression of PSD-95 and SYN was up-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were increased in O+ E group ( P<0.05). Conclusions:The mechanism by which electroacupuncture attenuates postoperative cognitive dysfunction is associated with inhibition of activation of NF-κB/NLRP3 signaling pathway in microglial cells and improvement in synaptic plasticity in aged mice.

Sepsis-associated coagulopathy refers to extensive coagulation activation accompanied by a high risk of bleeding and organ failure. In severe cases, it is manifested as disseminated intravascular coagulation (DIC) and leads to multiple organ dysfunction syndrome (MODS). Complement is an important component of the innate immune system and plays an important role in defending against invasion of pathogenic microorganisms. The early pathological process of sepsis involves excessive activation of the complement system, which forms an extremely complex network through interactions with the coagulation, kinin and fibrinolytic system, amplifying and exacerbating the systemic inflammatory response. In recent years, it has been suggested that uncontrolled complement activation system can exacerbate sepsis-associated coagulation dysfunction or even DIC, indicating the potential value of intervening in the complement system in the treatment of septic DIC, and related research progress is reviewed in this article in order to provide new ideas for the discovery of sepsis-associated coagulopathy therapy drugs.
Humans ; Blood Coagulation Disorders ; Complement Activation ; Blood Coagulation ; Multiple Organ Failure ; Sepsis

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone